Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149871 (deep vein thrombosis)
 12,364 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Moderate alcohol consumption is associated with lower levels of several coagulation factors. It is an established protective factor for cardiovascular disease; however, the effect on venous thrombosis is unknown. In a large population-based case-control study, we evaluated the association between alcohol consumption and the risk of venous thrombosis. The MEGA study included consecutive patients with a first venous thrombosis between March 1999 and September 2004 from six anticoagulation clinics in the Netherlands. Partners of patients were asked to participate, and additional controls were recruited using a random digit dialling method. All participants completed a standardized questionnaire, and blood samples were collected. A total of 4,423 patients and 5,235 controls were included in the analyses. Alcohol consumption was associated with a reduced risk of venous thrombosis, with 2-4 glasses per day resulting in the largest beneficial effect (odds ratio [OR] 0.67, 95% confidence interval [CI95] 0.58-0.77) compared to abstainers. The effect was more pronounced in women (OR 0.66, CI95 0.53-0.84) than men (OR 0.82, CI95 0.63-1.07) and also more striking for pulmonary embolism (OR 0.56, CI95 0.46-0.70) than for deep venous thrombosis of the leg (OR 0.74, CI95 0.63-0.88). Compared to abstainers, fibrinogen levels were decreased in individuals who consumed alcohol (maximum decrease: 0.30 g/l). Factor VII and von Willebrand levels were mildly decreased in these individuals but not consistently over the categories of alcohol consumption. In conclusion, alcohol consumption is associated with a reduced risk of venous thrombosis, which may be in part mediated by decreased fibrinogen levels.
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PMID:Alcohol consumption is associated with a decreased risk of venous thrombosis. 1821 35

Hormone replacement therapy (HRT) in young postmenopausal women is a safe and effective tool to counteract climacteric symptoms and to prevent long-term degenerative diseases, such as osteoporotic fractures, cardiovascular disease, diabetes mellitus and possibly cognitive impairment. The different types of HRT offer to many extent comparable efficacies on symptoms control; however, the expert selection of specific compounds, doses or routes of administration can provide significant clinical advantages. This paper reviews the role of the non-oral route of administration of sex steroids in the clinical management of postmenopausal women. Non-orally administered estrogens, minimizing the hepatic induction of clotting factors and others proteins associated with the first-pass effect, are associated with potential advantages on the cardiovascular system. In particular, the risk of developing deep vein thrombosis or pulmonary thromboembolism is negligible in comparison to that associated with oral estrogens. In addition, recent indications suggest potential advantages for blood pressure control with non-oral estrogens. To the same extent, a growing literature suggests that the progestins used in association with estrogens may not be equivalent. Recent evidence indeed shows that natural progesterone displays a favorable action on the vessels and on the brain, while this might not be true for some synthetic progestins. Compelling indications also exist that differences might also be present for the risk of developing breast cancer, with recent trials indicating that the association of natural progesterone with estrogens confers less or even no risk of breast cancer as opposed to the use of other synthetic progestins. In conclusion, while all types of hormone replacement therapies are safe and effective and confer significant benefits in the long-term when initiated in young postmenopausal women, in specific clinical settings the choice of the transdermal route of administration of estrogens and the use of natural progesterone might offer significant benefits and added safety.
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PMID:Could transdermal estradiol + progesterone be a safer postmenopausal HRT? A review. 1877 9

The aim was to investigate different genotypes and haplotypes of methylenetetrahydrofolate reductase (MTHFR-677, -1298) and plasma concentration of total homocysteine (tHcy) in Macedonian patients with occlusive artery disease (OAD) and deep venous thrombosis (DVT). Investigated groups consists of 80 healthy, 74 patients with OAD, and 63 patients with DVT. Plasma tHcy was measured with Microplate Enzyme Immunoassay. Identification of MTHFR genotypes and haplotypes was done with CVD StripAssay. The probability level (P-value) was evaluated by the Student's t-test. Plasma concentration of tHcy in CC and CT genotypes of MTHFR C677T was significantly increased in patients with OAD and in patients with DVT. Plasma concentration of tHcy in AC genotype of MTHFR A1298C was increased in patients with OAD and in patients with DVT. Plasma concentration of tHcy was significantly increased in AA genotype of patients with OAD, but not in patients with DVT. We found a significant increase of plasma tHcy in patients with OAD in comparison with healthy respondents for normal:heterozygote (CC:AC), heterozygote:normal (CT:AA), and heterozygote:heterozygote (CT:AC) haplotypes. Plasma concentration of tHcy in patients with DVT in comparison with healthy respondents was significantly increased for normal:normal (CC:AA), normal heterozygote (CC:AC), and heterozygote:heterozygote (CT:AC) haplotypes. We conclude that MTHFR C677T and MTHFR A1289C genotypes and haplotypes are connected with tHcy plasma levels in Macedonian patients with OAD and DVT.
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PMID:Methylenetetrahydrofolate reductase (MTHFR-677 and MTHFR-1298) genotypes and haplotypes and plasma homocysteine levels in patients with occlusive artery disease and deep venous thrombosis. 1880 Jan 76

Evaluation of: Bellamy L, Casas JP, Hingorani AD, Williams DJ: Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis. Br. Med. J. 335(7627), 974 (2007). Evidence has emerged over the years suggesting that women who develop hypertensive pregnancy disorders, most notably pre-eclampsia, are at an increased risk for cardiovascular disease later in life. In this study, a systematic review and meta-analysis were performed, assessing the future risks of cardiovascular disease, cancer and all-cause mortality in women with a history of pre-eclampsia and eclampsia. Women with a history of pre-eclampsia or eclampsia, compared with women without such a history, had an increased risk for cardiovascular disease, including a fourfold increased risk for hypertension, a twofold increased risk for ischemic heart disease, stroke and deep venous thrombosis, and a 1.5-times higher all-cause mortality. The study suggests that affected women may be eligible for preventive therapies at an earlier age, especially if future studies establish the role of pre-eclampsia as an independent cardiovascular risk factor.
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PMID:Pre-eclamptic pregnancies: an opportunity to identify women at risk for future cardiovascular disease. 1907 14

Associations between combined estrogen/progestin oral contraceptives (OCs) and cardiovascular disease (CVD) have long been the focus of considerable concern. Initial, epidemiologic studies demonstrated increased risks of potential complications including deep venous thrombosis/pulmonary embolism, myocardial infarction and stroke. While the studies regarding venous thromboembolism consistently demonstrate at least some degree of risk associated with OC use, recent studies of both current and past OC users indicate that the association with arterial disease is dynamic, changing rapidly as OC formulations and OC-user populations change. As physicians increase selection, screening and monitoring of OC users, a healthier OC-user population is developing. Thus, many newer studies are demonstrating rates of angina and myocardial infarction that are either lower or the same as that of non-users, unless pre-existing risk factors are present leading to potential increases in risk of CVD. The evidence with regards to strokes is more complicated and controversial. While further study is necessary, current evidence suggests that OC use provides significant contraceptive benefits with minimal potential adverse effects in healthy users. The potential for CVD reduction in selected OC users merits the highest priority for further investigation.
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PMID:Oral contraceptives and cardiovascular disease: emerging evidence on potential associations with angina, myocardial infarction and stroke. 1980 54

Venous thromboembolism is the most preventable illness among patients in hospital. We prepared guidelines for the prophylaxis of venous thromboembolism, based on previous experience of perioperative risk factors. The aim of this study was to evaluate the effectiveness of these guidelines. All 1,467 patients who underwent surgery for thoracic or cardiovascular disease between April 2002 and July 2004, before the prophylactic guidelines were implemented, were assigned to group A. Another 1,389 patients who had surgery between August 2004 and December 2006, after the guidelines had been implemented, formed group B. The incidences of venous thromboembolism perioperatively in the 2 groups were compared. Six (0.4%) patients in group A developed deep vein thrombosis or pulmonary embolism, whereas no patient in group B experienced thromboembolism. The difference between groups was significant, so we consider our guidelines for venous thromboembolism prevention in the perioperative period to be clinically useful.
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PMID:Prevention of venous thromboembolism in thoracic and cardiovascular surgery. 1991 94

Acute coronary syndrome most commonly begins with atherosclerotic plaque rupture and intracoronary thrombus formation. Therefore, the primary goal of treatment for acute coronary syndrome is the achievement of early and complete reperfusion. The diagnosis of acute myocardial infarction (AMI) is made from typical symptoms, characteristic rises in serum enzyme levels, and changes in the electrocardiographic pattern. Although rapid developments in technology in the field of serum biomarkers have redefined the diagnosis of AMI, the electrocardiogram still remains significant in the diagnosis of AMI. Moreover, the identification of high-risk subgroups based on the admission electrocardiogram is essential to estimate the severity of AMI. Pulmonary embolism is an another thromboembolic disorder leading to mortality worldwide. The relationship between deep vein thrombosis and pulmonary embolism has been emphasized. The early detection of free-floating deep venous thrombosis by venous ultrasonography of the lower extremities is critical to prevent pulmonary embolism. For the detection of atherosclerosis, the identification of myocardial necrosis and thrombi by imaging tests is important. This paper reports the clinical usefulness of various noninvasive diagnostic approaches in cardiovascular disease.
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PMID:[Clinical significance of physiological function testing in cardiovascular disease]. 2007 24

The innate immune system and the blood haemostasis system function cooperatively in many pathological conditions such as acute respiratory distress syndrome, deep venous thrombosis, ischaemia/reperfusion injury and cardiovascular disease. Infiltration of neutrophils into thrombotic substrates such as fibrin clots supports fibrinolysis, tissue damage and inflammation. Despite the importance of integrins in neutrophil attachment to fibrin-coated surfaces under flow conditions, little is known about their role in migration processes in shear free two-dimensional (2D) and three-dimensional (3D) fibrin(ogen) environments. Therefore, the present study was designed to study the role of functional integrins in mediating neutrophil migration on and in fibrin matrices. Time lapse video sequences of neutrophil chemokinesis and chemotaxis were made under conditions of active- or non-active integrins. Interestingly, migration of neutrophils on 2D fibrinogen coated surfaces and 3D fibrin matrices is independent of integrins as the response is not sensitive to alphaM-(CD11b) and beta2-(CD18) blocking antibodies and/or chelation of Ca2+ and Mg2+ by EDTA in bivalent ion-free buffers. The blocking integrin antibodies were shown to be functionally active in regular adhesion assays. Our study shows that integrins are dispensable for migration on 2D and in 3D fibrin matrices, both when neutrophils enter into the fibrin matrix and when captured in the matrix.
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PMID:Integrins on neutrophils are dispensable for migration into three-dimensional fibrin gels. 2058 24

Previously, we reported the discovery of PSI-697 (1a), a C-2 benzyl substituted quinoline salicylic acid-based P-selectin inhibitor. It is active in a variety of animal models of cardiovascular disease. Compound 1a has also been shown to be well tolerated and safe in healthy volunteers at doses of up to 1200 mg in a phase 1 single ascending dose study. However, its oral bioavailability was low. Our goal was to identify a back up compound with equal potency, increased solubility, and increased exposure. We expanded our structure-activity studies in this series by branching at the alpha position of the C-2 benzyl side chain and through modification of substituents on the carboxylic A-ring of the quinoline. This resulted in discovery of PSI-421 with marked improvement in aqueous solubility and pharmacokinetic properties. This compound has shown oral efficacy in animal models of arterial and venous injury and was selected as a preclinical development compound for potential treatment of such diseases as atherosclerosis and deep vein thrombosis.
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PMID:Discovery of 2-[1-(4-chlorophenyl)cyclopropyl]-3-hydroxy-8-(trifluoromethyl)quinoline-4-carboxylic acid (PSI-421), a P-selectin inhibitor with improved pharmacokinetic properties and oral efficacy in models of vascular injury. 2071 94

The most frequent ultimate cause of death is myocardial arrest. In many cases this is due to myocardial hypoxia, generally arising from failure of the coronary macro- and microcirculation to deliver enough oxygenated red cells to the cardiomyocytes. The principle reason for this is occlusive thrombosis, either by isolated circulating thrombi, or by rupture of upstream plaque. However, an additionally serious pathology causing potentially fatal stress to the heart is extra-cardiac disease, such as pulmonary hypertension. A primary cause of the latter is pulmonary embolus, considered to be a venous thromboembolism. Whilst the thrombotic scenario has for decades been the dominating paradigm in cardiovascular disease, these issues have, until recently, been infrequently considered in cancer. However, there is now a developing view that cancer is also a thrombotic disease, and notably a disease predominantly of the venous circulation, manifesting as deep vein thrombosis and pulmonary embolism. Indeed, for many, a venous thromboembolism is one of the first symptoms of a developing cancer. Furthermore, many of the standard chemotherapies in cancer are prothrombotic. Accordingly, thromboprophylaxis in cancer with heparins or oral anticoagulation (such as Warfarin), especially in high risk groups (such as those who are immobile and on high dose chemotherapy), may be an important therapy. The objective of this communication is to summarise current views on the epidemiology and pathophysiology of arterial and venous thrombosis in cancer.
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PMID:Arterial and venous thrombosis in cancer patients. 2140 76


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