Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obesity is a risk factor for venous and arterial thrombosis. We examined relationships between body mass index (BMI) and a number of haemostatic and inflammatory variables in a community-based study of 150 adults (73 male, 77 female; age range, 23-80 years). Associations with BMI were sought after adjustment for age, smoking and diurnal variation. There were significant interactions of gender on the associations of BMI with fibrinogen (P = 0.002) and C-reactive protein (P = 0.02). In women, there were strong positive associations of BMI with fibrinogen (r = 0.57, P < 0.0001) and C-reactive protein (r = 0.40, P = 0.001). In men, these associations were non-significantly inverse. For all other variables there were no sex differences, so results for men and women were combined. Significant positive associations with BMI were seen for factor VIIc, activated factor XII, antithrombin activity, protein C activity and plasminogen activator inhibitor-1 activity. Inverse associations with BMI were seen for tissue plasminogen activator activity and activated protein C ratio. Increasing BMI is associated with elevation of certain coagulation factors, inhibitors of fibrinolysis, and inhibitors of coagulation, the latter potentially reflecting a compensatory response. Gender influences the association of certain inflammatory variables with BMI so the sexes should be considered separately in studies of inflammation and obesity.
 ...
PMID:Associations of haemostatic variables with body mass index: a community-based study. 1296 Jun 11

The resistance to activated protein C (APC-resistance) based on the presence of factor V Leiden (F V Leiden) is the most frequent thrombophilic condition in the white race population. It contributes to the origin of thrombosis especially in the venous part of blood vessels. Significant geographic differences have been detected within Europe. The aim of this retrospective study was to determine the frequency in the occurrence of F V Leiden: 1. in healthy (asymptomatic) Slovak population, 2. in their consanguineously unrelated members with thrombosis and 3. in patients with myocardial infarction (IM) without or with other known risk factors of this disease (nicotinism, obesity, hypertension, dyslipoproteinemia, diabetes mellitus), respectively. The detection of FV Leiden was made by molecular biology methods. The occurrence in a group of 152 healthy individuals was four % (6 persons) and this frequency corresponds to the geographic localization of the Slovak Republic in Europe. In a group of 349 patients with thrombosis in anamnesis, FV Leiden was detected in 103 persons (29.5%). The occurrence was higher than the usually reported incidence in these patients (20%). Likewise, in a group of 35 patients with IM without risk factors in anamnesis, the occurrence of FV Leiden (8.6%) was significantly higher in comparison with healthy population and the incidence further increased significantly in a group of 41 patients with IM and the presence of at least one risk factor (14.6%). The authors therefore suppose an active role of the Leiden mutation of FV gene in the pathogenesis of this disease.
 ...
PMID:[Factor V Leiden and the Slovak population]. 1468 80

Venous thromboembolism is a common and potentially fatal disease. If properly used, anticoagulation therapy is effective in preventing recurrence of venous thromboembolism and in improving survival. Symptomatic patients with an objective diagnosis of acute deep vein thrombosis (DVT) or pulmonary embolism (PE) should receive immediate systemic heparin anticoagulation at dosages sufficient to rapidly prolong the activated partial thromboplastin time into the laboratory-specific therapeutic range; this range corresponds to a plasma heparin concentration of 0.2 to 0.4 IU/ml (as measured by protamine sulfate titration), or 0.3 to 0.7 anti-Xa IU/ml. An oral vitamin K antagonist (e.g. warfarin) should be started within 24 hours after starting heparin; the starting dose should be the estimated patient-specific daily dose with no loading dose. Heparin and warfarin anticoagulation should be overlapped for at least 4 to 5 days and until the international normalized ratio (INR) is within the therapeutic range (2.0 to 3.0) on 2 measurements made at least 24 hours apart. The duration of warfarin anticoagulation should be individualized based on the respective risks of venous thromboembolism recurrence and anticoagulant-related bleeding. In general, warfarin should be continued for at least 3 months, and longer for patients with recurrent or idiopathic venous thromboembolism, malignant neoplasm, neurologic disease with extremity paresis, obesity, or laboratory evidence of a lupus anticoagulant/anticardiolipin antibody, homozygous carrier or combined heterozygous carrier for the factor V R506Q (Leiden) and prothrombin G20210A mutations, and possibly deficiency of either antithrombin, protein C, or protein S. Low molecular weight heparin (LMWH) is effective and well tolerated as acute therapy for patients with DVT or stable PE, and does not require laboratory monitoring or dose adjustment. Outpatient LMWH therapy is also well tolerated and cost effective for most patients with DVT, and possibly for selected patients with PE.
 ...
PMID:Current management of acute symptomatic deep vein thrombosis. 1472 51

Warfarin-induced necrosis of the breast is an unusual complication of warfarin therapy. Since its first description in 1943, up to 36 cases have been reported in the English literature. Close association between inherited or functional deficiency of protein C and S and warfarin therapy is frequently reported. A characteristic patient is an obese middle-aged female receiving anticoagulant treatment. The rapidly evolving painful lesion appears suddenly, usually within 3 to 6 days after initiation of warfarin therapy. Prevention may be achieved by identifying the high-risk patients-female gender, middle age, obesity, and avoiding large loading doses of warfarin. Early recognition and treatment are necessary to avoid significant long-term morbidity. Established necrosis necessitates debridement and sometimes mastectomy. A case of warfarin-induced necrosis of the left breast mimicking inflammatory cancer is reported. Current recommendations for the prevention and treatment of this uncommon condition are reviewed.
 ...
PMID:Warfarin-induced necrosis of the breast: case report. 1562 67

From 1998 to 2003, 133 Caucasian women aged 17-40 years (median 29 years) suffering from unexplained recurrent miscarriage (uRM) were consecutively enrolled. In patients and 133 age-matched healthy controls prothrombotic risk factors (factor V (FV) G1691A, factor II (FII) G20210A, MTHFR T677T, 4G/5G plasminogen activator inhibitor (PAI)-1, lipoprotein (Lp) (a), protein C (PC), protein S (PS), antithrombin (AT), antiphospholipid/anticardiolipin (APA/ACA) antibodies) as well as associated environmental conditions (smoking and obesity) were investigated. 70 (52.6%) of the patients had at least one prothrombotic risk factor compared with 26 control women (19.5%; p<0.0001). Body mass index (BMI; p=0.78) and smoking habits (p=0.44) did not differ significantly between the groups investigated. Upon univariate analysis the heterozygous FV mutation, Lp(a) > 30 mg/dL, increased APA/ACA and BMI > 25 kg/m(2) in combination with a prothrombotic risk factor were found to be significantly associated with uRM. In multivariate analysis, increased Lp(a) (odds ratio (OR): 4.7/95% confidence interval (CI): 2.0-10.7), the FV mutation (OR:3.8/CI:1.4-10.7), and increased APA/ACA (OR: 4.5/CI: 1.1-17.7) had independent associations with uRM.
 ...
PMID:Lipoprotein (a) and other prothrombotic risk factors in Caucasian women with unexplained recurrent miscarriage. Results of a multicentre case-control study. 1588 1

Thrombophilia was implicated in the development of pregnancy complications, including recurrent idiopathic pregnancy loss, and is aggravated in women who are carriers of factor V G1691A (FV Leiden) and prothrombin (PRT) G20210A single-nucleotide polymorphisms (SNPs). Previous studies examined the role of FV-Leiden and PRT G20210A in recurrent pregnancy loss with conflicting results. Here we examined the prevalence of FV Leiden and PRT G20210A SNPs, in 200 women with 3 or more consecutive early (n = 87), late (n = 41), or early-late (n = 72) recurrent pregnancy losses, and 200 age-matched fertile parous control women. APC resistance (APCR) was detected functionally (measuring the activated clotting time triggered by activated factor X in presence of a fixed amount of purified APC), and FV-Leiden and PRT G20210A genotypes were assessed by PCR. The frequency of the mutant FV (0.1400 vs. 0.0276; P < 0.001) but not PRT 20210 (0.0100 vs. 0.0225; P = 0.159) allele was higher in patients than controls, respectively. APC resistance with factor V Leiden was seen in 27% of patients compared to 11.5% of controls, while APC resistance without factor V Leiden was seen in 12.5% of patients compared to 9.5% of controls. Regression analysis demonstrated that the significant predictors for early abortion was FV Leiden; those for late abortion were oral contraceptive, APCR, and FV Leiden; and predictors for early-late abortions were oral contraceptives, obesity, FV Leiden, and smoking. APC resistance and FV Leiden, as well as combination of both, are common thrombotic defects seen in women with idiopathic recurrent pregnancy loss, thus testing for these is recommended in women who have experienced recurrent miscarriages.
 ...
PMID:Association between adverse pregnancy outcomes and maternal factor V G1691A (Leiden) and prothrombin G20210A genotypes in women with a history of recurrent idiopathic miscarriages. 1613 41

The present study was designed to examine the effects of lifestyle modification on key contributing factors to atherogenesis, including oxidative stress, inflammation, chemotaxis, and cell adhesion. Obese men (n = 31), 15 of whom had metabolic syndrome, were placed on a high-fiber, low-fat diet in a 3-wk residential program where food was provided ad libitum and daily aerobic exercise was performed. In each subject, pre- and postintervention fasting blood was drawn for circulating levels of serum lipids, glucose and insulin (for estimation of insulin sensitivity), oxidative stress-generating enzyme myeloperoxidase and marker 8-isoprostaglandin F2alpha, the inflammatory protein C-reactive protein, soluble ICAM-1 as an indicator of endothelial activation, sP-selectin as a marker of platelet activation, the chemokine macrophage inflammatory protein-1alpha, and total matrix metalloproteinase-9. Using subject sera and human aortic endothelial cell culture systems, we measured VCAM-1 cell surface abundance and monocyte chemotactic protein-1, nitric oxide, superoxide, and hydrogen peroxide production in vitro by fluorometric detection. Also determined in vitro was serum-induced, monocyte adhesion and monocyte chemotactic activity. After 3 wk, significant reductions (P < 0.05) in body mass index, all serum lipids and lipid ratios, fasting glucose, insulin, homeostasis model assessment for insulin resistance, myeloperoxidase, 8-isoprostaglandin F2alpha, C-reactive protein, soluble ICAM-1, soluble P-selectin, macrophage inflammatory protein-1alpha, and matrix metalloproteinase-9 were noted. In vitro, serum-stimulated cellular VCAM-1 expression, monocyte chemotactic protein-1 production, and fluorometric detection of superoxide and hydrogen peroxide production decreased, whereas a concomitant increase in NO production was noted (all P < 0.01). Additionally, both monocyte adhesion (P < 0.05) and MCA (P < 0.01) decreased. Nine of 15 were no longer positive for metabolic syndrome postintervention. Intensive lifestyle modification may ameliorate novel coronary artery disease risk factors in men with metabolic syndrome factors before reversal of obesity.
 ...
PMID:Effect of a short-term diet and exercise intervention on oxidative stress, inflammation, MMP-9, and monocyte chemotactic activity in men with metabolic syndrome factors. 1661 61

The development of thromboses is one of the most common causes of morbidity and mortality in the Western world. The perturbation of haemostasis is the central event in the pathogenesis of all thromboses. Most patients with thromboses have no recognisable associated haemostatic disorders. However, some patients do manifest hereditary hypercoagulable states, which contribute to the development of thromboses as well as other clinical manifestations, such as miscarriages and foetal complications. The major determinants of thrombosis include both environmental influences and genetic factors. Transient or long-lasting environmental influences may play important roles in arterial and venous thromboses. Haemostatic perturbance may also be genetically determined and exert a life-long influence. Specific mutations of genes predisposed to thrombosis, such as deficiency of antithrombin, protein C, or protein S, are found in relatively small number of families. In the absence of genetic deficiencies, thrombosis occurs in the older population, largely within the context of marked environmental influences (such as surgery, obesity, and malignancy). In contrast, familial thrombosis, associated with gene mutation, is associated with a younger age. The general importance of gene polymorphism was established after the recognition of activated protein C resistance (APCR) due to gene polymorphism G1691A in factor V (Factor V Leiden). This single gene defect increases the risk of venous thrombosis, without interaction with other genetic or environmental risk factors. The development of APCR led to many other investigations of gene polymorphism, such as prothrombin 20210, thrombomodulin, factors in the coagulation and fibrinolytic system, glycoproteins of platelet membranes, as well as polymorphism C677T of methylene tetrahydrofolate reductase. The number of potential genetic risk factors for occlusive thrombotic disease has increased significantly. Most of these gene polymorphisms increase the risk of venous thrombosis but there is no strong evidence of their influence as far as arterial thrombosis is concerned.
 ...
PMID:[Role of gene polymorphism in development of thromboses]. 1679 67

Obesity is a risk factor for cardiovascular disease and thromboembolic events. We investigated the effects of weight reduction by a 12-week calorie-restricted diet with or without aerobic exercise (diet group and diet plus exercise group) on leptin and anticoagulation proteins levels. Forty-two obese nondiabetic individuals were evaluated for blood levels of leptin, protein C activity, free protein S antigen and for body fat area calculated on computerized tomography before and after intervention. Before intervention, serum levels of leptin and free protein S antigen correlated positively with several adiposity-related parameters. After the program, body weight and fat area were significantly decreased in both groups. Body mass index and leptin levels decreased in both groups, with a larger change in the diet plus exercise group than in the diet group. Although protein C activity levels did not change in both groups, free protein S antigen levels decreased significantly in the diet plus exercise group. In conclusion, the 12-week programs had significant effects on the initial weight reduction and body fat mass, decreasing lepin levels in obese nondiabetic individuals. To clarify whether aerobic exercise has additional or direct effects on the anticoagulation system, a study in a large number of individuals is needed.
 ...
PMID:Effects of diet with or without exercise on leptin and anticoagulation proteins levels in obesity. 1758 11

Asthma control is a key point in patient management. GINA's most recent report emphasises the need to investigate uncontrolled asthma, of which non-compliance with treatment, COPD, smoking, chronic sinusitis, gastroesophageal reflux disease and obesity are the usual causes. The aim of this work is to evaluate the role of pulmonary thromboembolism (PTE) in cases of difficult- -to-treat asthma. We reviewed the case reports of patients with severe persistent asthma followed in our Asthma Outpatients Clinic between 2004 and 2006. We selected the ones that maintained uncontrolled disease despite an optimal therapeutical approach and investigated the causes. In this group (n=254), 28 (11%) had severe persistent asthma and their mean age was 44 +/- SD18 years old. 86% were females. Of these, 57% (n=16) had uncontrolled disease: 35% (n=6) due to non-compliance with treatment; 29% (n=5) pulmonary thrombombolism (scintigraphic confirmation); 12% (n=2) severe rhinosinusitis; 6% (n=1) hypereosinophilic syndrome; 6% (n=1) persistent allergen exposure and 6% (n=1) are still being investigated. Patients with TPE (mean age 56 +/- SD9 years old; 80% females; 80% Caucasians) were diagnosed with asthma as adults (mean age 37 +/- SD14 years old). The mean time until the diagnosis of TPE was 18 +/- SD12 years. Predisposing factors for TPE were venous insufficiency (40%), hypertension (40%) and deficit of functional protein C and S (20%). All these patients received anticoagulant therapy (80% are still medicated). It should be noted that after the beginning of anticoagulants, 40% of the patients achieved control of their asthma and 40% have partially controlled disease. There were no hospital admissions for asthma exacerbations after the beginning of anticoagulation in this group. This study supports the inclusion of TPE in the group of comorbidities to consider while investigating uncontrolled asthma.
 ...
PMID:[Pulmonary embolism and difficult-to-treat asthma]. 1818 29


<< Previous 1 2 3 4 5 6 7 8 9 Next >>