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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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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.
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PMID:Lipoprotein (a) and other prothrombotic risk factors in Caucasian women with unexplained recurrent miscarriage. Results of a multicentre case-control study. 1588 1

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.
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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.
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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.
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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.
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PMID:[Pulmonary embolism and difficult-to-treat asthma]. 1818 29

We carried out clinical-instrumental examination of 456 men aged 40-54 years. First degree arterial hypertension was revealed in 165 men. Left ventricular hypertrophy was found in 48 (30%), increased intima-media thickness (IMT) - in 67 (41%) patients. There was significant medium power relationship between IMT and left ventricular myocardial mass (correlation coefficient 0.41). Formation of left ventricular hypertrophy was related to parameters of 24 hour blood pressure monitoring, arterial hypertension in brothers and sisters, body weight, and duration of obesity. Significant medium power relation was obtained between tension of endothelial system of hemostasis (protein C) and severity of left ventricular hypertrophy (correlation coefficient - 0,3). Age, heredity, low density lipoprotein, cholesterol, uric acid level mattered for IMT increase.
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PMID:[Left ventricular hypertrophy and thickening of common carotid artery wall in men aged 40 - 54 years with I degree arterial hypertension]. 1842 55

Obesity is associated with a high risk of cardiovascular events. Several haemostatic disturbances which could contribute to this increased risk have been described in obesity; nevertheless, the state of coagulation inhibitors has been scarcely studied in these patients. The aim of the present study was to compare activated protein C levels in obese patients and in a control group, and to evaluate the effect of weight loss. In 67 severe or morbid obese patients, an evaluation was performed at baseline and 3 months after diet. The same determinations were performed in 67 healthy volunteers with normal body weight. We also quantified the levels of protein C and prothrombin fragment 1+2. Obese patients showed significantly higher levels of activated protein C, protein C and fragment 1+2. No correlation was found between activated protein C and fragment 1+2 levels in obese patients. After three months of diet, a significant decrease in activated protein C and fragment 1+2 was observed. In conclusion, activated protein C levels are increased in obese patients, but only a minor fraction of this increase may be explained by the higher thrombin generation and C protein levels. Activated protein C levels decrease with weight loss, due in part to a thrombin generation reduction.
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PMID:Activated protein C levels in obesity and weight loss influence. 1883 18

A comprehensive understanding of the pathogenesis of venous thrombosis is essential for identifying patients at increased risk and who may therefore benefit from more aggressive preventive and therapeutic measures. As for other pathologies, the pathogenesis of venous thromboembolism is multifactorial. All risk factors, either congenital or acquired, are relatively "innocent" when considered alone. However, when an individual is unlucky enough to inherit one or more abnormality, compounded in many cases by environmental hazards, that person may be propelled over a threshold that precipitates the development of thrombosis. An appropriate analogy is that where "the last drop makes the cup run over." A reinterpretation of the traditional Virchow's triad (abnormal vessel wall, abnormal blood flow, and abnormal blood constituents) was provided by Eberhard Mammen throughout his research, and this has contributed greatly to the understanding of the pathogenesis of this serious disorder. Mammen postulated immobility as the leading event, because it reduced blood flow as a result of decreased muscle contraction. The subsequent "stasis of flow" led to accumulation of blood within the intramuscular sinuses, especially of the calf, triggering hypercoagulability due to local accumulation of activated clotting factors and coagulation activation products and the simultaneous consumption of blood coagulation inhibitors. On Mammen's "hit list" nearly 20 years ago were included (among inherited abnormalities) decreased protein C, protein S, antithrombin III, plasminogen, and tissue plasminogen activator, and increased plasminogen activator inhibitor-1, whereas (among acquired predisposing conditions) surgery, trauma, previous thromboembolism, prolonged immobility and paralysis, malignancy, congestive heart failure, obesity, advanced age, pregnancy and puerperium, varicose veins, and oral contraceptives were also identified. Some two decades later, the situation has perhaps not changed so much, although studies continue to expand our knowledge of this topic, clarifying the relative contribution of each single risk factor in the pathogenesis of venous thrombosis.
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PMID:Pathogenesis of venous thromboembolism: when the cup runneth over. 1921 13

Obesity leads to inflammation of white adipose tissue involving enhanced secretion of cytokines and acute-phase proteins in response in part to the accumulation of excess lipids in adipocytes. Haptoglobin is an acute-phase reactant secreted by white adipose tissue and induced by inflammatory cytokines such as TNFalpha. In this study, we investigated the mechanisms regulating haptoglobin expression in adipocytes. Peroxisome proliferator-activated receptor (PPAR)-gamma agonists such as thiazolidinediones (TZDs) as well as non-TZD ligands can repress in vitro and in vivo haptoglobin expression in adipocytes and also prevent its induction by TNFalpha. This action requires direct involvement of PPAR gamma in regulating haptoglobin gene transcription because mutation of critical amino acids within helix 7 of the ligand-binding domain of PPAR gamma prevents repression of the haptoglobin gene by the synthetic ligands. Chromatin immunoprecipitation analysis shows active binding of PPAR gamma to a distal region of the haptoglobin promoter, which contains putative PPAR gamma binding sites. Additionally, PPAR gamma induces transcription of a luciferase reporter gene when driven by the distal promoter region of the haptoglobin gene, and TZD treatment significantly reduces the extent of this induction. Furthermore, the mutated PPAR gamma is incapable of enhancing luciferase activity in these in vitro reporter gene assays. In contrast to other adipokines repressed by TZDs such as resistin and chemerin, repression of haptoglobin does not require either CCAAT/enhancer-binding protein C/EBP alpha or the corepressors C-terminal binding protein 1 or 2. These data are consistent with a model in which synthetic PPAR gamma ligands selectively activate PPAR gamma bound to the haptoglobin gene promoter to arrest haptoglobin gene transcription.
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PMID:Mechanisms regulating repression of haptoglobin production by peroxisome proliferator-activated receptor-gamma ligands in adipocytes. 1995 71


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