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Risk factors for acute venous occlusion range from prolonged immobilization to hypercoagulability syndromes, trauma, and malignancy. The aim of this review article is to illustrate the different imaging options for the diagnosis of acute venous occlusion and to assess the value of interventional strategies for venous thrombosis treatment in an emergency setting.First, diagnosis and treatment of the most common form of venous occlusion, at the level of the lower extremities, is presented, followed by pelvic vein and inferior vena cava occlusion, mesenteric venous thrombosis, upper extremity occlusion, acute cerebral vein thrombosis, and finally acute venous occlusion of hemodialysis access.In acute venous occlusion of the lower extremity phlebography is still the reference gold standard. Presently, duplex ultrasound with manual compression is the most sensitive and specific noninvasive test. Limitations of ultrasonography include isolated distal calf vein occlusion, obesity, and patients with lower extremity edema. If sonography is nondiagnostic, venography should be considered. Magnetic resonance venography can differentiate an acute occlusion from chronic thrombus, but because of its high cost and limited availability, it is not yet used for the routine diagnosis of lower extremity venous occlusion only. Regarding interventional treatment, catheter-directed thrombolysis can be applied to dissolve thrombus in charily selected patients with symptomatic occlusion and no contraindications to therapy. Acute occlusion of the pelvic veins and the inferior vena cava, often due to extension from the femoropopliteal system, represents a major risk for pulmonary embolism. Color flow Doppler imaging is often limited owing to obesity and bowel gas. Venography has long been considered the gold standard for identifying proximal venous occlusion. Both CT scanning and MR imaging, however, can even more accurately diagnose acute pelvis vein or inferior vena cava occlusion. MRI is preferred because it is noninvasive, does not require contrast agent, carries no exposure to ionizing radiation, and is highly accurate and reproducible. Apart from catheter-directed thrombolysis, mechanical thrombectomy has proven to be a quick and safe treatment modality by enabling the recanalization of thrombotic occlusions in conjunction with minimal invasiveness and a low bleeding risk. Mechanical thrombectomy devices should only be used in conjunction with a temporary cava filter.Contrast-enhanced CT is at present considered the examination of choice for acute mesenteric vein occlusion which has mortality rates as high as 80%. Patients with proven acute mesenteric venous occlusion and contraindications to surgical therapy and no identified bleeding disposition without looming bowel ischemia or infarction are possible contenders to the less invasive percutaneous approach either by (in)direct thrombolysis or mechanical means. Ultrasonography is the primary imaging modality for the diagnosis of upper extremity thrombosis. Computed tomography and MRI are in addition helpful in diagnosing central chest vein occlusions. The interventionalist is rarely involved in the treatment of this entity. Catheter-directed thrombolysis is known to improve lysis rates. Together with balloon angioplasty good results have been obtained. If stenosis or thrombus remains after thrombolysis and angioplasty, stent placement should follow. Within the first two weeks, thrombosed dural sinus and cerebral venous vessels are typically hyperdense on CT compared with brain parenchyma; after the course of 2 weeks, the thrombus will become isodense. In MRI an axial fluid-attenuated inversion recovery sequence, an axial diffusion-weighted MRI, coronal T1-weighted spin-echo and T2-weighted turbo-spin-echo sequences, a coronal gradient-echo and a 3D phase-contrast venous angiogram should be performed. Local thrombolysis is needed only when patients have an exacerbation of clinical symptoms or imaging signs of worsening disease despite sufficient anticoagulation therapy. Acute occlusions of dialysialysis grafts and fistulae are a frequently encountered complication. Among the various methods described for acute occlusion screening, ultrasonography and MRI have been proven to be accurate and noninvasive; however, if immediate treatment can be anticipated, imaging should be performed directly by digital subtraction angiography before the percutaneous intervention. Initial percutaneous thrombectomy is very effective with success rates and patency rates comparable to those of surgical thrombectomy. A short thrombosis can be treated with balloon angioplasty alone, whereas an extensive thrombosis requires a combination of mechanical devices and/or thrombolytic agents with adjunctive balloon angioplasty.
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PMID:Nontraumatic vascular emergencies: imaging and intervention in acute venous occlusion. 1238 51

It has been speculated that hormone replacement therapy (HRT) containing relatively low dose of estrogen would be different from oral contraceptive pills in causing thromboembolism because activation of coagulation depends on the amount of estrogen. In contrast to this knowledge, activation of coagulation pathways has been detected in postmenopausal women treated with HRT in the observational and clinical studies. In this regard, recent studies have reported a 2 to approximately 4 fold risk of venous thromboembolism or pulmonary embolism in postmenopausal women receiving HRT than in non-users of estrogen. On the other hands, HRT has shown to enhance systemic fibrinolysis with decreased plasma plasminogen activator inhibitor-1 (PAI-1) levels. In addition, levels of D-dimer exhibited a significant inverse correlation with PAI-1 levels, suggesting enhanced fibrinolysis potential. However, small doses of estrogen/progestogen induce increases in fibrinolytic capacity via a marked reduction of PAI-1. In other words, HRT at conventional dosages may affect fibrinolytic activity to a greater extent than coagulation activity, whereas the converse trend holds at higher estrogen doses. The increase in fibrinolytic potential was independent of any effect on coagulation of CEE at conventional dosages. However, in contrast to healthy postmenopausal women, we recently reported that HRT did not significantly decrease PAI-1 antigen levels and rather, increased tissue factor activity and prothrombin fragment F(1+2) levels from baseline in hypertensive and/or overweight postmenopausal women. Activation of coagulation following HRT may not be balanced by activation of fibrinolysis in some postmenopausal women. Thrombogenic events are considered more likely in patients with certain heritable conditions, such as platelet antigen-2 (PIA-2) polymorphisms. Further, Factor V Leiden mutation increases the risk of primary and recurrent venous thromboembolic events by three to sixfold and the risk of myocardial infarction. Indeed, HRT may decrease or increase atherothrombosis risk depending on the presence of Factor V Leiden mutation. Thus, HRT should not be initiated in women with established coronary artery disease or the coexistence of other risk factors for hypercoagulability-malignancy, immobility, obesity, diabetes, advanced age, or inherited traits. However, HRT at conventional dosages improves fibrinolysis potential in healthy postmenopausal women.
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PMID:Effects of hormone replacement therapy on coagulation and fibrinolysis in postmenopausal women. 1243 Aug 99

A 1991 National Institutes of Health Consensus Conference concluded that severely obese adults could be eligible for bariatric surgery if they had a body mass index (BMI) > or =35 kg/m(2) with or > or =40 kg/m(2) without obesity comorbidity. It was thought at that time that there were inadequate data to support bariatric surgery in severely obese adolescents. An estimated 25% of children in the United States are obese, a number that has doubled over a 30-year period. Very little information has been published on the subject of obesity surgery in adolescents. Therefore we reviewed our 20-year database on bariatric surgery in adolescents. Severely obese adolescents, ranging from 12 to less than 18 years of age, were considered eligible for bariatric surgery according to the National Institutes of Health adult criteria. Gastroplasty was the procedure of choice in the initial 3 years of the study followed by gastric bypass, which was found to be significantly more effective for weight loss in adults. Distal gastric bypass (D-GBP) was used in extremely obese patients (BMI > or =60 kg/m(2)) before 1992 and long-limb gastric bypass (LL-GBP) was used for superobese patients (BMI > or =50 kg/m(2)) after 1992. Laparoscopic gastric bypass was used after 2000. Thirty-three adolescents (27 white, 6 black; 19 females, 14 males) underwent the following bariatric operations between 1981 and June 2001: horizontal gastroplasty in one, vertical banded gastroplasty in two, standard gastric bypass in 17 (2 laparoscopic), LL-GBP in 10, and D-GBP in three. Mean BMI was 52 +/- 11 kg/m(2) (range 38 to 91 kg/m(2)), and mean age was 16 +/- 1 years (range 12.4 to 17.9 years). Preoperative comorbid conditions included the following: type II diabetes mellitus in two patients, hypertension in 11, pseudotumor cerebri in three, gastroesophageal reflux in five, sleep apnea in six, urinary incontinence in two, polycystic ovary syndrome in one, asthma in one, and degenerative joint disease in 11. There were no operative deaths or anastomotic leaks. Early complications included pulmonary embolism in one patient, major wound infection in one, minor wound infections in four, stomal stenoses (endoscopically dilated) in three, and marginal ulcers (medically treated) in four. Late complications included small bowel obstruction in one and incisional hernias in six patients. There were two late sudden deaths (2 years and 6 years postoperatively), but these were unlikely to have been caused by the bariatric surgical procedure. Revision procedures included one D-GBP to gastric bypass for malnutrition and one gastric bypass to LL-GBP for inadequate weight loss. Regain of most or all of the lost weight was seen in five patients at 5 to 10 years after surgery; however, significant weight loss was maintained in the remaining patients for up to 14 years after surgery. Comorbid conditions resolved at 1 year with the exception of hypertension in two patients, gastroesophageal reflux in two, and degenerative joint disease in seven. Self-image was greatly enhanced; eight patients have married and have children, five patients have completed college, and one patient is currently in college. Severe obesity is increasing rapidly in adolescents and is associated with significant comorbidity and social stigmatization. Bariatric surgery in adolescents is safe and is associated with significant weight loss, correction of obesity comorbidity, and improved self-image and socialization. These data strongly support obesity surgery for those unfortunate individuals who may have difficulty obtaining insurance coverage based on the 1991 National Institutes of Health Consensus Conference statement.
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PMID:Bariatric surgery for severely obese adolescents. 1255 91

Frequently an inherited predisposition to thrombosis remains clinically silent until an additional environmental factor intervenes. The present study aimed to assess distribution of inherited risk factors of venous thrombosis in patients with venous thromboembolism (VTE). The prevalences of factor V Leiden (FV Leiden), prothrombin factor II G20210A (FII G20210A), C677T and A1298C of methylenetetrahydrofolate reductase (MTHFR) mutations were studied in 149 VTE patients and 100 controls. The following key risks were established: previous deep venous thrombosis or pulmonary embolism (23.5%), bed rest (34.2%), immobilisation of lower limb (10.1%), hospitalisation (30.9%) and obesity (28.9%). In 29 (19%) patients and in three (3%) controls FV Leiden was found. A significant association between VTE and FV Leiden was established. There were six (4%) carriers of the FII G20210A among VTE patients and one in the controls. No associations between VTE and MTHFR polymorphisms (C677T, A1298C) were found. In three of 149 patients both FV Leiden and FII G20210A polymorphisms were observed. The mean protein C activity was slightly, though nonsignificantly, smaller in VTE patients. In conclusion, there was a positive association between venous thromboembolism and factor V Leiden. Only a weak trend favouring a relationship between prothrombin factor II G20210A and venous thrombolism was present. No associations between common polymorphisms of methylenetetrahydrofolate reductase and venous thromboembolism were found.
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PMID:Genetic polymorphisms associated with acute pulmonary embolism and deep venous thrombosis. 1257 Jan 4

Venous thomboembolism (VTE) causes only about 2% of maternal deaths in the developing world but is a leading cause of direct maternal deaths in developed countries. Pregnancy increases the risk of VTE through venous stasis, changes in blood coagulability and damage to vessels. Early diagnosis of VTE depends crucially on awareness of the condition but clinical diagnosis is unreliable in pregnancy and objective testing is essential. Compression or duplex ultrasonography is used to diagnose deep venous thrombosis and a ventilation/perfusion scan for pulmonary embolism. Low molecular weight heparins are safe and effective for treatment and for thromboprophylaxis in pregnancy. All women should undergo risk assessment in early pregnancy or preferably before pregnancy. Identifying risk factors such as obesity, or a past or family history of thromboembolism, allows at-risk women to be offered thromboprophylaxis. Guidelines on thromboprophylaxis have reduced deaths after caesarean section and are now being developed for all women.
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PMID:Thromboembolism. 1471 63

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.
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PMID:Current management of acute symptomatic deep vein thrombosis. 1472 51

The prognosis of patients with myocardial infarction (MI) and normal coronary arteries (NCA) in the presence of an inherited coagulation disorder is unknown. The purpose of this study was to compare the clinical thrombosis outcome of patients with (GpI) or without (GpII), inherited coagulation disorders, who suffered from an acute MI with NCA. Eighty two consecutive patients (mean age 49 +/- 15 years; 29 females) with MI, but NCA, were recruited. Twelve patients (15%) had an inherited coagulation disorder. GpI and GpII were statistically similar regarding age (45 +/- 11 vs 50 +/- 16 years-old), gender (33 vs. 36% female), tobacco consumption (50 vs. 53%), diabetes mellitus (8 vs. 10%), hypertension (25 vs. 17%), obesity (8.3 vs. 14%), family history of coronary heart disease (33 vs. 19%), hypercholesterolemia (50 vs. 21%; p =.08), left ventricular ejection fraction (58 +/- 13 vs. 61 +/- 13%) and spasm (8.3% vs. 17%). All patients were initially treated with antiplatelet agents with the exception of one (8%) in GpI, and 6 (9%) in GpII who were taking oral anticoagulant therapy (ns). The mean follow-up was 57 +/- 26 (range from 2-91 months). During the outcome, 12/78 (15.4%) thrombosis events occurred, including venous thrombosis or pulmonary embolism (1/12 vs. 1/66), reinfarction (2/12 vs. 4/66), and stroke (2/12 vs. 2/66), with two events in one patient (GpI). Kaplan-Meier event-free survival, with combined end-point, defined as venous thrombo-embolic event, reinfarction, or stroke differed between the two groups: 4/12 (33.3%) in GpI and 7/66 (10.6%) in Gp II (p <.02). Patients with MI, NCA and congenital coagulation disorder present a high risk of thrombosis recurrence under antiplatelet agent.
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PMID:Long term prognosis of patients with myocardial infarction and normal coronary angiography: impact of inherited coagulation disorders. 1496 Nov 69

Pulmonary embolism (PE) is a prominent cause of morbidity and mortality in surgical patients. Here, we report two cases of PE following head and neck surgery: (1) in case 1, the patient underwent endoscopic sinus surgery (ESS), and (2) in case 2, the patient was suspected PE after resection of the parotid gland and radical neck dissection. Prophylactic compression devices were used during the operation in both cases. In case 1, PE was diagnosed 3 days following surgery after the patient complained of dyspnea while walking. PE was successfully treated by intravenous administration of heparin. In case 2, PE was strongly suspected 13 days following surgery after the patient experienced syncope and chest pain and exhibited abnormal findings on a cardiac echogram. This patient died 18 h after the onset of cardiac symptoms. Despite prophylactic measures taken during surgery, the prognosis was poor for this patient due to numerous high-risk factors (e.g., advanced age, obesity, prolonged immobilization). Although the incidence of postoperative PE in our department during the last 7 years is very low (0.04%), the frequency of postoperative PE in Japan has steadily increased in recent years. PE still is one of the most significant complications leading to morbidity and mortality following surgery. Given the gaining prominence of PE, we conclude that otolaryngologists including those in Japan should be reminded of high-risk factors associated with PE and be made aware of prophylactic treatments newly aimed at reducing the frequency of PE.
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PMID:Two cases of pulmonary embolism after head and neck surgery. 1536 71

Current evidence indicates that prolonged air travel predisposes to venous thrombosis and pulmonary embolism. An effect is seen once travel duration exceeds 6 to 9 hours and becomes obvious in long-haul passengers traveling for 12 or more hours. A recent records linkage study found that increase in thrombosis rate among arriving passengers peaked during the first week and was no longer apparent after 2 weeks. Medium- to long-distance travelers have a 2- to 4-fold increase in relative thrombosis risk compared with nontravelers, but the averaged absolute risk is small (approximately one symptomatic event per 2 million arrivals, with a case-fatality rate of approximately 2%) and there is no evidence that thrombosis is more likely in economy class than in business- or first-class passengers. It remains uncertain whether and to what extent thrombosis risk is increased by short-distance air travel or prolonged travel by motorcar, train, or other means. Most travelers who develop venous thrombosis or pulmonary embolism also have one or more other predisposing risk factors that may include older age, obesity, recent injury or surgery, previous thrombosis, venous insufficiency, malignancy, hormonal therapies, or pregnancy. Limited (though theoretically plausible) evidence suggests that factor V Leiden and the prothrombin gene mutation predispose to thrombosis in otherwise healthy travelers. Given that very many passengers with such predispositions do not develop thrombosis, and a lack of prospective studies to link predisposition with disease, it is not now possible to allocate absolute thrombosis risk among intending passengers or to estimate benefit-to-risk ratios or benefit-to-cost ratios for prophylaxis. Randomized comparisons using ultrasound imaging indicate a measurable incidence of subclinical leg vein thrombosis after prolonged air travel, which appears to increase with travel duration and is reduced by graded pressure elastic support stockings. Whether this surrogate outcome measure translates into clinical benefit remains unknown, but support stockings are likely to be more effective and have less adverse effects than the use of aspirin.
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PMID:Travel, venous thromboembolism, and thrombophilia. 1570 80

Ximelagatran is an oral direct thrombin inhibitor (DTI), the active form of which is melagatran. Approximately 20% of an oral ximelagatran dose becomes bioavailable as melagatran, which binds noncovalently and reversibly to both fibrin-bound and freely circulating thrombin. Oral ximelagatran dosing not only inhibits thrombin activity rapidly, competitively, and potently, but also delays and suppresses thrombin generation. In humans, oral ximelagatran exhibits anticoagulant, antiplatelet, and profibrinolytic effects, with only minor prolongation of the capillary bleeding time. Oral ximelagatran exhibits a stable and predictable pharmacokinetic profile during repeated dosing, with low intra- and inter-individual variation, and a low potential for interaction with other medications. It is excreted primarily as melagatran via the kidney, without unexpected bioaccumulation. Dosing requirements do not vary with age, gender, ethnicity, obesity, or food or alcohol intake. Clinical trials (total n>30,000) have evaluated oral ximelagatran in four indications: the prevention of venous thromboembolism (VTE, comprising deep venous thrombosis with or without and pulmonary embolism) after elective hip- or knee-replacement surgery (with approval granted by France, as the Reference Member State for the European Union); treatment and long-term secondary prevention of VTE; the prevention of stroke and other systemic embolic events associated with nonvalvular atrial fibrillation; and the prevention of cardiovascular events after an acute myocardial infarction. The results of these trials suggest that the benefit-risk profile of oral ximelagatran therapy, administered at a fixed-dose without coagulation monitoring, compares favorably with that of currently approved standard therapy.
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PMID:Ximelagatran--a promising new drug in thromboembolic disorders. 1572 69


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