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)

Dextran is used during surgery as a prophylactic agent to prevent deep venous thrombosis. Recently it has been shown that dextran increases t-PA plasma concentrations in patients. As dextran is a potential ligand for the mannose receptor, we studied whether this glucose-polymer would be able to inhibit mannose receptor-mediated clearance of t-PA. In this report we show that dextran 40 and dextran 70 were able to inhibit t-PA binding to the isolated human mannose receptor (IC50 14 and 4 mg/ml, respectively). Both glucose-polymers inhibited mannose receptor-mediated t-PA degradation by human monocyte-derived macrophages in vitro (IC50 7 and 2 mg/ml, respectively). The alpha2-macroglobulin receptor/low density lipoprotein receptor-related protein (LRP)-mediated t-PA degradation by the macrophages was not affected by dextran. During and after a 45 min infusion of dextran 70 (Macrodex) in rats, in plasma endogenous t-PA concentrations increased to 162 +/- 33% and 122 +/- 35% respectively. The plasma clearance of a bolus injection of exogenous t-PA was decreased by 33 +/- 9% in the same rats. We conclude that dextran inhibits mannose receptor-mediated t-PA clearance. The inhibition of t-PA clearance during dextran infusion results in increased endogenous t-PA plasma concentrations. Increased t-PA concentrations present during thrombus formation are known to increase thrombus lysability. Thus the inhibition of t-PA clearance can contribute to the antithrombotic effect of dextran.
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PMID:Inhibition of mannose receptor-mediated clearance of tissue-type plasminogen activator (t-PA) by dextran: a new explanation for its antithrombotic effect. 936 93

Strain DVT, a halotolerant, Gram-negative, facultatively anaerobic bacterium, was isolated from a hypersaline pond located in Death Valley, California. The cells were non-spore-forming, motile, curved rods (1.0-1.8 x 0.5-0.6 microns) and occurred singly, in pairs or rarely in chains. Strain DVT was oxidase-, catalase-, Voges-Proskauer-, amylase-, gelatinase- and lipase-positive and indole-negative. Nitrate, sulfate and fumarate were not used as electron acceptors. Carbohydrates served as energy sources both aerobically and anaerobically. Strain DVT grew optimally at 37 degrees C (temperature range 20-50 degrees C) with 2.5% NaCl (NaCl range 0-12.5%) and pH 7.3 (pH range of 5.5-8.5) in a glucose/yeast extract medium with a doubling time of 20 min (aerobically) or 41 min (anaerobically). The end products of glucose fermentation were ethanol, isobutyrate, propionate, lactate, formate and CO2. Strain DVT was resistant to penicillin, D-cycloserine, streptomycin and tetracycline (200 micrograms ml-1). The G + C content was 50 mol%. 16S rRNA gene sequence analysis indicated that it was closely related to Salinivibrio costicola (97.7%) and this was confirmed by DNA-DNA hybridization (93% relatedness). However, phenotypic characteristics such as halotolerance, gas production, growth at 50 degrees C, antibiotic resistance, sugar-utilization spectrum and phylogenetic signatures are sufficiently different from Salinivibrio costicola to warrant designating strain DVT as a new subspecies of Salinivibrio costicola, Salinivibrio costicola subsp. vallismortis subsp. nov. (= DSM 8285T).
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PMID:Salinivibrio costicola subsp. vallismortis subsp. nov., a halotolerant facultative anaerobe from Death Valley, and emended description of Salinivibrio costicola. 1075 67

Hypercoagulable states due either to inherited or acquired thrombotic risk factors are only present in approximately half of cases of DVT, but the causes in the other half, remain unknown. The importance of biological risk factors such as hyperlipidemia, hypofibrinolysis and hemorheological alterations in the pathogenesis of DVT has not been well established. In order to ascertain whether the above mentioned biological factors are associated with DVT and could constitute independent risk factors, we carried out a case-control study in 109 first DVT patients in whom inherited or acquired thrombophilic risk factors had been ruled out and 121 healthy controls age (42+/-15 years) and sex matched. From all the biological variables analyzed (cholesterol, triglycerides, glucose, fibrinogen, erythrocyte aggregation, hematocrit, plasma viscosity and PAI-1) only fibrinogen concentration reached a statistically significant difference on the comparison of means (290+/-73 mg/dl in cases vs 268+/-58 mg/dl in controls, p<0.05). After this continuous variables were dichotomized according to our reference values, the percentage of cases with cholesterolemia >220 mg/dl, hematocrit >45% and fibrinogen >300 mg/dl was higher in cases than in controls: 38% vs 22%; p<0.01; 43% vs 27%; p<0.05; 36% vs 23%; p<0.05, respectively. The percentage of cases with PAI-1 values >30 ng/ml, 37% vs 25% was borderline significant; p=0.055. Multivariate logistic regression analysis showed that cholesterolemia >220 mg/dl and fibrinogen >300 mg/dl constitute independent predictors of venous thrombotic risk. The adjusted OR's were 2.03 (95% CI; 1.12-3.70) for cholesterolemia and 1.94 (95% CI; 1.07-3.55) for fibrinogen. When these two variables combined DVT risk rose about fourfold (3.96; p<0.05). Our results suggest that hypercholesterolemia and hyperfibrinogenemia should be added to the list of known DVT risk factors and we recommend adopting measures to decrease these variables in the population with a high risk of DVT.
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PMID:Biological risk factors for deep vein trombosis. 1190 70

The case of a 26-year-old male chronic smoker is reported, who had thrombotic incidences on three occasions in both upper and lower limbs over a 10-month period. Laboratory examinations, including hematologic studies and creatinine, cholesterol, and glucose levels, were normal. However, IgG and IgM anticardiolipin antibodies were detected. Duplex ultrasonography confirmed deep venous thrombosis in both lower limbs (two occurrences) and computer tomography depicted an inferior cava vein thrombosis. The patient fulfilled all of Shionoya's criteria for Buerger's disease, thus suggesting an association between anticardiolipin antibodies and this disease.
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PMID:Buerger's disease and anticardiolipin antibodies: a worse prognosis? 1199 Dec 45

Reports regarding the question of whether oral contraceptive (OC) use enhances the risk of cancer or one of several serious cardiovascular disorders, i.e., thromboembolic disease, stroke, and myocardial infarction are reviewed. In 1974 the Royal College of General Practitioners (RCGP) issued an interim report of a large prospective study involving 46,000 women. The study found a 5-fold increase in the risk of deep venous thrombosis among women taking OCs. Laboratory studies have tried to establish a direct causal relationship between OC use and altered hemostatis. In review of these studies, Bingel and Benoit reported an increased incidence of thromboembolism in OC users with blood group A. Other hemostatic alterations in OC users were also noted. Other investigators have examined the effect of OCs on antithrombin 3. In 1 study, the inhibitory activity of antithrombin 3 on factor X was significantly reduced among 57 women using the combined OCs, but there was no substantial difference in the quantity of antithrombin 3 in these women as compared with 48 women in the control group. In 1 retrospective case control study of 60 surgical patients with complications of pulmonary embolism or venous thrombosis, the risk of postoperative thromboembolism was 6.7 times greater in OC users than in 97 well matched surgical controls. The RCGP study showed that the risk of cerebrovascular disease in women using OCs was 4 times greater than in nonusers. This finding was substantiated by the Boston-based Collaborative Group for the Study of Stroke in Young Women, which observed a 2-fold increase in risk for all types of stroke among OC users. Several studies have demonstrated that serum lipids are higher in women who use OCs than in those who do not, with estrogen being implicated as the cause of the elevation. Other studies have attempted to link serum lipid elevations to myocardial infarction, but the association is unclear. Both epidemiological and laboratory studies have implicated OCs in the genesis of essential hypertension. Several studies have examined mortality trends associated with OC use. In 1 analysis of data from 21 countries, women between 15 and 44 years of age were found to have a 3-fold to 5-fold increase in cardiovascular mortality that was associated with OC use. The principle evidence that suggested a possible link between OCs and breast carcinoma derived from experiments in laboratory animals. There is no conclusive evidence that OCs cause breast cancer in humans. The association between OC use and endometrial cancer is also inconclusive at this time. A marked increase in the incidence of hepatic adenomas among OC users has also been noted recently. The following other effects associated with OC use are reviewed briefly: glucose tolerance tests; birth defects; gallbladder disease; postpill amenorrhea; laboratory tests; and drug activity. Absolute and relative contraindications for OC use are listed.
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PMID:Oral contraceptive risks: a realistic appraisal. 1227 76

The main concern of physicians prescribing oral contraceptives (OCs) is the possibility of cardiovascular accidents, not because of their number but of their seriousness. Cardiovascular risk affects primarily women over 35. A 1986 survey of 600 physicians indicated that avoiding cardiovascular risk was their main objective when prescribing pills, with avoidance of modifications in lipid and glucose metabolism virtually as great a concern. Less than 50% were concerned with functional symptoms such as spotting which can be managed by therapeutic adjustments. Numerous cofactors participate in cardiovascular risk, including family history, life style, and intercurrent illness. The frequency of vascular accidents is only slightly higher among OC users than in the control population. Numerous Anglo-Saxon studies have found the risk of deep venous thrombosis to be multiplied by 4 or 5 for OC users and of superficial thrombosis to be multiplied by 2 or 3. Age and obesity play no role in the increased risk for OC users, smoking has a minor role, and family history and bed rest are the only major cofactors. Risk of venous thrombosis under OC use does not depend on duration of use and disappears the month after termination of use. The synthetic estrogen is primarily responsible because of the modifications it produces on coagulation factors. OC use increases the risk of coronary accidents by 3 or 4. 3 hypotheses have been advanced to explain the pathogenic mechanism: classic atherogenesis, alteration of the intima, or immunological factors. Atheromatous arterial accidents are related to age, smoking, problems of glucose or lipid metabolism, and blood pressure. The factors have a synergistic effect on each other. Risks increase with duration of use and dose level, and depend also on the biochemical properties of the estrogen and progestin. Some accidents in young women about 30 years old show no relation to duration of use or dose. The only elements differentiating the women involved are smoking, family histories of vascular accidents, and intense headaches in the days before a cerebrovascular accident. They seem to be associated not with atherogenesis but with thickening of the intima secondary to a proliferation of smooth muscle cells with subendothelial fibrosis. 90% of OC users experiencing vascular accidents have been found to have anti-ethinyl estradiol antibodies, compared to 30% of users never having vascular accidents and no nonusers. The practical import of this finding remains undetermined. Under some circumstances the causes of headaches should be investigated and OC use should be terminated. Careful attention to patient selection and development of new progestins with fewer androgenic and metabolic effects should reduce cardiovascular risks from OCs to a minimum. The new synthetic progestin gestodene has given very satisfactory results in a triphasic formulation and should be on the market soon.
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PMID:[Combined contraceptives and cardiovascular risk]. 1231 99

All stroke patients ideally should be admitted to a stroke unit in which personnel are familiar with strategies for taking care of stroke patients. Prevention of worsening cerebral ischemia by appropriate blood pressure and serum glucose management, fever control, and supplemental oxygen for hypoxemic patients is recommended. Recognition of common complications, such as aspiration pneumonia and deep venous thrombosis, highlights the need for swallowing evaluation and the use of pneumatic compression devices or subcutaneous heparin. Patients should be monitored closely for deterioration in their neurologic status and should have complications appropriately addressed. After evaluation of stroke etiology, appropriate secondary stroke prophylaxis should be selected and initiated before hospital discharge.
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PMID:Post-emergency department management of stroke. 1237 68

Sepsis and septic shock are the leading causes of death in non-cardiological intensive care units in developed countries despite recent advances in critical care medicine. Sepsis is the systemic inflammatory response to infection, often associated with hypoperfusion followed by tissue injury and organ failure. Activation of monocytes/macrophages and neutrophils with consecutive release of proinflammatory mediators and activation of the coagulation cascade, seem to play a key role in the pathogenesis of sepsis. Elimination of the septic focus,antimicrobial therapy and supportive treatment are the cornerstones of sepsis therapy. Adequate and rapid volume replacement and if necessary application of catecholamines are of highest priority to optimize tissue perfusion. Norepinephrine is the vasopressor of choice and dobutamine the preferred inotropic agent. Most experts recommend hemoglobin levels of 8-10 g/dl in severe sepsis. In addition,lung protective ventilatory strategies as well as enteral and parenteral nutrition are part of the clinical management of septic patients. In mechanically ventilated patients intensive insulin therapy to maintain blood glucose at a level between 80 and 110 mg/dl has significantly reduced mortality.Furthermore,prophylaxis of deep vein thrombosis and of stress ulcer bleeding are individually applied to septic patients. Treatment of septic patients with anti-mediator strategies or high dose AT III were not successful so far. In contrast,now two new promising treatment options may be emerging: application of small doses hydrocortisone and activated protein C [drotrecogin alfa (activated)]. Large and in part multicentric studies especially in the last 2 years now allow the practicing clinician to perform a partially evidence-based management of patients with sepsis. In addition, for the first time two options for specific therapy of sepsis,application of small doses hydrocortisone and activated protein C [drotrecogin alfa (activated)],are available which may further improve prognosis for septic patients.
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PMID:[Clinical management of patients with sepsis]. 1257 61

IVIg products may be applied for the provision of antibodies in patients with primary or secondary antibody deficiency syndromes or with the aim of immune modulation in patients with autoimmune diseases. The average dose for the provision of antibodies is 400 mg/kg per month while much higher doses are needed 1 to 2 g/kg in a single or in repeated occasions in the treatment of autoimmune diseases e. g. neurological diseases. Indications for treatment have been specified at two consensus meetings (1990 and 1999) and by different groups of experts but off-label use highly exceeds the recommended indications. For this reason risk benefit assessment is of great importance. Adverse events can be categorized as (1) early inflammatory, (2) infectious, (3) rare complications of (mainly) high dose treatment. Early inflammatory reactions are known since the initiation of immunoglobulin treatment, the rate varies greatly 10%-85% and reactions can usually be dealt with by lowering the infusion rate. Viral infections e. g. transmission of viral hepatitis by IVIg have been a problem in certain products until the mid-1990s and industry responded in a fast and efficient manner. Viral safety has been achieved and all IVIg products licensed are considered to be safe in this respect. Rare complications mainly of high dose treatment: renal complications were described already in the mid-1980s they were mainly but not only linked to products containing sucrose, maltose and glucose with or without glycine. These complications are rare (88 patients reported in 30 years) and older patients and patients with conditions predisposing to renal disease were at increased risk. Thromboembolic events were another rare but severe complication of high dose treatment also associated with rapid infusion, deep venous thrombosis, pulmonary embolism, myocardial infarction and stroke have been reported. Possible mechanisms have been discussed.
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PMID:Intravenous immunoglobulins in neurological disorders: safety issues. 1459 47

Congenital disorder of glycosylation (CDG) type Ic, the second largest subtype of CDG, is caused by mutations in human ALG6 (hALG6). This gene encodes the alpha1,3-glucosyltransferase that catalyzes transfer of the first glucose residue to the lipid-linked oligosaccharide precursor for N-linked glycosylation. In this report, we describe the first adult patient diagnosed with CDG-Ic, carrying two previously unknown mutations. The first is a three base deletion (897-899delAAT) leading to the loss of I299, the second is an intronic mutation (IVS7 + 2T > G) that causes aberrant splicing. Wildtype hALG6, delivered by a lentiviral vector into patient's fibroblasts, clearly improves the biochemical phenotype, which confirms that the mutations are disease-causing. Striking clinical findings include limb deficiencies in the fingers, resembling brachydactyly type B, a deep vein thrombosis, pseudotumor cerebri, and endocrine disturbances with pronounced hyperandrogenism and virilization. However, even in adulthood, this patient shows normal magnetic resonance imaging of the brain.
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PMID:Clinical and molecular characterization of the first adult congenital disorder of glycosylation (CDG) type Ic patient. 1600 12


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