Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute renal failure (ARF) has been frequently reported after bites from the Viperidae snake family. The lack of a reproducible animal model has hampered the study of renal damage mechanisms. Intravenous injection of rats with 0.4 mg/kg of Bothrops jararaca venom produced functional and morphologic changes similar to those observed in human snakebite-induced ARF. There was an acute and significant decrease in the glomerular filtration rate, diuresis, and renal plasma flow. Serum fibrinogen levels decreased significantly. There was intravascular hemolysis, as shown by a significant decrease in hematocrit, and an increase in plasma lactate dehydrogenase levels and free hemoglobin. Blood pressure and serum creatine phosphokinase levels were not affected. Light and electron microscopy showed massive fibrin deposition in glomerular capillaries, proximal and distal tubular necrosis, and hemolyzed red blood cell casts in renal tubules. Based on these findings, a model of snakebite-induced ARF was achieved. Ischemia related to glomerular coagulation and intravascular hemolysis were the most important pathogenic factors causing a decrease in the glomerular filtration rate, although a direct venom nephrotoxicity cannot be excluded.
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PMID:Snakebite-induced acute renal failure: an experimental model. 842 92

Increased blood and plasma viscosity has been described in patients with coronary and peripheral arterial disease. However, the relation of viscosity to the extent of arterial wall deterioration--the most important determinant of clinical manifestation and prognosis of the disease--is not well known. Therefore, the authors studied plasma viscosity as one of the major determinants of blood viscosity in patients with different stages of arterial disease of lower limbs (according to Fontaine) and its relation to the presence of some risk factors of atherosclerosis. The study encompassed four groups of subjects: 19 healthy volunteers (group A), 18 patients with intermittent claudication up to 200 m (stage II; group B), 15 patients with critical ischemia of lower limbs (stage III and IV; group C), and 16 patients with recanalization procedures on peripheral arteries. Venous blood samples were collected from an antecubital vein without stasis for the determination of plasma viscosity (with a rotational capillary microviscometer, PAAR), fibrinogen, total cholesterol, alpha-2-macroglobulin, and glucose concentrations. In patients with recanalization procedure local plasma viscosity was also determined from blood samples taken from a vein on the dorsum of the foot. Plasma viscosity was most significantly elevated in the patients with critical ischemia (1.78 mPa.sec) and was significantly higher than in the claudicants (1.68 mPa.sec), and the claudicants also had significantly higher viscosity than the controls (1.58 mPa.sec). In patients in whom a recanalization procedure was performed, no differences in systemic and local plasma viscosity were detected, neither before nor after recanalization of the diseased artery. In all groups plasma viscosity was correlated with fibrinogen concentration (r=0.70, P < 0.01) and total cholesterol concentration (r=0.24, P < 0.05), but in group C (critical ischemia) plasma viscosity was most closely linked to the concentration of alpha-2-macroglobulin (r=0.78, P < 0.01). These results indicate that in patients with peripheral arterial disease plasma viscosity increases with the progression of the atherosclerotic process and is correlated with the clinical stages of the disease.
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PMID:Plasma viscosity increase with progression of peripheral arterial atherosclerotic disease. 863 68

Granulocytes play a significant role in vascular diseases. The mechanisms of neutrophil-mediated vascular injury include their increased endothelial adhesion and activation with release of inflammatory mediators. Pentoxifylline (PTX) has a well-demonstrated ability to act on the activated neutrophils. It increases chemotaxis and decreases their adherence to endothelial cells, oxidative burst, and enzyme release. In this preliminary study, we investigated the effects of PTX on ischemia-induced changes in polymorphonuclear neutrophils (PMN) activation and cytokine release. A double-blind, randomized, placebo-controlled trial was carried out in 14 patients (age range 46-86 years) suffering from critical ischemia, as defined by the European Consensus Document, or subacute ischemia due to occlusive arterial disease of the lower limb. Femoral and antecubital venous blood samples on the side of the ischemic leg were obtained from patients immediately before (TO) and after infusion (T24) of PTX or placebo. PMN activation was evaluated by study of cell migration, beta 2 integrin expression (CD11b/ CD18), oxidative burst, and elastase release. Inflammation proteins were analyzed, such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-6 (IL-6), C-reactive protein (CRP), and fibrinogen. Before treatment, our results demonstrate an important activation in both femoral and antecubital venous blood. PMN activation markers, cytokine release, and other inflammation proteins were significantly increased compared with normal subjects. In the experimental group there was no significant difference between femoral and antecubital venous blood. Six patients received PTX infusion and seven patients were in the placebo group. The effect of PTX was evaluated after 24 h of treatment (1,200 mg). In the PTX group the following variables were improved compared with the placebo group: CD11b expression on PMNs, elastase released from PMNs, fibrinogen, CRP, TNF-alpha, and IL6 in plasma. These preliminary results should be interpreted with caution because of the small sample size. Further trials may contribute to more complete understanding.
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PMID:Leukocyte activation study during occlusive arterial disease of the lower limb: effect of pentoxifylline infusion. 869 73

Inflammation may play an important role in acute coronary syndromes. We studied the prognostic value of fibrinogen, an acute-phase protein directly involved in thrombotic process, measured serially in 1,473 patients with unstable angina and non-Q-wave myocardial infarction participating in the Thrombolysis in Myocardial Infarction IIIB trial. Overall, no association was found between baseline (pretreatment) fibrinogen and in-hospital (< or = 10 days) myocardial infarction (p=0.70) and death (p=0.64); however, patients with spontaneous ischemia (p=0.004) and the combined unsatisfactory outcome of death, myocardial infarction, and spontaneous ischemia (p=0.003) had higher fibrinogen concentrations than those without these events. This association was confined to patients with unstable angina. A baseline fibrinogen concentration > or = 300 mg/dl was associated with a modest trend toward an increased risk of death, myocardial infarction, or spontaneous ischemia (odds ratio 1.61, 95% confidence interval 1.02 to 2.52; p=0.04). Elevation of fibrinogen, a readily measurable acute-phase protein, at the time of hospital admission is associated with coronary ischemic events and a poor clinical outcome in patients with unstable angina.
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PMID:Prognostic value of plasma fibrinogen concentration in patients with unstable angina and non-Q-wave myocardial infarction (TIMI IIIB Trial) 916 83

Percutaneous coronary revascularization in patients with unstable angina and coronary thrombus carries a high complication rate. A new strategy to reduce thrombus burden before revascularization was tested in a multicenter prospective trial. Patients with unstable angina and coronary thrombus (n = 45) received alteplase through an infusion catheter at the proximal aspect of the target lesion and concomitant intracoronary heparin via a standard guiding catheter. Angiography was performed before and alter lesion-directed therapy and post-intervention. Systemic fibrinogen depletion and thrombin activation were not observed, while fibrinolysis was evident for > or = 4 hr after treatment. Target lesion stenosis did not change significantly after lesion-directed therapy, but thrombus score was reduced, particularly among patients who had large thrombi (mean 2.2 vs. 1.6, P = 0.02). Revascularization was successful in 89% of patients. Median final stenosis was 30% and mean final thrombus score was 0.4. Complications included recurrent ischemia (11%), MI (7%), abrupt closure (7%), severe bleeding (4%), and repeat emergency angioplasty (2%). Patients with overt thrombus appeared to derive the most angiographic benefit from lesion-directed alteplase plus intracoronary heparin. Later revascularization was highly successful. This strategy may be a useful adjunct to percutaneous revascularization for patients with unstable angina and frank intracoronary thrombus.
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PMID:Lesion-directed administration of alteplase with intracoronary heparin in patients with unstable angina and coronary thrombus undergoing angioplasty. 872 95

In 154 subjects (age 63 +/- 11 years; 63 women and 91 men) randomly selected from the population, we tested the hypothesis that inflammatory parameters are associated with vascular risk factors and particularly with a history of ischemic vascular diseases. The subjects were part of the control group (n = 197) in a case-control study investigating recent infection as a risk factor for acute cerebrovascular ischemia and had been matched for sex and age with patients suffering from acute ischemic stroke or transient ischemic attack. Subjects with malignant or inflammatory diseases, with recent trauma, surgery or vascular diseases (n = 43) were excluded from the present analysis. In multivariate analysis, current smoking, diabetes mellitus, age > or = 65 years, and a history of stroke independently increased the leukocyte count. Hypertriglyceridemia, peripheral arterial disease, and diabetes mellitus were positively associated with C -reactive protein (CRP). Age > or = 65 years and diabetes mellitus independently increased fibrinogen. (p < 0.05, respectively) Subjects with a history of cerebrovascular, cardiovascular or peripheral arterial disease had higher leukocyte counts, fibrinogen and CRP than subjects without vascular risk factors and higher leukocytes and fibrinogen than subjects with one or more risk factors. Subjects under the age of 65 with vascular risk factors but without ischemic diseases had higher leukocyte count, fibrinogen and CRP and subjects older than 65 with risk factors had higher CRP than subjects without risk factors or ischemic diseases in the same age group. (p < 0.05, respectively) These results support the hypotheses that low-grade inflammation is associated with vascular risk factors and that inflammatory mechanisms may contribute to the risk of organ ischemia.
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PMID:The association of leukocyte count, fibrinogen and C-reactive protein with vascular risk factors and ischemic vascular diseases. 873 28

CVI is a common disease with significant morbidity that results from venous hypertension of the extremities. Increased perfusion pressure probably traps excessive numbers of white blood cells in the capillaries. Activated leukocytes subsequently damage capillary endothelium, increase capillary permeability, and cause ischemia of the overlying skin as a result of leakage of fibrinogen and formation of a fibrin cuff. Diagnosis of CVI is not difficult because its clinical manifestations are usually evident. Vascular compression therapy remains the foundation of medical management for CVI. Refractory cases may require a combined medical and operative approach.
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PMID:Chronic venous insufficiency: mechanisms and management. 883 77

The intercellular adhesion molecule (ICAM) 1 is an Ig-like cell adhesion molecule expressed by several cell types, including leukocytes and endothelial cells. It can be induced in a cell-specific manner by several cytokines, for example, tumor necrosis factor-alpha, interleukin-1, and interferon-gamma, and inhibited by glucocorticoids. Its ligands are the membrane-bound integrin receptors LFA-1 and Mac-1 on leukocytes, CD43, the soluble molecule fibrinogen, the matrix factor hyaluronan, rhinoviruses, and Plasmodium falciparum malaria-infected erythrocytes. ICAM-1 expression is predominantly transcriptionally regulated. The ICAM-1 promoter contains several enhancer elements, among them a novel kappa B element which mediates effects of 12-O-tetradecanoylphorbol-13-acetate, interleukin-1, lipopolysaccharide, tumor necrosis factor-alpha, and glucocorticoids. Expression regulation is cell specific and depends on the availability of cytokine/hormone receptors, signal transduction pathways, transcription factors, and posttranscriptional modification. ICAM-1 plays a role in inflammatory processes and in the T-cell mediated host defense system. It functions as a costimulatory molecule on antigen-presenting cells to activate MHC class II restricted T-cells, and on other cell types in association with MHC class I to activate cytotoxic T-cells. ICAM-1 on endothelium plays an important role in migration of (activated) leukocytes to sites of inflammation. ICAM-1 is shed by the cell and detected in plasma as sICAM-1. Regulation and significance of sICAM-1 are as yet unclear, but sICAM-1 is increased in many pathological conditions. ICAM-1 may play a pathogenetic role in rhinovirus infections. Derangement of ICAM-1 expression probably contributes to the clinical manifestations of a variety of diseases, predominantly by interfering with normal immune function. Among these are malignancies (e.g., melanoma and lymphomas), many inflammatory disorders (e.g., asthma and autoimmune disorders), atherosclerosis, ischemia, certain neurological disorders, and allogeneic organ transplantation. Interference with ICAM-1 leukocyte interaction using mAbs, soluble ICAM-1, antisense ICAM-1 RNA, and in the case of melanoma mAb-coupled immunotoxin, may offer therapeutic possibilities in the future. Integration of knowledge concerning membrane-bound and soluble ICAM-1 into a single functional system is likely to contribute to elucidating the immunoregulatory function of ICAM-1 and its pathophysiological significance in various disease entities.
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PMID:Intercellular adhesion molecule-1. 883 67

Patients with heparin-induced thrombocytopenia (HIT) require an alternative antithrombotic treatment to heparin during arterial reconstruction. Ancrod and Iloprost have been employed but are not readily available and carry the risks of systemic side effects (depletion of fibrinogen, hypotension). A patient with HIT in whom intraoperative intraarterial urokinase (UK) was successfully utilized to enable safe arterial reconstruction is described. An 80 year old white female with diffuse arteriosclerotic cardiovascular disease and multiple vascular reconstructions had thrombotic complications following use for heparin during two of her prior operations associated with documented thrombocytopenia and anti-platelet antibodies. She presented with limb-threatening ischemia which was evaluated with angiography revealing severe stenosis of the proximal left superficial femoral artery, occlusion of both anterior tibial and peroneal arteries and several digital vessels, with intact posterior tibial runoff. A common femoral to mid-superficial femoral artery bypass was performed, utilizing contralateral reversed greater saphenous vein, while being treated with aspirin and a continuous intravenous infusion of low molecular weight dextran. During the procedure the clamped arteries were locally perfused with a high volume of dilute UK solution to prevent blood stasis, and enable local delivery of a thrombolytic agent. Although clot formation was observed in the operative field, none occurred within the clamped arteries. A total of 191,200 units of UK were employed with no bleeding complications. Following surgery the patient had a palpable pedal pulse and markedly improved perfusion of her toes. She was discharged on aspirin and coumadin on postoperative day five. It is concluded that for patients with HIT, systemic aspirin and dextran combined with local intraarterial UK are a simple and effective substitute for systemic anticoagulation with heparin during arterial reconstruction.
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PMID:Intraoperative urokinase as an alternative to heparin for patients with suspected heparin-induced thrombocytopenia requiring arterial reconstruction: report of a case and review of the literature. 894 86

Coagulation activation and fibrinolysis parameters were studied in eleven cases of thrombotic microangiopathy concerning eight adult patients. In addition to routine coagulation tests, antithrombin III, von Willebrand factor (vWF), prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), D-dimer (DD), and plasminogen activator inhibitor type 1 (PAI-1) were measured in the plasma at the time of diagnosis and as soon as remission was achieved after therapy with plasma exchange and Iloprost. In the acute phase all patients showed normal aPTT, normal or slightly prolonged prothrombin time, normal or enhanced plasma levels of fibrinogen and antithrombin III, at variance with results in patients affected by disseminated intravascular coagulation. Mean F1+2, TAT, DD, vWF and PAI-1 were elevated in the acute phase, but decreased significantly in the early phase of remission. Our data provide evidence of increased thrombin generation rate which takes place in the acute phase of the disease and does not result in consumption coagulopathy, due to appropriate inhibition by antithrombin III; blood coagulation activation promptly decreased as soon as remission was achieved. Cross-linked fibrin deposition together with PAI-1 may consolidate the platelet plug, eventually resulting in microvascular occlusion and ischemia.
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PMID:Plasmatic parameters of coagulation activation in thrombotic microangiopathy. 895 55


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