Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q9UE34 (fibrinogen)
 30,244 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of ticlopidine treatment (250 mg b.i.d. for 21 months) on fibrinogen and other rheological variables, as compared to placebo, were studied in 44 patients with intermittent claudication due to peripheral arterial occlusive disease. Blood samples were collected every 3 months during this double-blind, randomised placebo-controlled trial which lasted 21 months. Consistently lower values of fibrinogen, haematocrit and whole blood viscosity at high and low shear rate levels were found in the ticlopidine group; the intergroup differences were statistically significant at most but not all follow-up examinations. A significant time-related variance was observed in the ticlopidine group for the measured variables, also after correction for the variability found in the placebo group. Thus, the observed changes in the ticlopidine group are mainly treatment related. These effects on fibrinogen and haemorheology may contribute, besides the known antiplatelet activity of the drug, to the clinical improvement reported in a larger group of claudicants to which the present subset of patients belong.
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PMID:Long-term effects of ticlopidine on fibrinogen and haemorheology in patients with peripheral arterial disease. 323 30

Traditionally, blood rheology tests have been used in diagnosis and monitoring of infection, rheumatic diseases and malignancy, and are still of clinical value in these conditions. In the last twenty years, clinical and epidemiological studies have shown that the haematological determinants of blood flow resistance (haematocrit, fibrinogen, white cell count and altered red and white cell rigidity) are also associated with nutritional, metabolic, endocrine and vascular disorders. Decreased red cell deformability may contribute to reduced red cell survival and anaemia in burns, malaria, liver disease and kidney failure. In trauma and inflammatory disease, overt hyperviscosity is usually prevented by vasodilatation and reduction in the haematocrit. However, low-flow states may arise systemically from haemoconcentration (contracted plasma volume, Chapter 3) in severe burns, inappropriate red cell transfusion, or dehydration due to illness; systemically in circulatory shock; and locally in venous thrombosis or arterial disease. In such circumstances, the intrinsic flow resistance of blood may perpetuate flow disturbance, ischaemia and thrombosis. Conversely, optimal levels of haematocrit, fibrinogen and white cell count may be lower than normal in low-flow states. Haemodilution by colloid infusion is beneficial in burns, shock, major surgery, prevention of postoperative venous thrombosis, chronic stable claudication and possibly in acute stroke and retinal vein thrombosis. Plasma exchange may be beneficial in severe Raynaud's phenomenon. Defibrination with ancrod is effective in prevention and treatment of venous thrombosis but its role in arterial disease is unproven. The benefits of streptokinase therapy in venous thrombo-embolism and acute myocardial infarction may be partly rheological, due to fibrinogen depletion. Drugs with rheological effects may be beneficial in intermittent claudication.
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PMID:Blood rheology in general medicine and surgery. 332 67

The effect of short-term (1 day-1 week) and long-term (6-12 weeks) femoral artery ligation on the oxygen tension (pO2), blood flow, metabolism and function of rat gastrocnemius muscle has been examined. Femoral artery ligation reduced resting blood flow, pO2 and pH. Concomitantly, the concentration of high energy phosphates was reduced and the muscle lactate concentration increased. The fatigue developed by the gastrocnemius/plantaris muscle, during a 10 min period of isometric exercise, was increased and the associated hyperaemia was attenuated. The surgery, performed to ligate the artery, induced an increase in the plasma fibrinogen concentration and whole blood viscosity. As the time interval increased after the femoral artery ligation there was a progressive reduction of the magnitude of the effects. Ten weeks after ligation resting muscle concentrations of high energy phosphates and lactate, whole blood viscosity and muscle pH had normalized. However, resting muscle blood flow, pO2, ability to sustained isometric exercise and the exercise induced hyperaemia were still reduced compared to intact animals. Comparison with literature data reveals that the changes produced by chronic femoral artery ligation in rat calf muscle mimic those seen in man with intermittent claudication.
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PMID:The effect of short-term and long-term femoral artery ligation on rat calf muscle oxygen tension, blood flow, metabolism and function. 335 Jun 22

A study was carried out in 127 patients (94 males and 33 females) presenting with arteriosclerosis (88 patients) or diabetic vasculopathy (39 patients) in different stages of severity (Fontaine) to assess the effectiveness and tolerance of treatment with high doses of pentoxifylline. Patients received a daily dosage of 2200 mg, given as 800 mg orally and 300 mg by intravenous infusion in saline twice daily, for a mean period of 15.8 days. Relevant clinical parameters were assessed and measurements made of biological and laboratory indices before and after treatment. The results showed that intermittent claudication was improved in 52.4% of the arteriosclerotic and 50% of the diabetic patients Stage II disease, pain at rest disappeared in 64% and 78% of patients in Stage III, respectively, and trophic lesions in Stage IV patients were reduced or became less clearly marked in 47% and 44%, respectively. Arterial blood pressure, recorded on the tibial arteries using Doppler ultrasound, showed a mean increase of 18%, but no significant changes in blood flow were evident from rheographic examination. Whole blood erythrocyte filtration time was reduced by a mean of 8%. The main changes in the biological indices after treatment were decreases in haematocrit, mean corpuscular volume and blood fibrinogen values, but these were not statistically significant. The other variables showed little if any change. Side-effects initially reported by the patients consisted of headache, nausea, sweating, pruritus and general malaise, and were mainly associated with the infusion time and regressed in most cases when this was extended.
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PMID:Results of clinical, laboratory and haemorheological investigations of the use of pentoxifylline in high doses. 360 22

The influence of the xanthine derivative pentoxifylline ('Trental' or BL191; Hoechst-Roussel) on exercise tolerance was measured in 38 subjects with stable, severe to moderately severe, intermittent claudication who completed a randomised, double-blind, placebo controlled, cross-over clinical trial. Patients received placebo tablets or 400 mg slow-release pentoxifylline tablets ('Trental 400') twice a day for one week, followed by three times daily for seven weeks, and then crossed over to receive the alternate preparation for another eight weeks. Claudication distance and walking distance were measured on a treadmill before starting treatment and again at four-week intervals during the trial. At the same times, red blood cell filterability, plasma fibrinogen concentration and blood viscosity, resting and post-ischemic calf muscle blood flow, and the resting and post-exercise ankle/brachial systolic pressure ratio were also measured. In this study, the observed effects of pentoxifylline treatment were no greater than those of placebo, even though serum levels of pentoxifylline and its hydroxy-metabolite were within the anticipated range. This was shown by a 'therapeutic effect ratio' of 0.98 for treadmill claudication distance and 0.96 for treadmill walking distance after within-patient analysis at the end of the cross-over (where a ratio of 1.0 means the test drug and placebo effects are identical). These ratios have 95% confidence limits of 0.72-1.34 and 0.74-1.25, respectively.
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PMID:Intermittent claudication: a double-blind crossover trial of pentoxifylline. 386 36

Sixty-two patients with intermittent claudication associated with peripheral arterial diseases were treated with clofibrate, 2 g daily, for a minimum of six months. Progress was compared with that in a similar pretreatment period and also with that of a matched untreated control group of 27 patients. The most striking effect of clofibrate was a steep and sustained fall in whole-blood viscosity measured over a wide range of shear rates. This was associated with a significant fall in abnormally raised initial plasma-fibrinogen levels. An increased proportion of patients on treatment showed evidence of clinical improvement. Clofibrate had no effect on the susceptibility of red blood cells to autoxidation but it led to a significant shift in the red cell fatty acid pattern.
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PMID:Effect of clofibrate on blood viscosity in intermittent claudication. 442 53

Increased blood viscosity has been shown to be an important factor in reducing blood flow in a review and analysis of the history, clinical findings, and haemodynamic, rheological, radiological, and biochemical measurements in 126 patients with intermittent claudication. In some patients increased viscosity seemed to be the determining cause of claudication. A raised plasma fibrinogen was the most common single biochemical abnormality. The results of conventional serum lipid and lipoprotein estimations were abnormal in the series as a whole but did not correlate with clinical findings or flow measurements at individual patient level. There was, however, a significant correlation between some clinical findings and the susceptibility of the red cells to autoxidation.
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PMID:Clinical, haemodynamic, rheological, and biochemical findings in 126 patients with intermittent claudication. 475 17

To assess the prognostic significance of clinical and laboratory findings in intermittent claudication a group of 62 untreated patients was followed up in detail for periods of from one to three years. There was a significant correlation between progressive deterioration of the peripheral circulatory disturbance and the initial blood viscosity, the plasma fibrinogen level, and the susceptibility of red cell lipids to autoxidation.
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PMID:Prognostic significance of rheological and biochemical findings in patients with intermittent claudication. 475 18

In a randomized double-blind study, the clinical and haemorrheological responses of 40 patients receiving oxpentifylline (200 mg 3-times daily) were compared with those of 40 patients receiving placebo. The treatment period in both groups was 2 months. The parameters measured before and after treatment were: subjective response; claudication and maximum walking distances; ankle systolic indices; maximum blood flow in the lower limb by gravimetric plethysmography; plasma fibrinogen; erythrocyte deformability and whole blood viscosity. There was a significant increase (p less than 0.05) in mean erythrocyte deformability in the oxpentifylline group but not in the placebo group; this apparent difference between the groups, however, was not significant. The placebo group showed a significant improvement (p less than 0.05) in claudication distance and mean plasma fibrinogen concentration, but no such improvements were observed in the oxpentifylline group. There were no significant differences in either of the two groups with regard to the subjective response, ankle systolic indices, maximum limb blood flow or whole blood viscosity. It is concluded that oxpentifylline , when taken in oral form at the dose used in this study, increased erythrocyte deformability without conferring any clinical or haemorrheological benefit to patients with intermittent claudication.
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PMID:Does oxpentifylline ('Trental') have a place in the treatment of intermittent claudication? 637 57

We assessed the simple method of measuring red cell deformability described by Reid et al. The technique was found to be reproducible. The validity of the method as a measure of red cell deformation was confirmed by (a) marked reduction of the deformability index after fixation of red cells with glutaraldehyde, and (b) an inverse correlation of deformability index with high-shear blood viscosity (r = 0.4; P < 0.001). There was no correlation of deformability index with low-shear blood viscosity, plasma viscosity, fibrinogen, or the white cell count. In normal subjects, deformability index was similar in males and females, and in smokers and non-smokers. Patients with acute myocardial infarction, or intermittent claudication, had reduced deformability compared to controls (P < 0.01).
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PMID:An assessment of red cell deformability using a simple filtration method. 677 88


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