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  • 1
    ISSN: 1432-1041
    Keywords: Atrial natriuretic factor (ANF) ; platelet aggregation ; aldosterone ; whole blood ; ex-vivo
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Atrial natriuretic factor (ANF) binding sites have been shown to be present on human platelet membranes. We investigated the effect of an infusion of ANF 5 pmol·kg−1.min−1 on platelet aggregation in whole blood ex-vivo in 8 normal volunteers. Spontaneous platelet aggregation, collagen (0.6–2 μg·ml−1)-induced or ADP (0.5–2.0 μM)-induced aggregation was not affected by ANF. Plasma aldosterone was however significantly attenuated by ANF. These results show that a pharmacological dose of ANF does not affect platelet aggregation in man. These results suggest that the high plasma levels of ANF normally achieved in chronic heart failure or acute myocardial infarction are unlikely to contribute to the platelet hyperreactivity, often observed in these conditions.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Retinopathy ; insulin treated diabetes ; blood viscosity ; plasma viscosity ; haematocrit ; fibrinogen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Blood viscosity (shear rates 100s-1 and 0.94 s-1) and several of its major determinants (haematocrit, plasma fibrinogen and plasma viscosity) have been measured in 38 male insulin-treated diabetics, aged 18–50 years, and in 38 non-diabetic control subjects matched for age and smoking habit. Diabetics without fundoscopic retinopathy (n=20) had higher mean blood viscosity than controls at the high shear rate (7.07 cP vs 6.75 cP, p〈0.05) and the low shear rate (21.2 cP vs 18.7 cP, p〈0.025). These differences persisted after correction of blood viscosity to a standard haematocrit, and were associated with increased plasma viscosity (1.41 cP vs 1.34 cP, p〈0.025) and plasma fibrinogen (2.9 g/L vs. 2.5 g/L, p〈0.025). Diabetics with retinopathy (n=18) had higher mean blood viscosity than diabetics without retinopathy at the high shear rate (7.53 cP vs 7.07 cP, p〈0.05) and the low shear rate (24.3 cP vs. 21.2 cP, p〈0.05), associated with a higher haematocrit (p〈0.05). Blood viscosity and haematocrit correlated with the duration of diabetes (r〉0.32, p〈0.05).
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  • 3
    ISSN: 1365-2044
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary We investigated the roles of the endothelial nitric oxide and cyclo-oxygenase pathways in mediating the vasoactivity of prilocaine in the skin. We injected prilocaine 1% intradermally into forearm skin of 10 healthy, male subjects. Nitric oxide synthesis was inhibited at a second site by co-injecting prilocaine with l-NAME 1%. We then repeated the injections while blocking the cyclo-oxygenase pathway with aspirin (4 × 600 mg). We measured blood flow responses to the injections using laser Doppler imaging. We found that, after the traumatic effects of injection had subsided, l-NAME reduced the vascular response to prilocaine by a third (p = 0.012), indicating an influence specifically on the drug response. Aspirin had no effect on the response (p = 0.588). We conclude that the vasoactive effects of prilocaine in human skin are mediated partly through the release of endothelial nitric oxide and, although other mechanisms might also be involved, the cyclo-oxygenase pathway does not appear to play a role.
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  • 4
    ISSN: 1437-160X
    Keywords: Thromboxane ; Thromboxane receptor antagonist ; Raynaud's-systemic sclerosis ; Vibration white finger disease ; Platelet aggregation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Raynaud's syndrome (RS) is characterized by intense blood vessel spasm resulting in finger blanching. Treatment primarily involves vasodilation. Thromboxane A2 (TXA2) has been shown to be a potent vasoconstrictor and platelet aggregant. It may be possible to produce a vasodilatory and anti-thrombotic effect by blockade of the TXA2 receptors. ICI 192,605 is a potent TXA2 receptor antagonist and we studied its effects on platelet aggregation and digital blood flow in patients with RS. Sixteen patients with RS completed this doubleblind, randomized, placebo controlled study. Each patient was seen on three separate occasions and was given ICI 192,605 (100 mg orally) on one occasion and matching placebo tablets on the other two. We measured platelet aggregation using platelet rich plasma (PRP) stimulated by U46619, a thromboxane (TX) mimetic. The concentration of U46619 required to cause just over 50% platelet aggregation before the administration of either ICI 192,605 or placebo (pre-dose) was noted. The same concentration of U46619 was used to stimulate the PRP sample at 1h after the administration of ICI 192,605 or placebo (post-dose) and the percentage of platelet aggregation was again noted. Fingertip skin blood flow was also measured 1.25 h post-dose using a laser Doppler flowmeter. Patients were seated in a temperature controlled chamber which was initially heated to 40°C to induce centrally mediated vasodilatation. The temperature was then lowered to 12°C followed by rewarming to 40°C. Steady blood flow values at these temperatures were measured and the rates of cooling and rewarming were also noted. There was significant inhibition of platelet aggregation 1 h following the administration of ICI 192,605 {post-dose % platelet aggregation [mean (standard deviation)]=4.8 (12.7)% vs control values of 65.6 (10.5)% and 62.7 (21.3)%, P〈0.0001 (Analysis of covariance)}. No demonstrable evidence of improved fingertip skin blood flow was observed and it may be that more prolonged dosing is required. As platelet aggregation is increased in Raynaud's phenomenon further evaluation of this group of drugs in patients with RS is required.
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  • 5
    ISSN: 1437-160X
    Keywords: Vasculitis ; Factor VIII ; Systemic sclerosis ; Systemic lupus erythematosus ; Atherosclerosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Factor-VIII_Related antigen (VIII R : Ag) is known to be produced by the blood vessel wall. Noxious stimuli increase endothelial release of VIII R : Ag. It might be expected that the development of vasculitis would be associated with increased levels of VIII R : Ag. To investigate this, eight different groups of subjects were studied: 25 patients with systemic sclerosis, 19 with systemic lupus erythematosus, 15 with rheumatoid arthritis (RA) plus vasculitis, 19 with systemic vasculitis and 14 with atherosclerosis. These groups were compared to 29 patients with primary Raynaud's disease, 15 with RA without vasculitis and 50 controls. Results showed that where there was evidence of vascular disease, then VIII R : Ag was elevated. VIII R : Ag appeared to be a more specific marker for vascular damage than erythrocyte sedimentation rate or C-reactive protein. Longitudinal studies in 11 patients showed good correlation between progression of vascular disease and VIII R : Ag.
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  • 6
    ISSN: 1434-9949
    Keywords: Hexopal ; Controlled Trial ; Raynaud's Disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The peripheral vasospastic symptoms associated with Raynaud's disease continue to be an unsolved clinical problem. Hexopal (Hexanicotinate inositol) has shown promise in uncontrolled studies and its use in patients with Raynaud's disease may reduce such vasospasm. This study examines the effects of 4 g/day of Hexopal or placebo, during cold weather, in 23 patients with primary Raynaud's disease. The Hexopal group felt subjectively better and had demonstrably shorter and fewer attacks of vasospasm during the trial period. Serum biochemistry and rheology was not significantly different between the two groups. Although the mechanism of action remains unclear Hexopal is safe and is effective in reducing the vasospasm of primary Raynaud's disease during the winter months.
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  • 7
    ISSN: 1434-9949
    Keywords: Vasculitis ; Leg Ulcers ; Iloprost
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Leg ulcers are a recognised manifestation of cutaneous vasculitis in connective tissue diseases (CTDs) including rheumatoid arthritis (RA). Iloprost a stable prostacyclin analogue has been sucessfully used to treat Raynaud's phenomenon and digital ulcers associated with CTD's. Our aim was to assess iloprost in the treatment of vasculitic leg ulcers in CTD. In this paper we describe eight cases of vasculitic leg ulceration in association with RA and CTD, treated with intravenous iloprost. The iloprost was administered for 6–8 hours daily and continued for 21–28 days. Immunosuppressive therapy was required in three patients with severe necrotising vasculitis (RAnv). Complete ulcer healing was achieved in four patients within 6 weeks of commencing therapy while rapid improvement occurred in the other four patients. This suggests that iloprost may be useful as an adjunct to therapy for vasculitic leg ulcers. A double-blind placebo controlled study of iloprost therapy for RA leg ulcers is under way.
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