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Biomedical subjects

G D Lowe

Publications and source records attributed to G D Lowe.

At least 127 records · Page 7Linked to original sources
PubMed1995

Tissue-plasminogen activator, plasminogen activator inhibitor and risk of peripheral arterial disease.

In this population-based case-control study, we examined the relationship between the fibrinolytic variables tissue-plasminogen activator (t-PA) antigen and plasminogen activator inhibitor (PAI) activity, cardiovascular risk factors and peripheral arterial disease. Cases and controls were selected from the Edinburgh Artery Study, a random sample survey of men and women, aged 55-74 years. Mean levels of t-PA antigen and PAI activity were significantly elevated in 121 cases compared to 126 controls. The increased risks of peripheral arterial disease with increasing PAI activity and t-PA antigen levels were partly mediated by interactions with serum triglycerides, high density lipoprotein (HDL) cholesterol and cigarette smoking. For example, adjustment for triglycerides significantly reduced the odds of disease for PAI activity from 1.41 (95% confidence intervals 1.08, 1.86) to 1.24 (0.93, 1.65) and from 1.47 (1.09, 1.98) to 1.34 (0.99, 1.82) for t-PA antigen. We conclude that impaired fibrinolytic potential (raised PAI activity and t-PA antigen) is associated with peripheral atherosclerosis and that this relationship is partly influenced by lipids and cigarette smoking.

Age Factors↗
PubMed1995

In vitro contact phase activation with haemodialysis membranes: role of pharmaceutical agents.

Contact phase activation was investigated in vitro using flat sheet type of haemodialysis membranes, Cuprophan (Akzo, Faser, Germany) and AN69S (Hospal, France), and a negatively charged polyamide Ultipor NR 14225 membrane as a control. The investigation focussed on the determination of factor XII-like activity (FXIIA) as an indicator of contact phase activation in the supernatant phase and at the membrane surface after plasma-membrane contact using an incubation test cell. The findings were compared with the observations from a plasma-free system utilizing purified unactivated factor XII. The plasma FXIIA bound to the membrane surface was significantly different between the membranes, while the supernatant phase FXIIA exhibited no significant differences. In contrast, the plasma-free system exhibited significant differences in the supernatant FXIIA and membrane-bound FXIIA for all the materials used and the magnitude of the activity was significantly greater for negatively charged materials. This finding demonstrated the strong influence of the interaction of other plasma constituents on the membrane surface and as such the binding and subsequent activation of factor XII may be altered possibly due to competitive binding and steric hindrance. On the addition of anticoagulants such as heparin, low-molecular-weight heparin, citrate and hirudin, no significant differences were observed in plasma supernatant phase FXIIA. However, each anticoagulant appears to have a distinct influence on the magnitude of plasma membrane-bound FXIIA. On the addition of aprotinin (a kallikrein inhibitor), no significant differences were observed in the plasma supernatant FXIIA. In contrast, aprotinin appears to significantly reduce membrane-bound FXIIA on Cuprophan and polyamide NR, but significantly increase the magnitude of the membrane-bound FXIIA on AN69S.

Anticoagulants↗
PubMed1995

Plasma fibrinogen and fibrin D-dimer in patients with atrial fibrillation: effects of cardioversion to sinus rhythm.

Cardioversion of atrial fibrillation carries a serious risk of major thromboembolism and stroke. To determine whether or not the procedure alters plasma levels of fibrin D-dimer (a marker of intravascular fibrin turnover and thrombus formation) and plasma fibrinogen (associated with stroke and thromboembolism), we performed a prospective study in 19 patients with atrial fibrillation in whom cardioversion was attempted: seven patients without prior oral anticoagulant therapy (but with intravenous heparin for 24 h) (Group I), and 12 patients with full oral anticoagulation pre- and post-cardioversion (Group II). Plasma fibrinogen and fibrin D-dimer were measured pre-cardioversion, and at Days 3, 7 and 14 post-cardioversion. In Group I, there was a significant reduction in median plasma fibrin D-dimer levels by 14 days following cardioversion (200 vs. 52 ng/ml; paired Wilcoxon test, P = 0.02). In Group II, there was no change in median plasma fibrin D-dimer levels over the 14 days following cardioversion. There were no significant changes in plasma fibrinogen with cardioversion in either group of patients. The reduction of plasma fibrin D-dimer in Group I suggests a beneficial reduction of intravascular fibrin turnover and thrombogenesis by the cardioversion of patients with atrial fibrillation to sinus rhythm. Furthermore, it strongly suggests that it is atrial fibrillation itself which is the major risk of thromboembolism and that the risk continues for up to 14 days post-cardioversion. In Group II, the low pre-cardioversion fibrin D-dimer levels and lack of change with cardioversion is consistent with the prophylactic effect of warfarin therapy against thromboembolism during the cardioversion of atrial fibrillation.

Adult↗
PubMed1995

Fibrinogen and markers of fibrinolysis and endothelial damage following resolution of critical limb ischaemia.

OBJECTIVES: To assess the effects of resolution of critical limb ischaemia on the elevated plasma fibrinogen, cross-linked fibrin degradation products (FDP), and von Willebrand factor antigen (vWF) levels, reported in peripheral arterial occlusive disease. DESIGN: A prospective study of patients undergoing surgery for chronic critical limb ischaemia. SETTING: Two vascular surgery units providing tertiary referral services for the West of Scotland. MATERIALS: Venous blood samples were assayed for plasma fibrinogen, FDP D-dimer, and vWF levels, prior to surgery, together with fibrinolytic and rheological parameters, in 82 patients. Sampling was repeated 4 months after resolution of critical limb ischaemia. OUTCOME MEASURES: Levels of these parameters following successful resolution of critical limb ischaemia were compared with pre-operative levels, and with an age-matched random population sample. MAIN RESULTS: Plasma fibrinogen and vWF levels were significantly lower (both p < 0.005, Wilcoxon matched pairs) following successful resolution of critical limb ischaemia in the 56 patients available for review, although levels remained higher than in population controls (p < 0.01, Mann-Whitney U-test). FDP levels were unchanged following surgery, remaining higher than in age-matched population controls (p < 0.01). CONCLUSIONS: Resolution of critical limb ischaemia fails to reduce plasma fibrinogen, fibrin turnover, and vWF levels to those seen in population controls. This implies that increased fibrinogen and fibrin turnover in peripheral arterial disease is not solely a consequence of tissue ischaemia, while the persisting prothrombotic state following resolution of critical limb ischaemia has potentially important implications for graft and patient survival.

Aged↗
PubMed1995

The relationship between cigarette smoking and cardiovascular risk factors in peripheral arterial disease compared with ischaemic heart disease. The Edinburgh Artery Study.

Cigarette smoking is probably the most important risk factor for the development of peripheral arterial disease, but it may be less important in the aetiology of ischaemic heart disease. The objectives of this study were to determine whether any other cardiovascular risk factors showed a significant interaction with cigarette smoking which would explain the greater association between smoking and peripheral atherosclerosis. One thousand five hundred and ninety-two subjects aged 55-74 years were selected randomly from the age-sex registers of 10 general practices in Edinburgh, Scotland. The presence of peripheral arterial disease was determined by the World Health Organisation questionnaire on intermittent claudication, the ankle brachial pressure index and a reactive hyperaemia test. Heart disease was identified by the patients' recall of a doctor diagnosis of angina or myocardial infarction. There were 131 subjects with peripheral arterial disease but no ischaemic heart disease, and 169 with heart disease without peripheral disease. Significantly more smokers occurred in the peripheral than the heart disease group (P <0.01), and in current smokers the age and sex adjusted odds ratio were highly significant for peripheral arterial disease (odds ratio 5.09, 95% confidence interval 2.97-8.72, P<0.001), but not for heart disease (odds ratio 1.72, 95% confidence interval 0.98-2.33, P>0.05). Subjects with lower limb disease also had higher systolic pressures (P<0.001), serum high density lipoprotein cholesterol (P<0.01) and plasma fibrinogen (P<0.05). On logistic regression, adjusting for a range of individual risk factors had no significant impact on the effect of smoking. Plasma fibrinogen produced the biggest reduction in odds ratio (4.23, 95% confidence interval 2.44-7.35, in current smokers with peripheral arterial disease). Therefore the stronger association between smoking and peripheral arterial disease than ischaemic heart disease does not appear to be influenced by the other risk factors examined here, and must be explained by some other mechanism.

Aged↗
PubMed1995

A pharmacokinetic study of an ion-exchange solvent-detergent-treated high-purity factor VIII concentrate. Haemophilia Directors for Scotland and Northern Ireland.

An ion-exchange chromatography purified factor VIII concentrate (Liberate) that had undergone a solvent-detergent viral inactivation treatment was compared with an intermediate-purity concentrate (Z8), which was terminally heated at 80 degrees C for 72 h, in 15 haemophilia A patients in a blinded crossover pharmacokinetic study. Both products achieved a peak level close to that predicted (100 IU/dl for Liberate and 103 IU/dl for Z8) and there were no significant differences in the recoveries achieved nor of any of the other pharmacokinetic parameters. We conclude that the pharmacokinetic properties of factor VIII:C, following solvent-detergent treatment and ion-exchange chromatography, are equivalent to those of the lower purity terminally heat-treated product (Z8), and it is therefore likely to be a clinically efficacious concentrate.

Adult↗
PubMed1995

Blood rheology and albumin excretion in diabetic pregnancy.

Blood rheology is altered in diabetes and also in non-diabetic pregnant women. The cumulative effect of hyperfiltration, abnormal rheology of pregnancy, and diabetes could be one mechanism contributing to increased intraglomerular pressure and albuminuria in diabetic pregnancy. We conducted a prospective study of 22 Type 1 (insulin-dependent) diabetic patients and 22 non-diabetic women to determine if there was an association of altered blood rheology on glomerular function in diabetic pregnancy. Albumin excretion showed no increment with increasing gestation and was similar in diabetic and non-diabetic women throughout pregnancy (first trimester: 5.0 (3.0-14.0) vs 5.8 (3.7-10.7) mg l-1, p = 0.89; second trimester: 6.0 (5.0-12.0) vs 5.1 (3.6-10.4) mg l-1, p = 0.25; third trimester: 7.5 (3.5-16.0) vs 4.9 (2.9-7.3) mg l-1, p = 0.18). Red cell aggregation index increased in both groups between the first and third trimesters (diabetic patients: mean difference 2.0; Cl: 1.0-2.9, p = 0.003, and control patients: mean difference 2.3, Cl: 1.0-3.5, p = 0.002). Fibrinogen levels were significantly higher between the third and first trimesters in diabetic patients (mean difference 0.7, Cl: 0.2-1.3 g l-1, p = 0.006). Pregnancy, therefore, was associated with increased red cell aggregation, related in part to increased fibrinogen levels but the extent of change was similar in diabetic and nondiabetic women and appeared to have no adverse effect on glomerular function in pregnant insulin-dependent diabetic women.

Adult↗
PubMed1995

Blood-contacting biomaterials: bioengineering viewpoints.

The investigation of blood-contacting biomaterials is an important challenge and is relevant for an improvement in the clinical application of biomaterials. With the purpose of improved clinical treatment, bioengineering viewpoints of blood-contacting biomaterials cover the material options and selection, the utilization of materials, the development of materials with better properties, and processing characteristics, and the design of relevant evaluation procedures. The bioengineering objective remains that of achieving an enhanced understanding of the relationship between a biomaterial and the biological response.

Biocompatible Materials↗
PubMed1995

Influence of age, systemic blood pressure, smoking, and blood viscosity on orbital blood velocities.

The influence of multiple systemic factors upon the blood velocities obtained from the orbital circulations was investigated. The velocities obtained by colour Doppler imaging from the ophthalmic artery, central retinal artery, and vein from 95 ophthalmologically healthy volunteers were analyzed. The effects of age, systemic blood pressure, and smoking habit were examined. In 24 volunteers blood viscosity was also measured and its relation with blood velocity assessed. Age was weakly negatively correlated with the blood velocities in the ophthalmic artery and weakly positively correlated with resistance to flow in the retinal circulation. Systolic blood pressure showed a positive correlation with the peak systolic velocities in the arteries while cigarette smoking was associated with lower ophthalmic artery velocities. Increased haematocrit and viscosity were positively correlated with resistance to flow proximal to the ophthalmic artery and red cell rigidity negatively correlated with the pulsatility of flow in the retinal vein. These results help to identify the roles of systemic conditions in the ocular circulation. The influence of blood viscosity on retinal venous flow may be relevant to the pathogenetic mechanisms of conditions such as central retinal vein occlusion.

Age Factors↗
PubMed1995

Increased markers of thrombogenesis in chronic atrial fibrillation: effects of warfarin treatment.

OBJECTIVE: To determine whether chronic atrial fibrillation is associated with abnormalities in plasma fibrinogen, von Willebrand factor (vWF) (a marker of endothelial disturbance), or fibrin D- dimer (a measure of fibrin turnover); and if so, whether such levels are related to haemodynamic disturbance (enlarged left atrium, poor left ventricular function) or existing treatment with warfarin or aspirin. To investigate the effects of introducing warfarin in patients with atrial fibrillation on fibrinogen and D- dimer levels. DESIGN: Cross sectional population sample controlled study and longitudinal study of patients undergoing anticoagulation. SETTING: District general hospital. SUBJECTS: 87 patients (44 men and 43 women of mean (SEM) age 63.0 (1.0)) with chronic atrial fibrillation. At the time of the study, 37 were taking no antithrombotic medication (group 1), 31 were taking warfarin (including two on warfarin and aspirin) (group 2) and 19 were taking aspirin alone (group 3). They were compared with 158 population controls from a random population sample (the second Glasgow monitoring trends and determinants in cardiovascular disease study). As part of clinical treatment warfarin was introduced in 20 patients with chronic atrial fibrillation (14 men and six women of mean (SEM) (range) age 63.9 (2.35 (32-74) years). RESULTS: Plasma fibrinogen remained significantly increased in patients of group 1 (no antithrombotic medication) compared with that of the population controls (median difference 1.23 g/l; 95% confidence interval (CI) 0.88 to 1.62, P < 0.0001). There was also a significant increase in plasma D-dimer levels (median difference 77 ng/ml; 95% CI 38 to 122, P < 0.01) and vWF (median difference 63 IU/dl; 95% CI 38 to 89, P < 0.0001). There was no significant difference in plasma fibrinogen (median difference 0.14 g/l; 95% CI -0.44 to 0.77, P = 0.65) or vWF (median difference 3.5 IU/dl; 95% CI - 41 to 41, P = not significant in patients of group 2 (warfarin treatment) compared with that of patients in group 1. Levels of D-dimer were significantly lower in group 2 (median difference 90 ng/ml, 95% CI 39 to 150, P < 0.0001) than in group 1. There were no significant differences in plasma fibrinogen (median difference 0.08 g/l; 95% CI - 0.52 to 0.77, P = 0.73), D-dimer (median difference - 34 ng/ml; 95% CI - 114 to 21.0, P = 0.25), or vWF (median difference 2%; 95% CI - 35 to 41, P = not significant) levels between patients of groups 1 and 3. There were no significant correlations between the coagulation indices and left atrial volume or ventricular function. There was a significant positive correlation between plasma fibrin D-dimer and vWF levels in patients of groups 1 and 3 (r = 0.52, P < 0.001). There was a significant reduction in median plasma fibrin D-dimer levels at 2 months after the introduction of warfarin (181 ng/ml v 80 ng/ml, P < 0.001), but no effect on plasma fibrinogen. CONCLUSIONS: Increased median plasma fibrinogen and vWF levels were found in patients with chronic atrial fibrillation. Plasma D-dimer levels were also increased in patients with chronic atrial fibrillation not receiving warfarin, suggesting increased intravascular thrombogenesis in such patients. Introduction of warfarin normalised circulating fibrin D- dimer levels, suggesting that warfarin treatment was effective in preventing excessive fibrin turnover, consistent with the antithrombotic effects of warfarin. These results suggest three possible thrombotic markers to assess patients with atrial fibrillation who are at high risk of thrombogenesis; D-dimer also merits assessment as a measure of reduction in thrombotic risk in patients receiving warfarin.

Adult↗
PubMed1995

Determinants of fibrin D-dimer in the Edinburgh Artery Study.

There is growing evidence that fibrin D-dimer is associated with coronary and peripheral atherosclerosis. Using data from the Edinburgh Artery Study, we examined the distribution of fibrin D-dimer in 1592 men and women 55 to 74 years old and assessed its relationship with a range of cardiovascular risk factors. Fibrin D-dimer levels were higher in women than in men (P < or = .05) and increased with age (P < or = .001). Current cigarette smokers had higher levels than ex-smokers, who, in turn, had higher levels than those who had never smoked. On multiple regression analyses with age and plasma fibrinogen as covariates, only lifetime smoking in men and systolic blood pressure in women were independent predictors of fibrin D-dimer levels. Since fibrin D-dimer does not appear to be independently related to many of the common cardiovascular risk factors, it may be a useful index of the thrombotic contribution to arterial disease.

Aged↗
PubMed1995

Fibrin D-dimer, haemostatic factors and peripheral arterial disease.

Several haemostatic factors have been shown to have a predictive role in cardiovascular disease, although their relationship with prevalent peripheral arterial disease is not well reported. Using a random sample of 1592 men and women aged 55-74 years from Edinburgh, Scotland, we examined the relationship of von Willebrand factor (vWF), tissue plasminogen activator (t-PA) and fibrin D-dimer antigens and factor VII activity to peripheral arterial disease. t-PA antigen and fibrin D-dimer showed significant linear trends of increased levels with increasing severity of disease in both sexes (p < or = 0.01) and vWF showed a similar pattern in men only (p < or = 0.01). On multivariate analysis, fibrin D-dimer was independently related to the risk of intermittent claudication (p < or = 0.01) and, among men, to the extent of arterial narrowing in the lower limb, as measured by the ankle brachial pressure index, (ABPI) (p < or = 0.001). These results are further evidence of a role for intravascular fibrin deposition in the development of peripheral atherosclerosis.

Aged↗
PubMed1995

Relation of haemostatic, fibrinolytic, and rheological variables to the angiographic extent of peripheral arterial occlusive disease.

We investigated the relationships between the angiographic severity of peripheral arterial occlusive disease (PAOD) and haemostasis, fibrinolytic, and rheological variables in 219 patients with symptomatic peripheral arterial occlusive disease (PAOD). White cell count, fibrinogen, cross-linked fibrin degradation products (FDP), von Willebrand factor, and plasminogen activator inhibitor levels were all elevated in comparison with age-matched population controls (all p < 0.0001, Mann-Whitney U test), while fibrinogen (Spearman r = 0.30), von Willebrand factor (r = 0.40), and log (FDP) (r = 0.56), (all p < 0.0001) showed a strong correlation with the angiographic extent of PAOD. Multivariate analysis indicated that log (FDP) was a strong independent predictor of the angiographic severity of PAOD (p < 0.0001), in addition to increasing age (p < 0.0001), presence of tissue sepsis (p < 0.02), prior vascular surgery (p = 0.007), and other vascular pathology (p = 0.007). These results confirm that increase in fibrinogen, von Willebrand factor, plasminogen activator inhibitor and fibrin turnover, are strongly associated with the presence of symptomatic peripheral arterial disease, and suggest that there may be a causal link between fibrin turnover, as determined by FDP levels, and the extent of peripheral arterial occlusive disease.

Adult↗
PubMed1995

Relation of haemostatic, fibrinolytic, and rheological variables to the angiographic extent of peripheral arterial occlusive disease.

We investigated the relationships between the angiographic severity of peripheral arterial occlusive disease (PAOD) and haemostasis, fibrinolytic, and rheological variables in 219 patients with symptomatic peripheral arterial occlusive disease (PAOD). White cell count, fibrinogen, cross-linked fibrin degradation products (FDP), von Willebrand factor, and plasminogen activator inhibitor levels were all elevated in comparison with age-matched population controls (all p < 0.0001, Mann-Whitney U test), while fibrinogen (Spearman r = 0.30), von Willebrand factor (r = 0.40), and log (FDP) (r = 0.56), (all p < 0.0001) showed a strong correlation with the angiographic extent of PAOD. Multivariate analysis indicated that log (FDP) was a strong independent predictor of the angiographic severity of PAOD (p < 0.0001), in addition to increasing age (p < 0.0001), presence of tissue sepsis (p < 0.02), prior vascular surgery (p = 0.007), and other vascular pathology (p = 0.007). These results confirm that increases in fibrinogen, von Willebrand factor, plasminogen activator inhibitor and fibrin turnover, are strongly associated with the presence of symptomatic peripheral arterial disease, and suggest that there may be causal link between fibrin turnover, as determined by FDP levels, and the extent of peripheral arterial occlusive disease.

Age Factors↗
PubMed1994

Geographical variations in plasma viscosity and relation to coronary event rates.

Plasma viscosity is reported to be predictive of coronary heart disease (CHD) and stroke. To find out whether regional differences in CHD event rates correlate with differences in plasma viscosity, we compared plasma viscosity in a high-risk area for CHD (Glasgow Multinational Monitoring of Trends and Determinants in Cardiovascular Disease [MONICA] and Scottish Heart Health Study population surveys, 1985/86; n = 1166) and in a lower-risk area (MONICA Augsburg survey, 1984/85; n = 3258) in men and women aged 25-64 years. Mean plasma viscosity (37 degrees C) was 1.261 (SD 0.067) mPa s in Augsburg and 1.327 (0.093) mPa s in the west of Scotland for men, and 1.248 (0.066) mPa s and 1.318 (0.087) mPa s, respectively, for women. The unadjusted difference of the means between the west of Scotland and Augsburg was 0.066 (95% CI from weighted regression 0.058-0.073) mPa s for men and 0.070 (0.062-0.078) mPa s for women. Adjustment for age, smoking behaviour, total and high-density-lipoprotein cholesterol, systolic and diastolic blood pressure, and body-mass index had no effect on these differences. Age-standardised coronary event rates in 1985-87 were at least two times higher among men, and four times higher among women, in MONICA Glasgow than in MONICA Augsburg. This large geographical difference in plasma viscosity might partly explain the differences in CHD event rates between these populations. Further studies are needed on the determinants of plasma viscosity, and on its potential roles in atherosclerosis, thrombosis, and ischaemia.

Adult↗