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Biomedical subjects

G D Lowe

Publications and source records attributed to G D Lowe.

At least 145 records · Page 8Linked to original sources

Relationship between plasma essential fatty acids and smoking, serum lipids, blood pressure and haemostatic and rheological factors.

We aimed to determine whether levels of plasma fatty acids are correlated with other potential risk factors for cardiovascular disease, using a sample of patients from a cross-sectional survey of the general population, in the City of Edinburgh. 306 men and women aged 55-74 years of whom half had clinical evidence of arterial disease were tested. The main outcome measures were plasma fatty acids and potential risk factors for cardiovascular disease (age, sex, smoking, blood pressure, serum cholesterol, HDL cholesterol (HDL-C), triglycerides (TGs), lipid peroxides (LPx), plasma fibrinogen, von-Willebrand factor (vWf), beta-thromboglobulin (beta TG), cross-linked fibrin degradation products (FIBDP) and plasminogen activator inhibitor PAI). High levels of several known risk factors for cardiovascular diseases were associated with low levels of certain essential fatty acids. Eicosapentaenoic (EPA), docosahexaenoic acid (DHA) and arachidonic acid (AA) were negatively associated with smoking and TG levels. High levels of certain haemostatic factors, including plasma fibrinogen, blood viscosity and LPx were also associated with low levels of EPA, DHA, AA and HDL-C. In conclusion, plasma fatty acids show strong correlations with many potential risk factors for cardiovascular disease, emphasising their possible importance in pathogenesis.

Aged↗

Management of thrombosis in peripheral arterial disease.

There is accumulating evidence that thrombosis contributes to peripheral arterial disease, and that antithrombotic therapy should be considered at all symptomatic stages. In claudication, antiplatelet therapy is indicated in addition to lifestyle advice and sometimes surgery or angioplasty; the place of thrombolysis is unproven. In chronic critical limb ischaemia, prophylaxis of venous thromboembolism by low-dose heparin is indicated during hospitalisation, as is long-term antiplatelet therapy; local thrombolysis or systemic prostanoid infusions are increasingly used. In acute critical limb ischaemia, full dose heparinisation is followed by thromboembolectomy, local thrombolysis, angioplasty and surgery as appropriate. Antiplatelet therapy and/or anticoagulation are employed following such procedures, according to risk factors in the individual patient. Collaboration between vascular surgeons, radiologists and physicians is important in comprehensive patient care.

Arm↗

Plasma essential fatty acids, cigarette smoking, and dietary antioxidants in peripheral arterial disease. A population-based case-control study.

The aim of this study was to determine the levels of plasma fatty acids in patients with peripheral arterial disease and in control subjects and to identify whether any risks of disease related to these differences were influenced by smoking and antioxidant intake. A random sample of 1592 men and women aged 55 to 74 years was selected from the general population (the Edinburgh Artery Study), from which 153 cases of peripheral arterial disease were identified by the presence of intermittent claudication and low ankle systolic pressures at rest and during reactive hyperemia; these were matched by age and sex to 153 control subjects with no evidence of cardiovascular disease. In 113 case and 122 control subjects, fatty acid levels were measured in three plasma fractions (triglyceride, cholesteryl ester, and phospholipid), and smoking habits and dietary antioxidant intake were determined by questionnaire. Arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, and docosapentaenoic acid (DPA/n-3) were significantly lower in the cases than controls (P < .01). More case than control subjects were current or exsmokers (86% versus 50%; P < .001), and the case subjects had lower vitamin C intake (64.8 mg versus 71.1 mg; P < .05). By logistic regression adjustment for smoking and vitamin C intake, only DPA/n-3 (odds ratio, 0.19; P < .01) and arachidonic acid (odds ratio, 0.44; P < .05) remained significantly related to disease; only DPA/n-3 reduced the risk associated with smoking. We conclude that in subjects with peripheral arterial disease compared with healthy control subjects, the largest differences occurred in fatty acids of the n-3 series, particularly DPA/n-3.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Sex differences in susceptibility to etiologic factors for peripheral atherosclerosis. Importance of plasma fibrinogen and blood viscosity.

Cardiovascular risk factors in men, such as cigarette smoking, hypercholesterolemia, and hypertension, also increase risk in women, but the relative susceptibility to risk factors between the sexes is not established. Our aim was to investigate a wide range of possible etiologic factors in a single population study and identify those that were more strongly related to peripheral atherosclerosis in men or women. We studied personal factors (age and social class), lifestyle factors (smoking, exercise, alcohol intake, and dietary nutrients), and intermediary factors (obesity, diabetes, serum lipids, coagulation, and rheological factors). In the Edinburgh Artery Study in 1988 we measured cardiovascular risk factors in a random population sample of 1592 men and women aged 55 to 74 years. The ankle-brachial pressure index (ABPI), which is inversely related to the degree of peripheral atherosclerosis, was assessed in each subject. Lifetime cigarette smoking was correlated with a lower ABPI equally in men and women (r = -.27, P < .001). Dietary nutrients and alcohol intake were not related differently between the sexes with ABPI. However, recall of strenuous and moderate leisure time exercise during the age range of 35 to 45 years was related more strongly to a higher ABPI in men than in women (P < .05). Plasma fibrinogen, plasma viscosity, and blood viscosity were the only intermediary factors that had stronger univariate correlations with lower ABPI in men than in women. On multivariate analysis, the sex differences persisted for plasma fibrinogen (P < .05) and blood viscosity (P < .001); high-density lipoprotein cholesterol was related to ABPI in men only (sex difference, P < .1).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Percutaneous angioplasty, endothelial markers, and fibrin turnover.

PURPOSE: A number of thrombotic mediators have been related to peripheral arterial disease in both epidemiological and pathological studies. METHODS: We measured preoperative levels of fibrinogen, cross-linked fibrin degradation products (FDP), and the endothelial markers, von Willebrand factor (vWF), tissue plasminogen activator (tPA), and plasminogen activator inhibitor (PAI), in the venous blood of 43 claudicants undergoing percutaneous transluminal angioplasty (PTA). Samples were repeated 4 months later, and changes in the levels of thrombotic mediators were compared with ten controls undergoing angiography alone. Additional perilesional arterial samples were obtained from 11 of the patients. RESULTS: Arterial sampling indicated that successful PTA led to an immediate fall in tPA levels and a rise in arterial vWF (p < 0.05), together with a trend toward a significant rise in cross-linked FDP levels. Only the increase in FDP following successful PTA (36 cases) (p < 0.05) was observed in 4-month postangioplasty venous samples, whereas all variables remained unchanged in cases of restenosis (4 patients) and in controls (all comparisons made by Wilcoxon matched pairs test). CONCLUSIONS: These findings suggest that successful PTA in patients with intermittent claudication results in acute endothelial disturbance and increased fibrin turnover at the site of angioplasty and in sustained increases in fibrin turnover (as reflected by FDP levels). The observation that this increase in fibrin turnover is absent in cases of restenosis within 4 months of PTA merits further study to determine whether increases in fibrin turnover are necessary to maintain patency following PTA.

Angioplasty, Balloon↗

Polymeric biomaterials: influence of phosphorylcholine polar groups on protein adsorption and complement activation.

The introduction to polymeric biomaterials of phosphorylcholine polar groups represents an approach towards the development of materials with improved blood compatibility. In this respect, two biomaterials, one a copolymer of butyl methacrylate and 2-methacryloyloxyethylphosphorylcholine (MPC), (poly(BMA-co-MPC) and the other, MPC-grafted Cuprophan, were examined with respect to their influence on protein adsorption and complement activation. Protein adsorption was studied by measurement of the adsorption of radiolabelled single proteins (albumin and fibrinogen), while complement activation was measured using radioimmunoassay for C3a des Arg. The investigation demonstrated that the polymers containing phosphorylcholine polar groups can achieve a marked reduction in protein adsorption and complement activation and supports the utilization of phosphorylcholine polar groups as a means of improving the compatibility of biomaterials for blood-contacting applications.

Adsorption↗

Biocompatibility of cardiopulmonary bypass: influence on blood compatibility of device type, mode of blood flow and duration of application.

The biocompatibility of artificial organs is recognised as an area presenting difficulties in terms of the complexity of the situation. The nature of the blood response involving interactions of systems, pattern and extent of change, patient status and the influence of the whole device contribute to the complexity. Recognising these, the profile of the blood response to cardiopulmonary bypass (CPB), with respect to type of device, mode of blood flow, duration of the procedure and patient status, has been evaluated by monitoring contact phase activation [Factor XII-like activity (FXIIA)], fibrinolytic activity [Fibrin degradation products (X-FDP's)], complement activation (C3a, C5a), leucocyte activation [Granulocyte elastase (GE)] and platelet and white cell imaging. FXIIA, X-FDP's, and GE rose gradually during CPB, with levels remaining elevated post-operatively for up to 48 h. In contrast, C3a levels rose sharply with no significant elevation in the post-operative period, while C5a did not show significant changes during bypass. The use of pulsatile perfusion resulted in lesser activation of the parameters, although these were significantly less only for GE. The alterations in FXIIA, X-FDP's, C3a and GE correlated positively with the duration of CPB, with this effect pronounced in the post-operative period for FXIIA, X-FDP's and GE. However, these changes had no apparent influence on clinical outcome and the majority of patients had uncomplicated post-operative recoveries. With respect to the use of bubble/membrane oxygenators, platelet and white cell deposition and the patterns of change for FXIIA and C3a were similar in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Biocompatible Materials↗

Association of severe haemophilia A with osteoporosis: a densitometric and biochemical study.

Following a femoral neck fracture and vertebral compression fractures in two patients with severe haemophilia A, bone density and turnover were measured in 19 males with severe haemophilia A (all HIV negative, 18/19 hepatitis C antibody positive) and in 19 age/sex matched controls. Bone density at the lumbar spine (L2-4), measured by dual energy X-ray absorptiometry, was significantly lower in the haemophiliac patients (HPs) at (mean +/- SEM) 1.109 +/- 0.042 g/cm2 vs. 1.234 +/- 0.027 in controls; p = 0.018. Femoral neck density was also lower at 0.877 +/- 0.034 g/cm2 (HPs) vs. 1.067 +/- 0.032; p < 0.0005. No significant differences were evident between the groups for serum calcium, parathyroid hormone, luteinizing hormone, follicle-stimulating hormone or 1,25 dihydroxyvitamin D3, nor for fasting urinary hydroxyproline, pyridinoline or deoxypyridinoline excretion. Serum total alkaline phosphatases was elevated in HPs at 200 +/- 10 U/l vs. 158 +/- 8; p = 0.004. Similarly, gamma-glutamyl transferase was elevated at 42 +/- 7 U/l (HPs) vs. 20 +/- 2; p = 0.007. Serum total testosterone and sex-hormone-binding globulin (SHBG) were higher in HPs at 26 +/- 2.5 nmol/l vs. 17.4 +/- 1.6 (p = 0.009) and 56 +/- 6 nmol/l vs. 27 +/- 3 (p = 0.0005), respectively. Free androgen index, however, was lower in HPs at 44 +/- 5 vs 69 +/- 7; p = 0.008. These results suggest significant osteopenia associated with haemophilia A. This may be partly due to liver dysfunction in HPs, but other factors, e.g. relative immobilization, may also be relevant.

Absorptiometry, Photon↗

Cross-linked fibrin degradation products, progression of peripheral arterial disease, and risk of coronary heart disease.

Haemostatic and rheological factors may predict cardiovascular disease. We studied patients with intermittent claudication to see if the progression of peripheral arterial disease and the risks of coronary events could be predicted by baseline packed cell volume, plasma fibrinogen, blood and plasma viscosites, von Willebrand factor antigen, cross-linked fibrin degradation products (XLFDP), urinary fibrinopeptide A, and plasma leucocyte elastase. In 617 patients with claudication followed up for one year, baseline XLFDP was related most strongly to coronary events, relative risk 4.4 (95% CI 1.3-19.0) between top and bottom quintiles. Plasma fibrinogen was the strongest independent predictor of death from coronary disease. XLFDP was the only factor, in addition to age and cigarette smoking, that was independently associated (p = 0.008) with deterioration in peripheral arterial disease. We conclude that, in patients with peripheral arterial disease, plasma concentration of XLFDP, a measure of ongoing fibrin formation and degradation, is a strong predictor of both disease progression and future coronary risk. These results accord with the hypothesis that fibrin formation contributes to progression of coronary and peripheral atherosclerosis.

Adult↗

Association of fibrinolytic tests with outcome of acute upper-gastrointestinal-tract bleeding.

Endogenous fibrinolysis may play a part in acute upper-gastrointestinal-tract bleeding by causing digestion of haemostatic plugs. We assessed the predictive value of fibrinolytic tests for hospital outcome in a prospective study of 122 patients with acute upper-gastrointestinal-tract bleeding who underwent endoscopy. Serum fibrin degradation products (FDP) were above the normal range in 32% (95% CI 21-44%) of patients who survived and did not require transfusion or surgery, in 53% (37-69%) of patients who survived without surgery but required transfusion, and in 100% (82-100%) of patients who required surgery or died. Multivariate analysis showed that after adjustment for the effects of established risk factors (age, pulse rate, blood pressure, haemoglobin, site of bleeding, and stigmata of active bleeding at endoscopy), serum FDP was a powerful independent predictor of outcome (p = 0.003). Doubling of serum FDP was associated with a 59% increase in the risk of a poor outcome (95% CI 14-120%). These findings are consistent with roles for endogenous fibrinolysis in gastrointestinal-tract bleeding, for fibrinolytic tests in prediction of adverse outcome, and for fibrinolytic inhibitors in treatment.

Acute Disease↗

Comparison of metabolic responses to laparoscopic and minilaparotomy cholecystectomy.

This randomized study compared the metabolic responses to laparoscopic cholecystectomy (n = 10) and minilaparotomy cholecystectomy with a 5-7-cm incision (n = 10). Venous blood samples were taken before operation and at 3, 6, 9, 12, 18, 24, 48, 72 and 168 h after incision and analysed for levels of C-reactive protein, interleukin 6, cortisol, albumin, transferrin, iron, fibrinogen, fibrin degradation products and polymorphonuclear elastase, and for neutrophil and lymphocyte counts. Urine samples (24 h) were analysed for urea, creatinine, 3-methylhistidine and catecholamines. The magnitude of the metabolic changes from baseline levels was quantified by calculating areas under each individual curve. A significant metabolic response with a similar time course and magnitude of changes occurred after laparoscopic and minilaparotomy cholecystectomy but with wide variation in magnitude between individuals.

Adult↗

Smoking, haemostatic factors and lipid peroxides in a population case control study of peripheral arterial disease.

The aim of this study was to determine differences between cases of peripheral arterial disease and healthy controls in levels of haemostatic factors and lipid peroxides and the influence of cigarette smoking. The study groups were selected from the Edinburgh Artery Study which is a random sample survey of men and women aged 55-74 years. Mean levels of plasma fibrinogen, von Willebrand factor, beta-thromboglobulin, plasminogen activator inhibitor (type I), cross-linked fibrin degradation products and lipid peroxides were markedly elevated in 121 study cases compared with 126 age- and sex-matched controls. For example, cross-linked fibrin degradation products had a geometric mean of 106.8 ng/ml (95% confidence interval (CI) 95.3, 119.8) in study cases and 74.7 ng/ml (95% CI 67.0, 83.4) in controls (P < 0.001). Inclusion of smoking in logistic regressions of each factor on peripheral arterial disease significantly reduced the odds of disease for von Willebrand factor and for cross-linked fibrin degradation products, but had little effect on the increased odds associated with fibrinogen, beta-thromboglobulin, plasminogen activator inhibitor and lipid peroxides. We conclude that, in men and women in Edinburgh, peripheral atherosclerosis is associated with lipid peroxidation, endothelial disturbance, platelet activation, elevated fibrinogen, fibrin formation and increased inhibition of fibrinolysis. The most important effects of cigarette smoking in promoting atherosclerosis may be endothelial disturbance and fibrin formation.

Aged↗

Foot microcirculation and blood rheology in diabetes.

Diabetes mellitus is associated with circulatory abnormalities. The blood flow in the skin of the dorsum of the foot and haemorheological variables were measured in 36 subjects. They were divided into three equal groups of diabetic patients: those with neuropathy, and both age and sex matched non-diabetic subjects; all were characterized by age, duration of diabetes and blood biochemistry. High and low shear rate blood viscosities were measured; aggregation was characterized using a Myrerene Aggregometer. The microcirculation in the skin of the dorsum of the foot was measured using a laser Doppler flowmeter. Measurements were made at room temperature with the subjects supine with the leg horizontal, and then with the lower leg vertical; the measurements were repeated at 42 degrees C. Both diabetic groups had significantly increased low shear whole blood viscosity compared with normal subjects. The aggregation index was significantly greater in diabetic neuropaths than normal subjects. There were significant differences in the depth of vasomotor activity between the three groups, with the diabetic neuropaths commonly showing no motor activity at room temperature. The only significant correlations were between equilibrium laser Doppler values with the limb horizontal and both the low and high shear whole blood viscosities.

Blood Viscosity↗