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Biomedical subjects

G D Lowe

Publications and source records attributed to G D Lowe.

At least 19 recordsLinked to original sources
PubMed1992

Fibrinogen genotype and risk of peripheral atherosclerosis.

There is conflicting evidence about the influence of fibrinogen genotype on plasma fibrinogen concentrations, and the relation between genotype and atherosclerotic disease has not been studied. In a population-based case-control study we aimed to find out whether certain fibrinogen genotypes are associated with an increased risk of peripheral atherosclerosis. 121 subjects with peripheral arterial disease and 126 healthy controls matched for age and sex were selected from a random population sample aged 55-74 years in the Edinburgh Artery Study. Mean fibrinogen concentrations were higher in cases than in controls (3.12 [95% confidence interval 2.99-3.26] vs 2.75 [2.64-2.85], p less than 0.001). A greater proportion of cases than controls were homozygous or heterozygous for an allele at the beta fibrinogen locus (4.2 kb allele, Bcl I digestion); the allele frequency was 0.197 in cases and 0.097 in controls (p less than 0.005). Extended haplotypes for 4.2 kb heterozygotes were also associated with an increased risk of peripheral arterial disease. However, haplotype had only a small effect on the association of plasma fibrinogen concentration with disease, and the relation of haplotype with disease was independent of age, sex, social class, smoking status, plasma fibrinogen, alcohol consumption, body mass index, and diabetes mellitus. We conclude that variation at the beta fibrinogen locus is associated with an increased risk of peripheral atherosclerosis. The influence is not mediated simply by way of increased fibrinogen concentrations but could be due to a structurally variant fibrinogen or linkage disequilibrium with a neighbouring gene.

Aged↗
PubMed1992

Prevention of venous thromboembolism after surgery: a review of enoxaparin.

This review discusses the problem of deep vein thrombosis (DVT) after operation and identifies three levels of risk of DVT: low (less than 10 per cent), moderate (10-40 per cent) and high (40-80 per cent). Special emphasis is placed on the most recent prophylactic treatment, low molecular weight heparins (LMWHs), particularly enoxaparin. Several LMWHs are now available, but they differ slightly and each must be evaluated on its own merits. In general, however, LMWHs are both effective and safe in those patients at moderate or high risk of DVT. Thromboprophylaxis is cost effective when analysed using health-economic methodology.

Adult↗
PubMed1992

Rheological determinants of blood pressure in a Scottish adult population.

OBJECTIVES: To examine the relationship of blood pressure with haematocrit, plasma viscosity, whole blood viscosity and plasma fibrinogen. DESIGN: A random population sample of 1264 men and women aged 25-64 years from the west of Scotland, UK. RESULTS: Strong correlations between age, body mass index and blood pressure were noted: these were higher for women than men. Blood viscosity, haematocrit and plasma viscosity correlated with blood pressure independently of age, body mass index and smoking status. No evidence was found for an effect of erythrocyte rigidity upon blood pressure; plasma fibrinogen showed an inverse correlation with blood pressure and the rheological variables on multivariate analysis. CONCLUSIONS: Our findings support the role of blood viscosity in determining blood pressure as suggested by other, smaller studies. The magnitude of the effect upon blood pressure levels across the normal range of blood viscosity was of clinical importance. Further studies of factors that influence blood and plasma viscosity may help in the understanding of the aetiology of essential hypertension and its management.

Adult↗
PubMed1992

Increased interleukin 6 concentrations in the absence and presence of HIV-1 infection in haemophilia.

AIMS: To measure IL-6 concentrations in asymptomatic HIV-1 antibody positive and negative haemophilic patients and to correlate these with IgG concentrations and CD4 positive cell numbers. METHODS: IL-6 concentrations were measured by bioassay in stored serum from a prospective cohort of haemophilic patients in whom immunoglobulins and T cell subsets had been determined. Values of IL-6 and immunoglobulins were also correlated with severity of liver disease. RESULTS: IL-6 concentrations were raised in haemophilic patients independent of HIV-1 antibody status. In HIV-1 antibody positive patients there was no correlation between IL-6 concentrations and CD4 positive cell numbers, but there was a correlation with IgG (r = 0.4; p = 0.05). In HIV-1 antibody negative patients there were no significant correlations. CONCLUSIONS: Haemophilic patients have increased IL-6 concentrations; in HIV-1 positive patients this is independent of the decline in CD4 cell count. The raised concentrations do not correlate with the clinical severity of liver disease.

Adult↗
PubMed1992

Changes in neutrophil deformability following in vitro smoke exposure: mechanism and protection.

We have previously demonstrated a reduction in the deformability of neutrophils, exposed to whole particulate cigarette smoke in vitro, by measuring their ability to filter through a micropore membrane with pore dimensions similar to those of the average pulmonary capillary segment. In this study, we exposed neutrophils to the vapor phase of cigarette smoke and investigated the mechanism of the reduction in neutrophil filterability. Although both stimulated neutrophils and smoke-exposed neutrophils demonstrated an increase in filtration pressures, and thus a reduction in cell deformability, compared with control untreated cells, the spontaneous release of the reactive oxygen intermediates hydrogen peroxide and the superoxide anion was depressed following in vitro smoke exposure and there was no shape change to suggest that smoke-exposed cells were activated. The presence of erythrocytes, plasma, or the antioxidants albumin and glutathione prevented the reduction in cell filterability following smoke exposure, suggesting that in vitro smoke exposure, in our system, was mediated by oxidants. Indeed, the increase in filtration pressures, produced by smoke, could be mimicked by the addition of the oxidant hypochlorous acid. The cytoskeletal inhibitors cytochalasin B and D improved the filterability of smoke-exposed cells, suggesting that smoke may change neutrophil deformability through an effect on the actin component of the cytoskeleton. By contrast, colchicine, a specific inhibitor of the microtubules, had no effect. Preincubation with a monoclonal antibody to the CD18 antigen, to block this major neutrophil adhesive glycoprotein, did not alter the filtration pressure developed by stimulated or smoke-exposed neutrophils, suggesting that increased adhesivity was not the mechanism of the increase in filtration pressures observed following smoke exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Antioxidants↗
PubMed1992

Free radical activity and hemostatic factors in NIDDM patients with and without microalbuminuria.

In non-insulin-dependent diabetes mellitus (NIDDM) patients, microalbuminuria predicts early mortality, predominantly from cardiovascular disease. Increased free radical activity and abnormalities in hemostasis have been implicated in the development of vascular disease. Therefore, we measured markers of free radical activity (nonperoxide-conjugated diene isomer of linoleic acid [PL-9,11-LA'] and lipid peroxides expressed as malondialdehyde [MDA]) along with the hemostatic variables: fibrinogen, von Willebrand factor (vWf), plasminogen activator inhibitor (PAI-1), tissue plasminogen activator (t-PA), and plasmin activity (B beta 15-42) in 24 NIDDM patients (12 patients with microalbuminuria and 12 without microalbuminuria) and in 12 age-matched control subjects. There were no differences in linoleic acid (PL-9,12-LA) concentrations between the three groups. PL-9,11-LA' was elevated in the microalbuminuric patients compared with control subjects (P less than 0.05), but there was no difference between the two diabetic groups. MDA was elevated in the microalbuminuric diabetic patients compared with those patients without microalbuminuria (P less than 0.05) and control subjects (P less than 0.001). MDA was also increased in the patients without microalbuminuria compared with control subjects (P less than 0.01). Except for B beta 15-42, all the hemostatic variables were increased (P less than 0.05) in the diabetic patients compared with control subjects. The microalbuminuric diabetic patients had further increases in vWf (P less than 0.03) and t-PA (P less than 0.03) compared with patients with microalbuminuria. Our study suggests that there is an increase in free radical activity and abnormalities in hemostatic variables favoring a hypercoagulable state in NIDDM, especially in those with microalbuminuria.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Genetic variation at fibrinogen loci and plasma fibrinogen levels.

In view of the controversy regarding genetic variation at the fibrinogen loci and plasma fibrinogen levels, we have analysed DNA polymorphisms at the alpha (TaqI), beta (BclI and HaeIII), and gamma (KpnI/SacI) fibrinogen loci in 247 subjects whose plasma fibrinogen was determined by clotting and nephelometric assays. Strong linkage disequilibrium was found between the alpha/TaqI and gamma/KpnI/SacI markers and between the beta/BclI and beta/HaeIII markers. A lesser association was found between the alpha/TaqI and beta/BclI loci, beta/BclI and gamma/KpnI/SacI markers, alpha/TaqI and beta/HaeIII markers, and the gamma/KpnI/SacI and beta/HaeIII markers. This is consistent with the known physical order of these loci and suggests a relative excess of recombination in the alpha/gamma to beta interval. Plasma fibrinogen levels, by either assay method, when corrected or uncorrected for age, sex, and smoking habit, did not show any statistically significant associations with the four fibrinogen polymorphisms examined at the alpha, beta, and gamma fibrinogen loci either singly or when analysed as a haplotype.

Blotting, Southern↗
PubMed1992

Blood viscosity and retinopathy of prematurity: a preliminary report.

Whole blood viscosity (WBV) and haematocrit (Hct) were measured in 8 very low birth weight premature neonates developing acute severe retinopathy of prematurity (ROP) and 7 control neonates without retinopathy or mild ROP. Single samples were collected at 32-34 weeks conceptual age. There was no statistically significant difference in WBV or Hct between the two groups. The results of this preliminary report suggest that WBV does not appear to play a major role in the development of advanced ROP, though larger studies are required to investigate this further.

Blood Viscosity↗
PubMed1992

Patterns of blood response during cardiopulmonary bypass.

Monitoring of cardiopulmonary bypass (CPB) in terms of alterations to the concentrations of selected blood constituents leads to contrasting patterns of response. This has been verified by determining the influence of CPB on the activation of fibrinolysis, complement, leucocytes and the contact phase of coagulation. Fibrinolytic activity was determined by fibrin degradation products (X-FDP's), complement activation by C3a and C5a, leucocyte activation by granulocyte elastase and contact activation by factor XII-like activity (FXIIA). Five patients undergoing elective coronary artery surgery using a bubble oxygenator and pulsatile perfusion were studied. X-FDP's rose gradually during CPB and remained elevated. Similar patterns were observed for elastase and FXIIA. In contrast, C3a rose sharply with peak values at 1 1/2-2h of bypass while C5a did not show significant changes during bypass. The data obtained have enabled the establishment of response patterns for parameters in CPB which will provide information relevant to the clinical application of biomaterials.

Biocompatible Materials↗
PubMed1991

Relationships of plasma viscosity, coagulation and fibrinolysis to coronary risk factors and angina.

Plasma viscosity, molecular markers of activated coagulation and fibrinolysis (fibrinopeptides A and B beta 15-42), coagulation factors (fibrinogen and factor VII) and antiplasmins were measured in 529 men aged 35-54 years and related to new angina pectoris (n = 117) and to coronary risk factors in controls without angina (n = 412). Five major risk factors (cigarette-smoking, blood pressure, cholesterol, triglyceride and body mass index) were each associated with increases in plasma viscosity, coagulation factors, and imbalance of coagulation over fibrinolysis (increased ratio of fibrinopeptide A/fibrinopeptide B beta 15-42). Increased viscosity and fibrinogen in smokers were partly reversed in ex-smokers, but the imbalance of coagulation and fibrinolysis persisted. Cholesterol and triglyceride were also associated with increased antiplasmin activity. In men with angina, only fibrinogen was elevated compared to controls. We suggest that increased plasma viscosity and an imbalance of coagulation over fibrinolysis may be mechanisms by which known risk factors promote arterial thrombosis, but are not present in stable angina.

Adult↗
PubMed1991

B cell dysfunction in haemophilia in the absence and presence of HIV-1 infection.

56 haemophiliacs selected on the basis of HIV-1 antibody status, liver disease grade and mean annual dose of clotting factor concentrate used were studied. Spontaneous and stimulated IgG and IgM production in vitro were measured. HIV-1 infection was associated with increased spontaneous immunoglobulin production and an impaired response to pokeweed mitogen and Staph Aureus protein A. Implying a shift in the proportions of partially and fully activated B cells. In the absence of HIV-1 infection there was a shift to a greater proportion of partially activated B cells in patients with severe liver disease. The remainder had in vitro immunoglobulin production comparable to controls. B cell abnormalities occur early in the course of HIV-1 infection. Liver disease and not clotting factor concentrate treatment cause B cell abnormalities in the absence of HIV-1 infection in haemophilia.

Adolescent↗
PubMed1991

Effects of acute insulin-induced hypoglycaemia on haemostasis, fibrinolysis and haemorheology in insulin-dependent diabetic patients and control subjects.

1. The effects of acute hypoglycaemia on haemostasis, fibrinolysis, blood viscosity and erythrocyte aggregation were examined after acute insulin-induced hypoglycaemia in six normal male subjects and in six male patients with poorly controlled insulin-dependent diabetes. In the control subjects hypoglycaemia caused a significant increase in the concentration of von Willebrand factor, with no change in the concentrations of fibrinogen and cross-linked fibrin degradation products. Fibrinolysis was enhanced, as indicated by significant increases in tissue plasminogen activator concentration and the fibrin plate lysis area, with a fall in plasminogen-activator inhibitor activity, suggesting complex formation. Whole-blood and plasma viscosity increased significantly after hypoglycaemia, but there was no significant change in erythrocyte aggregation tendency. 2. In diabetic patients the increase in the concentration of von Willebrand factor was significantly greater than in the control group (analysis of variance, P less than 0.02). The basal concentration of tissue plasminogen activator was reduced at 3.7 +/- 0.7 mg/l (mean +/- SEM) in the diabetic group compared with 8.5 +/- 1.3 mg/l in the control group (Student's t-test, P less than 0.01), but thereafter the increase in response to hypoglycaemia was similar. The changes in the other variables were not significantly different from the changes in the control group. 3. During acute hypoglycaemia in poorly controlled diabetic patients there is promotion of haemostasis with a greater increase in the concentration of von Willebrand factor, which, in association with the increase in viscosity, might reduce perfusion in diabetic microangiopathy, leading to aggravation of the microvascular complications of diabetes.

Acute Disease↗