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Biomedical subjects

A Rumley

Publications and source records attributed to A Rumley.

102 records · Page 6Linked to original sources

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↗

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↗

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↗

The relationship between blood viscosity and blood pressure in a random sample of the population aged 55 to 74 years.

Blood viscosity is elevated in hypertensive subjects, but the association of viscosity with arterial blood pressure in the general population, and the influence of social, lifestyle and disease characteristics on this association, are not established. In the Edinburgh Artery Study, 1592 men and women aged 55-74 years selected randomly from the general population attended a university clinic. A fasting blood sample was taken for the measurement of blood viscosity and its major determinants (haematocrit, plasma viscosity and fibrinogen). Systolic pressure was related univariately to blood viscosity (P < 0.001), plasma viscosity (P < 0.001) and plasma fibrinogen (P < 0.01), but the association with fibrinogen did not persist after adjusting for body mass index. Diastolic pressure was related univariately to blood viscosity (P < 0.001) and plasma viscosity (P < 0.001) and haematocrit (P < 0.001) but not to fibrinogen. The only difference between the sexes was that the association between blood viscosity and systolic pressure was confined to males. Blood viscosity was associated equally with systolic and diastolic pressures in males, and remained independently related on multivariate analysis adjusting for age, sex, body mass index, social class, smoking, alcohol intake, exercise, angina, HDL and non-HDL cholesterol, diabetes mellitus, plasma viscosity, fibrinogen, and haematocrit.

Aged↗

Increased fetal hemoglobin in insulin-treated diabetes mellitus contributes to the imprecision of glycohemoglobin measurements.

An increased prevalence of fetal hemoglobin (HbF) has been described in pediatric insulin-dependent patients. The popular electroendosmotic method for glycohemoglobin includes HbF. In an adult population comprising 50 insulin-treated and 57 non-insulin-treated diabetic patients and 57 control subjects, we measured HbF by HPLC and measured glycohemoglobin by both HPLC and an electroendosmotic method. Of the insulin-treated patients, 46% had concentrations of HbF > or = 0.5%, compared with 25% of non-insulin-treated patients and 23% of controls (P < 0.02). In the insulin-treated patients, the two glycohemoglobin methods correlated best when the HPLC measurements included HbF (r = 0.92 vs r = 0.84). Fructosamine concentrations correlated best with glycohemoglobin concentrations determined by methods that accounted for HbF. The true between-batch CV of the electroendosmotic assay increased (from 4.33% to 8.33%) when variable interpatient HbF concentrations were included. Thus, HbF must be considered when interpreting glycohemoglobin measured by an electroendosmotic method and when comparing it with other measures of glycemic control.

Adolescent↗

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↗

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↗

Neuroendocrine activation after acute myocardial infarction.

The extent of neuroendocrine activation, its time course, and relation to left ventricular dysfunction and arrhythmias were investigated in 78 consecutive patients with suspected acute myocardial infarction. High concentrations of arginine vasopressin were found within six hours of symptoms, even in the absence of myocardial infarction (n = 18). Plasma catecholamine concentrations also were highest on admission, whereas renin and angiotensin II concentrations rose progressively over the first three days, not only in those with heart failure but also in patients with no clinical complications. Heart failure, ventricular tachycardia, and deaths were associated with extensive myocardial infarction, low left ventricular ejection fraction, and persistently high concentrations of catecholamines, renin, and angiotensin II up to 10 days after admission, whereas in uncomplicated cases concentrations had already returned to normal.

Arginine Vasopressin↗

Long-term use of the low molecular weight heparin tinzaparin in haemodialysis.

Fifty-two patients with chronic renal failure undergoing hospital haemodialysis were given a single bolus dose of tinzaparin (Innohep, Leo Laboratories, UK) into the arterial side of the dialyser, for up to 43 consecutive dialyses. The mean tinzaparin dose at the beginning was 2,139 IU anti-Xa and at the end 2,186 IU anti-Xa. Overall, tinzaparin proved a satisfactory anticoagulant for 1,370 (96.0%) out of 1,427 dialyses. Significant clot formation was prevented in 1,326 (92.8%) out of 1,429 dialyses. The clinically effective dose was associated with a mean plasma anti-Xa activity 1 h after dosing of 0.4 IU/ml and suppressed fibrinopeptide A formation for up to 4 h. Bleeding, from the skin or mucous membranes, was recorded at 27 (1.9%) of 1,408 dialyses. Prolonged fistula bleeding on completion of dialysis was recorded on only 20 occasions. Other haemorrhagic events included haematemesis, bruising and subconjunctival haemorrhage (each in 1 patient) and epistaxis (2 patients). Three patients died during the study of causes considered unrelated to tinzaparin therapy, myocardial infarction (2 patients) and multiple myeloma. Other adverse events reported included vomiting (3 patients) and hypotension (3 patients). Three patients ceased treatment due to haematemesis, prolonged bleeding from fistula puncture and thrombosis of the arteriovenous access, respectively. A small, but statistically significant, increase within the normal reference range was recorded in the mean values for aspartate aminotransferase and alanine aminotransferase.

Adult↗