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Biomedical subjects

T L Dormandy

Publications and source records attributed to T L Dormandy.

At least 19 recordsLinked to original sources
PubMed1991

Platelet function and conjugated diene concentrations in diabetic and non-diabetic survivors of acute myocardial infarction.

STUDY OBJECTIVE: The aim was to compare platelet function in diabetic and non-diabetic survivors of acute myocardial infarction and to relate it to an index of free radical activity in these patients. DESIGN: In vivo and in vitro indices of platelet function and diene conjugate molar ratios were measured in diabetic and non-diabetic infarct survivors on admission to hospital and sequentially for 72 h. PATIENTS: The patients were 17 diabetics (age 61.9 years, range 32-74) and 12 non-diabetics (60.8 years, range 39-75) admitted to hospital with acute myocardial infarction confirmed according to WHO criteria. MEASUREMENTS AND MAIN RESULTS: Agonist induced platelet aggregation, beta thromboglobulin levels, and linoleic acid 18:2(9,11)/18:2(9,12) molar ratios did not differ between diabetic and non-diabetic patients on admission. Concentrations of adrenaline producing 50% maximum platelet aggregation (EC50) in whole blood on admission were lower than non-infarct controls in both patient groups. The EC50 values in platelet rich plasma in both groups fell during the 72 h following admission (increases in platelet sensitivity). beta Thromboglobulin concentrations fell following admission in the diabetic group. Diene conjugate molar ratios were higher at 12 h and 24 h compared to admission in diabetic patients. Increases in diene conjugate ratios between admission and 24 h correlated with peak aspartate transaminase levels in both patient groups. No correlations were observed between platelet aggregation, beta thromboglobulin levels, or diene conjugate molar ratios. CONCLUSIONS: During 72 h following myocardial infarction there is a reduction in platelet activation in vivo and an increase in platelet sensitivity to exogenous agonists in vitro. Free radical generated isomers of linoleic acid increase in relation to infarct size, but are unrelated to platelet function. There were no differences in platelet function between diabetic and non-diabetic subjects.

Acute Disease↗
PubMed1990

Lipid peroxidation associated with successful thrombolysis.

In 50 patients receiving thrombolytic treatment for acute myocardial infarction, peripheral venous blood samples were taken before streptokinase and 2 h later for assay of markers of free radical activity. Coronary arteriography was carried out within 72 h of thrombolysis. In the 42 patients with patent arteries after thrombolysis, the levels of thiobarbituric-acid-reactive material (TBA-RM), which reflects lipid peroxidation by free radicals, rose after streptokinase by 10.5 (SD 9.6) [corrected] nmol/g albumin, whereas in the 8 whose arteries remained occluded TBA-RM fell by 14.7 (8.0) [corrected] nmol/g albumin. There was no significant change in the 18:2 (9,11)/18:2 (9,12) molar ratio, an indicator of lipid isomerisation, either between the groups or after streptokinase. Thus, after successful thrombolysis there is a rise in lipid peroxidation, not seen in patients whose arteries remain occluded. This finding suggests free-radical-mediated damage at the time of reperfusion, and provides indirect evidence of reperfusion injury in man. This study provides evidence associating indicators of free radical activity with documented myocardial reperfusion in man.

Adult↗
PubMed1990

Studies on cervical intraepithelial neoplasia: the level of octadeca-9,11-dienoic acid and measurement of free radical content by electron spin resonance spectroscopy.

The efficacy of electron spin resonance spectroscopy (a technique that measures free radicals) in detecting cervical intraepithelial neoplasia was evaluated in 68 women. In addition, electron spin resonance spectroscopic data were correlated with the phospholipid-esterified octadeca-9,11-dienoic acid (18:2(9,11]/octadeca-9,12-dienoic acid (18:2(9,12] molar ratio, a suggested marker of free radical damage to linoleic acid. Incubation of cervical epithelial cells with the spin-trap N-tert-butyl-alpha-phenylnitrone and subsequent examination by electron spin resonance spectroscopy gave signals from a nitroxide radical, which has been tentatively assigned to an adduct from either a carbon-centered lipid radical or a lipid alkoxyl radical; no significant differences in either the type of radical detected or the intensity of the signals was found between patients with cervical intraepithelial neoplasia and normal control subjects. There was no significant correlation between the intensity of the electron spin resonance signal and the phospholipid-esterified 18:2(9,11)/18:2(9,12) molar ratio. This finding provides no support for the classification of 18:2(9,11) as a "free radical product."

Cervix Uteri↗
PubMed1990

Systemic pattern of free radical generation during coronary bypass surgery.

Diffuse impairment of ventricular function after cardiac surgery may be related to the generation during reperfusion of the myocardium of free radicals derived from oxygen. Fifteen patients undergoing elective coronary bypass surgery were studied by previously described assays for peroxidised lipids and for isomerised lipids which were used as indices of free radical activity. Serial blood samples were obtained from systemic arterial, mixed venous, and coronary sinus catheters before, during, and after the ischaemic period. The patients underwent coronary artery surgery on cardiopulmonary bypass with a membrane oxygenator, relative hypothermia 30-34 degrees C, and intermittent cross-clamping of the aorta. During the ischaemic periods there were no significant changes in the indices of free radical activity. During the reperfusion phase there was a significant increase in free radical indices in arterial and mixed venous blood. A small rise in free radical indices in coronary venous blood was not statistically significant. These data indicate that free radical activity is increased in patients shortly after the cessation of cardiopulmonary bypass. The pattern of distribution between the different sampling sites suggests that much of the observed increase in isomerised and peroxidised lipids originates from tissues other than the myocardium.

Adult↗
PubMed1989

Aberrant free radical activity in cystic fibrosis.

It has been suggested that the molar ratio of octadeca 9,11 dienoic acid to linoleic acid in biological material provides an index of activity along the non-peroxide pathway of a free radical attack on polyunsaturated fatty acids. In 17 adults with cystic fibrosis the 'molar ratio' in nasal epithelial cells--a recognised target of the disease--exceeded that in 20 controls (median 2.09%, range 1.70-3.01% versus 1.56, 0.92-2.23%, p = 0.0002). The difference was also apparent, although less stark, upon analysis of serum in a further 22 CF patients (2.48%, 1.60-5.24%) and 25 controls (1.96%, 0.81-3.90%, p = 0.0348). There was no correlation between the 'molar ratio' and blood white cell count or erythrocyte sedimentation rate, severity of lung or liver disease, indicating that the raised values are a primary feature, rather than reflecting disease severity. Aberrant free radical activity may underlie cellular dysfunction in cystic fibrosis.

Adolescent↗
PubMed1988

In praise of peroxidation.

Free-radical-mediated lipid peroxidation has become closely associated with destructive biochemical processes and, more recently, with disease. Its potential survival value may be overlooked.

Cell Survival↗
PubMed1988

Effect of cardiopulmonary bypass on circulating concentrations of leucocyte elastase and free radical activity.

Circulating concentrations of leucocyte elastase and free radical activity were measured in 11 adults undergoing cardiopulmonary bypass. In all patients the bypass procedure was associated with pronounced changes in plasma elastase concentrations, and peak enzyme concentrations correlated closely with the duration of bypass (r = 0.91, p less than 0.001). Serial measurement of octadeca-9, 11-dienoic acid, a non-peroxide marker of free radical activity, showed significant changes only in the plasma free fatty acid fraction, suggesting a direct relation to the action of heparin rather than to the bypass procedure as such. These studies support the hypothesis that neutrophil activation plays a central role in the organ dysfunction that may complicate cardiopulmonary bypass and suggest that elastase release rather than free radical generation may be the appropriate marker of the event.

Aged↗
PubMed1985

Increased free-radical activity in alcoholics.

The identification of the main dieneconjugated "free-radical marker" in human serum led to a study of free-radical activity in chronic alcoholics. 66 patients were investigated immediately after alcohol withdrawal and over 1-4 weeks' follow-up. The control groups were 76 normal subjects, 78 patients with liver disease, 30 patients on long-term antiepileptic drug treatment, 9 pregnant women, and 99 unselected hospital patients. 82% of chronic alcoholics had a significantly higher than normal level of phospholipid-esterified 9,11 linoleicacid isomer in blood collected within 24 h of their last alcoholic drink. The levels fell to normal over the next 2-4 days but continued to decline within the normal range for 2-3 weeks. There was no rise in the level of the isomer in normal controls after an acute alcohol load. The results suggest that chronic alcoholism may induce a specific detoxifying mechanism which is activated by alcohol and which entails or depends on greatly increased free-radical activity.

Adolescent↗
PubMed1979

Fluorescent lipid-peroxidation products in synovial fluid.

1. Samples and extracts from synovial effusions were examined for the presence of fluorescent degradation products of free-radical oxidation (peroxidation). 2. Two classes of fluorescent compounds were identified and their fluorescence and physical properties are described. The fluorescence in the aqueous methanol phase of the extracts had the characteristics of conjugated Schiff bases. 3. Changes in synovial fluid and synovial fluid extracts in vitro induced by u.v. irradiation, prolonged incubation and the enzymic generation of oxidizing free radicals, with or without admixed peroxidizing arachidonic acid, and in the absence and presence of antioxidants, suggest that the fluorescent material is derived from peroxidized polyunsaturated lipids in damaged synovial tissue.

Arachidonic Acids↗
PubMed1979

Serum antioxidant activity in normal and abnormal subjects.

Serum oxidant activity (AOA) was correlated with the serum caeruloplasmin and serum copper concentration and with the total and available serum iron-binding capacity in 313 normal and abnormal subjects. In all groups except in patients with Wilson's disease (hepatolenticular degeneration) there was a highly significant direct correlation between serum AOA and serum caeruloplasmin concentration. A statistically significant direct correlation between serum AOA and the available iron-binding capacity of serum was found only in normal subjects and in children with thalassemia major and iron overload. There was no correlation between serum AOA and the serum tocopherol concentration in any of the groups studied.

Adult↗
PubMed1978

Free-radical oxidation and antioxidants.

Cells and tissues are protected against oxidising free radicals by a complexity of antioxidant mechanisms. In disease these mechanisms may fail; or the mechanisms may fail and cause disease. The primary products of free-radical oxidation undergo rapid and spontaneous fragmentation. Many of these fragments are highly active in biological systems. Some may have considerable survival value. Others are potentially lethal.

Acid-Base Equilibrium↗