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Biomedical subjects

D J Betteridge

Publications and source records attributed to D J Betteridge.

At least 109 records · Page 6Linked to original sources
PubMed1988

Exercise-induced changes in platelet aggregation; a comparison of whole blood and platelet rich plasma techniques.

Studies have been performed to assess the effect of exercise on spontaneous platelet aggregation in shaken whole blood, and on agonist-induced platelet aggregation in whole blood and platelet rich plasma (PRP). Spontaneous platelet aggregation in shaken whole blood was increased following exercise compared to pre-exercise values. The increase in spontaneous aggregation after exercise correlated inversely with the increase in white cell count in whole blood. Platelet sensitivity in whole blood to adrenaline, collagen and adenosine diphosphate (ADP) was increased following exercise. Changes in platelet sensitivity to adrenaline following exercise correlated with increases in plasma noradrenaline levels but not with changes in blood cell counts. In PRP, platelet sensitivity to ADP and to collagen was increased following exercise when the pre and post-exercise PRP platelet counts were not corrected to allow for the increase in platelet count which occurred with exercise. When the PRP platelet counts were corrected, no changes in platelet sensitivity to any agonist after exercise were observed.

Adenosine Diphosphate↗
PubMed1988

Decreased prostacyclin sensitivity of platelets in patients with Behçet's syndrome.

Patients with Behçet's syndrome have an increased risk of arterial and venous thrombosis, and abnormal platelet function has been implicated. Platelet function was studied in nine patients with Behçet's syndrome and in nine age- and sex-matched healthy volunteers. Platelet aggregation in response to ADP was measured, and the threshold concentration required to produce irreversible aggregation determined. Sensitivity of platelets to the inhibitory effect of prostacyclin was also determined. In addition, plasma levels of the platelet-specific proteins, beta-thromboglobulin and platelet factor 4, and stimulated platelet thromboxane B2 production, were measured. Platelets from patients with Behçet's syndrome showed normal aggregation in response to ADP, irrespective of disease activity. Platelet sensitivity to prostacyclin was, however, decreased compared with controls--with a mean prostacyclin ID50 of 5.5 +/- 1.3 ng ml-1 (mean +/- SEM) and 1.9 +/- 0.3 ng ml-1, respectively (P less than 0.01). This reduction in platelet sensitivity to prostacyclin was greatest in patients with the most active disease. These results suggest that Behçet's syndrome may be associated with altered platelet function, and this may have important consequences with regard to the increased risk of thrombosis associated with this condition.

Adenosine Diphosphate↗
PubMed1988

Raised concentrations of glucose and adrenaline and increased in vivo platelet activation after myocardial infarction.

Plasma concentration of beta thromboglobulin was used as an index of in vivo platelet activation in 36 patients after acute myocardial infarction. Twelve patients had diabetes, seven had pulmonary oedema or cardiogenic shock (pump failure) or both, and 17 had uncomplicated infarcts. On the first day of admission, concentrations of beta thromboglobulin were higher in the patients with diabetes and those with pump failure than in those with uncomplicated infarcts. Concentrations of beta thromboglobulin in the non-diabetic patients were studied by multiple regression analysis and were significantly associated with plasma concentrations of adrenaline, pump failure, and glucose but not with noradrenaline or infarct size. When all subjects were considered together, glucose, adrenaline, and pump failure were associated with the beta thromboglobulin concentration but diabetes was without significant effect. Hyperglycaemia and raised plasma adrenaline concentration after myocardial infarction may activate platelets, and this could contribute to poor outcome in such patients.

Aged↗
PubMed1988

Clinical and laboratory responses to niceritrol in the treatment of hypercholesterolaemia.

Twenty-five hypercholesterolaemic patients from three centres in the UK were investigated in an open study of the efficacy and side effects of niceritrol. Five patients dropped out of the study at an early stage and had insufficient data for analysis. There were 13 males and 7 females (mean age 49.2 years, range 18-69). Fourteen patients had heterozygous familial hypercholesterolaemia, and six polygenic hypercholesterolaemia. Niceritrol was started at a dose of 750 mg/day and this was increased at weekly intervals over 4 weeks to the maximum tolerated dosage up to 3 g/day. This was then maintained for a further 8 weeks. There were statistically significant decreases in total plasma cholesterol, total triglyceride, LDL cholesterol and VLDL triglyceride; HDL cholesterol remained unchanged after 12 weeks of treatment (Wilcoxon matched pairs, signed ranks test). The 14 patients with familial hypercholesterolaemia showed a 13.9% fall in total cholesterol and a 19.8% fall in LDL cholesterol. All patients reported flushing and some had gastrointestinal symptoms but 19 would have been prepared to continue with the therapy at doses up to 3 g/day. Thus niceritrol has been found to be beneficial in the treatment of both familial and polygenic hypercholesterolaemia.

Adolescent↗
PubMed1988

Ex vivo platelet studies following oral nisoldipine in normotensive insulin-dependent diabetics and non-diabetic controls.

The effect of 24 hours and 7 days treatment with nisoldipine (10 mg, twice daily) on platelet function was studied in 12 normotensive volunteers of whom six were insulin-dependent diabetics without clinical evidence of vascular complications. Platelet aggregation was assessed by platelet rich plasma (PRP) and whole blood (WB) techniques. In addition, the effect of nisoldipine on platelet hyperaggregability following exercise was assessed. After taking nisoldipine for 24 hours, in vitro platelet hypersensitivity to adenosine diphosphate was observed in PRP (p less than 0.01) and WB (p less than 0.01), to adrenaline in WB (p less than 0.03), and to collagen in PRP (p less than 0.02). After seven days treatment, platelet sensitivities to all agonists at rest in both PRP and WB showed no differences from pre-treatment values. Exercise-induced platelet hypersensitivity in WB to all three agonists was unchanged after nisoldipine treatment. Plasma noradrenaline and adrenaline concentrations increased after 24 hours treatment, although changes in agonist EC50s at 24 hours were not related to changes in plasma catecholamine levels. No effects of nisoldipine were observed on platelet thromboxane B2 release in PRP, or on plasma beta-thromboglobulin levels. No differences in the effects of nisoldipine were observed between diabetic and non-diabetic subjects. Nisoldipine treatment for seven days is not associated with altered platelet function, but platelet hypersensitivity is observed after treatment for 24 hours in both insulin-dependent diabetics and controls.

Adenosine Diphosphate↗
PubMed1987

Platelet catecholamines and platelet function in normal human subjects.

We have used high-performance liquid chromatography with electrochemical detection to measure plasma and platelet catecholamines in 24 normal subjects. In the same subjects platelet function was assessed by measuring platelet aggregation in response to adenosine 5'-pyrophosphate, thrombin, adrenaline and collagen. Platelet sensitivity to prostacyclin was also examined. Platelet noradrenaline showed a positive correlation with extent of aggregation induced by 'low-dose' collagen (1 microgram/ml). No correlation was seen at the higher collagen concentration. Platelet noradrenaline content also correlated with sensitivity of platelets to prostacyclin. High platelet noradrenaline concentrations appeared to result in decreased sensitivity to prostacyclin. No other correlations were observed. These data suggest that platelet noradrenaline rather than plasma levels may be involved in modifying platelet function in vivo. Local release of platelet catecholamines may affect the platelet/vessel wall interaction, the primary physiological step in platelet activation.

Adult↗
PubMed1987

Glycaemic control in diabetic patients transferred from therapy with animal insulins to human crystalline zinc insulin of recombinant DNA origin: a multicentre study.

87 stable insulin-dependent diabetic patients from 6 diabetic clinics within the UK were transferred from their existing once or twice daily regimen of subcutaneous animal insulin to a similar regimen of human insulin of recombinant DNA origin in neutral soluble and crystalline zinc suspension formulations. Seven point blood glucose profiles, glycosylated haemoglobin concentrations and insulin dose were examined, in each patient, before and after 6 weeks therapy with human insulins. The 67 patients on twice daily insulin showed no significant change in mean blood glucose values or glycosylated haemoglobin but required a significantly higher dose of human crystalline zinc suspension than their previous long-acting animal insulin. In contrast the 17 patients on a once daily regimen experienced a significant deterioration in glycaemic control without a significant change in insulin dose or glycosylated haemoglobin. Three patients on twice daily insulin withdrew shortly after transfer to human insulin. The combination of human soluble and crystalline zinc suspension appears to be a more satisfactory substitute for animal insulin when used in a multi-dose regime rather than on a once daily basis.

Animals↗
PubMed1986

Determinants and importance of stress hyperglycaemia in non-diabetic patients with myocardial infarction.

Determinants of plasma glucose concentrations were studied in patients on admission to hospital with confirmed acute myocardial infarction but without previous glucose intolerance as evidenced by raised concentrations of glycosylated haemoglobin (HbAlc). Mortality in hospital increased significantly with increasing plasma concentrations of glucose in patients with both normal (p less than 0.0001, n = 311) and borderline (p less than 0.02, n = 70) concentrations of HbAlc. There was a weak relation between plasma glucose concentrations and infarct size as estimated by peak aspartate transaminase activity in both HbAlc groups (rs = 0.26, n = 101 and rs = 0.41, n = 35 respectively). A correlation was found between adrenaline and plasma glucose concentrations (r = 0.47, n = 27) and cortisol and plasma glucose concentrations (r = 0.75, n = 19), but the relation of plasma noradrenaline and plasma glucose suggested a threshold effect. Concentrations of adrenaline, but not those of noradrenaline or cortisol, correlated with infarct size as measured both by peak aspartate transaminase activity and cumulative release of creatine kinase MB isoenzyme. Multiple regression analysis showed that concentrations of cortisol, adrenaline, and noradrenaline (but not the concentration of HbAlc, infarct size, or age) are the main determinants of plasma glucose concentration measured in non-diabetic patients when admitted to hospital after acute myocardial infarction.

Aged↗
PubMed1986

Stimulus-induced release of endogenous catecholamines from human washed platelets.

Using high-performance liquid chromatography with electrochemical detection, we have studied the release of endogenous catecholamines from washed platelets induced to aggregate by ADP and thrombin. Washed platelets exhibit irreversible aggregation with 10 mumol/l ADP and 0.3 unit of thrombin/ml, extents of aggregation being 27% and 76% respectively. ADP (10 mumol/l) increased noradrenaline release to the medium by 20% and adrenaline by 28%. As observed with aggregation, 0.3 unit of thrombin/ml produced a more marked effect on release than ADP, noradrenaline and adrenaline being increased by 570% and 169% respectively. Values for platelet noradrenaline content were found to mirror those for the release from platelets induced by thrombin. A correlation was observed between catecholamine release and the concentration of thrombin present in incubations. These data reflect the changes observed with platelet aggregation. This is the first study to determine catecholamine release from platelets by direct measurement. Local catecholamine release after platelet aggregation in vivo may have important consequences for tissue perfusion.

Adenosine Diphosphate↗
PubMed1986

Short PR intervals and tachyarrhythmias in Fabry's disease.

Two brothers with Fabry's disease presenting with palpitations were found to have intermittent supraventricular tachycardias. Their electrocardiograms, when symptom-free, revealed short PR intervals consistent with ventricular pre-excitation. Treatment of one of the brothers with verapamil resulted in improvement of the palpitations and reduction in frequency of the tachycardia. Recurrent supraventricular tachycardia associated with ventricular pre-excitation has not previously been described in Fabry's disease. Evidence suggests that this complication may be due to glycolipid deposition in the conducting system around the atrioventricular node.

Electrocardiography↗
PubMed1986

Stability of catecholamines in whole blood, plasma, and platelets.

Checking catecholamine stability in whole blood, plasma, and platelets, we found that specimens stored at room temperature or frozen for periods ranging from 1.5 h to three weeks show no significant difference in measured catecholamine concentration. The implications of these findings are discussed.

Adrenal Gland Neoplasms↗
PubMed1985

Effects of acipimox, a nicotinic acid derivative, on lipolysis in human adipose tissue and on cholesterol synthesis in human jejunal mucosa.

The mode of action of acipimox (5-methyl-pyrazine carboxylic acid 4-oxide), an hypotriglyceridaemic agent, was examined in human adipose tissue and intestinal mucosa. The rates of release of fatty acids and glycerol from human adipose tissue were measured in vitro. The release of fatty acids and glycerol from adipose tissue maximally stimulated by isoprenaline (10(-5) mol/l) fell by 40 and 25% respectively (P less than 0.025 and P less than 0.025) in the presence of acipimox (10(-5) mol/l). In submaximally stimulated adipose tissue (isoprenaline 10(-7) mol/l) acipimox (10(-4) mol/l) fully inhibited release of fatty acids (P less than 0.05) and glycerol (P less than 0.025) to basal rates. In unstimulated adipose tissue acipimox (10(-3) mol/l) reduced the rate of glycerol release (P less than 0.05), but not the rate of fatty acid release. Cholesterol synthesis in jejunal mucosa was measured in vitro by the incorporation of [2-14C]-acetate into sterols. Addition of cholesterol to the incubation reduced [2-14C]acetate incorporation into sterols from 8.7 +/- 2.1 (mean +/- standard error) to 3.7 +/- 1.0 pmol h-1 mg-1 of tissue (P less than 0.01). Acipimox at 10(-4)-10(-2) mmol/l had no consistent effect on cholesterol synthesis. Acipimox appears to exert its main hypolipidaemic effect by reducing lipolysis and free fatty acid flux to the liver, thereby reducing the precursor pool size of very low density lipoprotein (VLDL)-triglyceride and VLDL synthesis.

Adipose Tissue↗
PubMed1985

The distribution of catecholamines between platelets and plasma in normal human subjects.

We have used high-performance liquid chromatography with electrochemical detection to measure content of adrenaline and noradrenaline in platelets in 13 normal subjects at rest. Subjects were exercised to raise plasma catecholamine levels and promote the platelet release reaction. There was a significant positive correlation between plasma noradrenaline concentrations and platelet noradrenaline content. Platelet/plasma concentration ratios were 1855 for noradrenaline and 268 for adrenaline at rest and 473 and 152 respectively after exercise. Plasma noradrenaline levels positively correlated with age. Determination of platelet factors released to the plasma showed increases of beta-thromboglobulin and platelet factor 4 with exercise, whereas thromboxane B2 remained unchanged. No change in platelet catecholamine levels occurred with exercise and no correlations were observed between platelet catecholamines and released platelet factors. These data suggest that plasma catecholamine levels influence platelet content and that noradrenaline and adrenaline are concentrated in platelets.

Adult↗
PubMed1985

Measurement of platelet aggregation in diabetics using the new electronic platelet aggregometer.

Platelet function has been studied in diabetic subjects using a new electronic platelet aggregometer which enables platelet aggregation to be studied in whole blood. This may be a more physiological approach to the assessment of platelet behaviour as centrifugation is avoided and platelets are studied in the presence of other blood elements which may be important modulators of platelet function in vivo. Twenty insulin-dependent diabetic subjects were studied along with 20 age and sex-matched controls. Platelet aggregation to collagen (1 microgram/ml) and arachidonic acid (1 mM) was significantly increased in the diabetic group. In addition the sensitivity of diabetic platelets to the antiaggregatory effects of prostacyclin was significantly reduced. A significant inverse correlation was found between platelet sensitivity to prostacyclin and glycosylated haemoglobin concentration in the diabetic group. It is unlikely that the platelet abnormalities in this diabetic group are due to underlying vascular disease as none of the patients had evidence of diabetic complications. These findings may have important implications for the development of vascular disease in diabetics.

Adult↗
PubMed1985

Non-enzymatic glycosylation of plasma lipoproteins in vitro.

Human very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoproteins (HDL2 and HDL3) were glycosylated in vitro by incubation with high concentrations of glucose and glucose-6-phosphate. Glycosylated lipoproteins showed enhanced mobility on agarose electrophoresis when compared to control lipoproteins, samples treated with glucose-6-phosphate being more strongly affected. Extent of glycosylation of LDL was determined using thiobarbituric acid, LDL incubated with glucose exhibiting degrees of glycosylation 15-117% in excess of control. LDL incubated with glucose-6-phosphate however, gave values similar to those obtained with control incubations. Amino acid analysis of protein hydrolysates prepared from VLDL and LDL fractions incubated with glucose revealed reductions of up to 53% in the levels of free lysine when compared to control lipoprotein samples. The appearance of 2 novel peaks, probably corresponding to glucosyllysine, was also observed. The effects seen with glucose-6-phosphate however, were not as marked as expected. None of the other amino acids measured were decreased. These data show that plasma lipoproteins can be glycosylated in vitro and that an indication of the degree of glycosylation (by glucose) may be obtainable using thiobarbituric acid. Amino acid analysis revealed that the probable binding site for glucose on the apoproteins are the lysine residues. Although glucose-6-phosphate also binds to lysine residues the effects produced by this agent on plasma lipoproteins may also involve other mechanisms requiring further investigation.

Amino Acids↗