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Biomedical subjects

A D Hargreaves

Publications and source records attributed to A D Hargreaves.

11 recordsLinked to original sources
PubMed2006

Risk stratification in acute coronary syndromes--does the TIMI risk score work in unselected cases?

BACKGROUND: Management of patients with an acute coronary syndrome (ACS) requires accurate risk stratification to guide appropriate therapy. AIM: To assess the utility of the TIMI risk score in stratifying patients with possible ACS in routine clinical practice. DESIGN: Prospective observational study. METHODS: We recruited 869 consecutive patients with a diagnosis of possible ACS attending the acute medical receiving unit of a district general hospital. The main outcome measures were recurrent myocardial infarction, urgent revascularization, and all-cause mortality. TIMI risk score was calculated for each patient, and each was also assigned a risk group based on electrocardiogram (ECG) changes and troponin levels only. After follow-up, Cox univariate and multivariate regression was used to evaluate the influence of potential risk factors on duration of event-free survival, and likelihood ratio tests to assess the fit of the models. RESULTS: Increasing TIMI risk score was associated with increased risk of events (p<0.001), as was higher risk group from ECG plus troponin stratification (p<0.001). The likelihood ratio comparison favoured the TIMI risk score (difference 13.910, 5 degrees of freedom, p = 0.016). DISCUSSION: The TIMI risk score is a valid tool for risk stratification in unselected cases with possible acute coronary syndrome. It is superior to ECG changes and troponin alone, although this simpler method also achieves good risk stratification.

Adolescent↗
PubMed1992

Glucose tolerance, plasma insulin, HDL cholesterol and obesity: 12-year follow-up and development of coronary heart disease in Edinburgh men.

The insulin response to a standard oral glucose tolerance test (OGTT) and other anthropometric and biochemical risk factors for coronary heart disease (CHD) were measured in a random sample of 107 Edinburgh men, who were initially studied in 1976 when they were 40 and who were reexamined in 1988-89. Fasting glucose and glucose response to OGTT were higher in 1988-89 than in 1976. In contrast, insulin levels did not differ between the initial and follow-up study either before or after the glucose load. Body mass indices increased, except triceps skinfold. Changing patterns in both fasting and OGTT insulin or glucose levels in individuals were related to changes in bodyweight or in subscapular skinfolds. Modifications in serum total and HDL cholesterol were related to changes in fasting insulin and insulin area, respectively, but not to glucose data. Eleven men developed clinical CHD. Neither glucose nor insulin measures obtained in 1976 differed between those with and without CHD. Weight-height index and abdominal skin-folds were higher in those with CHD. HDL cholesterol was significantly lower (P less than 0.05). Abdominal skin-fold but not body mass index remained significant when adjusted for HDL cholesterol. This small study confirms the importance of central obesity and low HDL cholesterol but failed to identify insulin as a risk factor for CHD in this Scottish population.

Blood Glucose↗
PubMed1992

Haemodynamic responses to glyceryl trinitrate: influence of rate and duration of delivery.

Glyceryl trinitrate (GTN) is known to be a potent venodilator, but the effects might differ depending on the regime of administration. Using a radionuclide blood pool method we examined the changes in peripheral (and pulmonary) venous volume induced by GTN administered in three ways: short (4 min) intravenous infusions at 75 micrograms.min-1 (n = 7), prolonged intravenous infusion at 50 micrograms.min-1 (n = 7) or 500 micrograms sublingual tablet (n = 5). Sublingual GTN and the prolonged infusion caused similar decreases in systolic blood pressure (-23 +/- 12, -24 +/- 10 mmHg) and increases in calf venous volume (12 +/- 4%, 12 +/- 5%). For both, the peak effect occurred around 20 min after starting GTN administration (blood pressure 18 +/- 12 vs 25 +/- 12 min, venous volume 21 +/- 1 vs 22 +/- 7 min). Only the prolonged infusion caused a significant fall in diastolic pressure (-14 +/- 6 mmHg). The short infusion had a similar effect on systolic pressure (-21 +/- 16 mmHg) to the other two regimes, but caused a significantly smaller increase in venous volume (6 +/- 2%), which occurred much earlier (5 +/- 2 min). Anterior lung blood volume decreased in response to intravenous GTN and the posterior lung blood volume did not change, suggesting this alteration was secondary to peripheral venodilatation. In conclusion, GTN causes venous dilatation at low levels of delivery with the maximum response occurring after 20 min. In contrast, arterial effects are seen more rapidly and at higher rates of delivery.

Administration, Sublingual↗
PubMed1992

Lack of variation in venous tone potentiates vasovagal syncope.

OBJECTIVE: To investigate the peripheral venous response to head up tilting in malignant vasovagal syndrome. PATIENTS: 31 Patients with unexplained syncope or dizziness referred from the cardiology department. METHODS: Changes in calf venous volume were studied by a radionuclide technique during 45 degrees head up tilt testing. RESULTS: During tilt testing six patients became syncopal but 25 were symptom free. The syncopal group had greater increases in calf venous volume after the change in posture and perhaps more importantly considerably less variability in the venous volume during the tilted period. CONCLUSIONS: The venous response was different in the syncopal patients. The lack of response of the peripheral venous circulation to changes in the central circulation may be responsible for triggering the Bezold-Jarisch reflex and malignant vasovagal syncope.

Adolescent↗
PubMed1992

Early vasodilator treatment in myocardial infarction: appropriate for the majority or minority?

OBJECTIVE: To assess the influence of vasodilator treatment started early after myocardial infarction on left ventricular size and function. SETTING: Coronary care unit, Royal Infirmary, Edinburgh. PATIENTS: 105 patients with acute myocardial infarction (systolic blood pressure > 90 mm Hg) were randomised within 24 hours of the start of pain. Unlike previous studies 88% of the patients received thrombolysis. METHODS: Double blind randomised placebo controlled study with either 12.5 mg of captopril three times daily or 20 mg of isosorbide mononitrate three times daily for 28 days. MAIN OUTCOME MEASURES: Clinical outcome and left ventricular size and function assessed by echocardiography, radionuclide ventriculography, and magnetic resonance imaging. RESULTS: There was no difference in left ventricular size or function in either treatment group as measured one week after the end of the trial. Even the placebo group tended to decrease left ventricular diameter over the four week study period (one week: 5.0 (0.1) v, five weeks: 4.8 (0.1) cm, NS). Four patients had an adverse clinical outcome in the placebo group whereas no adverse outcome was seen in the captopril group. CONCLUSIONS: Vasodilator treatment may be of limited value or of no benefit for most infarct patients, particularly those treated with thrombolytic agents. Captopril, however, may benefit patients at high risk.

Captopril↗
PubMed1991

Total cholesterol, low density lipoprotein cholesterol, and high density lipoprotein cholesterol and coronary heart disease in Scotland.

OBJECTIVE: To investigate long term changes in total cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol concentrations and in measures of other risk factors for coronary heart disease and to assess their importance for the development of coronary heart disease in Scottish men. DESIGN: Longitudinal study entailing follow up in 1988-9 of men investigated during a study in 1976. SETTING: Edinburgh, Scotland. SUBJECTS: 107 men from Edinburgh who had taken part in a comparative study of risk factors for heart disease with Swedish men in 1976 when aged 40. INTERVENTION: The men were invited to attend a follow up clinic in 1988-9 for measurement of cholesterol concentrations and other risk factor measurements. Eighty three attended and 24 refused to or could not attend. MAIN OUTCOME MEASURES: Changes in total cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol concentrations, body weight, weight to height index, prevalence of smoking, and alcohol intake; number of coronary artery disease events. RESULTS: Mean serum total cholesterol concentration increased over the 12 years mainly due to an increase in the low density lipoprotein cholesterol fraction (from 3.53 (SD 0.09) to 4.56 (0.11) mmol/l) despite a reduction in high density lipoprotein cholesterol concentration. Body weight and weight to height index increased. Fewer men smoked more than 15 cigarettes/day in 1988-9 than in 1976. Blood pressure remained stable and fasting triglyceride concentrations did not change. The frequency of corneal arcus doubled. Alcohol consumption decreased significantly. Eleven men developed clinical coronary heart disease. High low density lipoprotein and low high density lipoprotein cholesterol concentrations in 1976, but not total cholesterol concentration, significantly predicted coronary heart disease (p = 0.05). Almost all of the men who developed coronary heart disease were smokers (91% v 53%, p less than 0.05). CONCLUSION: Over 12 years the lipid profile deteriorated significantly in this healthy cohort of young men. Smoking, a low high density lipoprotein concentration and a raised low density lipoprotein concentration were all associated with coronary heart disease in middle aged Scottish men, whereas there was no association for total cholesterol concentration. The findings have implications for screening programmes.

Adult↗
PubMed1984

Hormone-induced cell death. 2. Surface changes in thymocytes undergoing apoptosis.

In vivo, apoptotic cells are swiftly recognized by phagocytes, presumably because of changes on their surface. This article describes surface changes in rat cortical thymocytes undergoing apoptosis induced by glucocorticoid treatment in vitro. Homogeneous populations of thymocytes early in apoptosis were prepared by isopyknic centrifugation. These cells were compared with purified nonapoptotic cells in terms of several surface characteristics, including binding to macrophages, surface ultrastructure, microelectrophoretic mobility (a measure of surface charge density), and ability to bind four lectins and four monoclonal antibodies to thymocyte antigens. Apoptotic cells bound to macrophages more avidly than did nonapoptotic cells by a process not dependent upon serum factors. Their surfaces lost microvilli and became " blistered ," apparently through fusion of vesicles of endoplasmic reticulum with the plasma membrane. The surface charge density of apoptotic cells was less than that of nonapoptotic cells. Surface antigens and lectin-binding sites were less abundant on apoptotic than on normal cells, in proportion to the general reduction in cell size observed in apoptosis. Differences between apoptotic and normal cells were not detected, however, in the relative quantities of exposed galactose, N-acetyl galactosamine, N-acetyl glucosamine, N-acetyl neuraminic acid, or of several surface antigens, including the major sialoglycoproteins of the thymocyte membrane. It appears that although several changes occur in the surface of apoptotic cells, many cell membrane structures remain intact. The changes responsible for the recognition of apoptotic cells by phagocytes are more subtle than those detectable by the binding of lectin and antibody probes, but preliminary data suggest that a lectin-sugar interaction is involved.

Animals↗
PubMed1981

Chromatin changes in apoptosis.

Murine lymphoid cell lines and rat thymocytes treated in vitro with glucocorticoid hormones provide a convenient system for studying the nuclear changes in apoptosis. Morphologically the nucleolus disintegrates and chromatin undergoes an unusual generalized condensation. This is associated with excision of most of the nuclear DNA to short but well-organized chains of nucleosomes, apparently by an endogenous non-lysosomal nuclease. The process is dependent upon macromolecular synthesis and probably is mediated, at least remotely, by the classical steroid-receptor-gene activation pathway. A similar process of chromatin condensation and excision can be produced by the calcium-magnesium ionophore A23187. In other circumstances of 'programmed cell death', analogous chromatin condensation, excision and requirements for macromolecular synthesis have been documented.

Animals↗