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Biomedical subjects

M J Metcalfe

Publications and source records attributed to M J Metcalfe.

At least 19 recordsLinked to original sources
PubMed2006

Alterations in purinoceptor expression in human long saphenous vein during varicose disease.

OBJECTIVES: Varicose veins are dilated tortuous veins of varying tone. Purinergic signalling is important in the control of tone and in mediating trophic changes in blood vessels. The expression of P2 receptors in control and varicose veins will be examined. METHODS: Purinergic signalling in circular and longitudinal smooth muscle of the human long saphenous vein was studied in control and varicose tissues using immunohistochemistry, organ bath pharmacology and electron microscopy. RESULTS: P2X1, P2Y1, P2Y2, P2Y4 and P2Y6 receptors were present on circular and longitudinal smooth muscle. Purine-mediated circular and longitudinal muscle contractions were weaker in varicose veins. Electron microscopy and immunohistochemistry findings support the view that smooth muscle cells change from the contractile to synthetic phenotype in varicose veins, associated with an upregulation of P2Y1 and P2Y2 receptors and a down regulation of P2X1 receptors. CONCLUSIONS: Down regulation of P2X1 receptors on the smooth muscle of varicose veins is associated with loss of contractile activity. Upregulation of P2Y1 and P2Y2 receptors is associated with a shift from contractile to synthetic and/or proliferative roles. The phenotype change in smooth muscle is associated with weakening of vein walls and may be a causal factor in the development of varicose veins.

Adult↗
PubMed2006

Blood oxygen level-dependent (BOLD) magnetic resonance imaging in patients with dypiridamole induced ischaemia; a PET comparative study.

BACKGROUND: Blood oxygen level-dependent (BOLD) MRI relies on changes in deoxyhaemoglobin level in tissues under stress for signal variation and may be used for detection of ischaemic myocardium. METHODS: 15 patients with stress induced myocardial ischaemia on PET scanning underwent rest and dypiridamole stress MRI using a double breath-hold T2-weighted, ECG gated sequence to produce BOLD contrast images and cine-MRI for wall thickening assessment. Signal change on BOLD MRI and wall thickening were compared between rest and stress images in ischaemic and non-ischaemic myocardial segments. RESULTS: Using PET, 156 segments were identified with reversible ischaemia and 324 as non-ischaemic. The ischaemic segments were found on BOLD MRI to have an average signal change between rest and stress of -16.7% compared to -14% in the non-ischaemic segments (p=0.04). The average wall thickening was 7.8 mm in the ischaemic segments compared with 9.5 mm in the non-ischaemic segments (p<0.0001). CONCLUSION: BOLD MRI with wall thickening assessment may differentiate ischaemic from non-ischaemic myocardium in patients with stress induced myocardial ischaemia. Larger studies with improved spatial resolution would help define a threshold for detection of ischaemia as well as determine this technique's sensitivity and specificity.

Aged↗
PubMed2004

Benign complications of expandable metal stents used in the palliation of oesophageal carcinoma: two case reports.

We describe two patients who were treated with self-expanding metal stent (SEMS) insertion as palliation of malignant oesophageal strictures. Both patients re-presented with dysphagia several months after SEMS insertion due to benign strictures. Initial treatment with balloon dilation and medical management had limited success so both patients had further SEMS inserted across the secondary benign strictures. This provided very good symptomatic relief. Chemotherapy and chemo-radiation in patients with inoperable oesophageal carcinoma are prolonging patient survival. As patients survival lengthens benign complications of SEMS may become an increasing clinical problem.

Adenocarcinoma↗
PubMed2002

Automatic detection of coronary artery disease in myocardial perfusion SPECT using image registration and voxel to voxel statistical comparisons.

The purpose of this study was to compare the performance of automatic detection of coronary artery disease (CAD) with that of expert observers. A male and female normal image template was constructed from normal stress technetium-99m single photon emission computed tomography (SPECT) studies. Mean and standard deviation images for each sex were created by registering normal studies to a standard shape and position. The test group consisted of 104 patients who had been routinely referred for SPECT and angiography. The gold standard for CAD was defined by angiography. The test group studies were registered to the respective templates and the Z-score was calculated for each voxel. Voxels with a Z-score greater than 5 indicated the presence of CAD. The performance of this method and that of three observers were compared by continuous receiver operating characteristic (CROC) analysis. The overall sensitivity and specificity for automatic detection were 73% and 92%, respectively. The area (Az) under the CROC curve (+/-1 SE) for automatic detection of CAD was 0.88+/-0.06. There was no statistically significant difference between the performances of the three observers in terms of Az and that of automatic detection (P> or =0.25, univariate Z-score test). The use of this automated statistical mapping approach shows a performance comparable with experienced observers, but avoids inter-observer and intra-observer variability.

Algorithms↗
PubMed1995

Effects of warfarin therapy on plasma fibrinogen, von Willebrand factor, and fibrin D-dimer in left ventricular dysfunction secondary to coronary artery disease with and without aneurysms.

Cardiac impairment in patients is associated with intracardiac thrombus formation and thromboembolism. A high prothrombotic state may exist in such patients, and abnormalities in plasma markers of thrombogenesis may be indicative of such a state. The aim of this study was to determine the associations of left ventricular (LV) aneurysm formation and dysfunction with plasma fibrinogen, von Willebrand factor, and fibrin D-dimer, which are markers associated with thrombus formation (thrombogenesis) and to investigate the effects of warfarin given to patients with LV aneurysms on fibrinogen and D-dimer levels. A cross-sectional study of 112 patients with coronary artery disease was initially performed: 34 patients had normal LV function (group 1); 30 had LV dysfunction without aneurysm formation (group 2); 29 had LV aneurysms without anticoagulation (group 3a); and 19 patients had LV aneurysms with warfarin therapy (group 3b). Results were compared with 158 population controls from a random population sample. A longitudinal study of 10 patients given warfarin was also performed. In group 1, plasma fibrinogen (median difference 0.36 g/L; p = 0.0009) and von Willebrand factor (median difference 17 IU/dl; p = 0.04) were elevated, whereas plasma D-dimer levels (median difference 23.0 ng/ml; p = 0.001) were lower than those in population control subjects. There were no significant differences in plasma fibrinogen, von Willebrand factor, or D-dimer levels between groups 1 and 2. In group 3a, plasma fibrinogen was elevated when compared with group 1 (median difference 0.6 g/L; p = 0.0001), with a trend toward high von Willebrand factor levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1995

Is diastolic dysfunction associated with thrombogenesis? A study of circulating markers of a prothrombotic state in patients with coronary artery disease.

Clinical data on the contributory role of heart failure to thromboembolic risk does not differentiate between systolic and diastolic left ventricular dysfunction. We therefore conducted a population-controlled cross-sectional study to determine levels of plasma fibrinogen (associated with thromboembolism), fibrin D-dimer (a marker of fibrin turnover) and von Willebrand factor (a marker of endothelial dysfunction) in patients with ischaemic heart disease (a common cause of diastolic dysfunction) in whom left ventricular diastolic function was defined by echocardiography. We studied 106 patients: those with normal left ventricular function (n = 42, Group 1); those with left ventricular dysfunction but without aneurysms (n = 34, Group 2); and those with left ventricular aneurysm formation (n = 30, Group 3). Each of these groups was subdivided into those with (a) and without (b) diastolic dysfunction. Diastolic dysfunction was present in over 60% of patients, irrespective of left ventricular systolic impairment. There were no significant differences in median levels of plasma fibrinogen, fibrin D-dimer or von Willebrand factor in each group of patients with ischaemic heart disease, whether or not left ventricular diastolic dysfunction was present (Mann-Whitney test; P = N.S.). Systolic (rather than diastolic) dysfunction was the main correlate of these (analysis of variance, general linear model--ANOVA-GLM--P < 0.05) and the greatest abnormalities of fibrinogen, endothelial dysfunction and intravascular fibrin turnover were seen in patients with left ventricular aneurysms whether or not diastolic dysfunction was present. This study demonstrates that there is no evidence of a significant additional contribution to thrombotic risk (as assessed by plasma fibrinogen, von Willebrand factor and fibrin D-dimer) for patients with left ventricular diastolic dysfunction. A relationship is noted between some prothrombotic factors and Doppler indices of flow, which suggests a possible association between cardiac haemodynamics and thrombogenesis.

Analysis of Variance↗
PubMed1995

Objective measurement of changes in regional wall motion characteristics following coronary artery bypass grafting using tomographic radionuclide ventriculography.

Difficulties arise when using non-invasive methods to measure changes in regional left ventricular function. With the increasing recognition of the entity of hibernating myocardium, and the known asymmetric effects of coronary artery disease, this is an important problem, as it prevents detailed investigation of the effects of revascularization upon ventricular function. We investigated the use of tomographic radionuclide ventriculography in assessing such changes. Twenty consecutive patients (18 males, 2 females, mean age 60 years), undergoing elective coronary artery bypass surgery, were identified and imaged prior to and after surgery. The mean global left ventricular ejection fraction was 42 and 45% pre- and post-surgery, respectively. Following revascularization, it was improved in 9 patients, unchanged in 3 and deteriorated in 8. By comparison with pooled normal data from 25 subjects, 10 patients were noted to have overall resting phase values within normal limits. After surgery, an improvement was seen in 5 patients, no significant change in 11 and a deterioration in 4. With respect to regional ejection fraction, 24 of 80 segments improved, 25 remained unchanged and 31 deteriorated. For regional phase analysis, 26 improved, 45 remained unchanged and 9 deteriorated. confirmed that important regional changes in left ventricular function occur following revascularization, even without a change in global ejection fraction.

Aged↗
PubMed1995

Do radionuclide and echocardiographic techniques give a universal cut off value for left ventricular ejection fraction that can be used to select patients for treatment with ACE inhibitors after myocardial infarction?

OBJECTIVE: To determine whether echocardiography and radionuclide angiography give comparable results when the left ventricular ejection fraction is measured early after myocardial infarction and thus whether, irrespective of the method used, a single value for the ejection fraction could be used as a guide for starting treatment with an angiotensin converting enzyme inhibitor. DESIGN: Prospective comparison of measurement of left ventricular ejection fraction by echocardiography and radionuclide angiography. SETTING: Coronary care units of two university teaching hospitals in Glasgow. PATIENTS: 99 patients studied within 36 hours of acute myocardial infarction. OUTCOME MEASURES: Left ventricular ejection fraction assessed by echocardiography and radionuclide angiography. RESULTS: 70 (77%) of the 99 patients had ejection fraction measured by both echocardiographic and radionuclide techniques, 30 in centre 1 and 40 in centre 2. In centre 1 the mean difference (SD) in ejection fraction (radionuclide angiography--echocardiography) was -8 (10%); 95% CI -12 to -4%. In centre 2 the mean difference was -14 (11%); 95% CI -17 to -11%. If patients had been treated with an ACE inhibitor on the basis of a radionuclide ejection fraction of < 40% then 93% in centre 1 (28 of 30) and 98% in centre 2 (39 of 40) would have been treated. This compares with 63% (19 of 30) and 50% (20 of 40), respectively if echocardiography had been used as a guide. CONCLUSION: Measurement of ejection fraction is highly dependent on the method used and it is therefore impossible to quote a universally applicable figure for left ventricular ejection fraction below which an ACE inhibitor should be used after myocardial infarction.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

A cross-over study comparing the efficacy of a combination of atenolol and nifedipine at different doses in angina pectoris.

Although the combined administration of atenolol and nifedipine has been shown to be effective in the treatment of angina pectoris the optimum dosage level of the combination has not yet been established. A double-blind, randomly assigned three period cross-over study was carried out therefore to investigate the effects of different daily doses of a fixed combination of 50 mg atenolol and 20 mg sustained-release nifedipine per capsule. Twenty-one patients with stable angina pectoris were randomized, after a 2-week run-in period, to receive treatment for 4 weeks with either 1 capsule twice daily (A), 2 capsules in the morning and 1 in the evening (B), or 2 capsules twice daily (C). A treadmill exercise tolerance test was performed together with a clinical evaluation after the run-in and each of the three treatment periods. Analysis of the results from the 19 patients who completed the study revealed there were no significant differences between the three treatment periods with respect to the general exercise test parameters, number of anginal attacks per week or nitrate consumption. Few side-effects were reported and were only mild in nature. On these findings, therefore, there would appear to be little justification for increasing the dose of the combination above the equivalent of treatment A.

Adrenergic beta-Antagonists↗
PubMed1994

Assessment of left ventricular regional wall motion with blood pool tomography: comparison of 11CO PET with 99Tcm SPECT.

Left ventricular contraction is routinely assessed by radionuclide ventriculography. Although a planar image is conventionally used, tomography has been to improve the detection of wall motion abnormalities. A blood pool image is often used in positron emission tomography on which to superimpose metabolic tracers. Can this image also be used to assess left ventricular contraction? Nine healthy controls, mean (S.D.) age 55 (5) years, and 12 patients, mean (S.D.) age 61 (8) years, with normal, proven or suspected left ventricular damage underwent blood pool tomography with 11CO positron emission tomography (PET) and 99Tcm single photon emission computed tomography (SPECT). A normal value of ejection fraction and range of phase were defined. The normal left ventricular ejection fraction was > or = 37% for PET and > or = 40% for SPECT. The ejection fractions obtained by the two methods in the patient group were positively correlated (r = 0.89, P < 0.001). Abnormalities of left ventricular contraction were detected in nine patients by PET and 10 patients by SPECT imaging. The discrepancy was in a patient with a previous inferior myocardial infarction. Blood pool imaging with 11CO PET can be used to assess left ventricular ejection fraction and regional wall motion.

Carbon Monoxide↗
PubMed1994

Polar map or novel three-dimensional display technique for the improved detection of inferior wall myocardial infarction using tomographic radionuclide ventriculography.

Tomographic radionuclide ventriculography has the potential to be a significant improvement over conventional planar imaging. Although tomographic imaging can now be performed with relative ease, it is little used. This is most probably due to a perceived imbalance between potential clinical benefit and the extra complications of imaging. We investigated this matter by examining a series of 30 patients with isolated inferior or anterior myocardial infarction, identified by cardiac catheterization. Using either radionuclide imaging method, a significant wall motion abnormality was defined as matching (and appropriately located) phase and amplitude values outwith of two standard deviations from control values. These values were obtained from a series of 25 controls and represent construction values used to create a conventional polar map display. Overall detection rates for anterior myocardial infarction were 93 and 100% for planar and tomographic imaging, respectively (ns). For inferior myocardial infarction the rates were 7 and 93%, respectively (p < 0.001). Identical results were found using a novel three-dimensional method of displaying wall motion abnormalities. Tomography is therefore superior to planar imaging for the detection of inferior myocardial infarction but similar to planar imaging for the detection of anterior myocardial infarction.

Cardiac Catheterization↗
PubMed1994

Factors influencing coronary artery bypass graft patency.

Coronary artery bypass surgery is one of the most frequently performed and successful operations in improving quality of life for patients with intractible angina. Unfortunately, there is accumulating evidence that angina will eventually return and consequently an increasing amount of repeat surgery is being undertaken. Subsequent operations have a reduced chance of benefit and many patients are only in early middle age at the time of initial surgery. It is obviously of paramount importance, therefore, to try and maintain graft patency for as long as possible. Various factors such as avoidance of certain surgical techniques, use of the internal mammary artery whenever possible, continued use of aspirin and attention to major risk factors are known to significantly influence graft patency. This review examines these factors in detail and provides practical advice on how to optimize long-term patency.

Coronary Artery Bypass↗