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Biomedical subjects

R M Norris

Publications and source records attributed to R M Norris.

At least 37 records · Page 2Linked to original sources
PubMed1997

Impaired glucose tolerance is normalized by treatment with the thiazolidinedione troglitazone.

OBJECTIVE: The primary purpose of this study was to assess the effects of 12 weeks of treatment with either troglitazone, an investigational thiazolidinedione that acts as an insulin-action enhancer, or placebo in patients with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: A total of 51 subjects with IGT between 24 and 77 years of age were enrolled in this multicenter, double-blind, placebo-controlled, parallel group study (troglitazone, 25 patients; placebo, 26 patients). Patients were randomly assigned to receive either 400 mg troglitazone (every morning [QAM]) or placebo (QAM). The main outcome measure was the oral glucose tolerance test (OGTT) assessing glucose, insulin, and C-peptide levels in the fasting state and every 30 min up to 2 h after ingesting the glucose load. Fasting serum levels of HbA1c, fructosamine, lipids, and blood pressure were also measured. RESULTS: A total of 46 patients completed the study. The glucose, insulin, and C-peptide responses after a glucose load were significantly reduced at 6 and 12 weeks in the troglitazone treatment group. After 6 weeks of treatment, 75% (n = 18) of those taking troglitazone had improved to normal glucose tolerance, whereas only 38% (n = 9) of those of placebo showed improvement (P = 0.008). After 12 weeks of treatment, 80% (n = 16) of the troglitazone treatment group had normalized their glucose tolerance, while only 48% (n = 10) of those on placebo had converted to normal (P = 0.016). Fasting triglyceride levels in the troglitazone treatment group had decreased by 40 mg/dl (0.45 mmol/l) (P = 0.0016). Other lipid measurements, blood pressure, glycosylated hemoglobin, and fructosamine were normal at baseline for both treatment groups and remained normal throughout the study. CONCLUSIONS: The glycemic response after a glucose load is statistically and clinically significantly improved for patients with IGT treated with troglitazone.

Adult↗
PubMed1996

Comparison of aspirin with a thromboxane antagonist for patients with prolonged chest pain and ST segment depression.

AIM: To compare a thromboxane antagonist (GR3219) with aspirin in patients with prolonged chest pain and ST segment depression to see if the frequency of attacks of chest pain was reduced. METHODS: The trial was part of a study comparing GR3219 with aspirin, and streptokinase with placebo and comprised the GR3219/aspirin leg. Thirty one patients were randomly assigned to GR3219 80 mg twice daily and 28 to aspirin 300 mg daily. The patients were under the age of 76 and admitted to a coronary care unit within 6 hours of continuous chest pain. The ECG showed at least 1 mm of flat or down-going ST segment. The patients kept diaries of their pain over the subsequent 31 days. RESULTS: Seventy percent of patients developed further chest pain. There was no difference between the pattern of recurrent chest pain according to which drug was used. CONCLUSIONS: The hypothesis that specific thromboxane A blockade with GR3219 would be more efficacious than aspirin was not supported by these results.

Aged↗
PubMed1996

Non-invasive diagnosis of infarct artery patency after acute myocardial infarction by use of serial plasma troponin T concentrations: importance of measurement of peak levels.

OBJECTIVE: To confirm the validity of a previously described method for assessment of infarct artery patency involving serial measurements of creatine kinase activity by use of troponin T concentration as an independent plasma marker. DESIGN: Streptokinase (1.5 x 10(6) units) was given intravenously to 60 patients within 6 h of onset of prolonged chest pain and ST segment elevation, and blood was taken for measurement of troponin T concentration at baseline and at 1, 2, 3, 4, 8, 12, 16, 20, and 24 h after starting treatment. Coronary arteriography was performed at 2.6 (SD 0.3) h. Plasma troponin T concentration was assessed by two methods: (1) as the absolute rise between 0 and 3 h; and (2) as the proportion of the total rise (from baseline to peak) over the same period. Accuracy for prediction of infarct artery patency, assessed by receiver operating characteristic curves, was compared for both methods of assessment using troponin T and was in turn compared with previously reported results on the same patients using serial measurements of creatine kinase activity. RESULTS: Sufficient values for prediction of patency using troponin T were available in 53 patients. A rise in troponin T between 0 and 3 h to > or = 9% of peak concentration predicted angiographic patency with sensitivity of 94% and specificity of 100%. By contrast, at the optimum cutoff for absolute rate of rise (0.5 micrograms/l/h) sensitivity was only 66% and specificity 86%. Comparable figures for creatine kinase were 92% and 91% (> or = 20% of peak by 3 h) and 62% and 78% (150 IU/l/h). Receiver operating curves confirmed better predictive accuracy for proportions over absolute rates of rise for both markers (P < 0.01). CONCLUSIONS: For accurate diagnosis of infarct artery patency using plasma markers it is necessary to express the rate of rise as a proportion of the peak level. Analysed in this way, both creatine kinase and troponin T are suitable for use in randomised trials of new thrombolytic or adjuvant drugs.

Adult↗
PubMed1995

Effects of streptokinase in patients presenting within 6 hours of prolonged chest pain with ST segment depression.

BACKGROUND: The effects of streptokinase on the occurrence of a combined clinical outcome in patients presenting with recent chest pain and ST depression were investigated in view of the role of thrombus in the pathogenesis of acute ischaemic syndromes. METHODS: 112 patients aged < or = 75 years presenting within 6 h of the last episode of ischaemic chest pain of least 20 min duration with > or = 1 mm ST depression were randomised in a double blind manner to receive either streptokinase 1.5 million units over 30 min (n = 57) or placebo (n = 55). The primary end point was the combination of death, frequency of myocardial infarction (defined as peak creatine kinase > 600 U/ml), need for angiography because of uncontrollable ischaemia, and an exercise test within 35 days showing > or = 1 mm ST depression at < or = 6 min. The secondary end points were safety, frequency of chest pain, readmission with myocardial infarction or unstable angina, or need for revascularisation between 35 days and 1 year. The severity of ST depression on presentation was analysed with respect to clinical outcome. RESULTS: The frequency of the combined hierarchical end point of death, myocardial infarction, early angiography, and a positive exercise test was 82% (47 of 57 patients) with streptokinase and 75% (41 of 55 patients) with placebo. There were four deaths, two in each group. 27 patients (47%) receiving streptokinase and 22 (40%) receiving placebo developed myocardial infarction. 11 patients (eight streptokinase and three placebo) required coronary arteriography and subsequent revascularisation because of angina uncontrolled by medical treatment. 44 patients (22 in each group) had a positive exercise test. There were three further cardiac deaths (one streptokinase, two placebo), and three noncardiac deaths within 1 year. A conservative approach to intervention was adopted and over a period of 1 year 29 patients (26%) (13 streptokinase and 16 placebo) underwent revascularisation procedures. Three patients (two streptokinase and one placebo) required transfusion. ST depression > or = 3 mm had 90% specificity but only 60% positive predictive value for myocardial infarction at presentation (P = 0.008, stepwise logistic regression). ST depression > or = 2 mm was predictive of death, late development of myocardial infarction, or a need for angiography (P = 0.02). CONCLUSION: Patients presenting with ischaemic chest pain and ST depression frequently develop myocardial infarction. Severe ST depression is predictive of an adverse outcome. The 35 day (3.6% cardiac and total) and 1 year mortality (8.9% total, 6.3% cardiac) are low with conservative management and expeditious revascularisation. Streptokinase treatment within 6 h of the last episode of pain does not seem to be beneficial.

Aged↗
PubMed1994

Long-term prognostic importance of patency of the infarct-related coronary artery after thrombolytic therapy for acute myocardial infarction.

BACKGROUND: After thrombolytic therapy, long-term patency of the infarct-related artery may reduce arrhythmias, limit ventricular dilatation, and provide collaterals to another infarct zone if further infarction occurs. However, independent long-term prognostic value of infarct artery patency has not been shown. METHODS AND RESULTS: We followed 312 patients with first myocardial infarction treated < 4 hours after pain onset with thrombolysis (streptokinase [n = 188] or recombinant tissue-type plasminogen activator [n = 124]). At 28 +/- 11 days, cardiac catheterization was performed. Flow of the infarct-related artery was assessed by the TIMI scoring system, and a scoring system relating coronary stenoses and flow to the amount of myocardium supplied was also used. Follow-up was for 39 +/- 13 months. Cardiac death occurred in 5.8% of patients, and there were two noncardiac deaths. Revascularization was performed in 11.5% of patients. On univariate and multivariate analysis, ventricular function (ejection fraction, P = .006 and .02, or end-systolic volume index, P = .01 and .06) was the most important prognostic factor. Patency of the infarct-related artery measured as TIMI 3 flow was marginally significant on univariate analysis (P = .08) but not on multivariate analysis (P = .2). Patency was an independent prognostic factor in univariate and multivariate analysis when measured as an occlusion score (amount of myocardium supplied by an occluded artery, P = .01 and < .05). When the ejection fraction was > or = 50%, only occluded arteries supplying > 25% of the left ventricle affected prognosis adversely. If the ejection fraction was < 50%, occluded arteries supplying < 25% of myocardium also adversely affected prognosis. Treadmill exercise duration 4 weeks after infarction was the only other prognostic factor identified. CONCLUSIONS: Ventricular function and infarct-related artery patency are independent prognostic factors after thrombolytic therapy for acute myocardial infarction.

Cardiac Catheterization↗
PubMed1993

Use of creatine kinase isoforms for diagnosis of infarct artery patency after thrombolytic therapy with streptokinase.

BACKGROUND: We investigated whether the proportion of creatine kinase (CK) MM3 to total MM isoform, measured in a single blood specimen taken at 3 hours after starting intravenous administration of streptokinase to patients with developing myocardial infarction, would give reliable information on patency or occlusion of the infarct-related coronary artery. METHODS: Fifty-nine patients received streptokinase 1.5 x 10(6) U intravenously within 6 hours of onset of prolonged chest pain and ST-segment elevation. Patency of the infarct-related coronary artery was assessed by arteriography at 2.6 +/- 0.3 (SD) hours after starting streptokinase. Creatine kinase MM isoforms were measured by chromatofocusing in blood taken at 3 hours after streptokinase. RESULTS: A proportion of CKMM3 to total CKMM of greater than 50% was present in 34 of 34 patients (100%) with a patent, infarct-related artery at arteriography and whose peak total CK activity reached twice the upper normal limit for our laboratory (600 U/L). CKMM3/total CKMM was less than 50% in 14 of 18 patients (78%) in whom the infarct-related artery was occluded. In five of six patients with a nondiagnostic total CK rise (peak < 600 U/L), 3-hour CKMM3/total CKMM was less than 50% despite a patent artery. CKMM3 was not measurable in one patient. CONCLUSIONS: A proportion of CKMM3/total CKMM of greater than 50% is highly sensitive for prediction of infarct artery patency at 3 hours after administration of streptokinase. However, the test used in this way is not reliable for patients with "prevented" myocardial infarction. Also, positive tests do occur in patients with angiographically occluded arteries, possibly signifying intermittent reperfusion and occlusion.

Adult↗
PubMed1993

Non-invasive diagnosis of arterial patency after thrombolytic treatment and its relation to prognosis.

OBJECTIVE: To validate a simple noninvasive method with serial creatine kinase measurements for diagnosis of early patency of the infarct related artery after thrombolytic treatment with streptokinase. To investigate the relation between early patency of the infarct related artery and prognosis. DESIGN: Patients under 76 years of age and seen within six hours of the start of prolonged chest pain and ST segment elevation were treated with streptokinase (1.5 x 10(6) U) intravenously over 30-60 minutes. Blood for measurement of total creatine kinase activity was taken at baseline and at 1, 2, 3, 4, 8, 12, 16, 20, and 24 hours after starting treatment. The rise in enzyme activity at each time from baseline was expressed as a proportion of the total rise from baseline to peak. PATIENTS: Patients studied were in the following groups: (a) Sixty patients took part in a validation study with angiographic determination of patency of the infarct related coronary artery at 2.6 (0.3) hours (mean (SD)) after starting streptokinase. (b) A further 258 patients did not have early arteriography, but data were added to those from the 60 validation patients to find the relation between enzymatically determined early patency of the infarct related artery and 30 day mortality. (c) A further subset of 232 patients with first infarctions (including patients from groups (a) and (b) had angiocardiography at three weeks after infarction, and data were used to investigate the relation between early patency of the infarct related artery and left ventricular function. MAIN OUTCOME MEASURES: Normalised rate of rise of creatine kinase activity at three hours after starting streptokinase in relation to angiographic patency of the infarct related coronary artery at 2.5 hours; 30 day cardiac mortality; and left ventricular function at three weeks in survivors of first infarction. RESULTS: In the validation study, a rise in three hour creatine kinase activity of > 20% of peak occurred in 34/37 patients with initially patent infarct related coronary arteries (sensitivity 92%), and a rise to < 20% of peak occurred in 21/23 patients with initially occluded arteries (specificity 91%). In the prognostic study, 30 day mortality was 2.1% in the 191 patients with three hour creatine kinase > 20% of peak and 8.7% in the 127 patients with three hour creatine kinase < 20% of peak (p < 0.01). Angiocardiography in three week survivors of anterior infarction (n = 95) showed better left ventricular function when three hour creatine kinase was > or = 20% than when it was < 20% of peak (mean (SEM) end systolic volume 71 (5) v 96 (9) ml, p < 0.02; ejection fraction 56% (2%) v 51% (2%), NS). CONCLUSION: Non-invasive determination of early patency of the infarct related artery by the normalised rate of rise of creatine kinase activity at three hours seems to be reliable, and may be prognostically important and of value for use in clinical trials.

Adult↗
PubMed1993

Aspirin does not improve early arterial patency after streptokinase treatment for acute myocardial infarction.

OBJECTIVE: To investigate the hypothesis that the magnitude of the life saving effect of aspirin in the second international study of infarct survival (ISIS-2) trial cannot be explained solely by prevention of late reocclusion of the infarct related artery. The aim of this study was to discover whether or not aspirin in combination with streptokinase had an adjuvant thrombolytic effect. DESIGN: Aspirin (150 mg) or placebo was given at the start of streptokinase infusion to 200 patients seen within six hours of the start of prolonged ischaemic cardiac pain and ST segment elevation. All patients received active aspirin at three hours. Patency of the infarct related artery was assessed non-invasively by the normalised rise of creatine kinase activity at three hours after starting streptokinase in these 200 patients and in a further 52 patients who had already taken aspirin within one week of the start of infarction. MAIN OUTCOME MEASURE: Rise in creatine kinase activity from baseline to > or = 20% or < 20% of the peak rise of activity in blood taken at three hours after starting infusion of streptokinase. This correlates with patency or occlusion of the infarct related coronary artery at about 2.5 hours after starting streptokinase. RESULTS: Assessed in this way, patency of the infarct related artery was 60% in patients given aspirin, 63% in those given placebo, and 62% in patients who had already taken aspirin within one week of infarction. CONCLUSION: The magnitude of the life saving effect of aspirin remains unexplained. Further investigation is needed into the mechanism of action of antiplatelet treatment in relation to thrombolytic treatment.

Aged↗
PubMed1992

Effects of progressive myocardial ischaemia on systolic function, diastolic dysfunction, and load dependent relaxation.

OBJECTIVE: The aims were to determine (1) the relationship between changes in contractile function (systolic shortening) and the appearance of diastolic dysfunction (postsystolic shortening) during progressive regional left ventricular ischaemia; (2) the effects of increased afterload (acute constriction of the descending thoracic aorta) on ischaemic contractile dysfunction; and (3) the effects of loading during ischaemia on load dependent relaxation. METHODS: Regional myocardial function, using sonomicrometry, was measured in the short and long axes of the apex of the left ventricle of eight open chest anaesthetised dogs (16-20 kg). Progressive apical ischaemia was induced by graded reductions in left anterior descending coronary artery flow (critical constriction, ischaemia 1, ischaemia 2, total coronary occlusion, and postocclusive maximum reactive hyperaemia). Acute afterloading was induced by a snare placed around the descending aorta. RESULTS: Consistent decreases in systolic shortening and increases in postsystolic shortening relative to the total segmental shortening in the short axis of the apical region were seen with worsening ischaemia. Aortic constriction increased the magnitude of apical postsystolic shortening and decreased apical systolic shortening in the short axis during critical constriction, ischaemia 1, and ischaemia 2. Long axis function changed in a qualitatively similar but quantitatively different manner. There was a significant decrease in the load dependency of relaxation with total coronary occlusion. CONCLUSIONS: (1) Changes in systolic and diastolic function occurred concomitantly as mild regional myocardial ischaemia developed and intensified; (2) afterloading significantly worsened regional systolic and diastolic dysfunction during mild ischaemia; and (3) progression of regional ischaemia resulted in loss of load dependent relaxation.

Animals↗