The glyco stampede. New tools are the key.
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Biomedical subjects
Publications and source records attributed to R Stevenson.
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OBJECTIVES: Silent myocardial ischemia is common in patients with diabetes. This study was designed to assess the role of subclinical autonomic impairment in diabetic patients with silent ischemia. BACKGROUND: Studies have suggested that silent ischemia is more common in diabetic patients with microvascular complications, but this has not been a consistent finding. METHODS: Twenty-two diabetic and 30 nondiabetic patients with proved coronary artery disease and a history of angina and ischemia on treadmill stress testing underwent clinical tests of autonomic function and measurement of 24-h heart rate variability. Diabetic patients with a history of microvascular complications were excluded. RESULTS: Although all 52 patients manifested ischemia during treadmill testing, only 36 patients experienced angina (angina group), whereas 16 did not (silent ischemia group). Diabetic and nondiabetic patients were similar in age (59 +/- 1 vs. 61 +/- 2 years, p = 0.56) and extent of coronary artery disease. However, clinical tests showed reduced parasympathetic function in the diabetic patients (Valsalva ratio 1.38 +/- 0.07 vs. 1.60 +/- 0.06; p = 0.007). Patients in the silent ischemia group were more often diabetic (33% vs. 63%, p = 0.05) and had prolonged time to ischemia on treadmill testing (200 +/- 20 vs. 271 +/- 20 s, p = 0.03). In addition, autonomic function was impaired in the silent group (supine/standing heart rate ratio 1.15 +/- 0.02 vs. 1.05 +/- 0.02, p = 0.002). Subgroup analysis showed that abnormalities of autonomic function were confined to the diabetic patients in the silent group. CONCLUSIONS: Despite the absence of overt microvascular complications, diabetic patients with silent exertional ischemia have evidence of significant autonomic impairment compared with findings in symptomatic patients. This difference is not seen in nondiabetic patients and indicates that subclinical neuropathy is an important cause of silent ischemia in patients with diabetes.
OBJECTIVE: To record prognosis and determinants of outcome in patients with acute myocardial infarction since thrombolysis was introduced. DESIGN: Observational study. SETTING: London district general hospital. PATIENTS: 608 consecutive patients admitted to the coronary care unit with acute myocardial infarction between 1 January 1988 and 31 December 1991. MAIN OUTCOME MEASURE: All cause mortality, non-fatal ischaemic events (myocardial infarction, unstable angina), and revascularisation. RESULTS: Of the 608 patients, 89 (14.6%) died in hospital. 507 [corrected] patients were followed up after discharge from hospital. Mortality (95% confidence interval) at 30 days, one year, and three years was 16.0% (13.4% to 19.2%), 21.7% (18.6% to 25.2%), and 29.4% (25.3% to 33.9%) respectively. Event free survival (survival without a non-fatal ischaemic event) was 80.4% (77.0% to 83.4%) at 30 days, 66.8% (62.8% to 70.5%) at one year, and 56.1% (51.3% to 60.6%) at three years. Survival in patients treated with thrombolysis was considerably higher than in those not given thrombolysis (three year survival: 76.7% v 54.3%), although the incidence of non-fatal ischaemic events was the same in the two groups. Multivariate determinants of six month survival were left ventricular failure, treatment with thrombolysis and aspirin, smoking history, bundle branch block, and age. For patients who survived six months, age was the only factor related to long term survival. CONCLUSIONS: Although patients treated by thrombolysis had a relatively good prognosis, long term mortality and the incidence of non-fatal recurrent ischaemic events remained high. Effective strategies for the identification and treatment of high risk patients need to be reassessed.
OBJECTIVE: To determine the circadian and seasonal variations in the incidence of acute myocardial infarction and the influence of environmental temperature. PATIENTS: 633 consecutive patients with acute myocardial infarction admitted to a coronary care unit over four years. SETTING: Coronary care unit in a district general hospital. DESIGN: An observational study. RESULTS: The onset of acute myocardial infarction had a circadian rhythm with a peak in the second quarter of the day. A seasonal variation was also found with a significant winter peak. There was, however, an excess of infarctions on colder days in both winter and summer indicating that the effect of environmental temperature on the onset of acute myocardial infarction is independent of the time of year. CONCLUSION: Acute myocardial infarction is more common in winter and more common on colder days, independent of season. Environmental temperature may play an important part in the pathogenesis of acute myocardial infarction.
OBJECTIVES: To evaluate the role of Holter ST monitoring for identifying patients at risk of recurrent ischaemic events after acute myocardial infarction treated by thrombolysis. BACKGROUND: The natural history of myocardial infarction has changed with the introduction of thrombolytic treatment. There is now a lower mortality but a higher incidence of recurrent thrombotic events (reinfarction, unstable angina). Preliminary evidence indicates that Holter ST monitoring may be of prognostic value in patients with acute myocardial infarction, but there are limited data available in patients treated by thrombolysis. METHODS: Prospective observational study of 256 consecutive patients who presented with acute myocardial infarction treated by thrombolysis. All underwent 48 hour Holter ST monitoring early after thrombolysis (mean 83, range 48-180 hours) and were followed up for eight (range three to 12) months. RESULTS: Recurrent ischaemic events occurred in 45 patients (fatal reinfarction 17, non-fatal reinfarction 12, unstable angina 16). Also four patients died as a result of progressive heart failure, and a further 15 patients required revascularisation. Analysis of the Holter data showed that 32% of patients had at least one episode of isolated ST depression (> or = 0.1 mV) and 41% either ST depression or elevation (> or = 0.2 mV). Ischaemic episodes were silent in 95% of cases. Event free survival analysis showed a significant association between Holter findings and recurrent ischaemic events (ST depression: p = 0.009; ST depression or elevation: p = 0.002). The association remained significant when the end point was restricted to fatal or non-fatal reinfarction (ST depression: p = 0.005; ST depression or elevation p = 0.001), the period of greatest risk for patients with an abnormal recording occurred early after investigation. An abnormal Holter recording identified patients at risk of early (within 30 days) reinfarction with 79% sensitivity and 60% specificity. Although positive predictive accuracy was low (11%), a normal Holter recording was associated with 98% negative predictive accuracy. CONCLUSIONS: In patients treated by thrombolysis, ST change on Holter monitoring may be useful for identifying patients at increased risk of recurrent ischaemic events, and in particular early reinfarction.
OBJECTIVES: To evaluate the role of a treadmill stress test for identifying patients at risk of recurrent ischaemic events after acute myocardial infarction treated by thrombolysis. BACKGROUND: The natural history of myocardial infarction has changed with the introduction of thrombolytic treatment; there is a lower mortality but a higher incidence of recurrent thrombotic events (reinfarction, unstable angina). The treadmill stress continues to be recommended for risk stratification after acute myocardial infarction even though its value has never been formally reassessed in the thrombolytic era. METHODS: Prospective observational study in which 256 consecutive patients who presented with acute myocardial infarction treated by thrombolysis underwent an early treadmill stress test and were followed up for 10 (range 6-12) months. RESULTS: Recurrent ischaemic events occurred in 41 patients (unstable angina 15, reinfarction 21, death five) and a further 21 required revascularisation. Both ST depression at a low workload and low exercise tolerance (< 7 metabolic equivalents of the task (METS) were predictive of recurrent events, with respective hazard ratios of 1.93 (95% confidence interval (95% CI) 1.17-3.20; p < 0.01)) and 1.67 (95% CI 1.0-2.78; p < 0.05). These variables identified 50% and 70% of patients who subsequently sustained a recurrent ischaemic event, but the corresponding values for positive predictive accuracy were only 26% and 21%. Thus they are of limited value as a screening measure for identifying patients likely to benefit from invasive investigation and revascularisation. None of the other variables (ST elevation, haemodynamic responses, ventricular extrasystoles, angina) was significantly associated with recurrent ischaemic events. CONCLUSIONS: The treadmill stress test is of limited value for identifying patients at risk of recurrent ischaemic events after acute myocardial infarction treated by thrombolysis.
OBJECTIVE: To evaluate Holter and treadmill responses in patients with stable angina or recent myocardial infarction in order to compare the mechanisms of ischaemia and its symptomatic expression in these two groups. PATIENTS: 75 patients with ischaemic ST segment depression on both a treadmill stress test and ambulatory Holter monitoring. Group A comprised 35 patients with stable angina, and group B comprised 40 patients in the early period after infarction. SETTING: The coronary care unit and cardiology department of a district general hospital. DESIGN: A prospective, between group, comparative study. RESULTS: Treadmill test showed demand driven ischaemia in both groups. Although ST depression occurred at comparable rate-pressure products and workloads, it was associated with angina in 80% of group A compared with only 40% of group B (p < 0.005). During Holter monitoring, ST depression was associated with an attenuated increase in rate in group A and almost no increase in rate in group B (18.2% v 3.7%; p < 0.005), suggesting that reductions in myocardial oxygen delivery were contributing to the ischaemic episodes, particularly in group B. Ischaemic episodes were more commonly silent during Holter monitoring, particularly patients in group B, only two of whom experienced angina in association with ST depression. Spectral and non-spectral measures of heart rate variability were significantly reduced in group B compared with group A. Patients with silent exertional ischaemia in group A had significantly less heart rate variability than patients who experienced angina but this difference was not seen in group B. CONCLUSION: In stable angina, myocardial ischaemia is usually painful and demand driven, whereas in the early period after infarction silent, supply driven ischaemia predominates. The failure of myocardial ischaemia to provoke symptoms in some patients with stable angina may be related to autonomic dysfunction affecting the sensory supply to the heart. In the early period after infarction despite clear evidence of autonomic dysfunction, other mechanisms must also be important as there was no tendency for the reduction in heart rate variability to be exaggerated in the subgroup with silent exertional ischaemia.
Cephalosporins with new aminoimidazole heterocycles at C-7 have been synthesized by reaction of anti-alpha-aminooximes with C-7 dihaloisocyanocephalosporins esters or by direct condensation of 2-fluoroimidazoles with C-7 aminocephalosporins esters. These compounds combine a broad spectrum of antibacterial activity, including Gram-negative and Gram-positive organisms with a good beta-lactamase stability. Activity is discussed in terms of its relationship to the pKa of the C-7 aminoimidazole heterocycle, basic C-7 aminoimidazole residues gave cephalosporins with the best beta-lactamase stability but the poorest activity against Gram-positive organisms. An additional interesting property of the C-7 imidazolylaminocephalosporins is the oral activity present in some compounds of this series.
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Liquid or granular cyfluthrin was applied in the spring and fall to different test plots at a rate of 0.41 (AI) kg/ha to control Ixodes dammini Spielman, Clifford, Piesman & Corwin and Amblyomma americanum (L.). Spring application of liquid cyfluthrin showed the most significant decreases of both species. I. dammini nymphs were reduced 97% at 10 d, 100% at 2 mo, and 100% at 1 yr; and A. americanum adults and nymphs were reduced 91-93% at 10 d and 100% at 2 mo posttreatment. Granular cyfluthrin applied in the spring gave 97 and 87% control of nymphal I. dammini 10 d and 2 mo posttreatment, respectively.
OBJECTIVE: To evaluate laboratory markers of defibrination early after thrombolytic therapy and to determine their relation to residual stenosis and left ventricular ejection fraction measured angiographically before discharge from hospital. DESIGN: Prospective analysis of defibrination after streptokinase measured by fibrinogen assay and thrombin time to provide a comparison of these coagulation variables for predicting angiographic responses to treatment in patients with acute myocardial infarction. SETTING: The coronary care unit of a district general hospital. PATIENTS: 44 patients with acute myocardial infarction treated by streptokinase infusion, all of whom underwent paired blood sampling before and one hour after streptokinase and cardiac catheterisation at a median of six (interquartile range 3-9) days later. MAIN OUTCOME MEASURES: Assay of thrombin time and plasma fibrinogen concentrations one hour after streptokinase infusion. Relations between these coagulation variables and residual stenosis in the infarct related coronary artery and left ventricular ejection fraction. Separate analyses are presented for all patients (n = 44) and those with patency of the infarct related artery (n = 35). RESULTS: Streptokinase infusion produced profound defibrination in every patient as shown by changes in thrombin time and circulating fibrinogen. Thrombin time after streptokinase infusion correlated significantly with both residual stenosis (r = -0.43, p < 0.005) and left ventricular ejection fraction (r = 0.38, p < 0.02). The importance of these correlations was emphasised by the interquartile group comparison which showed that a thrombin time > or = 49 seconds predicted a residual stenosis of 74% and an ejection fraction of 65%, compared with 90% and 49% for a thrombin time < or = 31 seconds (p < 0.01). When the analysis was restricted to patients with patency of the infarct related artery, the correlation between thrombin time and residual stenosis remained significant and group comparisons continued to show that patients in the highest quartile range had more widely patent arteries and better preservation of ejection fraction. Analysis of the fibrinogen data, on the other hand, showed insignificant or only marginally significant correlations with these angiographic variables. CONCLUSIONS: Early after streptokinase infusion for acute myocardial infarction, the level of defibrination measured by thrombin time has an important influence on residual coronary stenosis and left ventricular ejection fraction at discharge from hospital, values above 49 seconds being associated with the best angiographic result.
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