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Biomedical subjects

B Marchant

Publications and source records attributed to B Marchant.

At least 37 records · Page 2Linked to original sources

Reassessment of treadmill stress testing for risk stratification in patients with acute myocardial infarction treated by thrombolysis.

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.

Adult↗

Myocardial ischaemia and angina in the early post-infarction period: a comparison with patients with stable coronary artery disease.

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.

Angina Pectoris↗

Streptokinase induced defibrination assessed by thrombin time: effects on residual coronary stenosis and left ventricular ejection fraction.

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.

Aged↗

The perception of angina in diabetes: relation to somatic pain threshold and autonomic function.

Silent ischemia is common in diabetic patients with coronary heart disease. These patients may also have more subtle alteration in the perception of angina as reflected by prolongation of anginal perceptual threshold--the time from onset of 0.1 mV ST segment depression to the onset of chest pain during treadmill exercise. Silent ischemia may be associated with a generalized hyposensitivity to pain, although the pathophysiologic mechanism is obscure. The purpose of the present study was to determine whether diabetic patients with prolonged anginal perceptual thresholds are also hyposensitive to painful stimuli and to investigate whether this is associated with autonomic neuropathy. Nineteen diabetic and 25 nondiabetic patients with exertional angina were exercised on a treadmill to measure anginal perceptual threshold. Somatic pain threshold was measured by calf sphygmomanometry. The cuff was inflated rapidly until pain occurred, and six repeat inflations were done to test reproducibility. Because there was no significant difference between measurements (coefficient of variation = 0.156) the mean value for each patient provided a measure of somatic pain threshold. The diabetic group had a longer anginal perceptual threshold (138 +/- 64 seconds vs 34 +/- 51 seconds, p less than 0.001), which correlated positively with the somatic pain threshold (r = 0.5, p = 0.03); patients with more prolonged anginal perceptual thresholds tended to have higher somatic pain thresholds. In the diabetic group anginal perceptual (r = -0.3, p = NS) and somatic pain (r = -0.4, p = 0.05) thresholds tended to increase as the ratio of peak to minimal heart rate during the Valsalva maneuver fell below 1.21, but these variables were unrelated in the nondiabetic group.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗

Irregular coronary lesion morphology after thrombolysis predicts early clinical instability.

After successful thrombolytic treatment for acute myocardial infarction, recurrent ischemia and infarction may occur with little warning. Coronary lesion morphology was analyzed from angiograms performed in 72 consecutive patients at 1 to 8 days after streptokinase treatment for acute myocardial infarction and the data were evaluated in relation to the subsequent clinical course. All patients were clinically stable at the time of angiography and continued to receive heparin infusion for greater than or equal to 4 days after thrombolysis. The infarct-related artery was patent in 55 patients (76%). In the 10 days after angiography, 15 patients developed prolonged episodes of angina at rest; the condition of 4 stabilized with medical treatment, but 11 required urgent medical intervention (coronary angioplasty in 8 and bypass surgery in 3). There were no differences in age, gender, left ventricular function or extent of coronary artery disease between those patients who developed unstable angina and those who had a stable in-hospital course. However, the median plaque ulceration index of the infarct-related lesion was 6.7 (95% confidence limits 6.3, 10) in the 15 patients with an unstable course versus 3.3 (2, 4.4) in those with a stable course (p less than 0.001). There were no differences between the two patient groups in the severity of stenosis, length of diseased segment, symmetry/eccentricity, presence of a shoulder, location at branch point or bend, presence of globular or linear filling defects, contrast staining or collateral supply. These data show that after thrombolysis, the degree of irregularity of the infarct-related artery is a critical determinant of early clinical instability.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina, Unstable↗

Aging, autonomic function, and the perception of angina.

OBJECTIVE: To determine the effects of age and autonomic function on the perception of angina. DESIGN: Prospective evaluation of the relations between anginal perceptual threshold, autonomic function, and systolic blood pressure in patients with symptomatic coronary artery disease. Statistical analysis was by non-parametric techniques. SETTING: Cardiology departments of a district general hospital and a post-graduate teaching centre. SUBJECTS: 82 non-diabetic men with typical exertional angina and coronary artery disease confirmed by arteriography (n = 64) or a history of Q wave infarction (n = 18). MAIN OUTCOME MEASURES: Age, anginal perceptual threshold, autonomic function, and blood pressure. Anginal perceptual threshold was defined as the time from onset of 0.1 mV ST depression to the onset of angina during treadmill stress testing. Autonomic function was measured as the ratio of peak heart rate during the Valsalva manoeuvre to the minimum rate after release. RESULTS: Anginal perceptual threshold showed a weak but significant correlation with age, with older patients tending to have a longer interval between the onset of ST depression and the onset of angina. Comparison of patients in the upper and lower quartile age ranges showed a difference of 50 seconds between median threshold measurements. Blood pressure and heart rate responses to the Valsalva manoeuvre also correlated with age, but neither variable correlated with the anginal perceptual threshold. CONCLUSIONS: In non-diabetic men with coronary artery disease the perception of angina tends to deteriorate with advancing age. The mechanism is unclear but is not attributable solely to alterations in blood pressure or autonomic function.

Adult↗

Risks and benefits of therapy with flumazenil (Anexate) in mixed drug intoxications.

Flumazenil, the first specific benzodiazepine (BZD) antagonist, is one of the most innovative drugs to become available within the last few years. Flumazenil is indicated for the reversal of the centrally depressant effects of BZDs, in BZD-induced anaesthesia, in BZD sedation in intensive care and in patients comatose after drug overdoses including BZDs. A conference of experts experienced in the treatment of mixed drug overdoses by various means, including flumazenil, was held in order to try to reach a consensus regarding the safe use of flumazenil in this indication. From the knowledge and experience gained to date, it was concluded that flumazenil may be useful and safe in the treatment of suspected BZD and mixed drug overdoses, provided that the appropriate precautions are observed.

Antidepressive Agents, Tricyclic↗

Coronary lesion morphology in acute myocardial infarction: demonstration of early remodeling after streptokinase treatment.

Coronary lesion morphology was analyzed in 72 patients 1 to 8 days after streptokinase treatment for acute myocardial infarction and compared with lesion morphology in a control group of 24 patients with stable angina. In the streptokinase group the infarct-related artery was patent in 55 patients (76%). Compared with stenoses in the stable angina group, there were no differences in the stenosis length, severity, calcification or in the proportion located at an acute bend or at a branch point. However, lesions in the streptokinase group were more often irregular (p less than 0.005) and eccentric (p less than 0.01), had a shoulder (p less than 0.0001), globular filling defects (p less than 0.01), linear filling defects (p less than 0.00005) and contrast staining (p less than 0.05). Plaque ulceration index was higher in the streptokinase than in the stable angina group (6.2 +/- 7.9 versus 3.5 +/- 3.4, p less than 0.001). Of the 72 streptokinase-treated patients, 35 were maintained on heparin infusion until angioplasty 2 to 10 days later. At repeat angiography before angioplasty, globular lesion filling defects seen in eight patients had disappeared, whereas linear filling defects persisted in 7 of 14 cases. Fewer lesions were irregular (p less than 0.0001) and the ulceration index decreased from 7.4 +/- 10.4 to 3.0 +/- 1.6 (p less than 0.001). These data show that the lesion in the infarct-related artery after streptokinase treatment is irregular and often associated with filling defects, perhaps corresponding to plaque fissuring and intraluminal thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗

Pharmacokinetic factors influencing variability in human drug response.

It is well recognised that the clinical response to drug administration varies widely between individuals and that most of this variability is pharmacokinetic in origin. In general, variability arises because of inter-individual differences in rates of drug absorption, drug distribution and elimination, either by metabolism or excretion. Variability of drug response is also a consequence of a variety of drug interactions which may influence pharmacokinetic parameters. Among the many factors which are responsible for the variation in human drug response, age is relatively important. As a consequence of impaired metabolism and excretion the inter-individual variation in the kinetic of many drugs is much greater in the elderly. Also the degree of plasma-protein binding, in turn, influences the distribution, action, metabolism and renal excretion of drugs. Thus changes in plasma protein binding of drugs, e.g. in diseased states, may give rise to altered pharmacokinetic and possibly altered drug response. The above factors influencing variability in drug response are discussed with particular reference to examples of non-steroidal antiinflammatory drugs used in the treatment of rheumatic diseases.

Adult↗

Chemical ionisation mass fragmentographic measurement of dothiepin plasma concentrations following a single oral dose in man.

A method is described for the measurement of the antidepressant drug dothiepin in human plasma. The procedure involves the addition of deuterodothiepin as an internal standard, extraction and measurement by chemical ionisation mass fragmentography. The minimum measurable concentration of 0.5 ng/ml enabled the pharmacokinetics of dothiepin in man to be studied after a single oral dose of 75 mg of dothiepin hydrochloride. Unlike other tricyclic antidepressants the apparent half-life of elimination (approximately 24 h) showed very little intersubject variation. However, the apparent volume of distribution was much more variable and could account for the wide range of steady state concentrations which have been found in patients taking dothiepin.

Administration, Oral↗

Comparison of antithyroid drug metabolism in the rat and guinea pig.

The thyroid accumulation, metabolism and urine excretion of (35S) propylthiouracil was compared in the guinea pig and the rat. Per gram thyroid tissue, the guinea pig thyroid took up much less drug than the rat, metabolised it faster and had a shorter t 1/2 for total 35S and free (35S) propylthiouracil. Liver metabolism, clearance of the drug from the serum and excretion in the urine were also considerably faster in the guinea pig. It is likely that a much larger dose of propylthiouracil would need to be administered to induce goitre in the guinea pig than is necessary in the rat.

Animals↗