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Biomedical subjects

A Lahiri

Publications and source records attributed to A Lahiri.

At least 19 recordsLinked to original sources
PubMed1999

Comparison of safety and efficacy of carvedilol and metoprolol in stable angina pectoris.

In a double-blind, randomized, 3-month multicenter study, the safety and tolerability and the antianginal and anti-ischemic efficacy of carvedilol 25 to 50 mg twice daily were assessed in comparison with metoprolol 50 to 100 mg twice daily in younger and elderly patients with stable angina. After a 7-day placebo run-in at the end of which a symptom-limited bicycle ergometric exercise was performed, 368 patients were randomly allocated to the parallel treatment groups. After 4 weeks of therapy with a low dose, a further exercise test was performed and patients were titrated in single-blind fashion to the higher dose if the increase in total exercise time was < 1 minute, and there was no safety concern. After a further 8 weeks of treatment a third exercise test was performed. Carvedilol low dose/high dose was shown to be at least as safe and well tolerated as metoprolol low dose/high dose both in younger and elderly patients. There were no hitherto unknown adverse events and no marked change in the types of events after increase of the doses. Early adverse events after treatment initiation or uptitration were equal with both medications, indicating no particular risk associated with carvedilol's vasodilatory action. No rebound phenomena were observed. Both drugs showed good antianginal and anti-ischemic efficacy, with marked increases on uptitration including patients > or = 65 years of age. However, in the doses selected, which appeared equipotent with respect to beta blockade, carvedilol's improvement of time to 1-mm ST-segment depression was statistically significantly greater than that of metoprolol. This could be due to its additional vasodilatory or antioxidative actions. Based on the safety and efficacy data of the present study, use of the higher of the 2 recommended doses of carvedilol and metoprolol appears justified in younger and elderly patients without adequate therapeutic control at lower doses.

Adrenergic alpha-Antagonists↗
PubMed1999

Carvedilol prevents remodeling in patients with left ventricular dysfunction after acute myocardial infarction.

OBJECTIVE: The aim of the study was to assess the effects of carvedilol, a vasodilating nonselective beta-blocker, on the indexes of left ventricular remodeling after acute myocardial infarction in those with left ventricular dysfunction. METHODS AND RESULTS: Forty-nine patients with predischarge left ventricular ejection fraction <45% after acute myocardial infarction were evaluated in a double-blind, randomized, placebo-controlled, parallel group study (selected from the database of the Carvedilol Heart Attack Pilot Study: CHAPS). Patients received medication after thrombolysis and continued to do so for 6 months. Two-dimensional echocardiography was performed before discharge (7 to 10 days after admission) and at 3 months after acute myocardial infarction. Analysis of variance showed that wall thickness opposite the site of infarction decreased from (mean +/- SD) 12.3 +/- 2.1 mm to 11.0 +/- 2.4 mm with carvedilol compared with 11.6 +/- 1.9 mm to 12.2 +/- 1.9 mm with placebo (P =.01). Left ventricular mass changed from 235 +/- 74 g to 217 +/- 64 g with carvedilol compared with 227 +/- 80 g to 252 +/- 85 g with placebo ( P =.02). Carvedilol prevented alteration of sphericity index (ratio of long and short axis of left ventricle) that changed from 1.65 +/- 0.29 to 1.66 +/- 20 with carvedilol compared with 1.58 +/- 0.33 to 1.39 +/- 0.19 with placebo (P =.02); alteration was also prevented of wall thickening abnormality at infarct site, which changed from 9.2 +/- 3.1 cm2 to 9.1 +/- 3.5 cm 2 with carvedilol compared with 10.3 +/- 3.3 cm2 to 13.5 +/- 4.6 cm2 with placebo (P =.002). CONCLUSION: Carvedilol administered early after acute myocardial infarction results in attenuation of left ventricular remodeling in patients with persistent left ventricular dysfunction before discharge.

Adrenergic beta-Antagonists↗
PubMed1999

Value of ambulatory intra-arterial blood pressure monitoring in the long-term prediction of left ventricular hypertrophy and carotid atherosclerosis in essential hypertension.

The aim of this study was to compare the abilities of clinic and ambulatory blood pressure (BP) to predict the long term occurrence of left ventricular hypertrophy and carotid atherosclerosis in uncomplicated hypertensive patients. Two hundred and ninety-five patients who had undergone 24-h ambulatory intra-arterial BP monitoring on the basis of an elevated clinic BP, attended follow-up at a mean of 10.2 (+/- 3.5) years later. This consisted of a history, physical examination, risk factor profile and serum cholesterol level. Echocardiography and carotid ultrasonography were also performed to determine left ventricular mass index and maximal intima-media thickness (IMTmax), a measure of carotid atherosclerosis severity. The factors most strongly correlated with both left ventricular mass index and IMTmax were age, 24-h mean pulse pressure and 24-h mean systolic BP. Age, 24-h mean systolic BP and body mass index were independent correlates of left ventricular hypertrophy (R2 = 17%), whereas age, 24-h mean pulse pressure and pack years were independent predictors of carotid atherosclerosis (R2 = 34%). Clinic BP did not feature in the final model for the long term prediction of cardiovascular end-organ damage. These findings promote a role for ambulatory BP monitoring in guiding aggressiveness of drug therapy in an attempt to limit potential target organ damage.

Adult↗
PubMed1999

Biodistribution, radiation dosimetry and pharmacokinetics of 111In-antimyosin in idiopathic inflammatory myopathies.

UNLABELLED: In view of the established role of 111In-antimyosin in the detection of heart muscle pathology, radiation dose estimates were made for this substance. Biodistribution and biokinetic data were obtained from our studies, which failed to show abnormal uptake of 111In-antimyosin in localized sites of skeletal muscle involvement in patients with idiopathic inflammatory myopathies. METHODS: After intravenous administration of 74 MBq (2 mCi) 111In-antimyosin, gamma camera scintigraphy was performed in 12 adult patients with inflammatory muscle disease and in 2 control patients. Six whole-body scans were performed over 72 h, and uptake of 111In-antimyosin in organs was quantified using an attenuation-corrected conjugate counting method. Residence times in source organs were used with MIRDOSE software to obtain radiation dose estimates. Pharmacokinetic parameters were derived from serial whole-blood and plasma 111In concentrations. RESULTS: The tracer cleared slowly from the circulation, and highest organ uptakes were found in the marrow and liver; kidneys showed the highest concentrations. Uptake was also evident in spleen, the facial image and male genitalia. CONCLUSION: For a typical administered activity of 74 MBq 111In-antimyosin, the kidneys receive the highest dose (58 mSv), and the effective dose is 11 mSv. Radioactivity was cleared from plasma at an average rate of 136 mL/h, and the mean steady-state distribution was approximately 5 L plasma.

Adult↗
PubMed1998

Denaturation of supercoiled DNA: a Monte Carlo study.

A theoretical investigation of the denaturation characteristics of a supercoiled DNA has been presented employing a Metropolis Monte Carlo algorithm to examine the overall melting profiles of a supercoiled plasmid as the temperature is varied. We show that in contrast to a previously presented algorithm, this much simpler method is sufficient to explain almost all the overall denaturation characteristics and it also correctly calculates the detailed denaturation probabilities of each base pair at various degrees of supercoiling. We also present for the first time a theoretical investigation of the alkaline denaturation of a supercoiled plasmid. Although one can qualitatively reproduce the denaturation profiles using the present Monte Carlo algorithm, the agreement with experiment is not as good as in the case of thermal denaturation. The possible sources of discrepancy between theory and experiment have been discussed.

Algorithms↗
PubMed1998

Cardiovascular outcome in white-coat versus sustained mild hypertension: a 10-year follow-up study.

BACKGROUND: The aim of this study was to compare the risk conferred by white-coat versus sustained mild hypertension for the development of cardiovascular disease. METHODS AND RESULTS: Patients (n=479) who underwent 24-hour intra-arterial ambulatory blood pressure monitoring on the basis of a persistently elevated clinic systolic blood pressure of 140 to 180 mm Hg were followed up for the development of subsequent cardiovascular events during a 9.1+/-4. 2-year period. White-coat hypertension, defined as a clinic systolic blood pressure of 140 to 180 mm Hg associated with a 24-hour ambulatory systolic blood pressure <140 mm Hg and diastolic blood pressure <90 mm Hg, was present in 126 patients, and the remainder had sustained mild hypertension. A subgroup of patients without complications underwent follow-up echocardiography and carotid ultrasound. White-coat hypertensives were younger (44+/-12 versus 52+/-10 years, respectively; P<0.001) and had a significantly lower incidence of cardiovascular events (1.32 versus 2.56 events per 100 patient-years, respectively; P<0.001) than sustained hypertensives. Multivariate analysis revealed age (P=0.002), sex (P=0.007), race (P=0.001), smoking (P=0.005), and the presence of white-coat hypertension (hazard ratio, 0.29; 95% CI, 0.09 to 0.90; P=0.04) to be independent predictors of subsequent cardiovascular events. Subgroup analysis in patients without complications revealed a lower incidence of left ventricular hypertrophy and lesser degrees of carotid hypertrophy in the white-coat group. CONCLUSIONS: These findings indicate a relatively benign outcome in white-coat hypertension compared with sustained mild hypertension.

Adult↗
PubMed1998

Value of dobutamine stress echocardiography for the detection of multivessel coronary artery disease.

Dobutamine stress echocardiography has been shown to accurately detect coronary artery disease (CAD), but it is not clear whether it has the ability to detect multivessel CAD relative to clinical and exercise electrocardiography. Therefore, the aim of this study was to evaluate the ability of dobutamine stress echocardiography to identify multivessel CAD and ascertain its incremental value when combined with clinical and exercise test variables. One hundred twenty-one consecutive patients referred for coronary arteriography on the basis of symptoms and exercise electrocardiography underwent dobutamine stress echocardiography. Significant multivessel CAD was defined as the presence of > or =70% diameter stenosis in > or =2 major epicardial arteries. Stepwise logistic regression analysis was performed using the clinical exercise test and echocardiographic variables. The strongest independent variables predicting the presence of multivessel CAD were systolic wall thickening index at peak stress (p < 0.0001), presence of wall thickening abnormalities in multiple vascular territories (p = 0.001), and a history of acute myocardial infarction (p = 0.04). Furthermore, dobutamine echocardiography significantly enhanced the prediction of multivessel disease when combined with clinical and exercise test variables (p = 0.001). Dobutamine stress echocardiography adds independent and incremental information to clinical and exercise test variables for identifying multivessel CAD.

Adult↗
PubMed1998

Independent prognostic value of the extent and severity of systolic wall thickening abnormality at infarct site after thrombolytic therapy.

BACKGROUND: The prognostic value of systolic wall thickening abnormality after acute myocardial infarction in the thrombolytic era is not clearly known. METHODS AND RESULTS: Accordingly, 119 consecutive patients with acute myocardial infarction who underwent thrombolysis were investigated with exercise electrocardiography and rest echocardiography at predischarge evaluation and were followed up for cardiac events. During a mean follow-up period of 19 months, 43 patients had cardiac events. Multivariate analysis with clinical, exercise electrocardiographic, and rest echocardiographic parameters showed that the independent predictors of cardiac events were systolic wall thickening score at the site of infarct (p = 0.02), end-systolic volume (p = 0.03), and exercise time (p = 0.02). The only independent predictor for both recurrent ischemic (death, unstable angina, and reinfarction) and nonischemic events (congestive heart failure and ventricular tachycardia) was systolic wall thickening score at the site of infarct (p = 0.02 and p = 0.007, respectively). CONCLUSIONS: Systolic wall thickening abnormality at rest is an important independent predictor of cardiac events in patients who have undergone thrombolysis after acute myocardial infarction.

Echocardiography↗
PubMed1998

Influence of background correction in the estimation of myocardial uptake of 99mTc labelled perfusion imaging agents.

The effects of different corrections for background activity in the estimation of low organ uptake of radiopharmaceuticals have been examined using myocardial perfusion imaging agents. Estimates of myocardial uptake of 99mTc-labelled MIBI and tetrofosmin were made both at rest and after exercise. Patients were given one or other of the agents (12 MIBI; 17 tetrofosmin) and the measurements at rest and after exercise were made within a week of each other using a planar gamma camera method incorporating an attenuation-corrected, geometric mean technique. Myocardial uptakes were estimated using two different background corrections and also with no background subtraction. Mean values were in the range 1.3 to 3.0% and showed that, for both agents, uptakes estimated with and without background correction could differ by a factor of two. Although the study was not designed to compare myocardial uptakes of the two agents, a background correction which accounted separately for activity in tissue over- and under-lying the heart resulted in similar mean values for tetrofosmin (1.7% both at rest and after exercise) and for MIBI (1.8% rest; 1.9% exercise). For both agents, no significant difference was observed between myocardial uptakes at rest and after exercise measured at about two hours post-injection.

Adult↗
PubMed1998

Safety, tolerability, and antiischaemic efficacy of ITF-296, a nitric oxide donor, in patients with chronic stable angina.

A double-blind, placebo-controlled, parallel-group, dose-escalation study was performed to evaluate ITF-296, a new nitric oxide donor, in chronic stable angina. Twenty-four male patients underwent exercise electrocardiography in conjunction with echocardiography on three separate occasions within 2 weeks. After two reproducibility tests, the third exercise test was immediately preceded by a 30-min intravenous infusion of either placebo or 0.3, 1.0, or 3.0 microg/kg/min of ITF-296, with six patients in each treatment group. During ITF-296 infusion, systolic blood pressure decreased by a mean of 12 mm Hg compared with a 2 mm Hg increase in the placebo group [difference, -14; 95% confidence interval (CI), -23 to -6 mm Hg]. ITF-296 administration was followed by consistent increases in total exercise time, time to angina threshold, and time to 1-mm ST-segment depression. The mean change in total exercise time was 39 s on placebo and 94 s on ITF-296 (mean difference, 54 s; 95% CI, -48 to 157 mm Hg). The 1.0- and 3.0-microg/kg/min doses increased exercise time by >2 min with no important change in peak rate-pressure product compared with baseline. The trends exhibited in this small preliminary study were consistently pharmacologically plausible and indicate that ITF-296 shows potential antiischaemic efficacy in patients with chronic stable angina.

Aged↗
PubMed1998

Assessment of myocardial perfusion and contractile function by inotropic stress Tc-99m sestamibi SPECT imaging and echocardiography for optimal detection of multivessel coronary artery disease.

OBJECTIVE: To assess whether inotropic stress myocardial perfusion imaging, echocardiography, or a combination of the two could enhance the detection of multivessel disease, over and above clinical and exercise electrocardiographic data. DESIGN: 100 consecutive patients investigated by exercise electrocardiography and diagnostic coronary arteriography underwent simultaneous inotropic stress Tc-99m sestamibi SPECT (MIBI) imaging and echocardiography. MIBI imaging and echocardiographic data were analysed using a 12 segment left ventricular model, and each segment was ascribed to a particular coronary artery territory. The presence of perfusion defects with MIBI imaging or of wall thickening abnormality with echocardiography in at least two coronary artery territories at peak stress was taken as diagnostic of multivessel disease. Arteriographic evidence of > or = 50% stenosis was considered significant. RESULTS: 56 patients had multivessel disease. The sensitivity of the combination of MIBI imaging and echocardiography for detecting this was greater than either MIBI imaging or echocardiography alone (82%, 68%, and 68%, respectively; p = 0.005). Clinical and exercise electrocardiographic variables gave an R2 value of 18.2% for predicting multivessel disease. The addition of either MIBI imaging (R2 = 29.2%; p = 0.002) or echocardiography (R2 = 28.8%; p < 0.001) enhanced the detection of multivessel disease, and the inclusion of both had further incremental value (R2 = 34.8%; p = 0.003). Age (p = 0.03), MIBI imaging (p = 0.007), and echocardiography (p = 0.001) were independent predictors of multivessel disease. CONCLUSIONS: The assessment of both myocardial perfusion and contractile function by simultaneous inotropic stress MIBI imaging and echocardiography optimises the non-invasive detection of multivessel disease.

Cardiotonic Agents↗
PubMed1997

Superiority of nitrate-enhanced 201Tl over conventional redistribution 201Tl imaging for prognostic evaluation after myocardial infarction and thrombolysis.

BACKGROUND: 201Tl imaging has been widely used for postinfarction risk stratification. However, thrombolytic therapy and aspirin have significantly changed outcome, and there are few nuclear imaging studies that assess prognosis in such patients. Furthermore, newer techniques of 201Tl imaging, such as reinjection and nitrate-enhanced rest 201Tl imaging, have been shown to improve the detection of viable but jeopardized myocardium. METHODS AND RESULTS: We studied 100 consecutive patients, who remained event free 6 weeks after myocardial infarction and thrombolysis. Patients underwent conventional exercise and 4-hour redistribution imaging, followed on a separate day by nitrate-enhanced rest 201Tl study. Planar images were reported semiquantitatively by two experienced observers blinded to clinical data. Redistribution and rest injection images were classified as demonstrating reversible ischemia if they showed improvement in uptake by at least two grades in at least two segments in comparison with the initial exercise scintigram. Patients were followed up for 8 to 32 months (mean, 21 months); during this period, 37 patients had first cardiac events. Reversible ischemia was present in 29 patients on redistribution, of whom 14 (48%) had events; of 71 without reversible defects, 23 (32%) had events (hazard ratio, 1.5; 95% CI, 0.8 to 3.0; P=NS). Nitrate-enhanced rest 201Tl imaging detected reversible defects in 68 patients, of whom 33 (49%) had events, whereas of 32 without reversible defects, only 4 (13%) had subsequent cardiac events (hazard ratio, 8.1; 95% CI, 2.7 to 23.8; P<.001). CONCLUSIONS: Thus, after myocardial infarction and thrombolysis, even "stable" patients have a high (68%) incidence of viable but jeopardized myocardium, causing a high event rate. Those identified to be at high risk by perfusion imaging may benefit from early intervention.

Adult↗
PubMed1997

Detection of coronary artery disease with myocardial contrast echocardiography: comparison with 99mTc-sestamibi single-photon emission computed tomography.

BACKGROUND: The purpose of this study was to determine whether myocardial contrast echocardiography (MCE) can be used to detect coronary artery disease (CAD) during rest and pharmacological stress in humans through the use of venous injections of contrast. METHODS AND RESULTS: Thirty patients with known or suspected CAD underwent MCE and 99mTc-sestamibi single-photon emission computed tomography (SPECT) at baseline and after dipyridamole (0.56 mg x kg(-1)) infusion. Ten myocardial segments (5 each in the apical two- and four-chamber views) from the two sets of images using both methods were scored for myocardial perfusion as follows: 1=normal, 0.5=mildly reduced, and 0=severely reduced. The information from baseline and postdipyridamole images was then used to determine whether an abnormal segment was irreversible (similar abnormal perfusion at baseline and after dipyridamole) or reversible (perfusion better at baseline compared with after dipyridamole). Concordance between segmental scores was 92% (kappa=.99) for both methods. Concordance between normal perfusion and reversible or irreversible segmental defects was 90% (kappa=.80). Agreem between the two methods for each of the three vascular territories in each patient was 90% (kappa=.77), while agreement for the presence or absence of CAD in each patient was 86% (kappa=.86). In the 4 patients with disagreement, the perfusion scores were 0.5 for SPECT and 1.0 for MCE. CONCLUSIONS: This study shows that MCE, with venous injection of contrast, can define the presence of CAD during rest and pharmacological stress. The location of perfusion abnormalities and their physiologic relevance (reversible or irreversible) by MCE is similar to that provided by SPECT. MCE, therefore, holds promise for the noninvasive assessment of myocardial perfusion in humans.

Adult↗
PubMed1997

Beneficial effects of intravenous and oral carvedilol treatment in acute myocardial infarction. A placebo-controlled, randomized trial.

BACKGROUND: Evidence of efficacy and safety of beta-blockers after thrombolysis for acute myocardial infarction (AMI) is equivocal. Newer beta-blockers such as carvedilol have not been tested in this setting. METHODS AND RESULTS: This study investigated the effects of acute (intravenous) and long-term (6 months, oral) treatment with carvedilol versus placebo in 151 consecutive patients with AMI. Exercise ECG, ambulatory monitoring, and two-dimensional echocardiography were performed before hospital discharge and at 3 and 6 months. All patients were followed up and cardiovascular events recorded. The Cox proportional hazards model was used to compare time from randomization with the occurrence of a cardiovascular event, and Kaplan-Meier survival curves were calculated. Carvedilol was found to be safe, and it significantly reduced cardiac events compared with placebo (18 on carvedilol and 31 on placebo, P < .02). Fifty-four patients had heart failure at study entry; 34 received carvedilol. There were no adverse effects of carvedilol therapy and no excess events in this subgroup. Carvedilol produced significant reductions in heart rate (P < .0001), blood pressure (P < .005) at rest, and rate-pressure product at peak exercise (P < .003), but exercise capacity was unchanged. Left ventricular ejection fraction was not altered significantly by carvedilol, but stroke volume was higher at pre-hospital discharge examination (63 versus 53 mL; P < .01). Diastolic filling of the left ventricle (E/A ratio) was also improved (1.2 versus 0.9; P < .001). In a subgroup with left ventricular ejection fraction < 45% (n = 49 patients; 24 on carvedilol and 25 on placebo), carvedilol showed attenuation of remodeling. CONCLUSIONS: Carvedilol was well tolerated and safe to use in patients immediately after AMI, including those with heart failure, and significantly improved outcome.

Administration, Oral↗
PubMed1997

Prognostic value of dobutamine stress echocardiography in patients undergoing diagnostic coronary arteriography.

There are only a few studies addressing the prognostic value of dobutamine stress echocardiography in patients with suspected coronary artery disease and none have assessed its value compared with coronary arteriography. Accordingly, graded dobutamine stress echocardiography was performed in 121 patients who underwent coronary arteriography based on symptoms and the findings of treadmill exercise electrocardiography. During the follow-up period of mean (SD) months (15 +/- 9) there were 41 cardiac events (death [n = 5], acute myocardial infarction [n = 2], unstable angina [n = 29], and congestive heart failure [n = 5]). There were a greater number of patients with inducible wall motion abnormality (88%) on dobutamine stress with cardiac events compared with those without (55%, p <0.001). The wall motion score indexes at rest (1.6 +/- 0.6) and at peak stress (2.1 +/- 0.8) were worse in patients with cardiac events compared with those without (1.2 +/- 0.3, p <0.001 and 1.5 +/- 0.6, p <0.001, respectively). When multivariate analysis was performed using clinical, exercise, echocardiographic, and coronary arteriographic data the independent predictors of cardiac events were exercise duration (p = 0.01), presence of inducible wall motion abnormality (p = 0.03), and wall motion score index at peak stress (p <0.001). Thus, dobutamine stress echocardiography is a powerful predictor of future cardiac events in patients undergoing exercise testing and coronary arteriography for evaluation of chest pain and is superior to both exercise electrocardiography and coronary arteriography for the prediction of subsequent cardiac events.

Adult↗
PubMed1997

Longitudinal association of ambulatory pulse pressure with left ventricular mass and vascular hypertrophy in essential hypertension.

OBJECTIVE: To determine the longitudinal relationship between clinic and ambulatory blood pressures and subsequent left ventricular and carotid artery structure. DESIGN: A retrospective follow-up study. SETTING: A large district general hospital in Harrow, UK. PATIENTS: One hundred and forty patients who had been subjected to 24 h ambulatory intra-arterial blood pressure monitoring on the basis of their having an elevated clinic blood pressure were followed up randomly a mean of 9.4 +/- 3.4 years later. The ambulatory blood pressure parameters measured were the mean systolic, mean diastolic and mean pulse pressures. Follow-up variables assessed included the clinic blood pressure, body mass index, total cholesterol, number of years of follow-up, left ventricular mass index, carotid intima-media thickness and carotid artery cross-sectional area. MAIN OUTCOME MEASURES: The left ventricular mass index, carotid intima-media thickness and carotid artery cross-sectional area. RESULTS: The mean pulse pressure and mean systolic blood pressure were correlated significantly with the left ventricular mass index (r = 0.46, P < 0.001 and r = 0.36, P < 0.001, respectively), carotid intima-media thickness (r = 0.45, P < 0.001 and r = 0.37, P < 0.001, respectively) and carotid artery cross-sectional area (r = 0.46, P < 0.001 and r = 0.41, P < 0.001, respectively). The mean pulse pressure was associated independently with all three outcome measures. In addition, the body mass index was an independent determinant of the left ventricular mass index, whereas the serum cholesterol level was associated independently with the carotid artery cross-sectional area; the number of years of follow-up was related independently to the left ventricular mass index and carotid intima-media thickness, but not to the cross-sectional area. CONCLUSIONS: These findings suggest that ambulatory blood pressure monitoring can play a role in guiding the choice of doses in drug therapy to limit potential target organ damage.

Aged↗