ac conductivity of incommensurate lattices: Anatomy of wave functions.
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Biomedical subjects
Publications and source records attributed to A Lahiri.
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A binding isotherm in the form of a modified McGhee-Von Hippel equation is proposed, on the basis of thermodynamical considerations, to include the non-cooperative binding of extended ligands to supercoiled DNA, where a stretch of non-B form may be present under superhelical stress. It is then studied, on the basis of a non-linear Scatchard plot, how the presence of an intercalating ligand can relax the supercoiled molecule and thus destabilise the non-B stretch, which may be recognised by the existence of a significant kink in the Scatchard plot.
1. The non-invasive method of near-infrared spectroscopy was used to measure myocardial oxygenation and haemodynamics in response to left anterior descending coronary artery occlusion in a porcine model. 2. Near-infrared spectroscopy measures changes in haemoglobin (and myoglobin) oxygenation and blood volume to yield information on tissue perfusion and flow. It also measures the redox state of cytochrome aa3, thus providing information about intracellular oxygen utilization. 3. Left anterior descending coronary artery occlusion was induced to produce periods of ischaemia lasting between 24s and 13.5 min (n = 13). The changes in deoxyhaemoglobin, oxyhaemoglobin and cytochrome aa3 measured during occlusion were all highly significant compared with baseline variation. In all occlusions (n = 13) a rapid decrease in oxyhaemoglobin concentration (-75.83 +/- 3.27 mumol/l, mean +/- SEM) with a simultaneous increase in deoxyhaemoglobin of 9.27 +/- 1.69 mumol/l was measured. The total haemoglobin concentration also fell by -71.3 +/- 5.32 mumol/l. Cytochrome aa3 was also reduced during occlusion (-8.35 +/- 1.044) mumol/l. 4. Over the range 24-60s occlusion, the magnitude of the fall in total haemoglobin and oxyhaemoglobin correlated with the duration of occlusion (P < 0.003 and 0.013 respectively). For total haemoglobin only the magnitude of the fall correlated with the increase upon release of occlusion (r = 0.89, P < 0.003). 5. Release of occlusion (n = 8) resulted in an immediate increase in the concentration of deoxyhaemoglobin at 9.88 +/- 1.06s, then total haemoglobin at 13.62 +/- 1.23s and finally oxyhaemoglobin at 29.75 +/- 5.96s. The difference between the timing of the maxima after reperfusion is significant (P < 0.002 and P < 0.007 respectively). Moreover, the time for the deoxyhaemoglobin signal to reach maximum values was found to correlate with the duration of occlusion (P < 0.04). This could be indicative of the PO2 of the ischaemic tissues and an immediate off-loading of oxygen from oxyhaemoglobin. The results are reliable, reproducible and sensitive enough to detect the kinetics of haemoglobin oxygenation from a beating heart in situ.
The majority of post-myocardial infarction studies with beta-blocking drugs involved earlier generations. Newer drugs of this family with additional vasodilating and free-radical suppression properties, such as carvediol, are now available which may improve the prognosis still further. This double-blind, randomized, placebo-controlled, parallel group study was designed to assess the extent of myocardial ischaemia in clinically stable patients 6 weeks after acute myocardial infarction and thrombolysis, and to determine the influence of carvedilol on ischaemic events during the subsequent 6 months. One hundred and one patients who remained event free at 6 weeks post myocardial infarction underwent rest and exercise thallium-201 (TI-201) imaging. Reversible ischaemia was detected in 70 of the patients and there were 13 events in this group compared to one event in the 31 patients without ischaemia (P = 0.07). Four of the 56 patients on carvedilol and 10 of the 45 on placebo had adverse cardiac events (P = 0.04). In patients with reversible ischaemia carvedilol was more effective in reducing these events than was placebo (P = 0.03). These studies demonstrate that reversible myocardial ischaemia detected by TI-201 imaging is present in a large proportion of clinically stable patients following thrombolysis. In these patients, there is an increased cardiac event rate which is significantly reduced by carvedilol.
To compare the diagnostic accuracy between dobutamine echocardiography and treadmill exercise electrocardiography in detecting coronary artery disease in hypertensive patients, 43 patients without electrocardiographic evidence of left ventricular hypertrophy and basal ST-T changes, who had also undergone coronary angiography, were further evaluated by dobutamine echocardiography. The patients also underwent treadmill exercise echocardiography. Left ventricular mass index was calculated by echocardiography. Twenty-nine patients had coronary artery disease, of whom 22 had multi-vessel disease and 14 a normal coronary anatomy. Twenty-eight patients had an increased left ventricular mass index. The sensitivities of dobutamine echocardiography and exercise electrocardiography for detecting coronary artery disease were 93% and 72% (P = 0.08), respectively, and the specificities were 100% and 29% (P < 0.005), respectively. Logistic regression analysis showed exercise electrocardiography to be a poor predictor of coronary artery disease (P < 0.09) but dobutamine echocardiography was significantly better (P < 0.001). When patients with increased left ventricular mass index were excluded, prediction of coronary anatomy by exercise electrocardiography improved only marginally (p = 0.4) while dobutamine echocardiography was significantly better (P < 0.001). Thus dobutamine echocardiography is superior to exercise electrocardiography for diagnosis of coronary artery disease in hypertensive patients.
Technetium-99m tetrofosmin is a new myocardial imaging agent with improved handling and kinetic characteristics. The purpose of this study was to compare the ability of planar and SPECT Tc-99m tetrofosmin imaging with Thallium-201 planar data to detect coronary artery disease and individual vessel lesions ( > 50% diameter stenosis). Seventy-two patients with definite or suspected coronary artery disease were included. Sixty-three had angiographic evidence of coronary artery disease, among whom 42 had had a previous myocardial infarction, while 21 had not. The total number of diseased arteries was 111. Patients underwent symptom-limited treadmill or bicycle exercise to similar endpoints. Thallium and tetrofosmin images were analysed separately by consensus reading. Interpretation was made for five standard anatomical regions (anterior, septal, inferior, lateral and apex), classified into four categories (normal, reversible, fixed and mixed defects). Sensitivity and specificity to detect coronary artery disease were 71% and 78% for Thallium-201 vs 68% and 78% for tetrofosmin by planar imaging, and 87% and 89% for tetrofosmin by SPECT. The improved sensitivity of SPECT was confirmed both in patients with and without previous myocardial infarction. The sensitivity to detect individual vessel lesions was improved by SPECT (59% tetrofosmin SPECT vs 50% thallium planar and 51% tetrofosmin planar). Individual vessel lesion detection by SPECT was 50% for the left anterior descending coronary artery, 42% for the left circumflex and 86% for the right coronary artery. This study confirms the value of technetium-99m tetrofosmin as a myocardial imaging agent. Improvements in diagnosis and in evaluating extent of disease can be expected from using SPECT.
This double-blind, placebo-controlled, parallel-group, multicenter study was designed to evaluate the safety and efficacy of a new controlled-onset, extended-release formulation of verapamil hydrochloride called physiologic pattern release (PPR) verapamil. The study was conducted at 24 sites (13 United States, 5 Canada, 6 overseas; see Appendix). Following a 1- to 3-week single-blind placebo lead-in period, 278 patients with chronic stable angina pectoris (247 males, 31 females, mean age 60.8 years, range 32 to 78) were randomly assigned to 1 of 4 once-daily, fixed-dose treatment groups: verapamil 180, 360, or 540 mg, or placebo. PPR verapamil at all doses significantly increased (p < 0.05) time to moderate angina and symptom-limited exercise duration, and verapamil 360 mg significantly increased (p < 0.05) time to > or = 1 mm ST-segment depression, after 4 weeks of treatment when assessed 24 hour after the previous dose. Larger doses of verapamil were associated with proportionately greater improvements in exercise tolerance. Frequency of anginal attacks was also reduced by verapamil. The most frequently observed adverse events were dizziness, headache, constipation, and nausea. The incidence of constipation was high (20.9%) within the 540 mg treatment group. This verapamil formulation can be clinically titrated within a 180 to 540 mg dosing range, permitting effective once-daily administration for the treatment of chronic stable angina.
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The platelet glycoprotein (GP) IIb/IIIa receptor can bind fibrinogen, von Willebrand factor, and other adhesive ligands; this binding is the final common pathway mediating platelet aggregation. The purpose of this study was to evaluate the safety and platelet inhibitory characteristics of the Fab fragment of the murine monoclonal anti-GPII/IIIa 7E3 antibody (m7E3 Fab) when administered intravenously as a single bolus dose, as a single and repeat bolus dose, and as a single bolus dose followed by continuous infusions of varying duration. Various dosage regimens of m7E3 Fab were studied in 74 patients with stable angina. Dosage regimens included single doses of m7E3 Fab from 0.1 to 0.3 mg/kg, a single dose of 0.20-0.30 mg/kg, and a repeat dose of 0.05 mg/kg, or a loading dose followed by a continuous infusion of m7E3 Fab for up to 36 hours. To assess the effect of m7E3 Fab on platelet function, quantitative blockade of GPIIb/IIIa receptors, inhibition of ex vivo platelet aggregation, and template bleeding time were measured in all patients. Dose-dependent inhibition of platelet function was evident in response to escalating bolus doses of m7E3 Fab, with maximum inhibition observed at 0.25-0.30 mg/kg body weight; at the 0.30 mg/kg dose, mean (+/- SE) GPIIb/IIIa receptor blockade was 81 +/- 3%, ex vivo platelet aggregation in response to 20 microM ADP was 14 +/- 6% of baseline, and the median bleeding time was > 20 minutes. Although platelet function gradually recovered following a single bolus injection, platelet inhibition could be sustained by continuous, low-dose infusion of the antibody. Platelet inhibition occurred within minutes, but m7E3 Fab that did not bind to platelets cleared rapidly from circulation. Sixteen percent of the m7E3 Fab-injected subjects exhibited low titer, human anti-murine antibody responses. No significant bleeding or allergic reactions were observed in any patients. One of the 74 patients developed transient thrombocytopenia soon after receiving m7E3 Fab. These studies establish that m7E3 Fab can be administered safely at doses that cause profound inhibition of platelet function.
OBJECTIVES: We sought to assess the ability of the "biphasic" response (i.e., initial improvement in wall thickening followed by reduced wall thickening) during serial dobutamine stress echocardiography to detect ischemia in patients with a wall motion abnormality. Furthermore, we compared the power of the biphasic echocardiographic response with that of myocardial perfusion imaging for the detection of myocardial ischemia. BACKGROUND: Stress echocardiography has been shown to be less sensitive than radionuclide perfusion imaging for detecting ischemia in patients with a wall motion abnormality. Peak stress wall thickening in such areas may not give a full account of the intermediate changes, whereas initial improvement (the biphasic response) may enhance diagnosis. METHODS: Patients with a wall motion abnormality and documented coronary artery disease underwent simultaneous graded dobutamine (5 to 40 micrograms/kg body weight per min) stress echocardiography and radionuclide perfusion imaging with single-photon emission computed tomography using either technetium-99m sestamibi or technetium-99m tetrofosmin. Semiquantitative analyses of image groups were performed in blinded manner by two separate groups of observers. RESULTS: Myocardial ischemia was detected by perfusion imaging in 45 of the 54 patients. High dose dobutamine echocardiography detected ischemia in only 25 (56%) of these patients. However, when the biphasic response was taken into account, ischemia was detected in 44 (98%) of the 45 patients (p < 0.001). Agreement between radionuclide imaging and echocardiographic findings for the detection of ischemia was significantly enhanced (p = 0.03) when the biphasic response was used (89%, kappa = 0.51) instead of high dose stress dobutamine echocardiography (56%, kappa = 0.10). CONCLUSIONS: The detection of myocardial ischemia may be significantly enhanced by utilizing the biphasic response during serial stress dobutamine echocardiography in patients with a wall motion abnormality.
OBJECTIVES: To evaluate the concordance between thallium-201 uptake and echocardiographic wall thickening, which are both indicators of potentially reversible myocardial dysfunction, in patients with chronic ischaemic left ventricular failure and to assess their relative contribution to predicting improvement in regional function after revascularisation in a subgroup. PATIENTS AND METHODS: 45 patients with chronic ischaemic left ventricular dysfunction (mean (SD) ejection fraction 25 (8)%) underwent echocardiography before and after dobutamine infusion (10 micrograms/kg/min). Of these, 22 patients underwent rest echocardiography at a mean (SD) of 9 (1) weeks after revascularisation. 201Tl imaging was performed during dobutamine echocardiography and at rest, 1, and 4 h after treatment with sublingual glyceryl trinitrate on two separate days. Potentially reversible dysfunction was thought to be present when a myocardial segment contained a Tl score of > or = 3 (ascending score 1-4), or showed improved wall thickening of a dysynergic segment during dobutamine stimulation. RESULTS: Of the 201Tl protocols, the redistribution scan 1 h after treatment with glyceryl trinitrate best demonstrated myocardial viability. Concordance between 201Tl and dobutamine induced wall thickening was 82% (kappa = 0.59) for detecting potentially reversible myocardial dysfunction before revascularisation (n = 45). Regional function improved in 18 of 22 patients after revascularisation. There were 168 dysynergic segments before intervention. The sensitivity of echocardiography and 201Tl imaging for detecting "recoverable" or viable segments after revascularisation was 87% and 92% respectively and specificity was 82% and 78% respectively (P = NS). CONCLUSIONS: Dobutamine echocardiography and 201Tl imaging may be used to predict mechanical improvement in dysynergic segments after revascularisation in patients with chronic ischaemic left ventricular dysfunction.
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It has been well documented that it is not uncommon for a thallium-201 perfusion defect to develop or become more evident on delayed exercise thallium scintigraphic imaging, as compared with the initial image immediately following stress. The pathophysiology and clinical significance of the phenomenon are currently unclear. Literature on this subject is reviewed, and it is concluded that reverse redistribution of 201Tl in the post-myocardial infarction patient is indeed a "fact". In this context it represents a low-risk condition and may imply successful thrombolysis, patent infarct-related coronary artery, improved wall motion at the infarct site and retained myocardial viability in that segment.
The aim of the study was to evaluate the prevalence and clinical significance of reverse redistribution on thallium-201 imaging in post-myocardial infarction patients who have undergone thrombolytic therapy. Sixty-two patients aged 35-79 (mean 60) years with proven myocardial infarction who had undergone thrombolysis were studied 6 weeks post infarction. Standard stress and 4-h redistribution imaging was performed with 201Tl following treadmill exercise. Separate day rest injection of 201Tl was given after sublingual nitroglycerine; imaging was performed at 1 h. Planar images were acquired in three standard views and semiquantitative segmental analysis of the images was performed from the unprocessed images. All patients had radionuclide ventriculography for the assessment of left ventricular ejection fraction and wall motion abnormality. Thirty-three patients also had coronary angiography. 201Tl scintigraphy revealed fixed defects in 19 patients, reversible defects in 22, and reverse redistribution in 21. Those with reverse redistribution had a significantly higher exercise capacity (P < 0.01). Mean (SD) left ventricular ejection fraction was 46 (12)% for those with fixed defects, 47 (9)% for those with reversible defects and 45 (15)% for patients with reverse redistribution (P = NS). The regional wall motion abnormality score was 8 (5), 11.8 (2.2) and 14.2 (6) respectively in patients with reverse redistribution, redistribution alone and fixed defects. Regions with reverse redistribution revealed less regional wall motion abnormality compared to the other two groups (P < 0.01). Fifteen patients demonstrated significant 201Tl uptake in the region showing reverse redistribution, with rest injection of 201Tl following sublingual nitroglycerine, suggesting viable myocardium in that region.(ABSTRACT TRUNCATED AT 250 WORDS)
The aim of the study was to examine the efficacy of a new controlled release formulation of diltiazem administered in a twice-daily dose in patients with essential hypertension using 24 hour intra-arterial ambulatory blood pressure monitoring. Sixteen patients (2 female) of mean age 53 years with mild to moderate essential hypertension, defined as a supine resting diastolic cuff blood pressure > or = 95 mm Hg, were recruited to a sequential dose ranging study of controlled release (CR) diltiazem. After a six week run-in period without any anti-hypertensive medication, intraarterial blood pressure monitoring with 60 degrees tilt, isometric handgrip and bicycle exercise testing were performed. Patients were then treated for one week with CR diltiazem 120 mg b.i.d. If supine resting diastolic cuff blood pressure fell by < 10 mm Hg compared to the last run-in value and remained > 90 mm Hg, the dose was increased to 240 mg b.i.d. for a week, and if necessary to 360 mg b.i.d. for a week. Patients continued for further one month on the dose of CR diltiazem at which they achieved target blood pressure reduction. At the end of this maintenance treatment, 24 hour intra-arterial blood pressure monitoring was repeated. Twelve patients were satisfactorily controlled on 120 mg b.i.d. CR diltiazem, three on 240 mg twice daily and one on 360 mg twice daily. During rest and exercise, blood pressure and heart rate were significantly lower after treatment with CR diltiazem than before treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
The relative value of exercise electrocardiography, simultaneous dobutamine technetium 99m-sestamibi (MIBI) single-photon-emission computerized tomography (SPECT), and echocardiography were evaluated for the diagnosis of coronary artery disease in patients with chest pain. Sixty-one consecutive patients underwent exercise electrocardiography and simultaneous graded dobutamine echocardiography and MIBI imaging. All patients underwent coronary arteriography. The exercise electrocardiogram was found to be a poor predictor of coronary artery disease (p not significant). Individually, MIBI SPECT and echocardiography were significantly predictive of coronary artery disease (p < 0.001). According to logistic regression analysis, the combined imaging modalities significantly increased the prediction of coronary artery disease for any vessel (p < 0.001), for multiple vessels (p < 0.001), and for the left anterior descending (p < 0.001), for right coronary artery (p < 0.001), and for left circumflex arteries (p < 0.01), compared with either MIBI SPECT or echocardiography alone. The results suggest a synergism in the detection of coronary artery disease when MIBI SPECT and echocardiography are combined during dobutamine stress.