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Biomedical subjects

A Lahiri

Publications and source records attributed to A Lahiri.

At least 145 records · Page 8Linked to original sources

Effect of supercoiling on the melting characteristics of heteropolynucleotides.

Considering a supercoiled DNA molecule, having equal numbers of two distinct types of base-pairs, it has been shown theoretically that even for the extreme cases of mixing of the two types of base-pairs in a supercoiled DNA, the melting temperatures as well as the melting curves do not differ significantly. This indicates that these properties are practically independent of the detailed base sequence when the molecule is a covalently closed one and may be replaced by an equivalent homopolynucleotide whose binding energy is equal to the average base-pairing energy of the original DNA. This conclusion has been further supported by comparing the theoretical results with those obtained experimentally in the cases of polyoma DNA and phi X174 DNA. Finally, the effects of supercoiling on the cooperativity of melting and a few aspects of the differential melting characteristics of a supercoiled DNA have been discussed which provide a clear physical understanding of the process.

Chemical Phenomena↗

Prolonged hypotensive effect of OPC-13340: a new, once-daily calcium channel blocking drug.

The duration and magnitude of the hypotensive effect of a new, once daily dihydropyridine calcium channel blocking drug, OPC-13340, was assessed in 14 patients with essential hypertension during normal daily activities and programmed exercise testing. Intra-arterial ambulatory blood pressure (BP) monitoring was performed before and after one month's treatment. Mean reduction in day-time BP was 27/14 mmHg and night-time BP 18/11 mmHg (P less than 0.001 and 0.05 respectively). There was no change in heart rate throughout the 24 h. Satisfactory day-time control of systolic and diastolic BP using the drug as monotherapy was achieved in 58% and 88% of patients respectively, although adequate control of nocturnal systolic and diastolic BP occurred in only 54% and 50% of patients respectively. No postural hypotension occurred during tilt testing, and there was a significant reduction in the peak BP observed during both dynamic and isometric exercise. Side effects were mild and transient. Thus OPC-13340, given once daily, is an effective and well tolerated anti-hypertensive drug, with a prolonged 24-h action.

Adult↗

Circadian variation and blood pressure: response to rapid weight loss by hypocaloric hyponatraemic diet in obesity.

Ambulatory intra-arterial blood pressure was monitored in 15 obese hypertensive and 10 obese normotensive subjects weighing more than 30% of their ideal body weight. Measurements were taken before and after 1 month in hospital on a diet of 330kCal/day designed to ensure 34 g protein and 65 mmol sodium. Mean +/- s.d. body mass index in the whole group fell from 40.8 +/- 7.6 to 37.2 +/- 7.4 kg/m2 (P less than 0.0001). Daytime intra-arterial blood pressure fell from 176 +/- 19/102 +/- 14 to 162 +/- 16/95 +/- 14 mmHg (P less than 0.0005 and P less than 0.002) in the hypertensive group and from 141 +/- 15/82 +/- 5 to 131 +/- 13/79 +/- 4 mmHg (P less than 0.005 for systolic pressure) in the normotensive group. Circadian variation of systolic intra-arterial blood pressure comparing the mean daytime with the mean night-time blood pressure recordings showed a day-night difference of 27 +/- 10 mmHg in the normotensive group compared with 12 +/- 13 mmHg in the hypertensive group (P less than 0.01). This trend was reversed after weight loss, when the normotensive group showed a day-night difference of 20 +/- 13 mmHg compared with 18 +/- 17 mmHg in the hypertensive group. Thus, circadian variation of systolic intra-arterial blood pressure in the hypertensive group was significantly (P less than 0.01) reduced compared with the normotensive group prior to, but not after, weight loss. These data show that, in obese subjects, weight loss produced a significant reduction in ambulatory intra-arterial blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The effects of intravenous carvedilol, a new multiple action vasodilatory beta-blocker, in congestive heart failure.

Recent studies have shown that beta-blockers may be effective in the management of heart failure. However, negative inotropic effects of these agents may offset the beneficial properties of up-regulation of the beta-receptors and reduction in myocardial oxygen demand. Carvedilol is a new drug which possesses a balanced combination of vasodilatation and beta-blockade. Previous studies have shown that carvedilol may have beneficial effects on left ventricular function in patients with ischemic heart disease. We have performed a preliminary study to address the safety and acute effects of intravenous carvedilol in 17 patients with chronic congestive heart failure secondary to ischemic heart disease. Acute hemodynamic changes were monitored by right heart catheterization and arterial cannulation. Ejection fraction was also monitored by radionuclide ventriculography. Significant reductions in heart rate (79 +/- 14 to 72 +/- 12 beats/min, p less than 0.001) systolic and diastolic blood pressure (137 +/- 20/72 +/- 8 to 119 +/- 19/66 +/- 8 mm Hg, p less than 0.001 and p less than 0.01), systemic vascular resistance (1766 +/- 367 to 1518 +/- 377 dynes/s/cm-5/m2, p less than 0.001) and pulmonary artery wedge pressure (20 +/- 8 to 15 +/- 7 mm Hg, p less than 0.001) were observed. Ejection fraction increased significantly from 24 to 28% (p less than 0.001) but there was little change in cardiac index or stroke volume index. The peak changes occurred at 10 min and the effect on pulmonary wedge pressure was maintained up to 30 min. No adverse effects were noted. The improvements in left ventricular filling pressure and systolic function, and the reduction in sympathetic activity may combine to produce an important therapeutic advantage in congestive heart failure. Further studies with this interesting agent are recommended.

Adrenergic beta-Antagonists↗

Clinical validation of a miniature nuclear probe system for continuous on-line monitoring of cardiac function and ST-segment.

A new, miniature cesium iodide/photodiode nuclear probe (the "Cardioscint") has been developed for continuous on-line measurement of left ventricular function and the ST-segment. Ejection fraction (EF) measurements in 77 patients were compared with gated equilibrium radionuclide ventriculograms. The probe was positioned over the left ventricle by first using a blind positioning algorithm and then by using the gamma camera. Background was measured both manually and automatically. There was good correlation between probe (positioned blind) and gamma camera EF with both manual (r = 0.80, n = 65) and automatic (r = 0.78, n = 66) backgrounds. Use of the gamma camera did not significantly alter the results. Correlation between the probe stroke counts and thermodilution-derived stroke index during atrial pacing in six subjects was also satisfactory (r = 0.69, n = 102). Thus, the Cardioscint is able to provide a reliable estimate of EF and can track rapid changes in cardiac volumes.

Cardiac Pacing, Artificial↗

Value of carvedilol in congestive heart failure secondary to coronary artery disease.

Despite considerable interest in the use of beta-blocking agents in congestive heart failure (CHF), their clinical application is limited because of their negative inotropic effects. Beta blockers with vasodilating properties may have the advantage of overcoming this, however. Carvedilol, a beta-blocking agent with vasodilating properties, was evaluated in 17 patients with chronic CHF secondary to ischemic heart disease with a resting left ventricular ejection fraction less than or equal to 45%, who were being maintained on diuretics. Exercise testing, radionuclide ventriculography, and right-sided cardiac catheterization were performed and intraarterial blood pressure measured before and after 8 weeks of carvedilol therapy in a dosage of 12.5 to 50.0 mg twice a day. Twelve patients completed the study and 5 withdrew. Symptomatic and hemodynamic improvement was demonstrated in 11 of the 12 patients. Heart rate and intraarterial blood pressure were both reduced by chronic therapy. Mean +/- standard deviation exercise time improved from 4.3 +/- 1.6 to 7.1 +/- 2.7 minutes (p less than 0.0001), as did resting left ventricular ejection fraction, from 27 +/- 9 to 31 +/- 11% (p less than 0.02). Pulmonary arterial wedge pressure fell from 19 +/- 7 mm Hg to 12 +/- 5 mm Hg (p less than 0.001) and total systemic vascular resistance from 1,752 +/- 403 to 1,497 +/- 310 dynes/s/cm-5/m2 (p less than 0.02). Stroke volume index improved also, from 31 +/- 6 ml to 40 +/- 6 ml (p less than 0.0005). These hemodynamic changes were mediated partly by vasodilation, diminished myocardial oxygen demand and reduction of sympathetic overactivity in the failing heart. These data suggest that carvedilol may have beneficial effects in patients with chronic CHF secondary to coronary artery disease.

Administration, Oral↗

Comparison of nicorandil and atenolol in stable angina pectoris.

The efficacy of nicorandil was compared with atenolol in 37 patients with chronic stable angina using a randomized, placebo-controlled, parallel study design. After a single-blind placebo phase, patients were randomized to receive nicorandil or atenolol using a double-dummy technique. Patients took nicorandil 10 mg twice daily or atenolol 50 mg once daily for the first 3 weeks, and if no adverse effects were encountered they took nicorandil 20 mg twice daily or atenolol 100 mg once daily, for the final 3-week phase. Treadmill exercise tests were performed at the end of each treatment phase immediately before and 2 hours after the morning dose of medication. Groups were demographically similar. Placebo exercise times were 7.06 (0.60) minutes (mean +/- standard error of the mean) in the nicorandil group and 6.81 (0.47) minutes in the atenolol group. After 6 weeks, improvements in exercise time were before dosing: +1.47 (0.40) minutes with nicorandil (p less than 0.005) and +1.33 (0.29) minutes with atenolol (p less than 0.001). Improvements after therapy was administered were +2.45 (0.41) minutes with nicorandil (p less than 0.001) and +2.37 (0.43) minutes with atenolol (p less than 0.0001). Whereas, the predose peak exercise double product (heart rate X systolic blood pressure mm Hg/100) was reduced with atenolol (-43.6 units; p less than 0.001), an increase (+7.56 units; difference not significant) was noted with nicorandil. One patient taking atenolol and 5 taking nicorandil developed persistent headaches. One subject with severe 3-vessel coronary artery disease had fatal myocardial infarction within 3 days of starting nicorandil, 10 mg twice daily.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗

Immunoscintigraphy for detecting acute myocardial infarction without electrocardiographic changes.

OBJECTIVE: To establish whether immunoscintigraphy with antibody to myosin may detect acute myocardial infarction without electrocardiographic changes. DESIGN: Prospective study of patients with suspected acute myocardial infarction or unstable angina with cardiac imaging with 111indium myosin antibody, estimation of cardiac enzyme concentrations, electrocardiography, 201thallium imaging, and radionuclide ventriculography. SETTING: Coronary care unit in a district general hospital. PATIENTS: 119 Consecutive patients with suspected acute myocardial infarction or unstable angina. Patients with cardiomyopathy, myocarditis, valvular heart disease, myocardial infarction or cardiac surgery in the previous two weeks or with left bundle branch block and women of childbearing age were excluded. RESULTS: Of 75 patients with suspected acute myocardial infarction, seven had no diagnostic electrocardiographic changes despite normal conduction patterns. Immunoscintigraphy with myosin antibody disclosed necrosis in all seven patients, which was localised in regions supplied by diseased coronary arteries in all but one. Six patients had abnormal images on 201thallium imaging, and all seven had abnormal wall motion at the site of antibody uptake. One patient with minimal left main stem and right coronary artery atheroma had uptake of antibody at two discrete sites. CONCLUSIONS: Immunoscintigraphy with antibody to myosin confirms myocardial infarction in the absence of electrocardiographic changes and discloses the site of infarction.

Adult↗

Clinical and prognostic significance of lung thallium uptake on rest imaging in acute myocardial infarction.

Exercise-induced pulmonary uptake of thallium-201 in patients with ischemic heart disease is probably due to transient pulmonary edema and left ventricular failure induced by exercise. The significance of increased lung uptake of thallium-201 at rest after acute myocardial infarction (AMI) has not been described. Ninety-six patients admitted with chest pain for suspected AMI or unstable angina underwent thallium-201 imaging at rest. Using conventional diagnostic criteria, 62 had AMI, 12 had unstable angina and 22 had neither. Increased lung uptake of thallium-201 was present in 24 of the total 96 (25%) patients, 20 of the 62 (32%) patients with AMI and 4 of 34 (13%) patients with no evidence of infarction. In the AMI group, those with increased lung thallium-201 uptake had a higher mean +/- standard deviation segmental thallium-201 defect score (22 +/- 7 vs 12 +/- 8, p less than 0.0001), lower ejection fraction (35 +/- 14 vs 49 +/- 14%, p less than 0.002), higher peak creatine kinase levels (2,410 +/- 1,247 vs 1,496 +/- 1,228 IU/liter, p less than 0.01), higher wall motion abnormality score (25 +/- 13 vs 13 +/- 12, p less than 0.0001), increased incidence of clinical in-hospital heart failure (15 of 20 vs 7 of 42, p less than 0.0001) and higher short-term mortality (4 of 20 vs 1 of 42, p less than 0.02) compared to those without increased lung thallium-201 uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina, Unstable↗

Ranolazine (RS-43285): a preliminary study of a new anti-anginal agent with selective effect on ischaemic myocardium.

Ranolazine (RS-43285) has been shown to possess significant anti-ischaemic properties in a canine model of reversible myocardial ischaemia. The clinical efficacy of this new agent was assessed by a single blind, placebo controlled study of 14 patients with chronic stable angina. A 2 week placebo phase was followed by therapy with 30 mg and 60 mg of ranolazine tid for 2 weeks each. Graded, symptom limited treadmill exercise tests were performed at the end of each phase, 1.5 h (AM) and 7 h (PM) after the morning dose. An additional exercise test 1.5 h after the first dose of 30 mg was included to assess the acute dose response. In the AM study, the mean exercise time increased from 6.9 min (placebo) to 7.8 min after the first dose of 30 mg and to 8.2 min and 8.5 min respectively at the end of 30 mg and 60 mg phases. In the PM study, exercise time improved from 6.5 min (placebo) to 8.2 min and 7.8 min respectively at the end of 30 mg and 60 mg phases. The time to onset of angina showed a similar improvement. No significant changes were observed in the resting and peak exercise heart rates and blood pressure. This preliminary study suggests that ranolazine may significantly prolong exercise time in patients with stable coronary artery disease without altering heart rates and blood pressure.

Acetanilides↗

Blood pool ventriculography with a new technetium-labelled complex (99mTc-DEPIC): a clinical evaluation.

A new, single bolus method of in vivo blood pool imaging using a technetium Tc99m phosphine isocyanide complex (DEPIC) which binds to pre-albumin was evaluated in volunteers (n = 4) and patients (n = 20). DEPIC was assessed for its safety and possible drug interactions. Its duration of action and quality of ventriculography were compared with imaging using standard in vivo red cell labelling (PYP) during two 3-h scanning periods 1 week apart. DEPIC had a mean plasma half-life of 3.3 h. The count rate over the left ventricle was initially 42% higher with DEPIC than with PYP. However, removal of DEPIC by the liver resulted in equivalent count rates by 1 h, and by 3 h PYP count rates were 22% higher than DEPIC. Immediately post injection mean (SD) difference in the left ventricular ejection fraction between the two methods was 2.4% (7.7%). Satisfactory DEPIC scans were obtained up to 2 h post injection, but by 3 h there was a mean difference of 13% (11.3%). DEPIC was found to be a safe alternative to red all labelling for blood pool angiography, suitable for routine work. The single bolus methodology and high initial count rates offer improved efficiency and a capability for truly emergency scanning.

Cyanates↗

Twenty-four hour ambulatory blood pressure profile of a new, sustained-release preparation of nicardipine.

The 24-hour blood pressure (BP) profile of a new sustained-release preparation of nicardipine was assessed in 16 patients with essential hypertension (supine cuff diastolic BP greater than 95 mmHg). Twenty-four hour ambulatory intraarterial BP monitoring (Oxford system) before treatment revealed a mean (SD) daytime BP of 174 (19) mmHg systolic and 105 (8) mmHg diastolic, and a mean nighttime BP of 142 (26) mmHg systolic and 83 (12) mmHg diastolic. Sustained release nicardipine (60 mg) was administered twice daily for 4-6 weeks and the ambulatory BP monitoring repeated. No significant change in heart rate occurred throughout the 24-hour period. However, there was a significant reduction (p less than 0.0001) in the mean daytime BP of 21 (13) mmHg systolic and 12 (9) mmHg diastolic and of mean nighttime BP of 21 (5) mmHg systolic and 13 (11) mmHg diastolic. A similar reduction in hourly mean BP occurred throughout the whole 24-hour period, including the steep early morning rise in BP. Although vasodilatory-type side effects occurred, they were generally mild to moderate and transient. This preparation produces a significant reduction in BP throughout the 24-hour period without reflex tachycardia.

Adult↗

Ambulatory intra-arterial blood pressure in normal subjects.

It has been suggested that ambulatory blood pressure monitoring is superior to casual cuff methods in predicting cardiovascular events, but lack of reference data from a normal population seriously limits this method's clinical applicability. We therefore performed 24-hour intra-arterial ambulatory blood pressure (BP) monitoring in 50 normal volunteers (cuff BP less than 140/90 mm Hg) whose ages ranged from 18 to 74 years. There were 30 men and 20 women in the study, but there was no significant difference between the sexes with respect to age, cuff BP, or body mass index. A diurnal variation in BP was observed, qualitatively similar to that seen in hypertensive individuals, including a prewaking BP rise. Mean daytime intra-arterial pressures differed little between the sexes (124/74 mm Hg for women and 127/76 mm Hg for men, p = NS), but was lower at night in women than in men (96/52 versus 102/59 mm Hg, respectively; p less than 0.02 for diastolic pressure). Based on this group of subjects, we defined the upper limit of normal daytime BP in both men and women as 150/90 mm Hg and the upper limit of mean nighttime BP as 130/80 mm Hg for men and 115/65 mm Hg for women. The lower nighttime pressures in women compared with their male counterparts with similar daytime pressures may explain why women appear to tolerate similar levels of BP better than men.

Adolescent↗

Assessment of right ventricular function with nonimaging first pass ventriculography and comparison of results with gamma camera studies.

A new technique has been developed for measuring right ventricular function by nonimaging first pass ventriculography. The right ventricular ejection fraction (RVEF) obtained by non-imaging first pass ventriculography was compared with that obtained by gamma camera first pass and equilibrium ventriculography. The data has demonstrated that the correlation of RVEFs obtained by the nonimaging nuclear cardiac probe and by gamma camera first pass ventriculography in 15 subjects was comparable (r = 0.93). There was also a good correlation between RVEFs obtained by the nonimaging nuclear probe and by equilibrium gated blood pool studies in 33 subjects (r = 0.89). RVEF was significantly reduced in 15 patients with right ventricular and/or inferior myocardial infarction compared to normal subjects (28 +/- 9% v. 45 +/- 9%). The data suggests that nonimaging probes may be used for assessing right ventricular function accurately.

Adult↗

111In-antimyosin antibody imaging for detection of myocardial infarction: a quantitative approach.

Indium-111-antimyosin imaging has been shown to be a sensitive and specific method for detecting myocardial necrosis, but a quantitative method for interpretation of 111In-antimyosin planar images is lacking. A prospective study was performed in 114 patients with suspected acute myocardial infarction using planar 111In-antimyosin imaging. A ratio of maximum myocardial uptake counts (H) (9 X 9 pixels) over adjacent lung background (L), i.e. H/L ratio, was obtained from 24 and 48 h images. This value was compared with peak creatine kinase (CK) enzyme and left ventricular ejection fraction (LVEF). The patients were classified into groups based upon standard criteria for Q-wave acute myocardial infarction (Q-MI) (n = 50), non-Q-MI (n = 21), unstable angina (n = 15) and those with no evidence of MI or ischaemia (n = 28). The mean +/- S.D. H/L ratio in the Q-MI group was 2.28 +/- 0.50 (24 h, left anterior oblique, LAO, view) and was greater than the non-Q-MI group (1.98 +2- 0.30) (P less than 0.02). In patients with unstable angina (UA), seven had a high ratio (1.75 +/- 0.29) and eight had a lower ratio (1.29 +/- 0.07). In the group of patients without MI or UA, the ratio was 1.24 +/- 0.11 and this was significantly lower than the Q-MI and non-Q-MI groups and those patients with UA and positive 111In uptake (P less than 0.001, respectively). However, there was no significant difference between old MI and patients without evidence of MI or UA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Indium-111-antimyosin images compared with triphenyl tetrazolium chloride staining in a patient six days after myocardial infarction.

The results of indium-111 (111In) antimyosin imaging during life and the findings on postmortem imaging and triphenyl tetrazolium chloride (TTC) staining of the heart are reported from a patient who received 111In-antimyosin on the sixth day following myocardial infarction and died after imaging the next day. The planar images obtained during life showed abnormal 111In-antimyosin uptake in the posterior, lateral, and apical walls of the left ventricle. Autopsy revealed extensive infarction of the left ventricular lateral and posterior walls with cardiac rupture, which was the cause of sudden death. Direct imaging of the sliced specimen of heart revealed abnormal tracer uptake in the lateral and posterior walls of the left ventricle, which correlated closely with the area of necrosis outlined by TTC staining. Our results confirm the experimental findings that antimyosin antibody binds specifically to the acute irreversibly damaged myocardial cells. A high degree of tracer uptake can be seen even when 111In-antimyosin is injected six days postinfarction.

Aged↗

Effects of long-term treatment with calcium antagonists on left ventricular diastolic function in stable angina and heart failure.

The appearance of impaired left ventricular diastolic function in chronic ischemic heart disease often precedes systolic dysfunction. Myocardial ischemia and increased calcium loading have been implicated in the genesis of increased left ventricular stiffness. We have assessed the effects of long-term therapy with different classes of calcium channel-blocking drugs on left ventricular peak filling rate in patients with chronic stable angina and congestive heart failure secondary to ischemic heart disease. Therapeutic effects of nicardipine (30 mg t.i.d.), nisoldipine (10 mg b.i.d.), and verapamil (120 mg t.i.d.) (4 weeks) have been assessed on radionuclide left ventricular diastolic filling parameters in patients with chronic stable angina using placebo-controlled studies. All three drugs significantly improved exercise capacity as compared with placebo. Verapamil produced significant improvements in peak filling rate (p less than 0.005), time to peak filling rate (p less than 0.01), and first one-third filling fraction (p less than 0.005), whereas nicardipine only improved peak filling rate (p less than 0.005); neither drug altered the mean ejection fraction (n = 20). Nisoldipine did not significantly alter diastolic filling parameters or ejection fraction (n = 10). Nisoldipine and digoxin were also assessed in congestive heart failure (New York Heart Association [NYHA] classes II and III) associated with ischemic heart disease (n = 26) (open parallel design). Neither produced significant alterations in peak filling rate and ejection fraction after 3 months of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗