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Biomedical subjects

B N Singh

Publications and source records attributed to B N Singh.

At least 19 recordsLinked to original sources
PubMed1992

Bepridil hydrochloride compared with placebo in patients with stable angina pectoris.

Bepridil is a calcium antagonist with a unique chemical composition and a long elimination half-life (42 hours). We evaluated the efficacy of bepridil 300 mg once/day in a crossover comparison with placebo in 45 patients with angina. Patients had an average of 7.6 anginal episodes/week during the placebo baseline phase of the trial. After 4 weeks of bepridil therapy, anginal frequency decreased to 2.9 episodes/week (p less than 0.05). Likewise, mean nitroglycerin consumption declined from 7.4 tablets/week during the placebo baseline phase to 4.0 tablets/week during bepridil therapy (p less than 0.05). Statistically significant increases over the previous period (placebo baseline or double-blind placebo) were seen in total exercise time, time to angina, and total work (p less than 0.05). During bepridil therapy, 13 of 45 patients (29%) no longer experienced angina as an exercise end point despite the increase in work and exercise time. Bepridil significantly prolonged both the QT and corrected QT (QTc) intervals; the mean increases were 10.0% and 5.6%, respectively. Side effects were reported with equal frequency in the placebo and bepridil arms of the trial, and no serious side effects were reported. In an intermediate fixed dose of 300 mg/day, bepridil relieved anginal symptoms with few side effects. Bepridil appears to be a safe and effective treatment for stable angina.

Analysis of Variance↗
PubMed1992

Safety profile of bepridil determined from clinical trials in chronic stable angina in the United States.

Bepridil is a unique calcium antagonist with a broad pharmacologic profile and demonstrated efficacy as an antianginal agent. Data from US clinical trials of bepridil in 840 patients (820 with chronic stable angina; 20 with vasospastic angina) indicated that the drug is well tolerated. The most frequent adverse reactions were of gastrointestinal or neurologic origin. Although bepridil has negative inotropic potential, a contributory role of the drug could not be precisely determined in 24 cases of congestive heart failure. Bepridil (median dose, 300 mg/day) lengthened the corrected QT (QTc) interval in most patients. The mean increase was 7.7%. Torsades de pointes occurred in 7 patients, an incidence of approximately 1%. Prolonged QT/QTc interval, low serum potassium level, or use of a potassium-wasting diuretic was present in each case. A life-table analysis involving 712 patients showed a 1-year overall survival rate of 97.1%. A 1-year survival rate of 97% was also determined by comparing 652 bepridil-treated patients with 1,361 matched control subjects from a data base of greater than 10,000 patients referred to the Duke University Medical Center for cardiac catheterization. Based on US clinical trials, the overall safety results indicate an acceptable safety profile of bepridil when this calcium antagonist is used in the treatment of chronic stable angina.

Adult↗
PubMed1992

Bepridil therapy: guidelines for patient selection and monitoring of therapy.

Bepridil is a calcium antagonist with a unique electrophysiologic profile, a long elimination half-life, and demonstrated efficacy as an antianginal agent in the setting of chronic stable angina. It is well tolerated, with relatively mild gastrointestinal and neurologic side effects. A major safety concern with bepridil is the occurrence of ventricular arrhythmias, especially torsades de pointes associated with QT interval prolongation, particularly in the context of hypokalemia with concomitant diuretic therapy. An appreciation of the electrophysiologic profile of this compound and the setting in which potentially serious proarrhythmic actions occur allows the identification of patients in whom the drug should be avoided. Among the exclusionary criteria are hypokalemia or risk of hypokalemia, baseline corrected QT interval greater than 0.44 sec, history of serious ventricular arrhythmias requiring treatment with major antiarrhythmic compounds, and concomitant use of other drugs that prolong the QT interval. Appropriate use of this effective antianginal agent requires a knowledge of its electrophysiology and adherence to patient selection and monitoring guidelines.

Arrhythmias, Cardiac↗
PubMed1992

Attenuation of the circadian patterns of myocardial ischemia with nifedipine GITS in patients with chronic stable angina. N-CAP Study Group.

The Nifedipine Gastro-Intestinal Therapeutic System (GITS) Circadian Anti-ischemia Program (N-CAP) was designed to test the effect of nifedipine GITS as monotherapy or in combination with a beta-adrenergic blocking agent on the circadian pattern of angina and silent ischemia in patients with chronic stable angina. At 118 sites in the United States, 1,174 patients were screened for entry into this study. To be eligible for participation patients were required to have at least two episodes of angina a week and at least two episodes of myocardial ischemia during 48-h ambulatory electrocardiographic (ECG) monitoring during the baseline placebo period. A total of 207 patients completed all phases of the study. Beta-blockers were continued in those patients already receiving them. In this 7- to 10-week single-blind placebo withdrawal study, a 1-week placebo run-in was followed by up to 5 weeks of single-blind titration with nifedipine GITS, a 4-week efficacy phase with an established dose and a final single-blind 2-week placebo withdrawal period. Ambulatory ECG monitoring was performed at the end of each placebo phase and at the end of the efficacy phase with a digital monitoring device that was validated in a pilot study. Overall, nifedipine GITS significantly reduced the weekly number of anginal episodes from 5.7 to 1.8 (p = 0.0001) and the number of ischemic events from 7.3 to 4 (p = 0.0001) reported during the 48-h monitoring periods, with a significant increase in both during the placebo withdrawal period. The baseline circadian pattern of ischemia showed an early morning peak and a secondary peak in the afternoon. Nifedipine GITS significantly reduced ischemia during the 48-h period when administered as monotherapy or in combination with a beta-blocker. Patients were also randomized to receive nifedipine GITS in either a morning or an evening dose. The two regimens resulted in equal anti-ischemic benefit. The primary side effect of nifedipine GITS was edema, which was dose related. In summary, nifedipine GITS reduced the number of anginal and ischemic episodes when given alone or in combination with a beta-blocker. Nifedipine GITS had a sustained effect: a single daily dose was effective over 24 h regardless of whether it was administered in the morning or evening. This study also suggests that combination therapy with nifedipine GITS and a beta-blocker is especially efficacious in reducing ischemia.

Adrenergic beta-Antagonists↗
PubMed1992

Electrophysiologic effects of ambasilide (LU 47110), a novel class III antiarrhythmic agent, on the properties of isolated rabbit and canine cardiac muscle.

Electrophysiologic effects of ambasilide in canine isolated cardiac muscle driven at 1 Hz and in rabbit sinoatrial (SA) node preparations were determined by standard microelectrode technique. Ambasilide (10(-7)-10(-5) M) produced concentration-dependent increases in action potential duration measured at -80 mV (APD-80) repolarization time in canine ventricular muscle and in Purkinje fibers. APD measured at -20 mV (APD-20) was also increased in ventricular muscle, but it shortened with 10(-5) M in Purkinje fibers; at this concentration, there was a negligible change in the amplitude and the maximum upstroke velocity (Vmax) of action potentials and in the resting membrane potential. With the stimulation frequency between 30/min and 120/min, ambasilide (10(-5) M) produced a parallel increase in APD-80 as well as in APD-20 of ventricular muscle. In Purkinje fibers, the prolonging effect of ambasilide on APD-80 was more pronounced at lower stimulation frequency, whereas APD-20 shortened at all stimulation frequencies. Ambasilide at 10(-5) M also produced a prolongation of the effective refractory period (ERP) in Purkinje fibers. The drug produced no significant change in the frequency-dependent relationship between ERP and APD-80. A small but significant frequency-dependent inhibition of Vmax was noted in both ventricular muscle and Purkinje fibers. When the stimulus cycle length was reduced from 1,000 to 300 ms, Vmax in ventricular muscle decreased by 8.4 +/- 3.4% in control solution but by 22.6 +/- 5.6% after 10(-5) M ambasilide (n = 8, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Aminobenzoates↗
PubMed1992

Antiarrhythmic actions of DL-sotalol in ventricular and supraventricular arrhythmias.

DL-Sotalol is a unique antiarrhythmic agent combining potent beta-blocking properties with the propensity to prolong cardiac repolarization in all myocardial tissues. Its beta-blocker-associated negative inotropic effects are attenuated by its action potential-lengthening effect. The drug has an elimination half-life of 10-15 h. Sotalol's major electrophysiologic profile constitutes the summed effects of beta-blockade and prolonged repolarization. It exerts a potent antifibrillatory action modulated by its antiadrenergic effects. The effectiveness and tolerance of sotalol in a variety of atrial and ventricular dysrhythmias is reviewed in the present article.

Animals↗
PubMed1992

Effect of ambasilide, a new class III agent, on plateau currents in isolated guinea pig ventricular myocytes: block of delayed outward potassium current.

The actions of ambasilide (LU-47110) on the action potential and membrane currents of isolated guinea pig ventricular myocytes were studied using voltage clamp techniques. Ambasilide (1 microM) prolonged the action potential (APD) at 20, 50 and 90% repolarization by 11.2 +/- 4.3, 13.8 +/- 3.9 and 13.6 +/- 3.7%, respectively, compared to control (n = 10). APD prolongation was attributed to the block of delayed rectifier outward current (Ik) in a concentration-dependent fashion (0.01-10 microM). The effects on the APD and Ik were both partially reversed after perfusion with drug-free Tyrode's solution. The block of Ik by ambasilide was compared to that by E-4031 (5 microM), a putative selective blocker of that fast, inwardly rectifying component of Ik identified in guinea pig ventricle. E-4031 produced about 65% block of Ik for pulse durations between 80 and 420 msec, but the block decreased as the pulse duration increased further, the block accounting for 34 +/- 5% of Ik at 6.3 sec. In contrast, the percentage of reduction of Ik by 10 microM ambasilide did not produce a consistent magnitude of block over a similar range of short depolarizations, but rather progressively decreased Ik as the pusle duration lengthened. Block at the end of a 2-sec pulse was about 48 +/- 8%, more block than could be attributed to an E-4031-sensitive current block alone. Whereas E-4031 (5 microM) shifted the activation curve of Ik 10 mV toward positive potentials and decreased the slope factor, k, by about 4 mV, ambasilide (5 microM) had no effect on these parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1992

Intraspecific sexual isolation in Drosophila.

Intraspecific sexual isolation was examined among wild strains of Drosophila malerkotliana, D. parabipectinata and D. pseudoananassae by multiple-choice method in Elens-Wattiaux mating chamber. In D. pseudoananassae, mating between two strains tested was random and isolation estimate was close to one. In one out of 6 crosses, involving geographic strains of D. malerkotliana, there was significant deviation from randomness and isolation estimate remained low which shows non-random (preferential or positive assortative) mating. In D. parabipectinata, the deviation from randomness was statistically significant due to higher number of homogamic matings in three crosses involving wild strains derived from geographically distant places and isolation estimate remained low in these crosses. The results provide evidence for incipient sexual isolation within D. malerkotliana and D. parabipectinata as a result of genetic divergence.

Animals↗
PubMed1992

Effect of directional selection on spontaneous male recombination in Drosophila ananassae.

Artificial selection was carried out for high and low spontaneous male recombination values in D. ananassae for nine generations by using cu b se marker (second chromosome) and wild stocks which were free from heterozygous chromosome inversions. The mean crossing-over frequency of nine generations was 2.22, 0.70 and 1.20% in high, low and control lines respectively. The values of regression coefficient and realized heritability also indicated that male recombination was affected by selection. However, response to selection was more pronounced in high line as compared to low line. This provides evidence that spontaneous male crossing-over in D. ananassae is under polygenic control.

Animals↗
PubMed1991

Comparative efficacy and safety of bepridil and diltiazem in chronic stable angina pectoris refractory to diltiazem. The Bepridil Collaborative Study Group.

The efficacy and safety of bepridil hydrochloride (200 to 400 mg/day) were evaluated in patients with chronic stable angina refractory to maximal tolerated doses of diltiazem (median 360 mg/day) in a randomized, multicenter, double-blind, parallel study. Baseline diltiazem data were obtained during a 2-week period, after which 86 patients were randomized to bepridil (n = 46) or diltiazem (n = 40). Angina frequency, nitroglycerin consumption and ischemic manifestations induced by exercise treadmill testing were evaluated over 8 weeks. Bepridil significantly (p less than 0.05) increased time to angina onset, time to 1 and 2 mm of ST-segment depression, total exercise time and total work over baseline values. Changes in time to angina onset and time to 1 mm of ST-segment depression were significantly (p less than 0.05) greater for bepridil than for diltiazem. Angina frequency and nitroglycerin consumption did not differ significantly between groups. Compared with baseline, bepridil significantly (p less than 0.001) decreased heart rate (mean 4 beats/min) and prolonged QTc (mean 35 ms). The most frequent adverse effects in both groups were nausea, asthenia, dizziness, headache and diarrhea. Four patients taking bepridil and 1 taking diltiazem withdrew from the study because of adverse reactions. No sudden deaths, myocardial infarctions or instances of sustained ventricular tachycardia or torsades de pointes occurred in either group. The data indicate that bepridil provided safe and effective antianginal and antiischemic therapy in patients with chronic stable angina who exhibited less than optimal response to maximal tolerated doses of diltiazem.

Adult↗
PubMed1991

Structures of glycophosphosphingolipids of Tritrichomonas foetus: a novel glycophosphosphingolipid.

The glycophosphosphingolipids of Tritrichomonas foetus, an aerotolerant parasite of the urogenital tract of cattle, have been characterized by a combination of metabolic labeling, chromatography, and tandem mass spectrometry. The acidic glycolipid fraction of T. foetus obtained by DEAE Sephadex A-25 column chromatography was subfractionated by high performance thin layer chromatography and the component lipids were purified by high performance liquid chromatography. Two nonsaponifiable lipid fractions, designated TF1 and TF2, could be metabolically labeled with [3H]myoinositol and [32P]orthophosphate. [3H]Fucose and [14C]ethanolamine were preferentially incorporated into the TF1 fraction. TF1 was partially hydrolyzed by alpha-fucosidase. Both TF1 and TF2 contain ceramides, the most abundant having either sphinganine or sphingosine and a 16:0 N-acyl group. TF2 contains inositolphosphoceramides. TF1, on the other hand, contains three closely related components, in each of which fucose is linked to inositol diphosphate with one of the phosphates linked to the ceramide moiety and the other phosphate either free or linked to ethanolamine or N-acetylethanolamine. TF1 appears to be a novel class of glycophosphosphingolipid which shows some structural similarities to the glycosylphosphatidylinositol anchors of eukaryotic membrane proteins.

Animals↗
PubMed1991

Synthesis, characterization, and antitumor activity of 5-iodouracil complexes.

Complexes of 5-iodouracil (5IU) with Mn(II), Co(II), Cu(II), Zn(II), and Cd(II) ions have been prepared, characterized, and subjected to a screening system for evaluation of antitumor activity against Sarcoma-180 (S-180) and L 929 tumor cells. The complexes were characterized by their elemental analysis, infrared spectra, electronic spectra, magnetic measurements, and powder x-ray diffraction. The antitumor activity results indicate that some complexes have good antitumor activity both in vivo and in vitro against S-180 and L 929 tumor cells.

Animals↗
PubMed1991

Phospholipid metabolism of cultured Trichomonas vaginalis and Tritrichomonas foetus.

Trichomonas vaginalis and Tritrichomonas foetus grown in a fetal calf serum-based culture medium were exposed to radiolabeled phospholipids and lipid precursors to determine the extent to which these organisms can incorporate complex lipids and/or de novo synthesize their major membrane phosphoglycerides. Phosphatidylethanolamine and phosphatidylcholine were the dominant phospholipids (40-50% of extractable phospholipids), with acidic lipids, phosphatidylinositol, phosphatidylserine, phosphatidylglycerol and O-acylphosphatidylglycerol accounting for the remaining phosphoglycerides. T. vaginalis was rich in sphingomyelin while T. foetus lacks significant amounts of this lipid. Incubation with [32P]orthophosphate resulted in only modest incorporation into extractable phospholipids; the most striking observation being the failure to label choline-containing lipids (phosphatidylcholine, lysophosphatidylcholine and sphingomyelin). Phosphatidylethanolamine was heavily labeled with modest labeling observed in the acidic phosphoglycerides. [U-14C]Glucose failed to label choline-containing lipids in T. foetus but did so in T. vaginalis, with phosphatidylethanolamine again being heavily labeled. Choline, phosphorylcholine, ethanolamine, serine, inositol, glycerol and methionine were incorporated poorly or failed to label the expected phosphoglycerides in either of the trichomonads, demonstrating an impairment in synthesis. Intact phosphoglycerides, labeled in the fatty acyl groups, labeled most phospholipids indicating that turnover of membrane lipids can occur with respect to the acyl component of the phospholipids. Fluorescent probes attached to phosphoglyceride molecules support observations seen with radiolabeled phosphoglycerides. Though trichomonads are able to transacylate phosphoglycerides, it is evident that the trichomonads lack a variety of enzymatic activities necessary for de novo synthesis of complex phosphoglycerides and must rely on environmental sources to supply them.

Animals↗
PubMed1991

Hypothyroidism renders protection against lethal ventricular arrhythmias in a conscious canine model of sudden death.

The protective effect of hypothyroidism against lethal ventricular tachyarrhythmias (VT) in the subacute phase of experimental myocardial infarction (MI) was investigated in 10 thyroidectomized dogs using a conscious model of sudden coronary death. Four weeks after surgical ablation of the thyroid, and having established biochemical hypothyroidism, anterior MI was produced by 120 min of occlusion-reperfusion of the left anterior descending coronary artery. In the subacute phase of MI, the inducibility of VT was investigated using programmed ventricular stimulation (PVS), and the effects on spontaneous development of ventricular fibrillation (VF) were studied by production of posterolateral ischemia at a site remote from the area of the previous infarction. Ischemia was produced by the passage of anodal direct current through a silver wire electrode implanted in the left circumflex coronary (LCX) artery. The results were compared to those from a cohort of 20 existing euthyroid controls that had undergone an identical experimental protocol. No differences were found in heart rate and other electrocardiographic parameters such as the PR, QRS, and QT (paced at 2.5 Hz) and the QTc interval between the hypo- and euthyroid groups. During PVS in the subacute phase of anterior MI, the measured threshold voltage and ventricular refractory periods were similar in both groups. The incidence of inducibility of VT was 100% in the euthyroid animals compared to 60% in the hypothyroid dogs, suggesting an antiarrhythmic effect of hypothyroidism. The incidence of sustained vs. nonsustained VT was similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Clinical electrophysiological effects of intravenous recainam: an antiarrhythmic drug under investigation for the treatment of ventricular and supraventricular arrhythmias.

This open-label, multicenter study was designed to assess the electrophysiological properties of intravenous recainam, an investigational Class I antiarrhythmic agent. In 25 patients undergoing electrophysiological studies for the evaluation of arrhythmias, recainam was administered intravenously in a loading infusion (0.1 mg/kg/min) for 40 minutes, followed by a maintenance infusion (0.02 mg/kg/min) until the completion of the study. Electrophysiological measurements were obtained at baseline, 30 minutes after initiation of the loading infusion, and 30 minutes after termination of the infusion during washout. Conduction intervals, refractory periods, and sinus node recovery times were measured during sinus rhythm and during atrial or ventricular pacing. Vital signs were obtained and recorded before, during, and after recainam infusion. The results showed no change in mean arterial pressure, but heart rate increased slightly by 4 beats/min following recainam infusion. Recainam produced a generalized slowing of intracardiac conduction. The mean intraatrial conduction time, measured at an atrial paced cycle length of 600 msec, increased during recainam loading infusion by 44%, from 38.8% +/- 2.8 to 53.0 +/- 5.4 msec; intranodal conduction time increased by 10%, from 102.0 +/- 5.5 to 112.1 +/- 5.2 msec; and infranodal conduction time increased by 31% from 53.1 +/- 3.0 to 70.7 +/- 3.8 msec. Slowed conduction persisted during washout. The mean right atrial effective refractory period was significantly prolonged (+7% at 600 msec cycle length and +8% at 450 msec cycle length, P less than 0.05 and P less than 0.01, respectively) during recainam loading and remained so during washout.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗