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Biomedical subjects

S N Singh

Publications and source records attributed to S N Singh.

At least 19 recordsLinked to original sources
PubMed1998

Prevalence and significance of nonsustained ventricular tachycardia in patients with premature ventricular contractions and heart failure treated with vasodilator therapy. Department of Veterans Affairs CHF STAT Investigators.

OBJECTIVES: This study sought to determine the prevalence and significance of nonsustained ventricular tachycardia (NSVT) in patients with premature ventricular contractions (PVCs) and heart failure treated with vasodilator therapy. BACKGROUND: Heart failure patients with ventricular arrhythmia and NSVT have a significantly increased risk of premature cardiac death. Recently there has been the question of whether these arrhythmias are expressions of a severely compromised ventricle or are they independent risk factors. We, therefore, determined the prevalence and significance of NSVT in patients with PVCs and heart failure and on vasodilator therapy. METHODS: Twenty-four hour ambulatory recordings were done at randomization, at 2 weeks, at months 1, 3, 6, 9 and 12 and then every 6 months in 674 patients with heart failure and on vasodilator therapy. The median period of follow-up was 45 months (range 0 to 54). RESULTS: Nonsustained ventricular tachycardia was present in 80% of all patients. Patients without (group 1) and with (group 2) NSVT were balanced for variables: age, etiology of heart disease, New York Heart Association (NYHA) functional class, use of amiodarone and diuretics and left ventricular diameter by echocardiogram. However, group 1 patients had significantly less beta-adrenergic blocking agent use and higher ejection fraction (EF) (p < 0.002 and p < 0.001, respectively). Survival analysis for all deaths showed a greater risk of death among group 2 patients (p=0.01). Similarly, sudden death was increased in group 2 patients (p=0.02, risk ratio 1.8). After adjusting for the above variables, only EF (p=0.001) and NYHA class (p=0.01) were shown to be independent predictors of survival. Nonsustained ventricular tachycardia showed a trend (p=0.07) as an independent predictor for all-cause mortality but not for sudden death. Only EF was an independent predictor for sudden death. CONCLUSIONS: Nonsustained ventricular tachycardia is frequently seen in patients with heart failure and may be associated with worsened survival by univariate analysis. However, after adjusting other variables, especially for EF, NSVT was not an independent predictor of all-cause mortality or sudden death. These results have serious implications in that suppression of these arrhythmias may not improve survival.

Aged↗
PubMed1998

Research-related burnout among faculty in higher education.

We investigated the effects of intrinsic motivation to do research and perceived lack of rewards contingent on doing research on burnout or disenchantment from research. Findings, based on a survey of 328 faculty at a major university, indicate that these two variables account for 74% and 81% of the variance in scores on a scale relating to burnout among 260 tenured and 68 untenured professors, respectively. The effect of perceived lack of rewards contingent on doing research on burnout was moderated by the tenure status.

Attitude↗
PubMed1997

Effects of amiodarone on the circadian pattern of sudden cardiac death (Department of Veterans Affairs Congestive Heart Failure-Survival Trial of Antiarrhythmic Therapy).

Some antiarrhythmic drugs have been shown to influence the circadian pattern of sudden cardiac death (SCD). The effect of chronic amiodarone therapy on this pattern is unknown. This study determines the circadian pattern of deaths in the Congestive Heart Failure-Survival Trial of Antiarrhythmic Therapy (CHF-STAT) and compares the distribution of SCD between the amiodarone and the placebo arms of the trial. CHF-STAT was a multicenter trial that determined whether amiodarone reduces mortality in patients with heart failure and asymptomatic ventricular arrhythmias. The time of death was retrospectively analyzed in patients who died from pump failure and SCD. In patients who died suddenly, the circadian pattern of deaths was compared between patients receiving amiodarone and those receiving placebo. In CHF-STAT, 274 patients died during follow-up. The time of death was available in 65 of the 74 patients who died from pump failure, and in 96 of the 139 patients who died suddenly. There was a circadian variation of all SCDs compared with other deaths with a distinct peak during the morning (p = 0.04). A similar morning peak of sudden cardiac death was found in both the amiodarone (n = 42) and the placebo (n = 54) groups, and the overall circadian pattern did not differ between them (p = 0.16). In contrast, death from pump failure occurred equally distributed over time. Thus, SCD occurs predominantly during the morning, whereas death from heart failure does not exhibit a morning peak. Amiodarone does not influence the circadian pattern of SCD.

Aged↗
PubMed1997

Intravenous dofetilide, a class III antiarrhythmic agent, for the termination of sustained atrial fibrillation or flutter. Intravenous Dofetilide Investigators.

OBJECTIVES: This study sought to determine the safety and efficacy of a single bolus of intravenous dofetilide, a pure class III antiarrhythmic agent, for the termination of sustained atrial fibrillation or flutter. BACKGROUND: Dofetilide is a highly selective blocker of the rapid component of the delayed rectifier current causing action potential prolongation. These effects, and preliminary clinical data, suggest that it may be effective in the treatment of atrial fibrillation and flutter. METHODS: Ninety-one patients with sustained atrial fibrillation (75 patients) or flutter (16 patients) were entered into a double-blind, randomized multicenter study of one of two doses of dofetilide (4 or 8 micrograms/kg body weight) or placebo. RESULTS: Dofetilide effectively terminated the arrhythmia in 31% of patients receiving 8 micrograms/kg, a statistically significant difference from those receiving 4 micrograms/kg (conversion rate 12.5%, p < 0.05) or placebo (no conversion, p < 0.01). Patients with atrial flutter had a greater response to dofetilide (54% conversion rate) than those with atrial fibrillation (14.5% conversion rate, p < 0.001). CONCLUSIONS: Intravenous dofetilide can convert sustained atrial fibrillation or flutter to sinus rhythm. However, its efficacy is greater in flutter--a response that contrasts with the poorer response seen with class I agents. This finding potentially represents an important advance in the pharmacologic termination of atrial flutter.

Anti-Arrhythmia Agents↗
PubMed1997

Pulmonary effect of amiodarone in patients with heart failure. The Congestive Heart Failure-Survival Trial of Antiarrhythmic Therapy (CHF-STAT) Investigators (Veterans Affairs Cooperative Study No. 320).

OBJECTIVES: The purpose of this study was to evaluate the pulmonary effects of amiodarone in patients with heart failure, in those with chronic obstructive pulmonary disease (COPD) and in those undergoing a surgical procedure. BACKGROUND: Amiodarone has been known to cause pulmonary complications; especially in those with COPD and in those undergoing a surgical procedure. METHODS: Patients receiving vasodilator therapy for congestive heart failure were prospectively randomized to placebo or amiodarone at 800 mg/day for 14 days, 400 mg/day for 50 weeks and then 300 mg/day thereafter. Chest X-ray film and pulmonary function tests with diffuse capacity of carbon monoxide (DLCO) were obtained at baseline and annually. The power to detect a 20% difference in DLCO at 1 year exceeded 90% in all patients and in those with COPD (two-sided alpha = 0.05). The sample allowed a 75% power to detect pulmonary complications (1% vs. 5%) between the two treatment groups. RESULTS: There was no difference in baseline characteristics between patients randomized to amiodarone (n = 269) or placebo (n = 250). The DLCO measurements at randomization were 18.3 +/- 6.9 and 17.7 +/- 7.6 ml/min per mm Hg for the amiodarone and placebo groups, respectively (p = 0.3). At 1 and 2 years, DLCO measurements were 17.7 +/- 7.0 and 18.3 +/- 7.7 ml/min per mm Hg for the amiodarone group and 17.9 +/- 7.2 and 18.2 +/- 7.2 for the placebo group, respectively. There were no significant differences between the groups, with corresponding p values of 0.73 ad 0.96 at years 1 and 2, respectively. Among patients with COPD, DLCO measurements at randomization were 17.9 +/- 6.7 and 15.8 +/- 6.8 ml/min per mm Hg for the amiodarone and placebo groups, respectively. At years 1 and 2, DLCO measurements were 16.6 +/- 7.8 and 17.8 +/- 9.5 ml/min per mm Hg for the amiodarone group and 16.5 +/- 6.6 and 16.3 +/- 7.0 ml/min per mm Hg for the placebo group, with corresponding p values of 0.95 and 0.48, respectively. There was no difference in survival free of noncardiac or perioperative deaths between patients assigned to amiodarone or placebo. Pulmonary fibrosis was diagnosed in four patients (1.1%) treated with amiodarone and in three patients (0.8%) receiving placebo. CONCLUSIONS: Our study shows that amiodarone can be safely used, with an acceptable pulmonary toxicity, in patients with heart failure.

Aged↗
PubMed1997

Antifilarial activity of a synthetic marine alkaloid, aplysinopsin (CDRI Compound 92/138).

CDRI Compound 92/138, a synthetic analogue of aplysinopsin, was evaluated in experimental filarial infections, Litomosoides carinii in cotton rats (Sigmodon hispidus) and Acanthocheilonema viteae in Mastomys coucha. The compound killed 63.8 and 90% of adult L. carinii and A. viteae at doses of 30 and 50 mg/kg (i.p.) respectively given for 5 days. By the oral route, at 100 mg/kg for 5 days the compound caused 50.9 and 57% mortality of adult L. carinii and A. viteae, respectively. At 200 mg/kg administered orally on days 0, 10 and 25 post-infection, it reduced establishment of adult A. viteae by 68.5%. We also found 43.7 and 37.8% effect in vivo respectively on L3 and L4 stages of A. viteae at a single dose of 250 mg/kg, p.o. The compound was active in vitro at 100 micrograms/ml concentration and caused a significant decline in MTT reduction and 14C-glucose uptake by adult filariids. Thus synthetic marine aplysinopsin could provide a new pharmacophore for the development of antifilarial agents.

Animals↗
PubMed1997

Congestive heart failure and arrhythmias: therapeutic modalities.

Congestive heart failure affects millions of Americans, and thousands of new cases are reported each year. The prognosis continues to be grim. Most deaths in heart failure patients can be attributed to low-output states (pump failure) and arrhythmias (sudden). Attempts have been made to decrease the incidence of pump failure deaths by using contractility agents that, in most cases, have been shown to be detrimental. The results of trials using beta blockers are encouraging. Vasodilators have made a positive impact on outcome. However, the use of pharmacologic antiarrhythmic agents to decrease sudden death has failed to improve survival. Studies with implantable devices are ongoing and will provide an answer to the question of whether a reduction in sudden death will translate into a reduction of all-cause mortality. Antiplatelet and antithrombotic agents appear to be favorable, and revascularization is recommended when feasible.

Anti-Arrhythmia Agents↗
PubMed1997

Safety and efficacy of monotherapy with fantofarone, a novel calcium channel antagonist, in patients with chronic stable angina pectoris. Fantofarone Study Group.

Fantofarone is a calcium channel antagonist of a class (sulfone indolizine) that is structurally different from the existing classes. The primary cardiac action of fantofarone is on the sinus node, although it is also a potent peripheral and coronary vasodilator. This is a multicenter, double-blind, randomized, placebo-controlled, dose-ranging study evaluating the efficacy and safety of fantofarone. Three hundred and thirty patients were included as intent-to-treat, and 299 patients completed the entire protocol. Doses of fantofarone studied were 50, 100, 150, and 200 mg twice daily. The 100- and 150-mg groups demonstrated antianginal activity, prolonging exercise time walking on a treadmill by 38 and 45 seconds to the endpoint of moderate angina, compared with the placebo group. Sinus bradycardia occurred in 23 patients and was somewhat dose-related. Systolic blood pressure at rest and while exercising was not altered by therapy. No deaths occurred in the treated group. Of the 20 patients in the treatment group who did not complete the protocol (compared with 23 in the placebo group) 6 were dropped because of symptomatic bradycardia, 5 because of increased angina, and 9 for miscellaneous reasons. In doses of 100 mg to 150 mg twice daily, monotherapy fantofarone was effective and safe in the treatment of patients with chronic, stable angina pectoris.

Adolescent↗
PubMed1996

Effect of amiodarone on clinical status and left ventricular function in patients with congestive heart failure. CHF-STAT Investigators.

BACKGROUND: Although trials of amiodarone therapy in patients with congestive heart failure have produced discordant results with regard to effects on survival, most studies have reported a significant rise in left ventricular ejection fraction during long-term therapy. In the present study, we determined whether this increase in ejection fraction is associated with an improvement in the symptoms and/or physical findings of heart failure or a reduction in the number of hospitalizations for heart failure. METHODS AND RESULTS: In the Department of Veterans Affairs cooperative study of amiodarone in congestive heart failure, 674 patients with New York Heart Association class II through IV symptoms and ejection fractions of < or = 40% were treated with amiodarone or placebo for a median of 45 months in a randomized, double-blind, placebo-controlled protocol. Clinical assessments and radionuclide ejection fraction were performed at baseline and after 6, 12, and 24 months. Compared with the placebo group, ejection fraction increased more in the amiodarone group at each time point (8.1 +/- 10.2% [mean +/- SD] versus 2.6 +/- 7.9% at 6 months, 8.0 +/- 10.9% versus 2.7 +/- 8.0% at 12 months, and 8.8 +/- 10.1% versus 1.9 +/- 9.4% after 24 months, all P < .001). However, this difference was not associated with greater clinical improvement, lesser diuretic requirements, or fewer hospitalizations for heart failure (11.1% for amiodarone and 13.6% for placebo group; overall relative risk in the amiodarone group, 0.81 [95% CI, 0.56 to 1.10], P = .18). Of note is the trend toward a reduction in the combined end point of hospitalizations and cardiac deaths (relative risk, 0.82 [CI, 0.65 to 1.03], P = .08), which was significant in patients with nonischemic etiology (relative risk, 0.56 [CI, 0.36 to 0.87], P = .01) and absent in the ischemic group (relative risk, 0.95). CONCLUSIONS: Although amiodarone therapy resulted in a substantial increase in left ventricular ejection fraction in patients with congestive heart failure, this was not associated with clinical benefit in the population as a whole. The substantial reduction in the combined end point of cardiac death plus hospitalizations for heart failure in the nonischemic group suggests possible benefit in these patients.

Aged↗
PubMed1995

Amiodarone in patients with congestive heart failure and asymptomatic ventricular arrhythmia. Survival Trial of Antiarrhythmic Therapy in Congestive Heart Failure.

BACKGROUND: Asymptomatic ventricular arrhythmias in patients with congestive heart failure are associated with increased rates of overall mortality and sudden death. Amiodarone is now used widely to prevent ventricular tachycardia and fibrillation. We conducted a trial to determine whether amiodarone can reduce overall mortality in patients with congestive heart failure and asymptomatic ventricular arrhythmias. METHODS: We used a double-blind, placebo-controlled protocol in which 674 patients with symptoms of congestive heart failure, cardiac enlargement, 10 or more premature ventricular contractions per hour, and a left ventricular ejection fraction of 40 percent or less were randomly assigned to receive amiodarone (336 patients) or placebo (338 patients). The primary end point was overall mortality, and the median follow-up was 45 months (range, 0 to 54). RESULTS: There was no significant difference in overall mortality between the two treatment groups (P = 0.6). The two-year actuarial survival rate was 69.4 percent (95 percent confidence interval, 64.2 to 74.6) for the patients in the amiodarone group and 70.8 percent (95 percent confidence interval, 65.7 to 75.9) for those in the placebo group. At two years, the rate of sudden death was 15 percent in the amiodarone group and 19 percent in the placebo group (P = 0.43). There was a trend toward a reduction in overall mortality among the patients with nonischemic cardiomyopathy who received amiodarone (P = 0.07). Amiodarone was significantly more effective in suppressing ventricular arrhythmias and increased the left ventricular ejection fraction by 42 percent at two years. CONCLUSIONS: Although amiodarone was effective in suppressing ventricular arrhythmias and improving ventricular function, it did not reduce the incidence of sudden death or prolong survival among patients with heart failure, except for a trend toward reduced mortality among those with nonischemic cardiomyopathy.

Actuarial Analysis↗
PubMed1994

A 53 kDa protein of Vibrio cholerae classical strain 0395 involved in intestinal colonization.

Mutants of Vibrio cholerae 01 strain 0395 (classical) mutated in genes encoding secretory or cell surface proteins were induced by TnphoA mutagenesis and were selected as blue colonies on L-agar plates containing 5-bromo-4-chloro-3-indolyl phosphate. Southern analysis of the total DNA from blue colonies showed that all mutants had TnphoA insertion in genomic DNA. These mutants were analysed for adherence, colonization and protein profile. Adherence to freshly isolated rabbit intestinal discs was affected in some mutants. The less adhesive mutants were examined for colonization of the intestine of infant mice. One mutant, designated T-87, was extremely poor at colonization and less diarrhaegenic than the parent strain. Analysis of T-87 by SDS-PAGE revealed that two proteins of 53 and 38 kDa were lacking. The 38 kDa protein was identified as OmpU. The 53 kDa protein was extracellular and cells treated with anti-53-kDa antibodies could not colonize the gut of infant mice. The expression of the 53 and 38 kDa proteins in T-87 was dependent of the growth medium. The data suggest that T-87 is mutated in a regulatory gene which regulates the expression of proteins involved in intestinal colonization.

Animals↗
PubMed1994

Activity of alpha-anilinobenzyl cyanides and 2-methoxycarbonylamino-1-phenylimidazoles, a new class of antifilarial agents.

The activity of alpha-anilinobenzyl cyanides (2a-f), 5-aryl-4,5-dihydro-2-methoxycarbonylamino-1-phenylimidazoles (5a-d) and 2-methoxycarbonylamino-1-phenyl-1,3-diazaspiro[4:5]dec-2-ene (5f) have been tested for their micro- and macrofilaricidal activity against Litomosoides carinii and Acanthocheilonema viteae in rodents. In this test alpha-anilinobenzyl cyanides (2a-b), 5-(4-methoxyphenyl)-4,5-dihydro-2-methoxy-carbonylamino-1-phenylim idazole (5b) and 2-methoxycarbonylamino-1-phenyl-1,3-diazaspiro[4:5]dec-2-ene (5f) were found to possess marked filaricidal activity at doses ranging from 3-100 mg/kg given parenterally or orally for 5 days.

Animals↗
PubMed1993

Veterans Affairs congestive heart failure antiarrhythmic trial. CHF STAT Investigators.

This is a prospective, double-blind, placebo-controlled trial to determine the effect of antiarrhythmic drug therapy on mortality in patients with congestive heart failure and ventricular arrhythmia. Patients will be assigned to receive either amiodarone or placebo. Eligible patients include those with ischemic and nonischemic congestive heart failure and with > or = 10 ventricular premature beats per hour. All patients must have shortness of breath with minimal exertion or paroxysmal nocturnal dyspnea, a left ventricular internal dimension (LVIDd) by echocardiogram of > or = 55 mm or a cardiothoracic ratio of > 0.5 and an ejection fraction of < or = 40%. All patients will receive vasodilator therapy, unless they find it intolerable. Patients will be entered into the study for 2.5 years and followed for an additional 2 years. Drug therapy will be continued for all patients throughout the entire study unless adverse reactions occur that necessitate individualized treatment. The expectation is that 674 patients will be entered into the study from 25 participating centers. This sample size will allow for the detection of a 33% decrease in 2-year mortality (20% vs 30%) in the treated patients compared with those in the placebo group, with a power of 0.90 and a 2-sided alpha level of 0.05. Intermittent Holter monitoring, radionuclide ventriculograms, pulmonary function tests, echocardiograms, and blood tests, including arterial blood gases, will be required for each patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiodarone↗