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Biomedical subjects

J L Anderson

Publications and source records attributed to J L Anderson.

At least 181 records · Page 10Linked to original sources
PubMed1991

Long-term (2 year) beneficial effects of beta-adrenergic blockade with bucindolol in patients with idiopathic dilated cardiomyopathy.

Beta-adrenergic blockade represents a promising therapeutic approach to idiopathic dilated cardiomyopathy. Bucindolol, a new beta-blocker, showed favorable effects in a short-term (3 month) trial in idiopathic dilated cardiomyopathy. To assess long-term response, 20 study patients (7 of 9 patients previously assigned to the placebo group and 13 of 14 patients previously assigned to bucindolol therapy) received long-term bucindolol therapy and were followed up for a mean of 23 +/- 4 months (range 17 to 30). The mean patient age was 49 years (range 29 to 66) and the median duration of disease was 11 months (range 1 to 190). Ten patients were in functional class II and 10 were in class III; 15 patients were men. At the end of the common follow-up time, all 20 patients were alive, 17 continued to receive bucindolol (mean dose 176 mg/day, range 25 to 200), and 2 underwent cardiac transplantation. Left ventricular ejection fraction increased from a baseline value of 25 +/- 8% to 35 +/- 13% (n = 19 pairs, p less than 0.001). Functional class improved in 12, was unchanged in 5 and deteriorated in 3 (p = 0.056). Exercise time was maintained (9.4 +/- 3.1 versus 9.1 +/- 3.5 min, n = 19, p = NS), as was maximal oxygen uptake (19.2 +/- 4.9 versus 18.8 +/- 5.7 ml/kg per min, n = 19, p = NS). Thus, long-term bucindolol therapy leads to substantial increases in ejection fraction and to improved functional class while stable exercise performance is maintained.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1991

Flecainide acetate prevents recurrence of symptomatic paroxysmal supraventricular tachycardia. The Flecainide Supraventricular Tachycardia Study Group.

Oral flecainide acetate was administered to 34 patients with documented symptomatic paroxysmal supraventricular tachycardia (PSVT) with a double-blind, placebo-controlled, 8-week crossover trial design. PSVT was defined as a regular tachycardia of at least 120 beats/min without evidence of atrioventricular dissociation. The study required considerable patient cooperation. Patients first entered a 4-week qualifying phase followed by a 3-week, open label, flecainide dose-ranging phase. They were then randomized in a blind fashion to receive either placebo or tolerated flecainide dose for an 8-week treatment period and then crossed over after four symptomatic documented episodes of PSVT or at the end of the treatment period. By all efficacy parameters analyzed, flecainide was superior to placebo. Flecainide was associated with an actuarial 79% freedom from symptomatic PSVT events compared with only 15% on placebo at 60 days (p less than 0.001). Of the 34 patients, 29 had recurrence of symptomatic PSVT at least once during the placebo phase; only eight patients had a recurrence during the flecainide phase (p less than 0.001). The median time to the first symptomatic PSVT event was 11 days in the placebo group and greater than 55 days in the flecainide group (p less than 0.001). Likewise, the interval between attacks was a median of 12 days on placebo compared with more than 55 days on flecainide (p less than 0.001). Finally, the flecainide slowed symptomatic PSVT heart rates to 143 +/- 12 beats/min from 178 +/- 12 on placebo (p less than 0.02) in the seven patients who had events in the placebo and flecainide treatment phases.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1991

Multicenter patency trial of intravenous anistreplase compared with streptokinase in acute myocardial infarction. The TEAM-2 Study Investigators.

Thrombolytic therapy has been shown to improve clinical outcome when administered early after the onset of symptoms of acute myocardial infarction; the mechanism of benefit is believed to be reestablishment and maintenance of coronary artery patency. Anistreplase is a second generation thrombolytic agent that is easily administered and has a long duration of action. To compare anistreplase (30 units/2-5 min) and therapy with the Food and Drug Administration-approved regimen of intravenous streptokinase (1.5 million units/60 min), a randomized, double-blind, multicenter patency trial was undertaken in 370 patients less than 76 years of age with electrocardiographic ST segment elevation who could be treated within 4 hours of symptom onset. Coronary patency was determined by reading, in a blinded fashion, angiograms obtained early (90-240 minutes; mean, 140 minutes) and later (18-48 hours; mean, 28 hours) after beginning therapy. Early total patency (defined as Thrombolysis in Myocardial Infarction grade 2 or 3 perfusion) was high after both anistreplase (132/183 = 72%) and streptokinase (129/176 = 73%) therapy, and overall patency patterns were similar, although patent arteries showed "complete" (grade 3) perfusion more often after anistreplase (83%) than streptokinase (72%) (p = 0.03). Similarly, residual coronary stenosis, determined quantitatively by a validated computer-assisted method, was slightly less in patent arteries early after anistreplase (mean stenosis diameter, 74.0%) than streptokinase (77.2%, p = 0.02). In patients with patent arteries without other early interventions, reocclusion risk within 1-2 days was defined angiographically and found to be very low (anistreplase = 1/96, streptokinase = 2/94). Average coronary perfusion grade was greater, and percent residual stenosis was less, at follow-up than on initial evaluation and did not differ between treatment groups. Enzymatic and electrocardiographic evolution was not significantly different in the two groups. Despite rapid injection, anistreplase was associated with only a small (4-5 mm Hg), transient (at 5-10 minutes) mean differential fall in blood pressure. In-hospital mortality rates were comparable for anistreplase and streptokinase (5.9%, 7.1%). Stroke occurred in one (0.5%) and three (1.6%) patients, respectively; one stroke was hemorrhagic. Other serious bleeding events and adverse experiences occurred uncommonly and with similar frequency in the two groups. Thus, for the end points of our study (patency, safety), anistreplase and streptokinase showed overall favorable and relatively comparable outcomes, with a few differences.(ABSTRACT TRUNCATED AT 400 WORDS)

Anistreplase↗
PubMed1991

HLA class II (DR and DQ) antigen associations in idiopathic dilated cardiomyopathy. Validation study and meta-analysis of published HLA association studies.

We previously reported antigen frequency differences for HLA-DR4 and HLA-DRw6 between idiopathic dilated cardiomyopathy (IDC) patients and healthy controls in a pilot study. To confirm these findings, we undertook an independent study with a prospective hypothesis regarding the frequencies of DR4 and DRw6; typing for a second family of class II antigens (HLA-DQ) was included because of the proximity of the DQ loci to the DR loci and the strong linkage disequilibrium between some of the DR and DQ alleles. Comparing a new consecutive series of IDC patients (n = 41) and healthy blood bank controls (n = 53), we confirmed an increase of DR4 antigen frequency in patients (49% versus 21%, p less than 0.005). A trend toward decreased expression of DRw6 among patients was also noted (10% of patients versus 23% of controls). HLA-DQw4 was significantly elevated in patients compared with controls (27% versus 6%, p less than 0.005; relative risk, 6.1; etiologic fraction, 0.22). We identified the combined DR4-DQw4 haplotype in five of 41 Caucasian IDC patients (12%) and none of 53 controls (p less than 0.007). A comparison of specific antigen frequencies between the preliminary and validation studies did not reveal significant differences; therefore, the data from the two studies were examined in combination. For the combined studies, DR4 was elevated (51% versus 27% in controls, p less than 0.001), and DRw6 was decreased (9% versus 24% in controls, p less than 0.01). The relative risk for DR4 was 2.8, and the etiologic fraction was 0.33.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiomyopathy, Dilated↗
PubMed1991

Evaluation of combination thrombolytic therapy and timing of cardiac catheterization in acute myocardial infarction. Results of thrombolysis and angioplasty in myocardial infarction--phase 5 randomized trial. TAMI Study Group.

Recent trials of myocardial reperfusion using single-agent thrombolytic therapy and sequential cardiac catheterization have supported a conservative approach to the patient with acute myocardial infarction. To evaluate combination thrombolytic therapy and the role of a previously untested strategy for the aggressive use of cardiac catheterization, we performed a multicenter clinical trial with a 3 x 2 factorial design in which 575 patients were randomly allocated to one of three drug regimens--tissue-type plasminogen activator (t-PA) (n = 191), urokinase (n = 190), or both (n = 194) - and one of two catheterization strategies--immediate catheterization with angioplasty for failed thrombolysis (n = 287) or deferred predischarge catheterization on days 5-10 (n = 288). Patients with contraindications to thrombolytic therapy, cardiogenic shock, or age of more than 75 years were excluded. Global left ventricular ejection fraction was well preserved and almost identical at predischarge catheterization (54%), regardless of the catheterization or thrombolytic strategy used (p = 0.98). Combination thrombolytic therapy was associated with a less complicated clinical course, most clearly documented by a lower rate of reocclusion (2%) compared with urokinase (7%) and t-PA (12%) (p = 0.04) and a lower rate of recurrent ischemia (25%) compared with urokinase (35%) and t-PA (31%). When a composite clinical end point (e.g., death, stroke, reinfarction, reocclusion, heart failure, or recurrent ischemia) was examined, combination thrombolytic therapy was associated with greater freedom from any adverse event (68%) compared with either single agent (urokinase, 55%; t-PA, 60%) (p = 0.04) and with a less complicated clinical course when the composite clinical end points were ranked according to clinical severity (p = 0.024). Early patency rates were greater with combination therapy, although predischarge patency rates after considering interventions to maintain patency were similar among drug regimens. No difference in bleeding complication rates was observed with any thrombolytic regimen. The aggressive catheterization strategy led to an overall early patency rate of 96% and a predischarge patency rate of 94% compared with a 90% predischarge patency in the conservative strategy (p = 0.065). The aggressive strategy improved regional wall motion in the infarct region (-2.16 SDs/chord) compared with deferred catheterization (-2.49 SDs/chord) (p = 0.004). More patients treated with the aggressive strategy were free from adverse outcomes (67% versus 55% in the conservative strategy, p = 0.004), and the clinical course was less complicated when the adverse outcomes were ranked according to severity (p = 0.016). No significant increase in use of blood products resulted from the aggressive strategy.(ABSTRACT TRUNCATED AT 400 WORDS)

Angioplasty, Balloon, Coronary↗
PubMed1991

Beta-blockade with bucindolol in heart failure caused by ischemic versus idiopathic dilated cardiomyopathy.

BACKGROUND: We investigated the effects of bucindolol, a nonselective, non-ISA beta-blocker with mild-vasodilatory properties, in patients with congestive heart failure from ischemic dilated cardiomyopathy (ISCDC, n = 27) and compared the results with those in subjects with heart failure from idiopathic dilated cardiomyopathy (IDC, n = 22). METHODS AND RESULTS: Patients were randomized in a double-blind fashion to receive 12 weeks' treatment with either bucindolol or placebo, with randomization stratified for IDC or ISCDC: Invasive (right heart catheterization) and noninvasive (echo, MUGA, central venous norepinephrine, exercise treadmill studies, and symptom scores) tests of heart failure severity were determined at baseline and end of the study. For all subjects (ISCDC plus IDC), relative to placebo treatment, bucindolol-treated patients had significant improvement in ejection fraction, left ventricular size and filling pressure, stroke work index, symptom score, and central venous norepinephrine. However, most of these differences could be attributed to improvement in the IDC subgroup, as the only parameter with a statistically significant degree of improvement in the bucindolol-treated ISCDC subgroup was left ventricular size. CONCLUSIONS: We conclude that beta-blockade may produce quantitatively different degrees of response in different kinds of heart muscle disease.

Adrenergic beta-Antagonists↗
PubMed1990

Impact of field-transmitted electrocardiography on time to in-hospital thrombolytic therapy in acute myocardial infarction.

To assess the impact of a field-transmitted electrocardiogram (ECG) on patients with possible acute myocardial infarction, randomized and open trials were performed with a portable electrocardiographic system coupled with a cellular phone programmed to automatically transmit ECGs to the base hospital. Consecutive patients served by the 6 units of the Salt Lake City Emergency Rescue System were studied; 71 patients were randomized to in-field ECG (n = 34) versus no ECG (n = 37). Time on scene was 16.4 +/- 9.7 minutes for the ECG group versus 16.1 +/- 7.0 minutes for the non ECG group (difference not significant). Time of transport averaged 18.2 +/- 9.9 and 17.6 +/- 13.1 minutes, respectively (difference not significant). Six of 34 patients with in-field ECG showed acute myocardial infarction, qualified for and received thrombolytic therapy at 48 +/- 12 minutes after hospital arrival (range 30 to 60) compared with 103 +/- 44 minutes (p less than 0.01) for 51 historical control patients and 68 +/- 29 minutes for 6 concurrent control patients without in-field ECG. Thus, in-field ECG causes negligible delays in paramedic time, leads to significant decreases in time to in-hospital thrombolysis and may make in-field therapy feasible. In-field ECG may be an important addition to reperfusion strategies.

Allied Health Personnel↗
PubMed1990

Biobehavioral variables and mortality or cardiac arrest in the Cardiac Arrhythmia Pilot Study (CAPS).

The frequency of ventricular premature complexes and the degree of impairment of left ventricular ejection fraction are major predictors of cardiac mortality and sudden death in the year after acute myocardial infarction. Recent studies have implicated psychosocial factors, including depression, the interaction of social isolation and life stress, and type A-B behavior pattern, as predictors of cardiac events, controlling for known parameters of disease severity. However, results tend not to be consistent and are sometimes contradictory. The present investigation was designed to test the predictive association between biobehavioral factors and clinical cardiac events. This evaluation occurred in the context of a prospective clinical trial, the Cardiac Arrhythmia Pilot Study (CAPS). Five-hundred two patients were recruited with greater than or equal to 10 ventricular premature complexes/hour or greater than or equal to 5 episodes of nonsustained ventricular tachycardia, recorded 6 to 60 days after a myocardial infarction. Baseline behavioral studies, conducted in approximately 66% of patients, included psychosocial questionnaires of anxiety, depression, social desirability and support, and type A-B behavior pattern. In addition, blood pressure and pulse rate reactivity to a portable videogame was assessed. The primary outcome was scored on the basis of mortality or cardiac arrest. Results indicated that the type B behavior pattern, higher levels of depression and lower pulse rate reactivity to challenge were significant risk factors for death or cardiac arrest, after adjusting statistically for a set of known clinical predictors of disease severity. The implication of these results for future research relating behavioral factors to cardiac endpoints is discussed.

Affect↗
PubMed1990

Cadmium deposition and hepatic microsomal activity in mice fed Swiss chard grown on municipal incinerator refuse ash.

Incineration of municipal solid waste results in the production of millions of tons of ash that may be typically high in heavy metals such as cadmium. Disposal of such ash in landfills capped with soil could lead to absorption of such metals by plants and deposition in foraging animal tissues. In this study, weanling, male mice were fed swiss chard that was grown on soil amended with 10% w/w municipal incinerator refuse ash. Cadmium was taken up by the swiss chard (8.15 ppm, dry wt). The mice fed diets containing 25% of ash-grown chard showed mean kidney and liver concentrations of cadmium (ppm, dry wt), respectively, of 2.80 +/- 0.30 and 0.45 +/- 0.03. Control mice fed soil-grown chard showed significantly lower kidney and liver concentrations of cadmium, i.e. 0.39 +/- 0.02 and 0.05 +/- 0.00 ppm. Since refuse incinerator ashes may contain various organic toxicants that can be hepatic microsomal inducers, the relative liver weights and hepatic microsomal aminopyrine N-demethylase and p-nitroanisole O-demethylase activities of mice fed control or ash-grown chard were measured. No consistent increases in these latter parameters were found in the ash-grown chard fed mice as compared with the control animals.

Animals↗
PubMed1990

Comparisons of efficacy and tolerance of moricizine with other antiarrhythmic agents in the treatment of chronic ventricular arrhythmias.

Comparative trials of a new drug with standard antiarrhythmic agents are important for establishing relative efficacy and tolerance. For moricizine, such trials have included comparisons with propranolol, disopyramide and quinidine. Furthermore, the Cardiac Arrhythmia Pilot Study compared moricizine in postinfarction patients with encainide and flecainide. These trials show moricizine to be superior in efficacy to a beta blocker (propranolol) and disopyramide and equivalent to quinidine. Although the class IC drugs (encainide and flecainide) showed somewhat greater efficacy in the Cardiac Arrhythmic Pilot Study, they are now known to increase the risk of mortality in postinfarction patients. Moricizine was also shown to be well tolerated in these trials and associated with fewer discontinuations than propranolol, disopyramide and quinidine. Thus, moricizine is a promising new agent when profiled against other drugs frequently used for therapy of chronic ventricular arrhythmias.

Anilides↗
PubMed1990

Clinical implications of new studies in the treatment of benign, potentially malignant and malignant ventricular arrhythmias.

For purposes of clinical management, ventricular arrhythmias have been divided into risk categories of benign, prognostically important (potentially malignant) and malignant. Benign arrhythmias occur in the setting of structurally normal hearts and do not require therapy unless associated with debilitating symptoms. Malignant arrhythmias such as sustained ventricular tachycardia or fibrillation deserve aggressive therapy to prevent recurrence. Arrhythmias occurring in the presence of organic heart disease (often ischemic disease) are frequently asymptomatic but prognostically important as a risk factor for sudden death or cardiac arrest. The common empiric practice to treat such arrhythmias (by about 40 to 50% of cardiologists in the United States) needs to be reassessed in the face of the Cardiac Arrhythmia Suppression Trial. For malignant arrhythmias, class IA agents (procainamide and quinidine) continue to be the standard of treatment, and class IB agents (e.g., mexiletine) may be used as alternative or additive therapy. Class IC agents are used as second-line therapy, especially in the setting of ischemic heart disease. Class III therapy with amiodarone is reserved for refractory patients because of potential toxicity. Sotalol, a new class II-III agent, may become a first-line drug. For prognostically important arrhythmias, beta blockers remain the agents of choice, class IC agents are contraindicated, and class IA or IB drugs, or both, should be used conservatively (i.e., only for symptomatic arrhythmias). For symptomatic but benign arrhythmias requiring treatment, beta blockers are safe although not always effective. Class IA, IB and IC agents may then be considered. In these patients, the proarrhythmic potential of quinidine and class IC agents remains a concern.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiodarone↗
PubMed1990

Effectiveness of sotalol for therapy of complex ventricular arrhythmias and comparisons with placebo and class I antiarrhythmic drugs.

In new antiarrhythmic drug development, key comparisons include those with placebo, standard (class I) agents and other beta blockers. This review will cover the first 2 comparisons. The effectiveness of 2 doses of sotalol for complex ventricular arrhythmias has been compared with placebo in a 6-week, multicenter study (parallel, double-blind design) in 102 patients. The frequency of ventricular premature complexes (VPCs) was reduced only 10% with placebo, 75% with low-dose sotalol (160 mg administered twice daily) and 88% with high-dose sotalol (320 mg administered twice daily) (both p less than 0.05 vs placebo). The defined efficacy criterion (greater than or equal to 75% VPC suppression) was achieved by 6% of patients taking placebo, 34% of patients taking low- and 71% of patients taking high-dose sotalol. Sotalol was generally well tolerated, especially with the lower dose. Heart rate decreased, and PR and QTc intervals increased modestly. An open, randomized, crossover study compared sotalol with procainamide in 33 patients. A reduction in VPCs of greater than or equal to 75% was achieved in 22 patients (67%) with sotalol and in 13 patients (39%) with procainamide. Quinidine and sotalol have also been compared in a multicenter study in patients with chronic, complex VPCs, with results to be presented in the near future. Thus, sotalol's antiarrhythmic efficacy is well demonstrated by comparisons with placebo, and its effectiveness and tolerance are likely to compare favorably with standard class I drugs, suggesting its potential as a first-line antiarrhythmic agent.

Anti-Arrhythmia Agents↗
PubMed1990

Treatment of ventricular arrhythmias by United States cardiologists: a survey before the Cardiac Arrhythmia Suppression Trial results were available.

To define the practice habits of United States cardiologists and the treatment of ventricular arrhythmias, a random sample of 1,000 of 12,000 cardiologists was sent a pretested questionnaire. After follow-up procedures, 252 responded, of which 18% were academically-based, 29% were hospital-based and 53% were office-based. Attitudes about antiarrhythmic drug therapy for the treatment of ventricular arrhythmias were influenced by the presence and severity of cardiac disease, the presence and severity of cardiac disease, the presence of symptoms and the type of ventricular arrhythmias. In this survey, only 1% of cardiologists treated patients with asymptomatic ventricular premature complexes and no heart disease, but 17% treated such patients if unsustained ventricular tachycardia was present. The treatment rate among cardiologists increased to 38% when coronary artery disease with left ventricular dysfunction was present in patients with asymptomatic ventricular premature complexes. The presence of any cardiac disease and symptomatic ventricular arrhythmias increased the treatment rate to 80 to 100%. Approximately 50% of responding physicians treated patients comparable to the Cardiac Arrhythmia Suppression Trial study population with antiarrhythmic drugs. Beta blockers were the most common antiarrhythmic drug class chosen as the most appropriate initial therapy in new patients with ventricular arrhythmias. Whereas no cardiologists thought that amiodarone was appropriate to initiate in new patients with benign or potentially malignant ventricular arrhythmias, as many as 33 to 43% of cardiologists would use amiodarone for refractory patients with such arrhythmias, a response contradictory to the approved labeling for this drug. Less than one half of cardiologists recognize the high potential organ toxicity for quinidine, procainamide and tocainide.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Arrhythmia Agents↗
PubMed1990

Tolerance and complications in a multicenter trial of intravenous APSAC and intracoronary streptokinase in acute myocardial infarction.

Adverse events data of a randomized, multicenter, angiographically controlled trial of intracoronary streptokinase and intravenous anistreplase, or anisoylated plasminogen streptokinase activator complex (APSAC) are presented. The frequency of severe adverse events is similar for streptokinase and anistreplase; no unexpected adverse experiences were reported with either drug. The most frequently encountered side effect was bleeding, overwhelmingly from the groin puncture site from angiography.

Acute Disease↗
PubMed1990

Variability of thrombolytic coronary reperfusion: an angiographic study of streptokinase and anistreplase.

A total of 1,615 angiographic readings in 240 patients with acute myocardial infarction were analyzed from a randomized trial of intravenous anistreplase (Eminase), also known as anisoylated plasminogen streptokinase activator complex (APSAC), versus intracoronary streptokinase. Coronary arteriography was performed at baseline and at 15, 30, 45, 60, 75, and 90 minutes after drug infusion. Coronary flow in the infarct-related artery was defined using the TIMI criteria. Some serial change in perfusion was noted in 25% of the total patient population and in 49% of all reperfusion patients. Complete loss of perfusion (grade 2 or 3 to grade 0 or 1) occurred in 35% of all reperfused patients. Half of these patients ultimately developed complete loss of perfusion at the study endpoint. All of these changes in flow were statistically more common for the circumflex coronary artery and early treatment (less than 4 h), but did not differ for anistreplase or streptokinase. We conclude that frequent alterations in coronary blood flow occur early during reperfusion therapy and that these findings may explain reports with varying results of thrombolytic therapy. Any angiographic assessment of thrombolytic drug efficacy should take these variations as well as interobserver variability into account.

Adult↗