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Biomedical subjects

J L Anderson

Publications and source records attributed to J L Anderson.

At least 271 records · Page 15Linked to original sources
PubMed1985

A randomized trial of low-dose beta-blockade therapy for idiopathic dilated cardiomyopathy.

Beta-blockade therapy to improve survival in idiopathic dilated cardiomyopathy (IDC) has been both advocated and criticized. However, randomized studies have not been performed. Thus, 50 patients with IDC were randomized in pairs to standard therapy (C) alone or with beta blockade (BB). Beta-blockade therapy with metoprolol was titrated from 12.5 to 50 mg twice daily as tolerated (final average dose, 61 mg/day). Groups were comparable in age (C, 50 +/- 15 years; BB, 51 +/- 13 years), gender (C, 76% male; BB, 56% male), entry functional class (C, 2.8 +/- 0.8; BB, 2.7 +/- 0.7), and left ventricular ejection fraction (C, 27 +/- 12%; BB, 29 +/- 10%). Follow-up averaged 19 months (range 1 to 38). One subject in each group was lost to follow-up. There were 3 early BB dropouts (within 2 days) due to low-output syndrome (2 patients) or fatigue (1 patient). Eleven patients died. By intention to treat, 5 BB and 6 C patients died (difference not significant). By actual treatment, 3 BB patients died, including 2 late dropouts (at 0.2, 10 and 17 months), and 8 C patients died (at 2, 9, 9, 15, 18, 24, 29 and 32 months, p = 0.12). In additional, functional evaluation on follow-up (functional class, San Diego questionnaire and exercise time) all tended to favor those receiving BB. Low-dose BB is tolerated in 80% of IDC patients on a long-term basis. Those continuing to take BB have a good prognosis. Mortality in C patients, however, is less than in some retrospective studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1985

The effect of carbidopa on the pharmacokinetics of intravenously administered levodopa: the mechanism of action in the treatment of parkinsonism.

The pharmacokinetics of short and long intravenous infusions of levodopa with and without concurrent oral administration of carbidopa was studied in 9 parkinsonian patients. Carbidopa reduced by 50% both the infusion rate required to produce a clinical response and the time required for plasma clearance of levodopa. Using this value for clearance, it is estimated that carbidopa doubles the bioavailability of orally administered levodopa. Carbidopa did not alter the therapeutically effective plasma concentration of levodopa, suggesting that carbidopa does not modify the so-called enzymatic blood-brain barrier. The decline of the plasma levodopa concentration was biphasic; carbidopa modestly increased half-lives of both phases. The apparent volume of distribution was not significantly altered. Carbidopa did not change the duration of the clinical response after the discontinuation of short infusions. From these observations we infer that the therapeutic effects of carbidopa can be attributed to doubling the bioavailability of orally administered levodopa and halving its plasma clearance.

Administration, Oral↗
PubMed1985

Initial and long-term outpatient experience with lorcainide for suppression of malignant and potentially malignant ventricular arrhythmias.

There is a need for effective, well-tolerated antiarrhythmic agents, particularly those effective by both intravenous and oral routes. Lorcainide, a new antiarrhythmic drug with such properties, was given long-term orally to 24 patients controlled initially with intravenous therapy--19 with frequent (greater than 1/min) complex premature ventricular complexes (PVCs) on a baseline 24-hour Holter monitor and five with ongoing sustained ventricular tachycardia (VT) or frequent paroxysmal sustained VT, for a mean of 13 months (range 0.03 to 39.4 months). Long-term lorcainide was given in divided doses of 200 to 800 mg/day (median 260, mean 269 +/- 90 mg/day). Response to long-term lorcainide therapy was assessed at a mean of both 26 days and 12.2 months. Frequency of PVCs on baseline averaged 13,490/24 hours (median 10,578, range 2,115 to 61,716); couplets averaged 309/24 hours (median 166, range 0 to 5,686), and runs averaged 33/24 hours (median 30, range 0 to 2,951). Median frequency of PVCs decreased by 94% (p much less than 0.001) and 97% (p less than 0.01) at the first and second lorcainide efficacy assessments, respectively. Couplets decreased by a median of 99% (p much less than 0.001) and 100% (p less than 0.005) at the first and second assessments, respectively. Runs were suppressed by a median of 100% at both evaluations (p much less than 0.001). Only three (16%) of the patients with complex PVCs failed to respond to therapy. No recurrence during lorcainide has been noted in the five patients with ongoing sustained VT or recurrent episodes of VT.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1985

Meobentine sulfate: antiarrhythmic and electrophysiologic effects assessed by programmed electrical stimulation and ambulatory monitoring in patients with complex ventricular tachyarrhythmia. Report of a multicenter evaluation.

Five cardiology centers conducted open-label prospective trials of meobentine sulfate, an intravenously and orally available analog of bethanidine, to assess its potential for treatment of recurrent, drug refractory ventricular tachycardia (VT) or fibrillation (VF), and complex ventricular arrhythmias. The study population comprised 26 patients (mean age, 61 years); 18 were men. Coronary artery disease was present in 15, cardiomyopathy in six, and valvular heart disease in three. Patients presented with both VT and VF (seven), sustained VT alone (12), or frequent ventricular ectopy (PVCs) and nonsustained VT (seven). Of the 26 patients, 5 were enrolled in antiarrhythmic studies (chronic PVC suppression) and 21 were enrolled in programmed electrical stimulation (PES) studies. Two of five in the chronic PVC study showed greater than 75% arrhythmia suppression. Among 21 patients in PES studies, there were eight intravenous (16 mg/kg) and 19 oral trials (400 to 1000 mg every 6 hours, 3 days/dose interval). Five of 22 patients showed efficacy at repeat PES study (neither VT nor VF), one showed partial efficacy, and four were not restudied because of clinical arrhythmia (three) and/or adverse effects (two). Overall, three patients (12%) were continued on the drug for an extended period of time. Adverse experience included hypotension in 50% and gastrointestinal effects (nausea, vomiting, or diarrhea) in 56% (oral trials only). Adverse reactions led to drug discontinuation in six and dosage reduction in eight patients. Thus, meobentine may prevent induction of VT or VF or reduce frequency of complex PVCs in selected patients refractory to other antiarrhythmic agents, but the response rate is relatively low. Symptomatic hypotension or gastrointestinal adverse effects are common and may limit utility of meobentine as a chronic oral antiarrhythmic agent.

Administration, Oral↗
PubMed1985

Effect of weekly testing on dexamethasone suppression test results in normal subjects.

Four weekly repetitions of the overnight dexamethasone suppression test (DST) in each of 10 healthy volunteers yielded plasma cortisol levels that were consistently suppressed. These results suggest that unlike some dynamic tests of hypothalamic-pituitary functioning, the DST does not produce false-positive results due to weekly repetition. This finding is of interest because previous research has demonstrated that a subgroup of melancholic initial nonsuppressors continue to resist cortisol suppression despite apparent clinical improvement. The present findings do not support the hypothesis that continued nonsuppression in clinically improved patients is an artifact of serial testing.

Adult↗
PubMed1985

Comparison of intravenous lorcainide with lidocaine for acute therapy of complex ventricular arrhythmias: results of a randomized study with crossover option.

There is a need for effective, well tolerated, intravenous antiarrhythmic agents. The effects of lorcainide, a new class I antiarrhythmic agent, were compared with those of lidocaine in a randomized parallel study with cross-over option in 30 hospitalized patients with frequent (greater than 1/min) complex ventricular arrhythmias. Lorcainide loading dose was 2 mg/kg (at 2 mg/min) supplemented, if needed, with 100 mg in 1 hour; maintenance dose was 8 mg/h. Lidocaine loading dose was 1 mg/kg (at 25 mg/min) supplemented, if needed, with 50 mg in 2 minutes; maintenance dose was 2 or 3 mg/min (as needed). Arrhythmias were compared for 2 hours before and after drug loading. Initially responding patients (minimum of 70% arrhythmia suppression) were continued on maintenance therapy for 24 hours. Patients initially failing or with later arrhythmia escape crossed over to alternating therapy (seven to lidocaine, nine to lorcainide). The median frequency of premature ventricular complexes decreased by 76% after lidocaine (p less than 0.05) and by 93% after lorcainide (p less than 0.001); this difference approached significance (p = 0.06). More than 95% arrhythmia suppression was achieved by lorcainide in 47% of patients and by lidocaine in only 13% (p less than 0.05). Couplets decreased by a median of 100% after lorcainide and by 89% after lidocaine. Couplets were eliminated in 62% of the patients after lorcainide and in 27% after lidocaine (p = 0.06). There was 100% suppression of runs of premature beats in 11 patients after lorcainide and 99% suppression in 10 patients after lidocaine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Rationale of combination antiarrhythmic drug therapy.

In summary, antiarrhythmic combinations have been explored as a matter of clinical necessity in many instances, and clinical circumstance has led to attempted combination therapy with two, and sometimes more, drugs. Few controlled studies using a specific combination have been performed. Therapy is thus usually empiric, based on available clinical, electrophysiologic and pharmacologic information. Nonetheless, certain general impressions are available, which may form the basis for clinical decisions and for structuring future trials (Table 6). Although single-drug antiarrhythmic therapy continues to be advisable, in certain instances combined-drug therapy may be appropriate and efficacious. The importance of potential adverse drug interactions must also be appreciated.

Adrenergic beta-Antagonists↗
PubMed1985

Bretylium tosylate: profile of the only available class III antiarrhythmic agent.

Bretylium tosylate, the only approved class III antiarrhythmic agent, is a unique quaternary ammonium compound with prominent experimental and clinical antifibrillatory effects. Intravenous bretylium causes a biphasic hemodynamic response; initial norepinephrine release is followed by sympathetic ganglionic blockade. Cardiac output is well maintained. Electrocardiographic intervals are unchanged, and global conduction unchanged or facilitated. With long-term experimental use, proportionate lengthening of ventricular action potential and refractory period occurs. Bretylium is largely eliminated unchanged in the urine, with a long terminal half-life of about 13 hours. Bretylium demonstrates substantial activity in several animal models and clinical circumstances of ventricular fibrillation, including those in which standard antiarrhythmic therapy is ineffective. Bretylium is thus currently approved as a first-line agent for prophylaxis and treatment of ventricular fibrillation, and as a second-line agent for ventricular tachycardia and other prefibrillatory ventricular arrhythmias. In contrast, bretylium's weak antiectopic activity and limited oral absorption make it a poor choice for management of simple ventricular ectopy. Side effects of bretylium are generally limited to its hemodynamic actions (eg, postural hypotension). Nausea may occur with rapid intravenous administration. Emerging clinical concepts emphasize the clinical importance of antifibrillatory action over antiectopic effects alone. Bretylium is thus likely to continue to find increasing usage in the acute management of malignant ventricular arrhythmia.

Administration, Oral↗
PubMed1985

Conventional and sustained-release procainamide: update on pharmacology and clinical use.

Hemodynamic and electrophysiologic effects of procainamide, the pharmacokinetic properties of conventional and sustained-release forms of the drug, guidelines for its administration and dosage, and contraindications for and adverse effects of its use are outlined. A review of clinical studies of procainamide therapy concludes that in the treatment of ventricular arrhythmia it is comparable to other class IA drugs and generally superior to beta-blockers and to class IB drugs. For atrial arrhythmias, procainamide is usually the drug of choice when intravenous therapy is indicated; for oral prophylaxis, quinidine or the sustained-release form of procainamide is more effective than conventional formulation oral procainamide. Because procainamide is the only class I antiarrhythmic drug currently available that is commonly administered intravenously and orally, it is frequently the drug of choice for patients requiring both immediate and intermediate periods of arrhythmia control. It is often the drug of choice for initial testing with programmed electrical stimulation.

Administration, Oral↗
PubMed1984

Evaluation of total artificial heart performance in man.

This report describes the method whereby total artificial heart (TAH) performance was evaluated in the first human implantation, the operating characteristics of the TAH and the accompanying circulatory response. The patient survived for 112 days. Weekly averages (+/- standard deviation) for left-heart drive pressure ranged from 146 +/- 5 to 171 +/- 10 mm Hg, right-heart drive pressure from 46 +/- 4 to 79 +/- 17 mm Hg, heart rate from 77 +/- 8 to 98 +/- 3 beats/min, diastolic vacuum from 0 to 7 +/- 0.5 mm Hg and percent systole 40 +/- 1 to 44 +/- 0. Left-sided cardiac output ranged from 3.0 +/- 0.4 to 3.9 +/- 0.2 liters/min/m2, and was consistently greater than right-sided cardiac output, which ranged from 2.6 +/- 0.4 to 3.6 +/- 0.1 liters/min/m2. Drive line air pressure and flow signals and cineradiography of the TAH demonstrated complete filling and ejection for the left ventricle and complete filling but partial ejection for the right ventricle. There was no significant change in cardiac index during variation in right atrial pressure between 4 and 14 mm Hg. During 21 days of invasive hemodynamic monitoring, daily average of mean systemic arterial pressure ranged from 81 +/- 5 to 107 +/- 11 mm Hg, pulmonary artery pressure from 22 +/- 2 to 28 +/- 8 mm Hg and left atrial pressure from 8 +/- 2 to 22 +/- 4 mm Hg. Prominent V waves on the left atrial pressure tracing suggested mitral regurgitation as a cause of the difference between the outputs of the 2 ventricles.(ABSTRACT TRUNCATED AT 250 WORDS)

Air Pressure↗
PubMed1984

Symposium on the management of ventricular dysrhythmias. Antifibrillatory versus antiectopic therapy.

The concept of antifibrillatory action distinct from antiarrhythmic effect has recently been recognized. An antiarrhythmic (antiectopic) action leads to a decrease in the frequency of ventricular ectopic beats. In contrast, an antifibrillatory drug action increases myocardial electric stability, decreasing the propensity for ventricular fibrillation. Agents with predominant antiarrhythmic action (designated class I) include lidocaine, quinidine, procainamide and disopyramide. Bretylium is an agent with predominant antifibrillatory action (class III). Amiodarone and sotalol are experimental class III drugs. The beta-blockers (class II) also possess antifibrillatory action, particularly in ischemic heart disease. The rationale for the use of agents with antiarrhythmic (antiectopic) effects is the reduction of triggering events for more complex ventricular tachyarrhythmias. These agents act by slowing conduction, decreasing abnormal automaticity and affecting phase IV depolarization. In contrast, agents with antifibrillatory action may exert little effect on cardiac conduction and automaticity. However, they raise the energy threshold required for premature electrical discharge to initiate ventricular fibrillation (ventricular fibrillation threshold). The inhomogeneity of electrophysiologic properties and adrenergic tone in different portions of the heart may be reduced or eliminated. Direct electrophysiologic effects of agents such as bretylium include a general lengthening of the refractory period and the action potential duration in the heart and a diminution in the disparity of their durations between normal and abnormal myocardium. Clinical studies are incomplete, but they support the concept of antifibrillatory therapy. In postmyocardial infarction patients at intermediate risk of sudden death, the broad use of oral antiarrhythmic agents has not decreased the incidence of sudden death, whereas high-dose beta-blocker therapy, which exerts experimental antifibrillatory effects, may reduce sudden death by 30 to 70%.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1984

HLA A, B and DR typing in idiopathic dilated cardiomyopathy: a search for immune response factors.

Several autoimmune diseases have been associated with increased frequencies of various histocompatibility antigen (HLA) types that may be linked to immune response genes. Idiopathic dilated cardiomyopathy (IDC) has been proposed as a disease with autoimmune features, but HLA associations have not been evaluated. We performed HLA typing in 37 consecutive patients with IDC. Patients with habitual alcoholism were excluded. Results showed that no single HLA type could account for most cases; IDC is a genetically heterogeneous disease. However, uneven distributions were noted for certain types. Haplotype frequency of B27 was 0.145 in patients vs 0.033 in 5,726 local control subjects (p less than 0.001). Other A and B frequencies (except A2) were evenly distributed. HLA DR typing also revealed differences. The DR4 locus was present in 54% (19 of 35) of patients, vs 32% (26 of 82) of blood bank control subjects (p less than 0.02). The associated relative risk of DR4 was 2.2 and the etiologic fraction 0.29. Sex, disease chronicity, functional class, ejection fraction and biopsy evidence of myocarditis did not distinguish DR4-positive from DR4-negative patients, but they were older (54 +/- 12 vs 42 +/- 14 years, p less than 0.02). Of note, 68% were positive for DR4 or B27, or both. HLA DR6Y was underrepresented; it was present in 9% (3 of 35) of patients, vs 26% (21 of 82) of control subjects (p less than 0.04). The relative risk of DR6Y was 0.27 and the preventive fraction 0.19. These associations will require independent confirmation. However, they suggest that genetically determined immune response factors associated with HLA loci may play a role in pathogenesis in certain patients with IDC.

ABO Blood-Group System↗
PubMed1984

The femoral venous approach to endomyocardial biopsy: comparison with internal jugular and transarterial approaches.

Endomyocardial biopsy is often used in the clinical evaluation of cardiac disease. Among 134 consecutive procedures (280 myocardial samples), 3 approaches were compared: right internal jugular (n = 69), femoral arterial (n = 30) and femoral venous (n = 35). The femoral venous approach is a new method with which a preformed guiding sheath is used to allow sampling of the apical right ventricular portion of the ventricular septum. Vascular access and myocardial sampling were successful in all femoral venous and left ventricular (LV) procedures; however, the internal jugular vein could not be located to allow biopsy in 12% of neck approaches (p less than 0.025). One case of pneumothorax occurred after an internal jugular approach. Chest pain occurred after 10% (3 patients) of the LV, 4% (3 patients) of internal jugular and 3% (1 patient) of femoral venous procedures. Hypotension associated with biopsy was noted after 3 internal jugular and 2 LV procedures. Pericardial effusion was observed in 3 patients after an LV procedure (p less than 0.01). In 1 of these patients tamponade developed. The femoral venous approach had the highest overall efficiency (successful biopsy, lack of adverse events, p less than 0.05). This approach may become the procedure of choice for routine endomyocardial biopsy because it allows reliable vascular access and myocardial sampling with a low incidence of adverse reactions.

Adolescent↗
PubMed1984

Experience with electrophysiologically guided therapy of ventricular tachycardia with flecainide: summary of long-term follow-up.

In a heterogeneous group of 15 patients with clinical syncope or documented sustained ventricular tachycardia (VT), with induced sustained or nonsustained VT at programmed electrical stimulation, flecainide prevented tachycardia induction in 9 of 15 patients (60%) and improved responses in 2, for a 73% initial favorable response rate. Cycle length of induced rhythms increased an average of 141 ms after the drug. Antiarrhythmic response rate was higher in the absence of coronary artery disease. Ten of these patients were selected for a long-term drug trial. After a median follow-up of 13.5 months, 8 patients (53%) continue to receive flecainide, 6 (40%) successfully treated with flecainide alone and 1 each treated with concomitant therapy with amiodarone and a programmable antitachycardia pacemaker. Minor dosage adjustments were made during early outpatient therapy in 5 patients. Those continuing on therapy show a remarkable absence of side effects and stable drug concentrations. Therapy failed in 2 patients at 0.5 and 4 months, in 1 in association with progression of cardiomyopathy and in another with recurrence of sustained (slow) VT. Although our results have been favorable, preliminary reports from other laboratories have been mixed. Therefore, further experience is needed. In summary, flecainide appears promising in selected patients with VT using a carefully monitored approach including electrophysiologic induction studies.

Adult↗
PubMed1984

A proposal for the clinical use of flecainide.

Effective antiarrhythmic therapy requires a carefully considered approach, including an understanding of the arrhythmia, the underlying cardiac disease and the drug's pharmacokinetics. Flecainide is a new antiarrhythmic drug that may soon be released for general use. Flecainide demonstrates unsurpassed efficacy in chronic ventricular arrhythmias in stable patients and may become a first-choice drug because of its ease of administration, efficacy and favorable tolerance. Twice-daily dosing with 100 to 200 mg usually provides effective therapy. Clinical experience suggests flecainide to be indicated in the treatment of uniform and multiform ventricular premature complexes, coupled ventricular premature complexes, and episodes of nonsustained ventricular tachycardia. A lower response rate is observed in preventing induction of sustained ventricular tachycardia, and these patients should be carefully selected. Flecainide is promising in the treatment of supraventricular tachycardias using atrioventricular nodal or extranodal reentrant pathways, although this use is still investigational in the United States. The drug's use for arrhythmias during acute myocardial infarction requires further study. Flecainide possesses modest negative inotropic potential. Proarrhythmic or other adverse reactions have occurred primarily in settings of high drug level, poor ventricular function or refractory, malignant arrhythmias, suggesting caution in these groups.

Anti-Arrhythmia Agents↗