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Biomedical subjects

B J Baker

Publications and source records attributed to B J Baker.

At least 55 records · Page 3Linked to original sources

Efficacy and tolerance of Ethmozine (moricizine HCl) in placebo-controlled trials.

To investigate the tolerance and efficacy of moricizine HCl, single-blind placebo-controlled trials were conducted. The early protocols involved patients hospitalized for 14 days, and daily Holter monitoring was used to document efficacy and the degree of spontaneous variability of ventricular premature complexes (VPCs). Moricizine HCl was given orally from 2.9 to 15.3 mg/kg 3 times daily. Patients with lethal ventricular arrhythmias were excluded. Additional outpatient trials were conducted to define long-term efficacy and safety. A dose-response relation between moricizine HCl and the percentage of reduction in frequency of benign or potentially lethal ventricular arrhythmias was documented. Eighty-five percent of patients achieved a reduction in VPCs greater than 75% with daily dosages ranging from 10.1 to 15 mg/kg. This corresponded to a 95% decrease in mean frequency of VPCs. Long-term studies demonstrated no evidence of compromise in left ventricular function, and the proarrhythmic rate was only 2%. Symptomatic side effects were mild and usually well tolerated. Nausea, the most common, occurred in 11% of patients and dizziness in 9%. These results indicate that moricizine HCl is an effective and well-tolerated antiarrhythmic agent.

Anti-Arrhythmia Agents↗

Effect of the left ventricle on the right ventricle.

The importance of the once-obscure right ventricle is becoming evident. Even in disorders that primarily affect the left ventricle, the once-considered-passive conduit has proved essential for maintenance of normal cardiac output. In coronary artery disease, the function of the right ventricle is affected by both its circulation and the after-load placed on it by dysfunction of the left ventricle. In congestive heart failure, right ventricular function relates to functional capacity, whereas left ventricular function does not, and right ventricular ejection fraction is a useful prognostic guide in these patients. In mitral and aortic valvular disease, the role of the right ventricle is only now becoming evident, and the precise interplay of all factors has yet to be explained. In systemic hypertension, it is likely that the pulmonary circulation is affected by the same humoral factors that elevate systemic pressures.

Coronary Disease↗

QRS voltage measurements in autopsied men free of cardiopulmonary disease: a basis for evaluating total QRS voltage as an index of left ventricular hypertrophy.

Use of total 12-lead QRS electrocardiographic voltage as a criterion for left ventricular (LV) hypertrophy has been of recent interest. Although upper and lower limits of QRS voltage for individual electrocardiographic leads have been reported in clinically healthy men and women, the upper limit of total 12-lead QRS voltage has not been established in adults free of cardiopulmonary disease by clinical and necropsy criteria. Therefore, the total QRS voltage from all 12 electrocardiographic leads was determined in 30 autopsied men known to be free of cardiopulmonary disease by clinical assessment and by a special cardiac examination using postmortem coronary angiography and chamber partition determination of LV weight. Gross heart weight, LV weight and total QRS voltage are reported. Comparisons were made between disease-free patients and previously reported patients with aortic valve stenosis, aortic regurgitation and cardiac amyloidosis with respect to total QRS voltage and gross heart weight. Total QRS voltage and gross heart weight were significantly greater in patients with severe aortic stenosis (mean 245 mm) and severe aortic regurgitation (mean 274 mm) than in our patients (mean 127 mm). Total QRS voltage was significantly less, whereas gross heart weight was significantly greater in patients with cardiac amyloidosis (mean 101 mm) than in our normal subjects (mean 127 mm). These data provide a basis for evaluating the total 12-lead QRS voltage as a criterion for LV hypertrophy.

Adult↗

Predictive value of M-mode echocardiography in patients with congestive heart failure.

The M-mode echocardiogram (ECHO) is widely used to follow patients with congestive heart failure (CHF), but the value of ECHO for this purpose is unclear. In 49 patients with symptomatic CHF, we obtained ECHO during baseline evaluation to determine the value of ECHO for predicting 1-year survival or maximal oxygen uptake during exercise (VOmax). The cause of CHF was coronary artery disease in 12 patients and idiopathic dilated cardiomyopathy in 37 patients. Overall mortality at 1 year was 10 of 49 (20%), but was higher in patients with coronary artery disease (42%) compared to those with idiopathic dilated cardiomyopathy (14%), p less than 0.001. ECHO indices of left ventricular contractility were greater in survivors (S) in whom shortening fraction averaged 16 +/- 8 (SD)% vs 10 +/- 4% in nonsurvivors (NOS), p less than 0.025. Velocity of circumferential fiber shortening averaged 0.53 +/- 0.25 Hz in S vs 0.35 +/- 0.15 Hz in NOS, p less than 0.05. No left ventricular dimensions, including systolic and diastolic diameters, volume, wall thickness, and mass differed significantly between S and NOS. No ECHO measure of left ventricular dimensions or contractility correlated significantly with VOmax. Thus, ECHO may be useful to predict survival but not functional capacity in patients with CHF.

Adult↗

Gastromotor mechanism of fenfluramine anorexia.

A gastric slowing effect of fenfluramine accounts for most of the drug's suppressant effect on food intake in freely feeding rats. It is conceivable on the evidence to date that this gastromotor action of fenfluramine explains all its effects on appetite and metabolism, but additional peripheral and central effects--such as motor inhibition--are likely. Rate of gastric emptying is quantitatively the dominant physiological control of appetite: it determines the duration for which absorption of a meal sustains metabolic satiety; it also influences gastric distension, which can be a source of innate satiation and of learned carbohydrate-specific satiation. Since most of the neurotransmitter serotonin (5HT) resides in the gastrointestinal wall, not the brain, gastromotor suppression of appetite should be the first working hypothesis for a serotoninergic drug such as fenfluramine. The largest effect on food intake that arises from gastric slowing by fenfluramine and active metabolites is a lengthening of the period of satiety after a meal of a given size. The residue of this extended satiety could reduce appetite at a subsequent fixed mealtime and hence the size of such a meal. Fenfluramine appears not to intensify satiation processes generated by a meal. Rather, it affects eating processes from the start. Also, fenfluramine disrupts learned carbohydrate-specific satiation operative within a meal. This negates the claim that fenfluramine reduces carbohydrate-specific appetite--which in any case (like other claims that drugs modulate nutrient selection) is not based on adequately designed dietary selection tests.

Animals↗

Fate of selectable marker DNA integrated into the genome of Nicotiana tabacum.

To compare the effects of different transformation methods on the integration behavior and structural stability of integrated foreign genes in plant cells, tobacco protoplasts were transformed with Escherichia coli plasmid pLGV2103neo DNA using the Ca phosphate DNA coprecipitation technique. Parallel transformations were done by cocultivation with Agrobacterium tumefaciens harboring the Ti plasmid derivatives pGV3850::2103neo or pGV3850::1103neo. A comparison of the fine structure of the integrated donor DNA obtained by direct gene transfer and by cocultivation indicates that the donor DNA in cells transformed by the former technique undergoes structural changes and concatemerizations, while the DNA integrated by the latter procedure is often unaltered. The cotransformed nopaline synthase gene, which is present in the donor Ti plasmid DNA, was inactivated in two out of nine cases. Once integrated, the arrays of selectable marker DNA appear to be structurally stable under different cell culture and selection conditions, as well as after genetic transmission.

Amino Acid Oxidoreductases↗

Efficacy of propafenone compared with quinidine in chronic ventricular arrhythmias.

A double-blind, randomized study was designed to evaluate the efficacy of oral propafenone and oral quinidine in suppressing premature ventricular complexes (PVCs). Twenty-five men were studied for 3 weeks. Twelve were randomized to the quinidine group and 13 to the propafenone group. Small doses of the drugs were administered for 1 week (200 mg of quinidine every 6 hours or 300 mg of propafenone every 12 hours) and large doses were administered for another week (400 mg of quinidine every 6 hours or 300 mg of propafenone every 8 hours). Strict criteria were used to define responders to antiarrhythmic therapy. For more than 85% reduction in total PVCs per hour: During the low-dose week, 36% in the quinidine group and 50% in the propafenone group were responders (difference not significant [NS]), while during the high-dose week 33% and 64% were responders (NS). For more than 95% reduction of ventricular couplets per hour: During the low-dose week, 45% in each group were responders, while during the high-dose week, 56% and 60% were responders (NS). For 100% abolition of ventricular tachycardia (VT) beats per 24 hours: During the low-dose week, 60% in the quinidine group and 56% in the propafenone group were responders (NS); during the high-dose week 80% and 67% were responders (NS). There was no significant difference in the 2 groups in incidence of side effects. This study shows comparable efficacy and tolerance of propafenone and quinidine for the control of ventricular arrhythmias in ambulatory patients with diverse forms of heart diseases.

Adult↗

Sensitivity of electrocardiographic criteria for left ventricular hypertrophy according to type of cardiac disease.

The sensitivity of 30 electrocardiographic criteria for left ventricular (LV) hypertrophy, isolated or combined, was examined to determine the relation to the underlying disease. Patients with coronary artery disease (CAD), systemic hypertension, valvular heart disease and cardiomyopathy were evaluated. A cardiac partition technique was used to define ventricular hypertrophy. Single electrocardiographic criteria often showed high sensitivity for 1 disease state, but not for others. Precordial voltage criteria were most sensitive for those with hypertensive and valvular disease. A QRS axis of more than -30 degrees occurred most often in patients with CAD. Both left atrial abnormality and abnormal T-wave inversion of more than 1 mm in V6 occurred with a high sensitivity in general; however, T-wave inversion of more than 1 mm in V6 had a low sensitivity in cardiomyopathy. Methods using combinations of various electrocardiographic criteria improved sensitivity. Using these methods, sensitivity of the electrocardiogram for LV hypertrophy was excellent for patients with systemic hypertension and valvular heart disease and acceptable by usual standards for patients with CAD and cardiomyopathy. Because the use of a single criterion is often ineffective, methods using multiple electrocardiographic criteria to detect LV hypertrophy are recommended when the patients under study have diverse cardiac diseases.

Adult↗

Coronary artery atherosclerosis observed in men over 14 consecutive years.

The incidence of cardiovascular death and myocardial infarction associated with ischemic heart disease has declined over the past 15 years. Whether this is associated with a decrease in the severity of coronary atherosclerosis is unknown. The extent of coronary atherosclerosis in men was determined by postmortem coronary angiography in 505 patients over an observation period of 14 years. Patients were divided into those with ischemic heart disease (42%) and those without (58%). Mean coronary scores showed no significant trends over the 14-year period in those without ischemic heart disease and for the last 10 years in those with ischemic heart disease. In those few patients evaluated early in the study with ischemic heart disease, a significantly lower coronary score was found compared to subsequent years. This study was performed during an era of declining cardiovascular death rates and a declining incidence of myocardial infarction, and suggests that this decline may relate to favorable changes in pathogenesis rather than to a decrease in extent of coronary atherosclerosis.

Adult↗

Pulmonary versus systemic hemodynamics in determining exercise capacity of patients with chronic left ventricular failure.

Right, but not left ventricular ejection fraction correlates with exercise capacity in patients with left ventricular failure, suggesting an important role of the pulmonary circulation. Hemodynamics were measured at rest and during bicycle exercise to symptomatic maximum in 41 patients with chronic left ventricular failure. Maximal oxygen consumption averaged only 12.8 +/- 5.2 ml/min/kg. Pulmonary wedge pressure rose from 21.9 +/- 8.2 to 35.9 +/- 9.3 mm Hg during exercise, while pulmonary arterial mean pressure rose from 31.8 +/- 10.9 to 50.4 +/- 12.9 mm Hg (both p less than 0.0001). Resting cardiac index and resting systemic arterial mean pressure did not correlate with maximal oxygen consumption (r = 0.23 and 0.20, respectively), which, however, did correlate with pulmonary wedge pressure (r = -0.54, p less than 0.001), pulmonary arterial mean pressure (r = -0.49, p less than 0.01), and total pulmonary resistance (r = -0.43, p less than 0.01). Maximal oxygen consumption did not correlate with resting systemic vascular resistance (r = -0.20) or resting pulmonary vascular resistance (r = -0.26). During exercise, total pulmonary resistance remained unchanged at 6.5 +/- 3.8 U while systemic vascular resistance fell significantly. The relation between total pulmonary resistance and exercise capacity and the failure of total pulmonary resistance to fall during exercise suggest that afterload on the right ventricle may be an important determinant of exercise capacity in patients with chronic left ventricular failure.

Aged↗

Effect of propafenone on left ventricular ejection fraction.

The effects of orally administered propafenone on ejection fraction (EF) determined by radionuclide angiography were studied in 2 groups of patients receiving different dosing regimens. Fourteen group A patients had no clinical evidence of left ventricular (LV) dysfunction and were not receiving digoxin therapy. In this group a mean daily dosage of 879 mg resulted in a decrease in resting LVEF from 52 +/- 9% to 48 +/- 11% (p less than 0.05). Eight group B patients had clinical radionuclide evidence of LV dysfunction and were receiving digoxin therapy. In this group, a daily dosage of propafenone of 600 mg/day resulted in no significant change in LVEF. No clinically significant effects on cardiac compensation were evident in either group. These data suggest a negative inotropic effect that is either related to propafenone dosage or at least partially attenuated by digoxin therapy. Further studies are necessary to define precisely the effects of propafenone on LV function.

Aged↗

Relation of right ventricular ejection fraction to exercise capacity in chronic left ventricular failure.

Although the left ventricle is traditionally viewed as the heart's main pumping chamber, no correlation has been shown between left ventricular (LV) ejection fraction (EF) at rest and exercise capacity in patients with chronic LV failure. Because vasodilators with venodilating activity increase exercise capacity more than predominant arterial dilators in patients with LV failure, right ventricular (RV) function may relate to exercise capacity in these patients. In 25 patients with chronic LV failure, caused by coronary artery disease in 12 patients and idiopathic dilated cardiomyopathy in 13 patients, RVEF and LVEF at rest were measured by radionuclide angiography. Maximal upright bicycle exercise testing was also performed to determine maximal oxygen consumption, which averaged only 13 +/- 4 ml/min/kg. The LVEF at rest was 26 +/- 10% and did not correlate with maximal oxygen consumption (r = 0.08). However, the RVEF was 41 +/- 12% and correlated with maximal oxygen consumption (r = 0.70, p less than 0.001) in the same patients. The correlation was stronger (r = 0.88) in patients with coronary artery disease than in those with idiopathic dilated cardiomyopathy (r = 0.60). Thus, RVEF at rest is more predictive of exercise capacity than LVEF in the same patients with chronic LV failure. These results are consistent with the clinical observation that only venodilating agents increase exercise capacity of patients with chronic LV failure.

Cardiac Output↗

Reevaluation of electrocardiographic criteria for left, right and combined cardiac ventricular hypertrophy.

Cardiac chamber weight was determined at necropsy in 323 men to develop correlative studies of electrocardiographic criteria for ventricular hypertrophy. Thirty recommended criteria for left ventricular (LV) hypertrophy, 10 for right ventricular (RV) hypertrophy, and combinations of both criteria for combined hypertrophy were evaluated. Four methods for electrocardiographic diagnosis of LV hypertrophy were derived: (1) a modification of the Romhilt-Estes point system; (2) the presence of any 1 of 3 criteria: (a) S V1 + R V5 or V6 greater than 35 mm, (b) left atrial abnormality, or (c) intrinsicoid deflection in lead V5 or V6 greater than or equal to 0.05 second; (3) a combination of any 2 criteria or of 1 criterion (above) plus at least 1 of the following 3 additional criteria: (a) left-axis deviation greater than -30 degrees, (b) QRS duration greater than 0.09 second, or (c) T-wave inversion in lead V6 of 1 mm or more; and (4) the use of a single criterion--left atrial abnormality. Sensitivity varied from 57 to 66% and specificity from 85 to 93% among these 4 methods. Myocardial infarction increased sensitivity of the foregoing methods, but the specificity was reduced. Method 2 is preferred for the electrocardiographic diagnosis of LV hypertrophy. Two methods were useful for right ventricular (RV) hypertrophy: (1) the use of any 1 of 4 criteria: (a) R/S ratio in lead V5 or V6 less than or equal to 1; (b) S V5 or V6 greater than or equal to 7 mm; (c) right-axis deviation of more than +90 degrees, or (d) P pulmonale; and (2) use of any 2 combinations of the foregoing criteria. Sensitivity ranged from 18 to 43% and specificity from 83 to 95%. Combined hypertrophy was best diagnosed using left atrial abnormality as the sole criteria of LV hypertrophy, plus any 1 of 3 criteria of RV hypertrophy: (a) R/S ratio in lead V5 or V6 less than or equal to 1, (b) S V5 or V6 greater than or equal to 7 mm, or (c) right axis deviation greater than +90 degrees.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Descriptive characteristics of the electrocardiogram from autopsied men free of cardiopulmonary disease--a basis for evaluating criteria for ventricular hypertrophy.

Most measurements establishing standard values for the normal electrocardiogram have been derived from a healthy population, whereas many electrocardiographic interpretations are necessary in hospitalized or seriously ill patients. Therefore, the characteristics of the electrocardiogram were described from 48 autopsied men known to be free of cardiopulmonary disease by clinical assessment and by a special cardiac examination using postmortem coronary angiography and a chamber partition technique. Highest values, mean and standard deviation, and the upper 97.5 percentile or lower 2.5 percentile when appropriate were noted for QRS voltage, QRS axis and duration, and intrinsicoid deflection in V5 or V6. Any ST-segment and T-wave changes were noted as well as left and right atrial abnormalities. Twenty-eight electrocardiographic criteria recommended to detect left ventricular hypertrophy and 10 recommended to detect right ventricular hypertrophy were evaluated for percentage of false-positive results and the 97.5 percentile value for each criterion was developed from the present data base. The data in this study can be used as a standard for comparing electrocardiographic variation in middle-aged men with specific relevance for electrocardiographic criteria of ventricular hypertrophy.

Adult↗

Concurrent use of quinidine and disopyramide: evaluation of serum concentrations and electrocardiographic effects.

The effects of concurrent disopyramide phosphate and quinidine sulfate therapy were studied in 16 normal healthy adults. No adverse effects serious enough to warrant discontinuation of therapy were observed. There was a small but significant increase in disopyramide serum concentration when concurrent quinidine therapy was given and a small decrease in quinidine serum concentration when disopyramide was added. No significant change in elimination half-life was seen for either drug. Both drugs produced prolongation of the corrected QT interval. This QT prolongation was greater for quinidine than for disopyramide.

Adult↗