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Biomedical subjects

R D Fletcher

Publications and source records attributed to R D Fletcher.

At least 91 records · Page 5Linked to original sources

Glucose and lipid metabolism during acebutolol and propranolol therapy of angina in nondiabetic patients.

The metabolic effects of acebutolol, a cardioselective beta-adrenergic blocker, and of propranolol, a nonselective beta blocker, were evaluated. Our subjects were 20 men with chronic stable angina; none had diabetes. An initial 4-wk, single-blind control phase was followed by two drug treatment periods, each a 3-wk double-blind titration phase (using increasing doses of acebutolol or propranolol), followed by a 5-wk double-blind maintenance phase. Metabolic studies were performed at the end of the control and maintenance phases. Propranolol induced elevation in basal serum glucose concentrations and both propranolol and acebutolol decreased glucose tolerance at 2.5 and 3 hr. There was no noticeable effect on insulin secretion by either drug. Neither propranolol nor acebutolol induced hyperlipidemia. There was a small decrease in total serum cholesterol after propranolol. Both drugs decreased low-density lipoprotein cholesterol. No effects were noted on the levels of serum triglycerides, high-density lipoprotein cholesterol, or free fatty acids.

Acebutolol↗

Ascorbic acid inhibition of Campylobacter jejuni growth.

The inhibitory effect of ascorbic acid on Campylobacter jejuni is described. In vitro growth of clinical strains, as measured spectrophotometrically, was inhibited by 0.5 mg of freshly prepared L-ascorbic acid per ml. Alkaline-treated or aged L-ascorbic acid increased inhibition, as did copper; however, L-cysteine, L-cystine, and glutathione prevented inhibition. Biochemical analysis of the medium and cultures indicated that one or more of the oxidation products of L-ascorbic acid, e.g., L-dehydroascorbic acid or L-diketogulonic acid, were more effective inhibitors than was reduced L-ascorbic acid.

Ascorbic Acid↗

Accuracy of calibrated-loop transfer.

The accuracy of the 0.001-ml calibrated platinum loop was tested by two methods: visible absorption spectroscopy and weight determinations. By both methods it was demonstrated that the volume of the loop delivery is related to the angle at which the loop is withdrawn from the solution being sampled and the diameter of the container, provided that the volume in the container is adequate to cover the loop. Vertical sampling from small-diameter containers (less than or equal to 7-mm inside diameter) delivered approximately 50% of 0.001 ml, and sampling at a 45 degree angle from larger containers (greater than or equal to 22-mm inside diameter) gave a delivery volume of greater than 150% of 0.001 ml, resulting in a threefold difference in the amount delivered and an error rate of +/- 50%.

Bacteriological Techniques↗

Echocardiographic features of traumatic disruption of the aortic valve.

The echocardiographic findings are presented of a patient who had evidence of aortic regurgitation one year after blunt trauma to the chest. Combined M-mode and 2-D imaging showed features suggestive of disruption of the posterior aortic leaflet, subsequently confirmed at operation, in the absence of infective endocarditis. Diagnosis of this uncommon cause of aortic regurgitation, heretofore confirmed only by direct visualization, may be made preoperatively by echocardiography.

Adult↗

Severe aortic regurgitation from systemic hypertension (without aortic dissection) requiring aortic valve replacement: analysis of four patients.

Clinical and morphologic observations are described in four patients who had severe aortic regurgitation from severe systemic hypertension unassociated with aortic dissection; each patient underwent aortic valve replacement. Although aortic regurgitation of minimal or mild degree is well recognized to occur in patients with systemic hypertension, severe degrees of aortic regurgitation are rare in such patients; aortic valve replacement in such patients has not previously been reported. Why these four patient had such severe aortic regurgitation was not determined. Although systemic hypertension is rarely a cause, it nevertheless must be added to the list of causes of severe pure aortic regurgitation.

Adult↗

Left ventricular relaxation, mitral valve prolapse, and intracardiac conduction in myotonia atrophica: assessment by digitized echocardiography and noninvasive His bundle recording.

Myotonia atrophica, a neuromuscular disease marked by autosomal dominant transmission and delayed relaxation of skeletal muscle, has been associated with cardiac failure, conduction abnormality and mitral prolapse (MVP). In order to determine the relaxation rate of cardiac muscle, left ventricular (LV) size and function, and the presence of MVP, 30 patients with myotonia atrophica were studied using digitized M-mode echocardiography (MME). Intracardiac conduction intervals were determined by noninvasive His bundle recording (HBR) from surface electrodes using a high-resolution, R-wave triggered, signal averaging computer. Neurologically unaffected first-degree relatives of the patients with myotonia atrophica were also studied to determine if cardiac abnormalities may be present in the absence of neurologic manifestations of the disease. Peak normalized diastolic endocardial velocity in patients with myotonia atrophica (3.7 +/- 0.8 sec-1) did not differ from unaffected first-degree relatives (3.8 +/- 0.8 sec-1) or normal subjects (3.6 +/- 0.8 sec-1). Systolic LV function and LV dimensions on MME were normal in both groups. However, MVP was present in 7 of 24 (29%) of patients who could be evaluated, but not in unaffected first-degree relatives. Despite normal LV systolic and diastolic function, infranodal intracardiac conduction was prolonged in patients with myotonia atrophica (average HV interval 50 +/- 5 SD msec) but not in neurologically unaffected relatives (average HV interval 40 +/- 5 msec). Delay in proximal intracardiac conduction was also found in patients with myotonia atrophica (average PH interval 140 +/- 20 msec) but not in neurologically unaffected relatives (average PH interval 115 +/- 6 msec). Hence cardiac findings in myotonia atrophica include proximal and distal conduction delay by external HBR even in the absence of abnormality of the standard 12-lead ECG. There may also be an increased frequency of MVP; however, early diastolic relaxation of the LV is unimpaired, and cardiac manifestations of myotonia are not transmitted independently of neurologic abnormality.

Adolescent↗

Simple method for quantitation of viable mycoplasmas.

A rapid, simple, and inexpensive method for quantitation of viable mycoplasmas is described. Serial dilutions were made in sterile microtiter plates with standard microtiter equipment. The results were multiplied by a factor of 2.38 to obtain colony-forming units comparable to those obtained with the laborious glass pipette-tube dilution method.

Agar↗

Treatment of frequent ventricular arrhythmia with encainide: assessment using serial ambulatory electrocardiograms, intracardiac electrophysiologic studies, treadmill exercise tests, and radionuclide cineangiographic studies.

The effects of encainide on ventricular arrhythmia and left ventricular function were studied in 21 patients with chronic, high-grade ventricular arrhythmia using a prospective, 3-month, placebo-controlled, single-blind trial design. Encainide caused a 96% decrease in the average hourly frequency of ventricular premature complexes (VPCs) and comparable reductions in salvos of nonsustained ventricular tachycardia (VT) and episodes of sustained VT. Intracardiac electrophysiologic testing showed prolonged intraatrial and intraventricular conduction times and increased atrial, atrioventricular nodal, and ventricular refractory periods with both i.v. and oral encainide without His-Purkinje block, despite marked prolongation of HV and QRS intervals. Induced repetitive ventricular beating after ventricular extrastimuli in 15 patients showed persistent repetitive ventricular beating with chronic oral encainide in seven patients, four of whom had sustained VT within 2 months of treatment on encainide. Encainide did not reduce exercise capacity or left ventricular ejection fraction at rest or during supine exercise. Minor adverse effects of encainide in 11 of 21 patients included dose-related visual disturbances, dizziness and sinus pauses (less than 3 seconds). Major adverse effects included the new appearance of sustained VT in three of 20 patients (15%). Oral encainide effectively reduces the frequency and grade of VPCs, prolongs intracardiac conduction times, and does not impair left ventricular performance. However, it is associated with frequent minor side effects and uncommon but potentially severe major side effects (sustained VT), both of which apparently have a direct relationship to the size of the dose.

Adult↗

Effects of antiarrhythmic agents on cardiac function.

Many, if not most antiarrhythmic drugs, even with differing pharmacologic properties, are capable of myocardial depression. That this has not occurred commonly with most drugs currently available may reflect several factors. These may include depression of myocardial function which is not clinically overt or which is masked by preexisting cardiac decompensation, limitation of dosages because of the difficulty in accurately determining a therapeutic endpoint, and the lack of physician awareness of the effects of these drugs on myocardial performance. However, as techniques for monitoring and quantifying arrhythmia permit more aggressive drug therapy, and as more drugs become available for clinical use, the incidence of clinically overt myocardial depression from anti-arrhythmic therapy will undoubtedly rise. Hopefully, awareness of the hemodynamic effects of these drugs and applications of new technology permitting accurate, noninvasive assessment of left ventricular function will identify and hence limit the occurrence of toxic hemodynamic effects, as well as permit the usage of maximum dosages of antiarrhythmic drugs when warranted by clinical circumstances.

Adrenergic beta-Antagonists↗

Pulmonary effects of acebutolol, a "cardioselective" beta adrenergic blocking agent.

The effect of chronic oral therapy with acebutolol, a cardioselective beta adrenergic blocking agent, was evaluated on resting pulmonary functions in a group of patients who were free of overt obstructive airways disease and who had chronic stable angina pectoris. The study design involved a 20-week, placebo-controlled, double-blind, randomized cross-over trial, using acebutolol, an agent with partial agonist activity that has been shown to be effective in the treatment of hypertension, cardiac arrhythmias, and angina pectoris. Utilizing spirometry, flow volume loops, and arterial blood gas analyses, this study demonstrated that acebutolol had no significant deleterious effect on resting pulmonary function when used in clinically effective dosages.

Acebutolol↗

Radionuclide angiographic assessment of left ventricular function during exercise in patients with a severely reduced ejection fraction.

To study the effect of exercise on left ventricular ejection fraction in patients with congestive cardiomyopathy and the relation of the response to the origin of the myocardial dysfunction, 30 patients with a severely reduced ejection fraction (30 percent or less) were evaluated with radionuclide angiography. Group I consisted of 16 patients with ischemic cardiomyopathy and a mean (+/- standard deviation) resting ejection fraction of 22.3 +/- 6.1 percent. Group II was composed of 14 patients with primary cardiomyopathy and a mean resting ejection fraction of 19.3 +/- 4.7 percent. The mean age, left ventricular end-diastolic pressure, cardiac index and resting left ventricular ejection fraction of Groups I and II were similar; however, the change in the ejection fraction during similar levels of exercise differed significantly. The mean exercise ejection fraction decreased to 16.7 +/- 6.8 percent in Group I, but increased to 24.6 +/- 6.4 percent in Group II (p less than 0.001). Thus, exercise usually results in a directionally opposite change in left ventricular ejection fraction depending on the origin of the congestive cardiomyopathy.

Adult↗

Echocardiographic abnormalities in chronic alcoholics with and without overt congestive heart failure.

To assess the type and prevalence of cardiac abnormalities in heavy drinkers with and without overt congestive heart failure, M mode echocardiography was performed in 11 symptomatic chronic alcoholics with dilated (congestive) cardiomyopathy and in 22 asymptomatic chronic alcoholics. Echocardiographic data in both groups were adjusted for age and body surface area using previously derived regression equations. All 11 symptomatic patients had a significantly decreased left ventricular percent fractional shortening (mean 14 percent, normal range 28 to 44) along with significant increases in left ventricular systolic and diastolic dimensions (mean increases of 105 and 48 percent above normal, respectively), left atrial dimension (mean increase 21 percent) and estimated left ventricular mass (mean increase 105 percent). Among the 22 asymptomatic patients, 15 (68 percent) demonstrated significant increases in at least one of the following echocardiographic variables: left ventricular mass, left ventricular dimensions, septal and left ventricular wall thicknesses, and left atrial dimension. Asymptomatic patients could be classified into two subgroups: (1) those with a left ventricular diastolic dimension less than 10 percent above the normal predicted value and an increased left ventricular wall thickness to radius ratio (mean increase 16 percent above normal) and upper normal percent fractional shortening, and (2) those with a left ventricular diastolic dimension 10 to 24 percent above normal and a slightly subnormal thickness to radius ratio and lower normal percent fractional shortening. Echocardiographic abnormalities in asymptomatic chronic alcoholics did not correlate with the presence or absence of auscultatory abnormalities on physical examination and appear to reflect an earlier stage in the spectrum of alcoholic disease before the development of dilated cardiomyopathy.

Adult↗

Acebutolol and left ventricular function: assessment by radionuclide angiography.

We assessed the effects of acebutolol, a cardioselective beta blocker, on global and regional left ventricular function in 26 patients with chronic angina pectoris. All patients underwent rest and maximal supine bicycle exercise radionuclide angiography while on placebo and oral acebutolol (400 mg three times a day). Resting ejection fraction on placebo was 51 +/- 3% and on acebutolol was 54 +/- 3% (p less than 0.05). No resting ejection fraction decreased greater than or equal to 7%. Only one patient (resting ejection fraction 28% on placebo and 21% on acebutolol) developed signs of fluid retention. Exercise nuclear studies on placebo revealed responses consistent with coronary artery disease (abnormal ejection fraction response to exercise and regional wall motion abnormalities) in 24 of 26 patients. Peak exercise ejection fraction was of the same order on placebo and acebutolol (51 +/- 3% and 54 +/- 3%, p = NS). In four patients the ejection fraction response to exercise became normal and in five patients all regional wall motion abnormalities became normal on acebutolol. Cardioselective beta blockade with acebutolol in effective antianginal doses is safe and may improve resting and exercise ventricular function.

Acebutolol↗

Inactivation of mycoplasmas by long-chain alcohols.

In this report, we describe the inhibitory activity of long-chain alcohols on the growth of Mycoplasma gallisepticum and Mycoplasma pneumoniae. Peak inhibition was recorded with saturated primary alcohols (64 microM) varying in chain length from 16 to 19 carbon atoms. The unsaturated alcohols (oleyl, linoleyl, and linolenyl) and the secondary alcohol (pentadecan-2-ol), when employed in the same test conditions, were considerably less effective growth inhibitors than the primary saturated alcohols. Stearic and palmitic acids were also ineffective as growth inhibitors of M. pneumoniae and M. gallisepticum at a 128 microM concentration. Because these antimycoplasma agents are fatty alcohols and cholesterol is known to be required for the growth of some mycoplasmas, additional cholesterol was added in an attempt to reverse the inhibition observed with these agents. Cholesterol at a 128 microM concentration did not significantly relieve the growth inhibition observed with stearyl alcohol at a 48 microM concentration. Mammalian cell cultures were found to be significantly more resistant to the effects of these inhibitory alcohols than were the mycoplasmas. Electron micrographs showed that inclusion of stearyl alcohol in the culture medium produced changes in the cellular morphology of the treated mycoplasmas.

Alcohols↗