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Biomedical subjects

W Shapiro

Publications and source records attributed to W Shapiro.

At least 19 recordsLinked to original sources
PubMed1992

Comparative efficacy of bepridil versus placebo in angina pectoris: treatment and withdrawal studies.

The efficacy and safety of once-daily doses of 200, 300, and 400 mg of bepridil hydrochloride were compared with placebo in a 14-week multi-center, double-blind parallel study. All doses of bepridil significantly reduced weekly anginal attacks and nitroglycerin consumption from baseline levels. Bepridil also significantly improved total exercise time, time to angina, time to 1 mm ST-segment depression, and total work. Reduction in heart rate (maximum mean decreases of 7-8 beats/min) and prolongation of QT and corrected QT (QTc) intervals were associated with bepridil therapy. Bepridil was well tolerated; most adverse reactions reported were mild and tolerable even at the 400-mg dose. This study provides strong support for the use of bepridil in patients with chronic stable angina pectoris that is not optimally controlled by other available antianginal therapies. A double-blind withdrawal study is also reported, in which patients stabilized on bepridil were randomized to either continue on bepridil therapy or receive placebo. Patients who were withdrawn from bepridil therapy showed significant increases in the number of weekly anginal attacks and nitroglycerin consumption compared with levels seen during long-term treatment. Patients withdrawn from bepridil therapy showed significant deterioration in exercise tolerance compared with baseline and with those maintained on bepridil.

Adult↗
PubMed1992

Treatment of malignant gliomas with interstitial irradiation and hyperthermia.

A Phase I study of interstitial thermoradiotherapy for high-grade supratentorial gliomas has been completed. The objective of this trial was to test the feasibility and toxicity of hyperthermia induced by ferromagnetic implants in the treatment of intracranial tumors. The patient population consisted of 16 males and 12 females, with a median age of 44 years and a median Karnofsky score of 90. Nine patients had anaplastic astrocytoma while 19 had glioblastoma multiforme. Twenty two patients were treated at the time of their initial diagnosis with a course of external beam radiotherapy (median dose 48.4 Gy) followed by an interstitial implant with Ir-192 (median dose 32.7 Gy). Six patients with recurrent tumors received only an interstitial implant (median dose 40 Gy). Median implant volume for all patients was 55.8 cc and median number of treatment catheters implanted per tumor was eighteen. A 60-minute hyperthermia treatment was given through these catheters just before and right after completion of brachytherapy. Time-averaged temperatures of all treatments were computed for sensors located within the core of (> 5 mm from edge of implant), and at the periphery of the implant (outer 5 mm). The percentage of sensors achieving an average temperature > 42 degrees C was 61% and 35%, respectively. Hyperthermia was generally well tolerated; however, there have been 11 minor toxicities, which resolved with conservative management, and one episode of massive edema resulting in the death of a patient. In addition, there were three major complications associated with the surgical implantation of the catheters. Preliminary survival analysis shows that 16 of the 28 patients have died, with a median survival of 20.6 months from diagnosis. We conclude that interstitial hyperthermia of brain tumors with ferromagnetic implants is feasible and carries significant but acceptable morbidity given the extremely poor prognosis of this patient population.

Adult↗
PubMed1979

Exercise testing in men with significant left main coronary disease.

The exercise tests of 26 male patients with significant left main disease were compared with those of 51 patients with three-vessel disease and 38 patients with two-vessel disease. Exercise-induced ischaemia (chest pain and/or greater than 1 mm ST segment change) occurred in 100 per cent of left main, 69 per cent of three-vessel, and 45 per cent of two-vessel disease patients. Though the mean peak work load was significantly higher in the two-vessel disease group than in those with three-vessel of left main disease, there was a wide overlap between groups. No intergroup differences were found in mean peak heart rates. In patients taking propranolol, no differences in mean peak work loads and heart rates were seen. The study showed that the absence of an exercise-induced abnormal electrocardiographic response virtually excludes left main disease. As judged by exercise performance, the presence of left main disease did not correlate with the severity of the patient's symptomatology. Propranolol did not influence the frequency of an ischaemic response in patients with left main or three-vessel disease.

Coronary Disease↗
PubMed1978

Correlative studies of serum digitalis levels and the arrhythmias of digitalis intoxication.

Correlative studies of serum digoxin levels, cardiac rhythm and related clinical laboratory data were carried out in 114 patients. Seventy-three patients who presented with 79 episodes of arrhythmias typical of digitalis intoxication could be separated into a normokalemic group of 55 patients whose serum digoxin level was 6.68 +/- 0.17 ng/ml (mean +/- standard error of the mean), and a hypokalemic group of 24 with a mean serum digoxin level of 1.13 +/- 0.04 ng/ml (P less than 0.001). Of 45 consectutive normokalemic patients with a high serum digoxin level (more than 2 mg/ml) who underwent serial studies, 17 had arrhythmias. Serial studies in 10 hypokalemic patients revealed an inconsistent relation between presence of arrhythmia and serum digoxin level. During repletion of serum potassium in seven of these patients with an arrhythmia, the arrhythmia disappeared without a significant change in serum digoxin level in four patients. A group of seven patients had 16 episodes of serum digoxin level greater than 2.2 ng/ml, but an arrhythmia occurred during only 3 of these episodes. A sharp border between toxic and therapeutic serum digoxin values was not found in these groups of study patients. The serum digoxin level at which arrhythmias occurred appeared to be variable for both groups and individual patients. However, correlative studies utilizing serum digoxin levels can define existing thresholds for therapeutic and toxic effects and may often be more useful than isolated observations.

Aged↗
PubMed1978

Efficacy of propranolol in the control of exercise-induced or augmented ventricular ectopic activity.

The effect of propranolol on exercise-induced or augmented ventricular ectopy was studied in sixteen male patients, six of whom had documented coronary artery disease. Fifteen patients were exercised after two weeks of oral therapy, fourteen after single oral therapy and eight patients after intravenous therapy. Propranolol dosage was titrated to produce maximal beta-adrenergic blockade. Effective reduction of exercise-induced ventricular ectopy occurred in ten of fifteen patients (P less than 0.001), and in five of six patients with coronary disease (P less than 0.02). Propranolol therapy abolished ventricular couplets in eight of twelve patients and ventricular tachycardia in four of the patients. Single oral and intravenous therapy had similar or greater effects. Plasma propranolol levels following different routes of administration did not correlate with exercise-induced maximal heart rates or percent reduction in ventricular ectopy. When compared to exercise in eleven patients, ambulatory monitoring underestimated the severity, particularly the highest grades, of ventricular ectopy.

Adult↗
PubMed1978

Current considerations in digoxin usage.

Basic considerations in biotransformation and pharmacodynamics are presented as a basis for understanding clinical usage. The role of polarity in determining a given glycoside's duration of action and extent of biotransformation is emphasized. The pharmacokinetics are summarized emphasizing the fact that digoxin is not completely absorbed by oral administration. The important relationship of serum digoxin levels to myocardial content and apparently to myocardial response is reviewed. This relationship and the development of precise methods for measurement of digoxin in serum provide the clinician with accurate means to assess myocardial tolerance for digoxin under diverse clinical circumstances. This review includes discussion of methods of digitalization, appropriate use of serum levels, apparent and real resistance to digoxin, and apparent and real sensitivity to digoxin. The limitations of serum levels as a precise guide to toxicity are analyzed. Finally, new developments in use of immunologic therapy for digoxin intoxication are presented.

Arrhythmias, Cardiac↗
PubMed1977

A comparison of the response to arm and leg work in patients with ischemic heart disease.

An exercise test based on arm work was evaluated in a series of 33 male patients, mean age 52 years, with ischemic heart disease. The responses to arm exercise on a modified table-mounted bicycle ergometer and to standard bicycle exercise were compared. Twenty six of 33 patients (79 per cent) had identical end-points with both tests. Three patients had an ischemic response, i.e., significant ST abnormality and/or angina pectoris during leg work only, and four patients during arm work only. 41 per cent of the peakload during leg exercise. Mean values were 181 and 439 kpm./min. (p less than 0.001). Comparison of individual data on peak load demonstrated only a weak correlation between arm and leg work capacity (r = 0.37, p less than 0.05). Peak heart rate was slightly higher during leg work, 129 compared to 122 beats/min. (p less than 0.05) but the mean heart rate-systolic blood pressure products were not significantly different. A subgroup of seven patients had a history of angina pectoris preferentially precipitated by arm work but their physiological responses did not differ significantly from those of patients without a history of arm work sensitivity. The data indicate that arm work is a satisfactory alternate diagnostic test method with respect to myocardial ischemia, but measurements of physical work capacity defined as aerobic capacity, cannot be based on arm work.

Adult↗
PubMed1977

Contraction and resting stiffness of isolated cardiac muscle: effects of inotropic agents.

The purpose of this study was to test the hypothesis that either hypoxia and its combined effects with extracellular calcium (Ca), digoxin, and ouabain, or these positive inotropic agents acting alone or in combination, influence contraction and resting stiffness of isolated papillary muscle. Stiffness was measured utilizing the sinusoidal forcing function technique. Neither an increase in extracellular calcium concentration (from 2.5 to 4.0 mM) nor digoxin or ouabain in either Ca concentration altered contraction or resting stiffness in the well-oxygenated environment. Resting stiffness for any given resting tension was increased at the end of hypoxia only in the presence of digoxin, and this occurred in both 2.5 mM Ca (P less than 0.02) and in 4.0 mM Ca (P = 0.05). Contraction stiffness for any given tension was increased in 2.5 mM Ca by hypoxia alone (P less than 0.05) and by hypoxia in the presence of digoxin (P less than 0.005) and ouabain (P less than 0.02), but was not increased in any experiments conducted in 4.0 mM Ca. The conclusions from these data are that certain experimental conditions of the study evoked different directional changes in stiffness and contractility. Further, changes in contraction stiffness are not always paralleled by changes in resting stiffness.

Animals↗
PubMed1976

Technetium stannous pyrophosphate myocardial scintigrams in the recognition of myocardial infarction in patients undergoing coronary artery revascularization.

Myocardial imaging using technetium 99m stannous pyrophosphate (99mTc-PYP) has been utilized preoperatively and three to five days postoperatively to detect myocardial infarction in 48 patients undergoing aortocoronary bypass grafting, including 7 having valve replacement (5 aortic, 2 mitral) in addition to revascularization. In the total group of patients operated on there were 3 deaths (6%). Preoperatively, 26 patients had unstable angina and 10 had severe left main coronary artery disease. Eleven of the 48 (23%) were women. ECG and enzyme-proved infarctions occurred in 6 of the 48 patients (12%), but the addition of 99mTc-PYP myocardial imaging demonstrated scintigraphic evidence of infarction in 15 patients (31%), including 2 who died in the operating room. The 99mTc-PYP myocardial imaging technique, which has proved safe, simple, and relatively inexpensive in these patients, suggests that the incidence of infarction after coronary bypass operations is somewhat higher than has been previously recognized from just ECG and enzyme changes. This technique also has been of value in helping to exclude myocardial infarction in difficult clinical situations such as postoperative arrhythmias and the postpericardiotomy syndrome.

Adult↗
PubMed1976

Differences between supine and sitting Frank-lead electrocardiograms.

Frank-lead electrocardiograms (ECGs) were recorded from 59 adult males with suspected coronary artery disease. Three records were recorded consecutively on frequency modulated tape for each patient in (1) supine position, (2) sitting position with arms relaxed, and (3) sitting position on bicycle with arms on bicycle handles. Electrodes were applied at the level of the fifth intercostal space with patients in the sitting position. Computer measurements of electrocardiographic amplitudes were averaged over ten seconds of each record with these results: (1) QRS spatial amplitudes and R amplitudes in lead z were significantly higher and R amplitudes in lead y lower for sitting than for supine positions. (2) Except for slightly higher R and S amplitudes in lead x for sitting with arms on bicycle, no significant differences were observed between the two sitting positions. (3) These postural differences are significantly greater than those resulting from day-to-day variability of electrode locations. It is hypothesized that electrode level shifts with postural changes are responsible for the observed x- and z-lead changes. For the y-lead changes, it is hypothesized that shifting blood volumes with postural changes are the cause. It is concluded that reference electrocardiographic measurements for stress testing should be obtained from resting ECGs with the patient in the same postural position as that maintained during exercise.

Electrocardiography↗
PubMed1976

Effects of digitalis and calcium on papillary muscles in normal and hypoxic states.

The effects of digoxin and ouabain in 2.5 and 4.0 mM extracellular calcium were studied in well-oxygenated and hypoxic isolated, isometrically contracting cat papillary muscles. Muscle digoxin content was measured at the conclusion of the digoxin experiments. In the well-oxygenated environment muscles in the higher Ca bathing media reached peak glycoside inotropic effect sooner and contained 2.7 times more digoxin. During hypoxia and reoxygenation muscles contracting with glycosides performed no differently than those without a glycoside present. Muscle digoxin content was lowered at the end of hypoxia (P less than 0.05) in 2.5 mM Ca; after reoxygenation digoxin content was significantly greater than either before or after hypoxia (P less than 0.001). Hypoxic depression of muscle performance was attenuated in 4.0 mM Ca but muscles in 2.5 mM Ca showed greater improvement during reoxygenation even though the muscles in 4.0 mM Ca had significantly greater digoxin content at the end of reoxygenation (P less than 0.02). It therefore is concluded that, although altered extracellular calcium can alter performance during hypoxia and reoxygenation, muscle performance is not aided by the presence of digitalis and under these conditions performance cannot be correlated with muscle digoxin levels.

Animals↗
PubMed1976

Perioperative myocardial infarction diagnosed by technetium 99m stannous pyrophosphate myocardial scintigrams.

Two groups of patients have been studied using 99mTc stannous pyrophosphate myocardial imaging prior to and 3-5 days after myocardial revascularization. The first group consisted of 48 patients undergoing revascularization, including 26 with unstable angina and seven with concomitant valve replacement. There were 3 deaths (6%), and the incidence of perioperative infarction by electrocardiogram (ECG) and enzyme analysis was 6/48 (12%), while 15 of 48 (31%) had positive myocardial scintigrams. The second group of 29 patients included one nonischemic death (3%) that was excluded. The operative technique was changed (optical magnification used, silastic tapes avoided, venting avoided, while aortic cross clamping was used frequently). In this latter group two of 29 (7%) had ECG evidence of infarction while four of 28 (14%) had positive scintigrams, compared to the pervious incidence of 31%. The imaging technique is simple, reliable, and probably more sensitive in the postoperative setting than ECG and enzyme analysis. It appears useful in evaluating the influence of changes in operative technique on myocardial preservation.

Female↗