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Biomedical subjects

P P Steele

Publications and source records attributed to P P Steele.

At least 19 recordsLinked to original sources

Caffeine does not potentiate gamma-radiation induced DNA damage in ataxia telangiectasia lymphoblastoid cells.

Ataxia telangiectasia (AT) cells display a profound sensitivity to ionizing radiation, exhibiting more frequent chromosomal breaks, increased micronuclei formation and abnormal DNA repair kinetics following exposure. Despite the recent cloning of the ATM gene there remains a need for a simple and rapid means of discriminating AT heterozygotes from normal individuals. Caffeine (1,3,7-trimethyl xanthine), known to inhibit the repair of double-strand DNA breaks following ionizing radiation, increases the frequency of radiation induced chromosomal breaks in normal cells. Here we report that caffeine potentiates the induction of chromosomal breaks in G2 arrested AT heterozygote and normal lymphoblastoid cells, but not in homozygous AT lymphoblastoid cells. This observation parallels the findings reported by others that caffeine fails to potentiate the effect of ionizing radiation in radiation-sensitive yeast strains and radiation sensitive CHO cells. It also suggests that caffeine may somehow mimic the effect of the ATM gene product in normal cells. We also report that caffeine is unlikely to be useful in helping to discriminate AT heterozygotes from normal individuals.

Ataxia Telangiectasia↗

Comparative efficacy and safety of oral tocainide and quinidine for benign and potentially lethal ventricular arrhythmias.

The antiarrhythmic efficacy and safety of oral tocainide hydrochloride and quinidine sulfate were compared in a double-blind, 3-center, parallel trial involving 133 patients with benign and potentially lethal ventricular arrhythmias. Baseline demographic, etiologic, functional and ventricular arrhythmia data were not significantly different between the 2 groups. Two weeks of an initial placebo period were followed by 8 weeks of active drug treatment, concluding with 4 weeks of washout. Frequent 24-hour ambulatory electrocardiographic monitoring was used to judge efficacy. Ten of 27 patients (37%) receiving tocainide and 12 of 24 patients (50%) receiving quinidine had a 75% reduction with drug treatment compared with the initial placebo period (p greater than 0.25). Total abolition of ventricular tachycardia occurred in 6 of 16 patients (37%) receiving tocainide and 6 of 13 patients (43%) receiving quinidine (p greater than 0.25). Conditions that required discontinuation of therapy occurred in 18 of 67 patients (27%) receiving tocainide and 16 of 66 (24%) receiving quinidine (difference not significant). More patients had dizziness during tocainide treatment and diarrhea during quinidine treatment. Quinidine caused a prolongation in the QT interval (0.03 second); tocainide caused a slight reduction (0.01 second). No important changes in vital signs or laboratory measurements were observed in left ventricular ejection fraction when measured. Thus, tocainide, the new oral analog of lidocaine, appears to be as safe as quinidine but is slightly less effective in suppressing ventricular arrhythmias.

Administration, Oral↗

Left ventricular platelet deposition after acute myocardial infarction. An attempt at quantification using blood pool subtracted indium-111 platelet scintigraphy.

Since indium-111 platelet scintigraphy for the detection of left ventricular thrombosis often shows considerable non-specific blood pool activity a subtraction method using simultaneous technetium-99m blood pool scintigraphy was undertaken in 11 subjects with well documented remote myocardial infarction, who served as positive or negative controls, and in 18 consecutive patients with acute myocardial infarction. The results were compared with those of cross sectional echocardiography. Thirteen patients had transmural myocardial infarction and the calculated count per pixel in the left ventricle of the subtracted indium-111 platelet scintigram was (mean (SD)) 0.28(0.35), but five patients with subendocardial myocardial infarction had a mean count of 0.04(0.06). In seven patients with transmural myocardial infarction (two anterior and five inferior) left ventricular thrombosis was detected by indium-111 platelet scintigraphy but in only one of these by cross sectional echocardiography. None of the patients with subendocardial myocardial infarction had left ventricular thrombosis. Subtracted left ventricular counts correlated well with the visual results. It is concluded that left ventricular platelet sequestration after acute myocardial infarction may be quantified and precisely located and that quantitative longitudinal studies of the natural history and drug intervention are now possible.

Adult↗

Seven-pinhole tomography--a technical description.

A single-photon emission tomography system was developed and studied. Based upon a seven-pinhile-collimated Anger camera, interfaced to a digital minicomputer, this imaging configuration yielded seven independent, nonoverlapping projection images of the radioactivity in a commonly viewed volume. The computer was used to implement an iterative algorithm that processed these projections to yield a three-dimensional reconstruction of the soruce distribution. The algorithm provudes a nonlinear first approximation to the reconstruction, then use a single iteration technique to reduce errors resulting from that approximation. Point spread functions (PSF) at various distances from the collimator face, and point-source sensitivity (PSS) at a location in the middle of the reconstruction volume were determined. The system was used for thallium-201 imaging, where it was shown to reduce imaging time and increase sensitivity without loss in specificity when compared with standard parallel-hole-collimated imaging. Seven-pinhole tomography is a practical three-dimensional imaging system that has been demonstrated to be useful in the emission cardiology setting.

Heart↗

Quality control of scintillation cameras using a minicomputer.

A minicomputer-based technique compiles objective indicators of scintigraphic system performance. The evaluation begins with the acquisition of a single image of an orthogonal hole pattern from which quantitative and regional measurements of point-source sensitivity, spatial resolution, and spatial linearity are derived. Two computer programs offer the user different but complementary features. The first program is the basis of an evaluation performed by a technologist for purposes of quality control. Operator intervention is minimal, and the entire protocol, including data acquisition and processing, can be completed in 20 min. The results are automatically compiled and displayed as graphs showing 100 consecutive sets of daily performance measurements. A second computer program is designed as an interactive diagnostic and research tool to display measurements as histograms and functional images. The operator can use the program to determine the quantitative and spatial characteristics of the system's intrinsic performance measurements made during the quality-control evaluations.

Computers↗

Improvement of platelet survival time with oxygen in patients with chronic obstructive airway disease.

Platelet survival time has been found to be shortened in hypoxemic patients, and these patients may have an increased risk of thromboembolism. Supplemental O2 was administered to 10 men with sever chronic obstructive airway disease and hypoxemia. Oxygen increased platelet survival time from a mean +/- SE of 1.9 +/- 0.16 to 2.5 +/- 0.21 days (P less than 0.005; normal half-time, 3.7 +/- 0.03 days); the survival half-time was increased by 0.03 days or more in 9 of these 10 men. Arterial Po2 was increased (46.0 +/- 1.1 to 60.0 +/- 1.5 mm Hg; P less than 0.001) in all men. Results suggest that hypoxemia is associated with shortened platelet survival time and that an increase in arterial Po2 is associated with an increase in platelet survival time. Although not established by this study, the increase in platelet survival time associated with supplemental O2 may decrease the risk of thromboembolism.

Blood Platelets↗

Methoxamine-induced increase in afterload. Effect on left ventricular performance in chronic obstructive pulmonary disease.

With a radionuclide technique, left ventricular ejection fraction and stroke volume index were measured in the basal state and after the stress of a methoxamine-induced increase in afterload in 10 men with severe chronic obstructive pulmonary disease. The resting mean left ventricular ejection fraction was normal in all 10 patients. After an acute increase in resistance to left ventricular ejection with methoxamine, the left ventricular ejection fraction and the stroke volume index did not decrease significantly, even in the presence of cor pulmonale in 5 patients. Mean pulmonary capillary wedge pressure was normal before, and did not change significantly after, methoxamine infusion. The data suggest that latent left ventricular dysfunction is not present in this group of patients with severe chronic obstructive pulmonary disease.

Aged↗

Effect of dextran loading on left ventricular performance in chronic obstructive pulmonary disease.

The status of left ventricular function in patients with chronic obstructive pulmonary disease remains controversial. With a radionuclide technique left ventricular ejection fraction, left ventricular end-diastolic volume, cardiac output, and stroke volume were measured at rest and following infusion of dextran in 23 men with severe COPD. Resting, mean LVEF was normal in 19 subjects with COPD alone; four with COPD and coronary artery disease had a depressed mean LVEF. Left ventricular end-diastolic volume index and pulmonary capillary wedge pressure were both normal at rest indicating that the left ventricle was not volume underloaded. There was a normal response to dextran infusion (750 ml.) with no deterioration in LVEF and a significant increase in cardiac index, stroke volume index, LVEDVI, and PCW. These data suggest that at rest and following volume loading with dextran left ventricular function is normal in patients with COPD.

Aged↗

Effects of isosorbide dinitrate and nitroglycerin on central circulatory dynamics in coronary artery disease.

This study compares the effects and duration of the effects of 5 mg. of sublingual (SL) isosorbide dinitrate (ISD), 20 mg. of oral ISD, and 0.4 mg. of SL nitroglycerin (TNG) on central circulatory dynamics. Twenty-seven patients with coronary artery disease were evaluated with radioisotope techniques and determinations made of heart rate (HR), blood pressure (BP), cardiac index (CI), stroke volume index (SVI), left ventricular enddiastolic volume index (LVEDVI), and left ventricular ejection fraction (LVEF). There were significant and equivalent reductions in BP, SVI, LVEDVI, and CI 15 minutes after TNG, 1 hour after SL ISD, and 4 hours after oral ISD in addition to comparative increases in HR and EF by all drugs at these same time intervals. The effects of TNG were gone at 30 minutes while changes in LVEDVI, LVEF, and CI were present 4 hours after SL ISD and persistent changes in LVEDVI and SVI present 6 hours after oral ISD. We conclude that nitrates have significant effects on both preload and afterload and that the duration of effects of sublingual and oral ISD are truly long acting as compared to TNG.

Administration, Oral↗

Quantitative radiocardiography in major pulmonary thromboembolism.

Cardiac index (CI) and pulmonary blood volume index (PVBI) were measured by quantitative radiocardiographic studies using radioactive 113mindium and a scintillation probe in 37 patients with confirmed major pulmonary thromboembolism. The mean PBVI was 185 +/- 11 ml/sq m (SE) and was significantly less than normal (310 +/- 5 ml/sq m [SE]; P less than 0.001). Six patients with major pulmonary thromboembilism had a PBVI within the normal range (262 to 358 ml/sq m; mean +/- 2 SD), and the mean pulmonary vascular occlusion was 21 percent in these patients. Eighteen patients (49 percent) died, and the most significant correlate of mortality was CI, which was depressed (less than 2.7 L/min/sq m) in all but two. Twenty-three serial determinations of pulmonary blood volume (PBV) ranging from 1 to 18 days after the initial study showed a mean increase in PBV of 27 ml/day in ten survivors. Quantitative radiocardiographic studies provide a means of diagnosing major pulmonary thromboembolism by measuring decreases in PBVI; it can assess the magnitude of major pulmonary thromboembolism and can assess CI and, thereby, predict risk of mortality; and it provides a means of following the resolution rate of major pulmonary thromboembolism.

Adult↗

A mathematical model for the determination of cardiac regurgitant and ejection fractions from radioisotope angiocardiograms.

A mathematical model taking into account the pulsatile pumping action of the heart has been developed which describes, in terms of a set of four recursive equations, the activity in the atrium and in the ventricle of the left or right heart at successive end-systoles and end-diastoles after bolus injection. The resulting closed form solutions permit calculations of chamber forward ejection fractions and valvular regurgitant fractions from computerized radioisotope angiocardiogram data. The method has been applied to a series of over thirty clinical studies with encouraging results.

Angiocardiography↗

Improvement of myocardial and other vital organ functions and metabolism with a simple method of pulsatile flow (IABP) during clinical cardiopulmonary bypass.

A simple, safe, and effective method of producing pulsatile flow during cardiopulmonary bypass (CPB) with intra-aortic balloon pumping (IABP) was used in 56 patients. No complications were associated with IABP. Myocardial metabolic studies, including coronary sinus lactates, mycoardial venous-arterial lactate differences, myocardial lactate extraction, and "excess lactate" were determined serially during the first hour of CPB. Changes in myocardial metabolism were statistically less abnormal in pulsatile flow (PF) patients when contrasted with a comparable group of nonpulsatile flow (NPF) patients. The changes were probably myocardial in origin since alterations in arterial lactates and lactate/pyruvate ratios were similar in both groups. In a comparable group of coronary bypass NPF patients, the percentage of left ventricular ejection fractions fell during the immediate postoperative period, whereas it rose in the PF group. Over-all body tissue injury (lactic dehydrogenase) and probably hepatocellular injury (serum glutamic oxalacetic transaminase) were less apparent in the PF patients. Postoperative low-cardiac-output syndrome did not occur in the PF patients and supportive drugs and diuretics were not needed. PF does not produce excessive hemolysis. This procedure may improve mortality rates by improving myocardial and other vital organ perfusion and by sustaining their function during weaning from CPB. This technique may prove superior to other forms of PF and is indicated in patients with severe left ventricular or other vital organ dysfunction and/or prolonged CPB.

Aspartate Aminotransferases↗