Kathryn Witztum

A Randomized Trial of Exercise Training in Patients With Coronary Heart Disease

In order to determine whether or not regular exercise could alter myocardial perfusion or function, we randomized 146 male volunteers with stable coronary heart disease to either a supervised exercise program (n = 72) or to a usual care program (n = 74). Subjects underwent exercise tests initially and one year later. Significant differences between the two groups included improved aerobic capacity, thallium ischemia scores, and ventricular function in the exercise intervention group. It was not possible to classify the conditions of patients as to the likelihood of improvement or deterioration. This study demonstrated changes in myocardial perfusion and function in a select group of middle-aged men with coronary heart disease who underwent a medically appropriate exercise program lasting one year, but these changes were relatively modest.

Agreement in human interpretation of analog thallium myocardial perfusion images.

To assess the agreement of human interpretation of analog thallium myocardial perfusion images, four experienced interpreters evaluated 100 images on two occasions using a form designed to limit reader variability. A high intraobserver agreement (agreement by same observer at separate times) of 89–93% was found when films were interpreted as normal or abnormal (a dichotomous decision). Interobserver agreement for a majority grouping of observers (three or four) was 75% for an abnormal and 68% for a normal interpretation. However, agreement ranged from 11–79% when interpreters were asked to read the anatomic location of defects. Posterior and lateral wall defects were interpreted with the least amount of agreement. These results indicate that caution must be taken when interpreting defect location. Using a scale of 1–10 to grade the severity of a defect, correlations of 0.82–0.86 were found when reading defects in the lateral and anterior projections. Higher correlations, from 0.86–0.94, were found in left anterior oblique views. Use of reporting forms with specific criteria, multiple observers at one occasion, and/or computer processing may improve agreement. A brief review of the agreement of cardiology testing procedures is also presented.

Can areas of myocardial ischemia be localized by the exercise electrocardiogram? A correlative study with thallium-201 scintigraphy

In order to determine whether areas of ischemia identified by thallium-201 scintigraphy could be localized by exercise ECG, we studied 54 patients with stable coronary heart disease. All 54 patients had exercise-induced thallium-201 scintigraphic defects. Their exercise ECG test results were compared to their thallium-201 images and also to 14 low-risk normal subjects. Exercise data were analyzed for spatial ST vector shifts, using a computer program in order to most accurately classify ST segment depression and elevation. Thallium-201 ischemic defects detected in our patients included areas in the septum and the inferior, lateral, and anterior walls. Twenty-six of these 54 patients also had coronary angiography for classification and comparison as having either localized or generalized disease. None of the scintigraphic ischemic sites or angiographic diseased areas could be specifically identified by exercise-induced ST vector shifts. Therefore, the surface exercise ECG has limitations in localizing ischemia to specific areas of the myocardium.

Controlled entry of orally administereddrugs: physiological considerations

AbstractPhysiological considerations bearing on the controlle entry into the systemic circulation of orally administered drugs in healthy man are reviewed. The most desirable site for drug absorption is the sterile portion of the small intestine, so that the time “window” available for absorption is not greater than the minimum small intestinal residence time in this segment. This appears to vary widely between individuals. Methodology for sampling intestinal content and for defining the fraction absorbed and the physical state of an administered drug are summarized. Small intestinal transit and gastric emptying rates are now estimated in man by imaging techniques using Tc99m labeled sulfur colloids. Small intestinal transit may also be estimated non-invasively by measuring breath H2 after administration of a meal containing a non-absorbable disaccharide such as lactulose, but the validity of such a method is uncertain because of the acceleration of intestinal transit by lactulose. The major determinants ...

Limitations of indirect methods of estimating small bowel transit in man

Experiments were carried out in healthy volunteers to explore the utility of a new [14C]lactulose breath test for measuring small intestinal transit time in man and to use this procedure to test whether two antidiarrheal agents, codeine and clonidine, alter small intestinal transit time during digestion of a liquid meal. In an initial validation study performed in 12 subjects (three studies in each subject), a liquid test meal containing 10 g [14C]lactulose was administered and the colonic entry time estimated from the time course of14CO2 excretion in breath compared with that of H2 excretion. There was a fair correlation (r=0.77;P<0.001) between results obtained by the two methods; both methods gave similar results, but14CO2 output was delayed when compared to H2 output and was incomplete. The meal also contained xylose and [13C]glycine, permitting the duodenal entry time of the meal to be estimated by the appearance of xylose in blood and13CO2 in breath, respectively. The same liquid meal was then used to examine the effect on small intestinal transit time (colonic entry time minus duodenal entry time) of codeine or clonidine.99Tc-sulphur colloid was also added to the meal to permit a comparison of small intestinal transit estimated by imaging with that estimated by the14CO2-lactulose breath test.99Tc radioactivity appeared in the cecum (as assessed using gamma scintigraphy) about 2 hr before14CO2 radioactivity appeared in breath; the correlation between transit time estimated by the two methods was moderate (r=0.61;P<0.05). Based on the [14C]lactulose data, small intestinal transit time ranged from<1 to 3 hr for a liquid meal containing 10 g lactulose; within-subject variation (coefficient of variation 17%) was considerably less than between-subject variation (coefficient of variation 56%). Codeine increased the small intestinal transit time significantly (from 2.7±0.3 hr to 5.0 ±0.9 hr; mean±SE), whereas clonidine did not alter small intestinal transit time, as estimated by the colonic entry time minus duodenal entry time. Neither drug influenced duodenal entry time. These results suggest that the [14C]lactulose breath test, which has only moderate accuracy, may have occasional utility as a convenient, noninvasive method for estimating small intestinal transit time in man. However, this study also suggests that indirect methods of estimating small bowel transit in man have limitations, variability, and possibly may lack the desired sensitivity.

Noninvasive assessment of changes in myocardial perfusion and ventricular performance following exercise training.

Seventeen coronary patients (CAD) underwent thallium (TI-201) treadmill and radionuclide (RNV) ejection fraction supine bicycle testing before and after 5.6 +/- 1.6 (mean +/- SD) months of an exercise program. Thallium data were assessed both using analog images and a computerized circumferential profile technique. Patients exercised on the treadmill to a higher workload after the exercise program, but achieved a similar pressure-rate product. When interpreting the analog thallium images, only 50% agreement was obtained for the assessment of changes in myocardial perfusion (pre/post-training). The computer technique, however, had low inter-intraobserver variability (6%) and better agreement (90.5%). Using the circumferential profile method, five patients improved (a total of 11 regions) and one patient worsened (with two regions). Before the exercise program, the ejection fraction (EF) response to supine bike exercise was normal (an increase greater than 11%) in four, flat in seven, and severely abnormal (a decrease of more than 4%) in six patients. After the exercise program, even though achieving similar or higher pressure-rate products, six patients improved their EF response, nine did not change, and two worsened. Of the five patients who improved their thallium images, one improved his EF response, two remained normal, and two did not change. One patient worsened both his thallium study and the EF response after the exercise program. Changes in thallium exercise images and the EF response to supine exercise occurred in our patients after an exercise program, but were not always concordant. Indeed, of five patients with exercise-induced ischemic ST changes before and after training, the EF response improved in three whereas myocardial perfusion was unchanged. Reasons for this lack of agreement are discussed, and have been considered in the planning of a randomized trial of the effects of an exercise program on myocardial perfusion and function.

Right and left ventricular response to subcutaneous terbutaline in patients with chronic obstructive pulmonary disease: Radionuclide angiographic assessment of cardiac size and function

To assess the response of the right and left ventricles to the subcutaneous administration of terbutaline sulfate, a beta-2 selective agonist, we evaluated 14 patients with chronic obstructive pulmonary disease (COPD) with equilibrium radionuclide angiography (RNA). Prior to injection, eight patients (57%) had an abnormal right ventricular ejection fraction (RVEF), four (29%) had a low left ventricular ejection fraction (LVEF), and three (21%) had low ejection fractions of both ventricles. After terbutaline injection, RVEF increased in 13 of 14 patients (93%) by 17 +/- 8% (p less than 0.001) while LVEF increased in all patients by 15 +/- 7% (p less than 0.001). Both left and right ventricular end-diastolic volumes decreased (p less than 0.01), while stroke volume was unchanged. Cardiac output rose by 0.8 +/- 1.3 L/min (p less than 0.05), primarily due to the increase in heart rate (10 bpm, p less than 0.001), since stroke volume did not significantly change. We conclude that in patients with COPD subcutaneous terbutaline has significant beta-1 cardiac effects; it increases the heart rate and decreases cardiac size.

Calculation of relative glomerular filtration rate and correlation with delayed technetium-99m DMSA imaging.

The relative renal uptake of Tc-99m DMSA was compared with the relative glomerular filtration rate (GFR) in ten patients with serum creatinines ranging from 0.3 to 2.5 mg/dl. Relative GFR was based on the renal uptake of Tc-99m DTPA determined by two methods: 1) Integrating the counts from 1 to 3 minutes postinjection and correcting for background. 2) Totalizing the individual renal counts in a single 15-second frame from 2:45 minutes to 3:00 minutes postinjection and correcting for background. The two methods of determining relative DTPA uptake showed excellent correlation, r = 0.98. Relative DMSA uptake determined at 24 hours post-injection using computer-assisted regions of interest showed excellent correlation with the relative GFR determined by either the integral or single-frame method, r = 0.98. The addition of background subtraction for the DMSA images at 24 hours did not improve the correlation.

Positive In-111 white cell scan in a patient with multiple metastases

A case of increased uptake of ln-111-labeled leukocytes in bony metastases from adenocarcinoma of the prostate is presented. Bone scintigraphy, subsequent to the white cell study, showed virtually identical abnormalities as the indium scan. Clinical course and laboratory data supported the diagnosis of widespread metastatic carcinoma. Although the exact cause(s) is unclear, possible mechanisms are discussed.

Expanded 99mTc-methylene diphosphonate (MDP) bone scan

Patients with prostatic cancer frequently require evaluation of bony metastases as well as renal function. 99mTc-methylene diphosphonate, a commonly used bone-imaging agent, is about 60 per cent localized in the bony skeleton and about 40 per cent excreted by the kidneys. Immediate imaging after intravenous injection of the isotope may yield high-quality radionuclide nephrourograms, which provide excellent visual and graphic displays of renal anatomy and excretory function. Our preliminary studies suggest that the immediate 99mTc-methylene diphosphonate scan may usefully expand the value of a routine bone scan to screen for ureteral obstruction. Patients with underlying malignancy who require simultaneous evaluation and follow-up of bony metastases and renal function might be conveniently served by the dual functions of the expanded bone scan to include immediate imaging of the kidneys.