Value of objective assessment of new radiopharmaceuticals.
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Biomedical subjects
Publications and source records attributed to R E Patterson.
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Left ventricular dysfunction has become one of the most common causes of death, disability, and health care costs. Left ventricular dysfunction is usually due to coronary artery disease (CAD) and can be improved considerably by successful revascularization in many, but not all, patients. The key issue determining whether revascularization will relieve left ventricular dysfunction is whether the patient has enough viable myocardium to improve after revascularization. Viable myocardium is located anatomically in the subepicardial layers of the left ventricular wall, above the infarct in the subendocardial layers in the distribution of a stenotic coronary artery. Clinical history, physical examination, resting or exercise ECG, and imaging studies of left ventricular function often fail to distinguish patients with viable myocardium. Thallium-201 myocardial imaging at stress and rest is better if performed with reinjection of thallium-201 at rest, but this method still misses many patients with viable myocardium. Positron emission tomographic (PET) myocardial imaging to compare distributions of a perfusion tracer versus a metabolic tracer (fluorine-18-fluoro-deoxyglucose, 18FDG) has been cited as the "gold standard" method to identify viable myocardium by position papers from several professional organizations. PET imaging of rubidium-82, a potassium analogue ("washout" from "early" [first 1.5 minutes] to "late" [next 5 minutes] images) and gated magnetic resonance imaging (MRI) also show promise.
Hypertension is common in patients undergoing stress and delayed single-photon emission computed tomography (SPECT) thallium-201 myocardial perfusion imaging. Investigators have reported that patients with end-stage renal disease and left ventricular hypertrophy due to hypertension have diminished lateral/septal count ratios on stress and delayed imaging mimicking lateral myocardial infarction in approximately 35% of patients. Subsequently, hypertension has been cited as a frequent cause of thallium-201 artifacts. The purpose of this study was to compare myocardial SPECT thallium-201 distribution in a broader group of patients with left ventricular hypertrophy resulting from hypertension with normal file subjects in order to determine the prevalence of abnormal studies and to compare the lateral/septal count ratio. Average counts in all myocardial regions in the male study group (n = 16) were compared with those in the normal male file patients (n = 49), with particular attention to the lateral and septal walls. In the group of 16 men with hypertension and left ventricular hypertrophy, as a whole, the mean lateral/septal wall count ratio was 4.4% lower (1.09 +/- 0.07) than that in the normal file (1.14 +/- 0.07; p < 0.01). At 3-hour delay, the ratio was virtually the same in the study group (1.06 +/- 0.09) as in the normal file (1.08 +/- 0.06; p = NS). Most important, for clinical purposes no patient had a defect, defined as a lateral/septal count ratio > 2.0 SD below normal limits. All thallium-201 studies were interpreted as normal. In conclusion, myocardial thallium-201 distribution is normal in patients with left ventricular hypertrophy due to hypertension.
BACKGROUND: Reaching national health objectives depends upon our ability to encourage the performance of multiple good health behaviors. There are cognitive, social, and biological reasons for expecting health behaviors to cluster. However, few studies have found significant associations among health behaviors, with the exception of the documented link between smoking and alcohol consumption. METHODS: We used cluster analysis to identify population subgroups with similar patterns of diet quality, physical activity, alcohol consumption, and cigarette smoking. This is the first study of health behavior interrelationships to include a measure of overall diet quality and a large sample from a nationally representative survey of U.S. adults. RESULTS: We identified seven health behavior typologies: 10% of the sample (health promoting lifestyle) had an overall healthy lifestyle, 25% had a good diet but sedentary activity level, 18% had fair diet but high activity level (fitness lifestyle). Individuals in the passive lifestyle cluster (25%) had no active health promoting activities but did avoid risk taking health behaviors. Six percent of the sample were in a drinking cluster, 15% in a smoking cluster, and 2% had a hedonic lifestyle characterized by heavy drinking and smoking. These lifestyle clusters could be characterized by demographic and socioeconomic factors. CONCLUSIONS: This research indicates that it is possible to identify a discrete number of health lifestyles in a population sample of U.S. adults. Understanding past, present, and changing health lifestyles may provide insights for health behavior research and information for the development and targeting of public health programs that can impact on multifactorial chronic diseases.
OBJECTIVE: Data for 5,484 adults (aged 21 years and older) who participated in the 1987-88 Nationwide Food Consumption Survey (NFCS) were used to develop an index of overall dietary intake that related to the major, diet-related, chronic diseases in the United States. The low response rate of the 1987-88 NFCS has raised concerns about potential bias, but this large data set is useful for methodologic studies and research that does not attempt to generalize the results to the US population. ANALYSES: Dietary recommendations from the 1989 National Academy of Sciences publication Diet and Health were stratified into three levels of intake for scoring. Individuals who met a dietary goal were given a score of zero. Those who did not meet a goal, but had a fair diet, were given one point, and those who had a poor diet were given two points. These points were summed across eight diet variables to score the index from zero (excellent diet) to 16 (poor diet). RESULTS: Lower index scores were positively associated with high intakes of other important measures of diet quality (eg, fiber, vitamin C). We found that single nutrients (such as dietary fat) were not necessarily associated with other measures of diet quality. CONCLUSION: We concluded that this index ranking of overall dietary patterns was reflective of total diet quality, though substantial misclassification can result from using single nutrients or foods as indicators of diet quality.
The purpose of this review is to compare several modalities available for detection of coronary artery disease (CAD). We compare the clinical history, rest/exercise electrocardiogram (ECG), rest/stress left ventricular (LV) function by radionuclide or echocardiographic methods, myocardial perfusion imaging (MPI) by single photon emission computed tomography (SPECT) or positron emission tomography (PET), contrast coronary angiography, magnetic resonance imaging (MRI), spectroscopy (MRS) and angiography (MRA), and ultrafast cine computed tomography (UFCT) to assess LV function, myocardial perfusion, and coronary calcification. We compare the modalities by answering six questions: (1) Does the modality provide unique clinical information? (2) What is the observer error? (3) What are sensitivities and specificities to detect CAD? (4) What patient selection criteria should be applied for each modality? (5) What incremental benefit is obtained from one modality versus another modality? and (6) Where do the modalities fit in the overall scheme of diagnostic testing for CAD? PET MPI appears to be the best noninvasive test for CAD, followed by SPECT thallium-201 and then dobutamine echocardiography. MRA and UFCT may soon play a larger role because they visualize the arteries. Contrast coronary angiography remains the gold standard despite its limitations. Exercise ECG is the least accurate test. The choice of tests critically depends on patient selection--based on clinical history, age, gender, and risk factors to estimate the pretest, clinical probability of CAD.
The stages of change construct, which addresses the readiness to change, has only recently been applied to dietary behavior, such as fat consumption. This article describes the application of the stages of change construct to dietary fat and fiber consumption and examines the association of dietary stages to eating practices and related demographic and psychosocial factors in a large, geographically diverse population of workers. We present results from the baseline survey of 17,121 employees in the Working Well Trial. We assessed stage from an algorithm based on seven items and measured dietary intake with an 88-item food frequency questionnaire. Findings indicated that a greater proportion of the population has actively tried to reduce fat intake than to consume more fiber. Stage of change was associated with fat, fiber, and fruit and vegetable intake in a stepwise manner, as predicted. In multivariate analyses that controlled for demographic characteristics, stage of change predicted between 8 and 13% of the variance in dietary intake, and more than demographic variables. These findings have implications for the design of nutrition interventions and for the evaluation of intermediate outcomes.
UNLABELLED: Technetium-99m-sestamibi images reflect tracer distribution at the time of injection. This "stay put" indicator allowed us to separate the effects of segmental left ventricular dysfunction per se versus myocardial blood flow on SPECT "perfusion" images in ten dogs. METHODS: An electromagnetic flow probe and hydraulic occluder were placed on the LAD coronary artery. Sonomicrometry was used to measure segmental wall shortening. At peak myocardial blood flow induced by adenosine, 35-45 mCi 99mTc-sestamibi were injected without occlusion. At 1 hr postinjection, during normal contraction, 40-50 msec end-diastolic and end-systolic SPECT images (#1) were acquired to reflect normal myocardial blood flow distribution. Later, during total LAD occlusion, and without reinjection of isotope, another gated scan (#2) was acquired. RESULTS: Coincident with abnormal contraction, large severe systolic defects [(28 +/- 5)% more severe compared to the baseline-scan #1; p < 0.01], and milder diastolic defects [(12 +/- 8)% more severe compared to the baseline-scan #1; p < 0.01] were observed during scan #2. Thus, abnormal contraction alone produced defects on SPECT images. CONCLUSION: Accordingly, defects in myocardial perfusion images must be interpreted as representing the integrated result of the combination of blood flow and segmental contraction heterogeneity.
We investigated the frequency and extent of changes in heart position and geometry independent of body motion during stress single-photon emission tomography (SPET) thallium-201 myocardial perfusion imaging. Following an exercise treadmill test, patients had a 22.1-min SPET acquisition which was followed immediately by a static image acquisition for 1 min with the camera position identical to the first view of the SPET study. Point sources were placed on the body to monitor patient motion. Cardiac motion was assessed by an approach which mimicked a cross-correlation technique applied to cardiac count profiles along the horizontal and vertical directions from the first view of the SPET study and the static image. A large percentage (87.5%) of cases had some degree of horizontal or vertical motion. Pixel shifts in cardiac position of > or = 2 pixels (12 mm) occurred in 60% of patients. In 37% of patients who moved the cardiac motion was consistent with simple translation of the heart and thus amenable to correction using proposed SPET motion-correction programs. The peak heart rate achieved during stress and the ratio of the heart rate immediately before SPET acquisition to the resting heart rate were determined to be independent predictors of patient motion during SPET acquisition. Cardiac motion changes were minimal at (13.3 +/- 2.2) min after cessation of exercise. The implications of these findings for the accuracy of SPET 201Tl require further investigation.
OBJECTIVES: Whether intracoronary papaverine or adenosine leads to reductions in regional left ventricular function was tested. METHODS: Fifteen anaesthetised dogs were prepared to record aortic pressure, left ventricular pressure dP/dt, electrocardiogram, regional ventricular shortening, and phasic and mean left circumflex coronary blood flow, and to give intracoronary boluses of papaverine (2, 4, or 6 mg) or adenosine (0.37 and 1.87 mg). RESULTS: Injected doses were chosen to mimic those given in the clinical setting. Papaverine (6 mg) reduced aortic pressure (mean 96(SD 17) to 89(18) mm Hg; p < 0.05), segmental shortening of the infused left circumflex zone (12(5) to 7(9)%; p < 0.05), and area of the pressure-length loop of the infused zone (120(71) to 53(47) mm.mm Hg; p < 0.05). Papaverine increased coronary blood flow (48(25) to 259(95) ml.min-1; p < 0.05), coronary vascular conductance (0.40(0.20) to 2.93(0.94) ml.mm Hg-1.min-1; p < 0.05), heart rate (88(27) to 100(28) beats.min-1; p < 0.05), and the segmental shortening (17(6) to 19(3)% p < 0.05) and area of the pressure-length loop (130(32) to 177(33) mm.mm Hg; p < 0.05) of the non-infused left anterior descending region. The hyperaemia elicited by papaverine was greater than that of reactive hyperaemia (p = 0.008). Papaverine also increased the QT interval corrected for heart rate (0.35(0.04) to 0.45(0.05) s; p < 0.05). When adenosine was given, coronary blood flow and coronary vascular conductance were increased to similar degrees as those during reactive hyperaemia (41(12) to 210(75) ml.min-1 and 0.46(0.14) to 2.43(0.83) mm Hg.ml-1.min-1, respectively; NS). No effects on segmental shortening or the area of the pressure-length loop in either zone were found. Also, adenosine had no effect on the QT interval. CONCLUSIONS: These adverse effects of intracoronary papaverine have important implications in its use in patients, particularly in those in whom abnormal cardiac function already exists. Adenosine, on the other hand, seems to be without deleterious effects.
By computer simulation, we have previously hypothesized, independent of the isotope imaged, that differences in view-to-view resolution and attenuation patterns predictably cause count density distortions in SPECT images. We tested the simulation predictions for both ECG-gated and ungated SPECT 99mTc-sestamibi and SPECT 201Tl myocardial perfusion images in normal dogs. In agreement with the predictions of the computer model, distortions in SPECT 99mTc-sestamibi myocardial perfusion images are virtually equivalent to SPECT 201Tl, dependent on the exact SPECT acquisition orbit and markedly different for a posterior 180 degrees acquisition arc compared to an anterior 180 degrees acquisition arc. Furthermore, ungated and gated SPECT 99mTc-sestamibi images show similar count inhomogeneities. These results suggest that little is to be gained from a 360 degrees acquisition with SPECT 99mTc-sestamibi, and that image distortions from gated or ungated SPECT 99mTc images with 180 degrees orbits will be similar to those in SPECT 201Tl images.
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OBJECTIVES: The purpose of the present study was to compare single-photon emission computed tomographic (SPECT) myocardial images of technetium-99m (Tc-99m) sestamibi and thallium-201 (Tl-201) isotopes in the same dog undergoing partial coronary occlusion during pharmacologic vasodilation. BACKGROUND: To date, no controlled study has been reported comparing SPECT Tc-99m sestamibi with SPECT Tl-201 imaging during stress with anatomic and physiologic standards. METHODS: Mongrel dogs were anesthetized with chloralose and instrumented to record left anterior descending coronary blood flow and aortic pressure. Partial coronary occlusion with a hydraulic cuff reduced coronary vascular conductance, which is equal to the coronary blood flow normalized to aortic pressure during peak vasodilation with intravenous adenosine. Each dog received 5 mCi of Tl-201, then 30 mCi of Tc-99m sestamibi during partial coronary occlusion at peak vasodilation. Tomographic myocardial imaging was performed in a 180 degrees anterior arc scan for 33.5 min, first with Tl-201, and later, without moving the dog, for 33.5 min with Tc-99m sestamibi. Postmortem staining defined the region underperfused because of its dependence on the artery that was partially occluded. RESULTS: In seven dogs with moderate reduction in coronary blood flow, coronary vascular conductance decreased with partial coronary occlusion (47 +/- 12%) during Tl-201 imaging and (47 +/- 8%, p = NS) during Tc-99m sestamibi imaging. The underperfused region was 23.9 +/- 6.4% of total left ventricular mass. Counts in the defects were 39% higher (0.86 +/- 0.08 of normal counts) for Tc-99m sestamibi than for Tl-201 (0.64 +/- 0.09 of normal counts, p < 0.001), and the defect on SPECT Tc-99m sestamibi images occupied only a fraction (0.37 +/- 0.30) of the area of the defect on the Tl-201 images of the same dog. Bull's-eye displays constructed from the pathologic slices showed that the Tl-201 defect size was closer to the underperfused region of the left ventricular mass determined pathologically than was the Tc-99m sestamibi defect size. In four additional dogs a severe, near total coronary occlusion was created during Tl-201 and Tc-99m sestamibi administration. In these dogs, similar defect contrast (0.55 +/- 0.12 vs. 0.62 +/- 0.09, p = NS) and areas (0.18 +/- 0.07 vs. 0.18 +/- 0.11, p = NS) were observed with Tl-201 and Tc-99m sestamibi, respectively. CONCLUSIONS: Tomographic myocardial imaging with Tc-99m sestamibi during moderately severe partial coronary occlusion underestimated the area of the defect relative to Tl-201 or to the pathologic reference standard in dogs. Defect contrast was sharper with tomographic myocardial Tl-201 than with tomographic myocardial Tc-99m sestamibi during moderately severe partial coronary occlusion.
This study compares dietary practices of persons aged greater than or equal to 65 y surveyed as part of the 1977-78 and 1987-88 Nationwide Food Consumption Surveys. Intakes of high-fat beef and pork, whole milk, and white bread decreased with increases in low-fat beef, pork, poultry and fish, low-fat milk, and whole-grain breads. However, consumption of many important sources of calories and fat (high-fat desserts, butter, and margarine) and fiber (fruits, high-fiber cereals, and vegetables) changed little between 1977 and 1987. The food-consumption trends translated into modest changes in overall nutrient intake. Gender differences were small and contradict the prevailing feeling that women are changing their diets more rapidly than are men. The authors suggest that public health messages have focused too heavily on foods to avoid while not giving adequate guidance for how to plan and prepare meals that will enable older Americans to meet the current diet and health recommendations.
We previously reported that coronary constriction following neuropeptide Y (NPY) was alleviated by cyclooxygenase blockade. To determine the role of thromboxane A2 (TxA2), anesthetized dogs received two paired doses of NPY given 2 h apart. Nine control dogs received NPY alone. Nine test dogs received one of three TxA2 receptor antagonists given between the doses of NPY. Also, five dogs received NPY during which prostaglandins were measured. In controls, NPY decreased coronary blood flow and increased aortic pressure; coronary resistance was increased significantly. Heart rate fell, and myocardial oxygen consumption was unchanged. Thromboxane receptor blockers significantly relieved the coronary constrictor effect of NPY. The reduction in coronary blood flow was blunted, while heart rate, first derivative of left ventricular pressure, and myocardial oxygen consumption were unchanged. Alleviation by TxA2 receptor blockade paralleled that reported for cyclooxygenase inhibitors. Also, significant increases in coronary venous TxA2 were seen at the time of maximal increases in coronary resistance, while prostacyclin was unchanged. In summary, TxA2 appears to mediate part of the coronary constrictor effect of NPY.
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The purpose of this study was to determine whether reperfusion of acute myocardial infarction (AMI) by recombinant tissue-type plasminogen activator (rt-PA) or percutaneous transluminal coronary angioplasty, or both, would improve left ventricular (LV) function when it is measured several months later at rest or maximal bicycle exercise, or both. Radionuclide angiography was performed in 44 patients 5 months (range 6 weeks to 9 months) after AMI to assess function, and tomographic myocardial thallium-201 imaging was performed at maximal exercise and delayed rest to determine whether there was any evidence of myocardial ischemia. As expected, no patient had chest pain or redistribution of a thallium defect during the exercise test, because patients had undergone angioplasty (n = 28) or coronary bypass graft surgery (n = 5) where clinically indicated for revascularization. The LV ejection fraction was plotted as a function of the time elapsed between the onset of chest pain and the time when coronary angiography confirmed patency of the infarct-related artery (achieved in 91% of 44 patients by rt-PA [n = 31] or percutaneous transluminal coronary angioplasty [n = 9] ). Functional responses differed markedly between patients with anterior (n = 20) versus inferior (n = 24) wall AMI. LV ejection fraction during exercise correlated with time to reperfusion in patients with an anterior wall AMI (r = -0.58; standard error of the estimate = 11.9%; p less than 0.02) but not in patients with an inferior AMI (r = 0.10; standard error of the estimate = 13.1%; difference not significant.(ABSTRACT TRUNCATED AT 250 WORDS)
STUDY OBJECTIVE: Neuropeptide Y is a peptide isolated from brain and neural tissue around human coronary arteries. It has been shown to produce coronary vasoconstriction and myocardial ischaemia. The purposes of this study were (a) to determine whether the vasoconstriction induced by neuropeptide Y was mediated by alpha adrenergic receptors in vivo, and (b) to determine the time course of the effect and whether it was reproducible with a second administration. DESIGN: Neuropeptide Y (200 micrograms over 2 min) was given by intracoronary injection on two occasions 1 h apart to group I dogs (control). In group II the second dose was preceded by treatment with the alpha blocker phenoxybenzamine (4-10 mg.kg-1). The time course and magnitude of the effect was studied in the two groups to determine the effects of alpha blockade and of repeated neuropeptide Y dosage. EXPERIMENTAL MATERIAL: 14 mongrel dogs (n = 7 per group) were anaesthetised with chloralose for a left thoracotomy to measure coronary blood flow, aortic pressure, left ventricular pressure, and heart rate. MEASUREMENTS AND MAIN RESULTS: Reproducible prolonged increases in coronary vascular resistance occurred after the first [33(SD 18)%] and second [34(17)%] doses of neuropeptide Y. At this infusion rate mean aortic pressure increased with each dose by 21% and coronary blood flow decreased by 7%. In group II dogs, phenoxybenzamine given intravenously 20 min after the first dose of neuropeptide Y reduced mean aortic pressure by 15-20 mm Hg. In this group neuropeptide Y also caused reproducible increases in coronary vascular resistance before (36%) and after (46%) alpha blockade. CONCLUSIONS: Neuropeptide Y constricts coronary arteries in vivo by mechanisms that do not require intact alpha adrenergic receptors, and the coronary vasoconstriction was prolonged and reproducible.