Biomedical subjects
Publications and source records attributed to T D Miller.
Adult onset Still's disease (AOSD) is an uncommon, systemic, inflammatory disorder of unknown etiology characterized by the triad of fever, arthritis and rash. We describe 2 cases of cardiac tamponade in patients with AOSD, review reported cases, and describe the features, and therapy of AOSD.
OBJECTIVE: To assess the incremental value and cost-effectiveness of exercise tomographic thallium-201 imaging compared with clinical and exercise electrocardiographic variables for detecting three-vessel or left main coronary artery disease in patients with normal at-rest electrocardiograms. DESIGN: Prospective cohort study. PARTICIPANTS: 411 patients (77 [19%] had three-vessel or left main disease) with normal at-rest electrocardiograms who underwent exercise tomographic thallium-201 studies and subsequently had coronary angiography. MEASUREMENTS: Clinical, exercise, and thallium-201 variables; univariate followed by multivariate logistic regression analysis to determine predictors of three-vessel or left main disease (clinical variables; clinical and exercise electrocardiographic variables; and clinical, exercise, and thallium-201 variables). Patients were classified by each of these models into low-, intermediate-, and high-risk groups. SETTING: A tertiary referral center. RESULTS: Among the clinical variables, diabetes mellitus, sex, age, and typical angina were independently associated with severe coronary disease (46% of patients were correctly classified into low- or high-risk groups). The peak exercise heart rate-blood pressure product and the magnitude of the exercise-induced ST depression added independent information to clinical variables. Among the thallium variables, the change in the global thallium-201 score (a measure of redistribution) added independent information to clinical and exercise variables, resulting in only 3% of the patients being reclassified regarding their predicted risk for severe coronary disease. The cost per additional reclassification was estimated to be $20,550. Twenty-one cardiac events occurred (7 cardiac deaths and 14 myocardial infarctions) after thallium study (follow-up, 2.8 +/- 1.0 years). Event-free survival was 94% to 97% regardless of the predicted probability of developing three-vessel or left main coronary artery disease by any model. CONCLUSIONS: When the at-rest electrocardiogram is normal, thallium-201 scintigraphy adds little information to clinical and exercise variables in identifying patients with severe coronary artery disease. The high cost of this information may not justify the routine use of sophisticated imaging for this purpose.
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OBJECTIVES: This study was conducted to determine whether severe exercise-induced ischemia identifies high risk patients with a normal left ventricular ejection fraction and one- or two-vessel coronary artery disease. BACKGROUND: Severe ischemia during exercise radionuclide angiography has been shown to identify high risk patients among certain other patient subsets. METHODS: Four hundred twenty patients with left ventricular ejection fraction > or = 50% and one- or two-vessel disease underwent exercise radionuclide angiography within 3 months of coronary angiography. Patients were treated initially with revascularization (n = 140) or medical therapy (n = 280) at the discretion of their physicians. Patients treated with revascularization were more likely to have angina by history, a positive exercise electrocardiogram, a lower exercise ejection fraction, two-vessel disease and proximal left anterior descending coronary artery disease. Two hundred sixty-four of the 280 patients given medical therapy who had complete follow-up data formed the study group. Outcome was compared between patients with (n = 56) and without (n = 208) severe exercise-induced ischemia, defined by previously published criteria (work load < or = 600 kg-m/min, ST segment depression > or = 1 mm and decrease in ejection fraction with exercise). RESULTS: During follow-up, there were 30 initial cardiac events (12 cardiac deaths and 18 nonfatal myocardial infarctions). There was no difference in the 5-year event-free survival rate: 91% in patients with and 87% in patients without severe ischemia (p = 0.89). There was no association between event-free survival and severe ischemia (chi 2 = 1.41, p = 0.24). The study had approximately 80% power at alpha = 0.05 to detect a 25% decrease in event-free survival in the group with severe ischemia. In addition, there was no association between severe ischemia and outcome if late revascularization was included as an event or if the total mortality rate (overall survival) was analyzed. CONCLUSIONS: Severe exercise-induced ischemia fails to identify a high risk subgroup among patients with normal left ventricular function and one- or two-vessel disease who are treated initially with medical therapy.
OBJECTIVE: To determine whether patients with impaired left ventricular function and one- or two-vessel coronary artery disease who manifest severe ischemia during exercise radionuclide angiography have a lower rate of subsequent cardiac events when initial management is revascularization rather than medical therapy. DESIGN: During a median follow-up of 100 months, we compared the outcome between 37 patients who underwent a revascularization procedure and 22 who received medical therapy at the Mayo Clinic between September 1980 and December 1985. MATERIAL AND METHODS: The revascularization therapy consisted of coronary artery bypass grafting in 31 patients and coronary angioplasty in 6. Overall survival and survival free of initial cardiac events were compared statistically for the medically and surgically treated patients. RESULTS: Eleven deaths occurred in the patients who received medical therapy and 9 in the revascularization group. Five-year overall survival was 58% in the medically treated patients versus 84% in the revascularization group. A significant association was noted between type of treatment and overall survival (adjusted chi 2 = 6.20; P = 0.013). Twenty patients had initial cardiac events--7 in the medically treated group (3 cardiac deaths and 4 nonfatal myocardial infarctions) and 13 in the revascularization group (3 cardiac deaths, 3 out-of-hospital cardiac arrests, and 7 nonfatal myocardial infarctions). Survival free of cardiac events at 5 years was 72% in the medically treated patients and 66% in those who underwent revascularization. No association was detected between type of treatment and survival free of cardiac events. CONCLUSION: These nonrandomized data suggest that overall survival for patients with one- or two-vessel coronary artery disease, impaired left ventricular function, and severe exercise-induced ischemia may be improved by revascularization, but the subsequent cardiac event rates are not.
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This study was designed to assess the effect of systemic hypertension on exercise thallium-201 imaging. The study group consisted of 38 patients with systemic hypertension who were compared with 68 normotensive patients. All patients had a low pretest likelihood of coronary artery disease to minimize the influence of selection bias. Patients with electrocardiographic evidence of left ventricular hypertrophy were excluded. Single-photon emission computed tomographic thallium-201 images were obtained immediately after exercise and 4 hours after exercise. Thallium tomographic images were assessed qualitatively by 14 short-axis segments and were grouped into three coronary distributions. Regional and global quantitative analysis was also performed by using a reference study group at low risk for coronary artery disease. The hypertensive group demonstrated higher resting systolic blood pressure (137 +/- 26 mm Hg vs 120 +/- 14 mm Hg in the normotensive group, p = 0.0002) immediately before exercise. There was no significant difference between hypertensive and normotensive groups in peak exercise systolic blood pressure (181 +/- 31 mm Hg vs 172 +/- mm Hg, p = NS). The normotensive group achieved a significantly higher peak exercise heart rate (162 +/- 18 vs 146 +/- 20 beats/min in the hypertensive group, p = 0.0001) and higher estimated oxygen uptake (11.0 +/- 3.4 vs 9.1 +/- 2.7 metabolic equivalents [METS] in the hypertensive group, p = 0.003). However, rate-pressure products for both groups were nearly identical.(ABSTRACT TRUNCATED AT 250 WORDS)
In order to test the safety of hot tub use for persons with heart disease, 15 men with clinically stable coronary artery disease underwent 15 minutes of immersion in a hot tube at 40 degrees C. On another day, they exercised on a cycle ergometer for 15 minutes; target heart rate was determined by standard methods. Tympanic temperature, skin temperature, electrocardiographic findings, blood pressure, plasma catecholamines, subjective comfort, and cardiovascular symptoms were monitored. The peak heart rate was significantly lower during the hot tub session versus the exercise session (85 +/- 14 versus 112 +/- 19 beats/min), as were the systolic (106 +/- 15 versus 170 +/- 21 mm Hg) and diastolic (61 +/- 6 versus 83 +/- 8 mm Hg) blood pressure measurements (P < 0.01). Tympanic temperature increased by a mean of 0.6 +/- 0.3 degrees C during immersion and 0.1 +/- 0.1 degrees C during exercise. No ischemic electrocardiographic changes or clinical complications occurred. Simple ventricular ectopic activity and "just noticeable" chest pain were more frequent during exercise than during immersion. Plasma norepinephrine increased during exercise but not during immersion. These data suggest that hot tub use within these time and temperature constraints should be safe for men with stable heart disease who can follow an exercise regimen at home.
Overall 37 patients with painful dysfunction of the temporomandibular joint (TMJ), characterized clinically by headaches and dizziness as well (25 persons) were examined. A study was made of REG. The responsiveness of the sinocarotid node (SCN) was recorded. Diverse changes in the REG readings that attested to the development of cerebral angiodystonia were recorded. Abnormal responsiveness of SCN was discovered. Skillful orthopedic correction of the spatial position of the mandible was associated with noticeable changes in the normalizing and optimizing character of numerous REG readings. These data together with optimization of the responsiveness of the SCN point to the role played by the irritative vascular mechanism in the pathogenesis of headaches and dizziness seen in TMJ dysfunction.
In the presence of coronary artery disease (CAD), thallium imaging has been reported to add prognostic information that is independent of coronary anatomy. To investigate the prognostic importance of thallium imaging in the absence of significant CAD, 87 patients (65 men, 22 women) with abnormal thallium images without significant CAD were followed for a median duration of 22 months (range 11 to 50). Tomographic thallium images obtained immediately and 4 hours after exercise were interpreted by 2 experienced observers who graded thallium uptake in 24 segments in 3 views (short axis, horizontal long axis, vertical long axis) on a 5-point scale (normal; mildly, moderately, or severely reduced; absent). All patients had an abnormal thallium study, defined as a reversible defect of at least mild severity or a fixed defect of at least moderate severity seen in > or = 2 views, or a combination of these, and a coronary angiogram with stenosis not > or = 70% in diameter narrowing. Eighty-two patients had at least 1 reversible segment, and 26 patients had defects in > or = 2 coronary artery distributions. During follow-up there were no deaths or myocardial infarctions. Coronary angioplasty and bypass surgery were performed in 2 patients. Three-year survival without myocardial infarction or revascularization was 97%. Patients with abnormal thallium images in the absence of significant CAD have an excellent short-term prognosis.
The ability of exercise thallium-201 tomographic imaging to predict the presence of left main or 3-vessel coronary artery disease (CAD) was examined in 688 patients who underwent both exercise thallium-201 testing and coronary angiography. Significant differences existed for multiple variables between patients with (n = 196) and without (n = 492) severe left main or 3-vessel CAD. Logistic regression analysis identified 4 variables as independently predictive of left main or 3-vessel CAD. These variables were the magnitude of ST-segment depression with exercise, the number of visually abnormal short-axis thallium-201 segments, the presence or absence of diabetes mellitus, and the change in systolic blood pressure with exercise. Using these variables, patients were classified by nomograms into low-, intermediate- and high-probability groups. Patients at high probability (n = 205) had a 52% prevalence of 3-vessel or left main CAD, whereas those at low probability (n = 170) had only a 12% prevalence. Only 53 patients (29%) with 3-vessel or left main CAD had perfusion abnormalities in all 3 coronary territories. Clinical and exercise parameters provide important independent information in the identification of left main or 3-vessel CAD by exercise thallium-201 tomographic imaging, because thallium scintigraphy alone is suggestive of extensive CAD in few patients.
To evaluate the influence of exercise on the apolipoprotein (apo) composition of very low density lipoprotein (VLDL) subfractions, we exercised 6 sedentary men for 30 min, 1 h after a fatty meal. VLDL fractions from samples drawn 4, 6 and 8 h post-prandially were separated from pre-stained plasma by high performance liquid chromatography and fractionated to apo E-poor (heparin-unbound) and apo E-rich (heparin-bound) fractions. The postprandial peak area (volts) and apo E, C-II and C-III concentrations (mg/dl) of post-exercise VLDL fractions were compared with corresponding postprandial values obtained at rest. Plasma triglycerides (TG) levels (mg/dl) were significantly lower 4 (P < 0.05), 6 (P < 0.02) and 8 h (p < 0.05) postprandially; the apo E-poor VLDL fraction was not modified by exercise and its apo concentrations were in the low range of detection; the apo E-rich VLDL peak area significantly decreased 4 (P < 0.01), 6 (P < 0.01) and 8 h (P < 0.05) postprandially; the apo E concentration of apo E-rich VLDL was significantly lower 4 (P < 0.02) and 6 h (P < 0.05) postprandially; the apo C-III concentration of apo E-rich VLDL significantly increased, 4 and 6 h postprandially (P < 0.05). Apo E-rich VLDL is, presumably, the metabolically active fraction of the particle and may regulate plasma TG level following exercise. The metabolic role of apo E-poor VLDL remains to be defined.
The purpose of this study was to determine the prognosis of medically treated patients with three-vessel coronary artery disease and normal left ventricular function who do not have severe ischemia on exercise radionuclide angiography. The absence of severe ischemia was defined prospectively (in accordance with previously published criteria) as the presence of at least one of the following: (1) workload more than 600 kg-m/min, (2) ST-segment depression of less than 1 mm, or (3) unchanged or increased left ventricular ejection fraction during exercise. Of 42 patients (33% in functional class III or IV) followed up for a median duration of 53 months (range, 1 to 84 months), 22 had initial cardiac events during follow-up, including 6 cardiac deaths, 5 nonfatal myocardial infarctions, and 11 late (a median of 29 months after the exercise study) coronary revascularization procedures. At 4 years of follow-up, the overall survival was 83%. Survival free of cardiac death or myocardial infarction was 77%, and survival free of all cardiac events was 59%. Even in the absence of severe exercise-induced ischemia, medically treated patients with three-vessel coronary artery disease and normal left ventricular function still have a poor long-term outcome.
In a retrospective analysis, 63 participants in a cardiac rehabilitation-preventive cardiology program were identified as having low blood concentrations (mean, 34 mg/dl) of high-density lipoprotein cholesterol (HDL-C) and a mean total cholesterol level of 223 mg/dl after 3 months of hygienic measures (aerobic exercise, avoidance of tobacco, diet, and weight loss) designed to increase the HDL-C level. These patients (treatment group) were treated with low-dose, time-release nicotinic acid (mean, 1,297 mg/day) for a mean duration of 7.4 months. All subjects were able to take the drug without intolerable side effects. Fifty-four patients similar to those in the treatment group participated in the same program but were not treated with nicotinic acid (control group). Exercise, diet, body weight, and smoking remained stable throughout the period of observation. For the treatment group, HDL-C levels increased a mean of 18% (+6 mg/dl), total cholesterol concentrations decreased 9% (-20 mg/dl), the ratio of total cholesterol to HDL-C decreased 25% (from 6.8 to 5.1), low-density lipoprotein cholesterol levels decreased 13% (-20 mg/dl), and triglyceride levels decreased 20% (from 165 mg/dl to 132 mg/dl). Aspartate aminotransferase and uric acid concentrations were minimally increased after treatment, and the blood glucose level was unchanged. In the control group, HDL-C levels increased a mean of 8% (+3 mg/dl) and the other blood lipid variables were not improved after a mean of 8.3 additional months of diet and exercise.(ABSTRACT TRUNCATED AT 250 WORDS)
Transtelephonic monitoring of a single-lead electrocardiogram and on-demand 2-way voice communication were accomplished at 1,865 exercise sessions for 67 cardiac patients. Exercise sessions occurred either at the patients' homes or at remote hospital sites and began an average of 25 or 14 weeks, respectively, after hospital dismissal. Monitoring centers provided experienced nurses to direct all exercise sessions. The transtelephonic monitoring equipment was reliable with only one instance of system failure observed. A broad spectrum of patients with coronary artery disease, including some classified at higher risk, participated in the program. Patients exercised with a variety of equipment (cycle ergometer, treadmill, arm ergometer, cross-country ski simulator, combination arm-leg cycle ergometer, rowing machine), for 30 to 50 minutes, 1 to 3 times each week. No medical emergencies occurred, although 18 specific problems were discovered that led to further evaluation or change in the medical program of specific patients. Transtelephonic monitoring of cardiac rehabilitation exercise sessions at home and at remote hospitals appears safe and is attractive because not all patients have access to supervised exercise programs; this exercise assessment helps to maximally use highly trained cardiac rehabilitation personnel.
The ability of supine exercise electrocardiography and exercise radionuclide angiography to predict time to subsequent cardiac events (cardiac death, nonfatal myocardial infarction or late coronary bypass grafting or angioplasty) were compared in 265 patients with normal resting electrocardiograms who were not taking digoxin. All patients had undergone coronary catheterization and were initially treated medically. Follow-up study was performed at a median of 51 months. Separate logistic regression models, which had been previously developed to predict 3-vessel or left main coronary artery disease (CAD), were compared using a Cox regression analysis to predict time to a subsequent cardiac event. The exercise electrocardiography model, consisting of the magnitude of ST depression, exercise heart rate and patient gender, was a powerful predictor (chi-square = 30.8, p less than 0.0001) of subsequent events. The exercise radionuclide angiography model, which included the exercise response of the pressure-volume ratio in addition to the exercise electrocardiography variables, had similar prognostic power (chi-square = 31.8, p less than 0.0001). In a separate analysis considering only cardiac death and nonfatal myocardial infarction, the exercise electrocardiography model remained a significant predictor of events (chi-square = 12.2, p less than 0.001). None of the radionuclide angiography variables added significantly to the prognostic power of the exercise electrocardiography model. Thus, in patients with a normal resting electrocardiogram who are not taking digoxin, the supine exercise electrocardiography model that predicts 3-vessel or left main CAD also predicts future cardiac events. Exercise radionuclide angiography does not provide any additional prognostic information in such patients.
Hepatitis developed in five patients who were taking low dosages (3 g/day or less) of time-release niacin. In four of the five patients, clinical symptoms of hepatitis developed after the medication had been taken for a relatively short time (2 days to 7 weeks). This manifestation of hepatotoxicity seems to differ from that previously reported in association with use of crystalline niacin, which occurred with high dosage and prolonged usage of the medication. In view of the recent increased frequency of prescribing niacin for the treatment of hyperlipidemia, physicians should be aware of the potential for hepatotoxicity with even low-dose and short-term use of time-release niacin.
Exercise is associated with release of catecholamines and vasoactive intestinal polypeptides. Recurrent exposure to catecholamines modifies the sensitivity of adrenoceptors. To test the hypothesis that exercise training may affect the sensitivity of the epicardial coronary arteries, we performed studies on isolated coronary arteries from male dogs capable of running on a treadmill. The animals were separated randomly into two groups: sedentary and exercise training. After 11 wk, rings of left circumflex and left anterior descending coronary arteries were studied in vitro. Contractions to alpha 1-adrenergic agonists (norepinephrine and phenylephrine) were not affected by exercise training. During contractions with prostaglandin F2 alpha, endothelium-dependent relaxations to alpha 2-adrenergic agonists (norepinephrine and UK 14304) were not reduced significantly by exercise training. The concentration-relaxation curves to beta-adrenergic agonists (norepinephrine, isoproterenol, and epinephrine) were shifted to the right after training. The concentration-response curves to vasoactive intestinal polypeptide, but not that to substance P, were shifted to the right in rings with endothelium from exercise-trained animals. These findings demonstrate a decrease in responsiveness of canine vascular smooth muscle to beta-adrenergic agonists and to vasoactive intestinal polypeptide after exercise training.