Search PubMed⌕ Search

Biomedical subjects

D D Miller

Publications and source records attributed to D D Miller.

At least 343 records · Page 19Linked to original sources

Symptom dimensions and brain morphology in schizophrenia and related psychotic disorders.

The heterogeneity of symptoms in schizophrenia may reflect heterogeneity of underlying pathophysiological mechanisms. Factor analytic studies have consistently identified three symptom factors, psychotic, negative and disorganized, as independent dimensions of schizophrenic psychopathology. This study examined the relationship of these symptom dimensions with volumes of specific brain regions. One-hundred and sixty-six schizophrenia spectrum patients were clinically evaluated with the Comprehensive Assessment of Symptoms and History (CASH) and scanned with a 1.5 Tesla magnetic resonance imaging scanner. Regions of interest (ROIs) were manually traced on 5 mm and 3 mm coronal slices by a single technician, blind to all aspects of subject identity. Correlations between ROI volumes and indices of symptom severity were determined. Analyses of covariance were then used to test for specific relationships between each of the three symptom dimensions and ROI volumes. Tests were made of each dimension, controlling for all others. Overall symptom severity was significantly correlated with larger ventricle volumes (lateral, third and temporal horns) and smaller temporal lobe, hippocampal and superior temporal gyral volumes. Both psychotic and negative symptom severity predicted increased third ventricular volume. Psychotic symptom severity uniquely predicted decreased superior temporal gyral volume as well as increased temporal horn volume. Within the psychotic symptom dimension, hallucinations alone predicted left superior temporal gyral volume. No significant associations between disorganized symptoms and any ROIs were demonstrated. These results provide clues to the localization of specific brain regions underlying symptom clusters in schizophrenia, and provide further validating evidence for the construct of independent dimensions of psychopathology within schizophrenia and related psychotic disorders.

Adolescent↗

Effect of hyperosmotic mannitol on magnetic resonance relaxation parameters in reperfused canine myocardial infarction.

To determine how administration of a hyperosmotic agent alters regional nuclear magnetic resonance (NMR) relaxation parameters and imaging characteristics in ischemic-reperfused myocardium, 7 dogs were infused with mannitol for 15 minutes before and after the release of a 3 hour left anterior descending coronary artery (LAD) occlusion. Nine control animals received normal saline during the 3 hour occlusion and 1 hour reperfusion periods. Normal posterior left ventricular (LV) wall and the ischemic anterior LV wall (risk area) myocardium was sampled for calculation of segmental microsphere myocardial blood flow, % tissue water content, NMR relaxation times (T1, T2) and myocyte ultrastructure using electron microscopy. Mean infarct T1 values were 14% greater than normal segments in saline-treated controls, but only 5% greater after mannitol. The difference in tissue water content between infarcted and normal segments was 4% in saline-treated (83 vs. 79%) compared to 2% in mannitol-treated dogs (79 vs. 77%). T1, T2 and % water content of control infarct segments were greater than treated infarcts (p less than 0.01). T1 and T2 rose as occlusion flow fell below 0.5 ml/min/g in control hearts but did not rise until flows were reduced to 0.1 ml/min/g in mannitol-treated hearts. Areas of increased signal in T1 and T2 NMR images correlated well with histochemical infarct volume (r = 0.98, SEE = 1.1 cc) in mannitol-treated dogs, but infarct borders were qualitatively less well-defined than in controls. We concluded that mannitol (1) diminishes tissue edema and reduces NMR relaxation parameters (T1, T2) in infarcted myocardium; and (2) attenuates the rise in T1 and T2 and ultrastructural myocyte injury in ischemic-reperfused myocardium.

Animals↗

Perioperative cardiac evaluation for noncardiac surgery noninvasive cardiac testing.

Prognostic risk stratification to identify perioperative and long-term cardiac risk in selected patients undergoing noncardiac surgery is part of good clinical practice. Exercise variables associated with significant increased risk include poor functional capacity (eg, <4 metabolic equivalents), marked exercise-induced ST segment shift or angina at low workloads, and inability to increase or actually decrease systolic blood pressure with progressive exercise. Approximately 40% of patients tested before peripheral vascular surgery will have an abnormal exercise electrocardiogram (ECG). The predictive value for a perioperative event, ie, death or myocardial infarction, ranges from 5% to 25% for a positive test and 90% to 95% for a negative test. Whereas exercise cardiac imaging is the modality of choice in patients with a noninterpretable exercise ECG, pharmacological stress imaging should be used in the 30% to 50% of patients who require perioperative noninvasive risk stratification and are unable to perform an adequate level of exercise to test cardiac reserve. Myocardial perfusion variables predictive of increased cardiac events include severity of the perfusion defect, number of reversible defects, extent of fixed and reversible defects, increased lung uptake of thallium-201, and marked ST segment changes associated with angina during the test. The reported sensitivity and specificity of dobutamine-induced echocardiographic wall motion abnormalities in patients with peripheral vascular disease is similar to myocardial perfusion scintigraphy, but the confidence limits are wider due to the smaller sample size in these more recent studies. In conclusion, noninvasive cardiac testing should be used selectively in patients undergoing noncardiac surgery; the results provide useful estimates of short- and long-term risk of cardiac events, and the magnitude of abnormal response on noninvasive testing should be used to formulate decisions regarding the need for coronary angiography and subsequent revascularization.

Activities of Daily Living↗

Safety of dipyridamole testing in 73,806 patients: the Multicenter Dipyridamole Safety Study.

BACKGROUND: Dipyridamole imaging is widely used as an alternative to exercise testing to identify and risk stratify patients with coronary artery disease. Safety data on intravenous dipyridamole stress testing has been derived largely from individual institutional data. METHODS AND RESULTS: Data were collected retrospectively by 85 coinvestigators from 73,806 patients who underwent intravenous dipyridamole stress imaging in 59 hospitals and 19 countries to determine the incidence of major adverse reactions during testing. The dose of dipyridamole infused was 0.56 mg/kg in 64,740 patients, 0.74 mg/kg in 6551 patients, and 0.84 mg/kg in 2515 patients. Combined major adverse events among the entire 73,806 patients included seven cardiac deaths (0.95 per 10,000), 13 nonfatal myocardial infarctions (1.76 per 10,000), six nonfatal sustained ventricular arrhythmias (0.81 per 10,000) (ventricular tachycardia in two and ventricular fibrillation in four), nine transient cerebral ischemic attacks (1.22 per 10,000), (with speech or motor deficit), one stroke, and nine severe bronchospasms (1.22 per 10,000) (one intubation and eight near intubations). In addition to the safety data, detailed demographic, peripheral hemodynamic, side effect, and concomitant drug data were examined in a subgroup of 3751 patients. End points from subsets of patients were compared with those of the group as a whole. Multivariate analysis revealed that dipyridamole-induced chest pain was more common in patients less than 70 years old (p = 0.0017), those with a history of coronary revascularization (p = 0.002), or patients taking aspirin (p = 0.0001). Minor noncardiac side effects were less frequent among the elderly (p = 0.0053) and more frequent in women (p = 0.0001) and patients taking maintenance aspirin (p = 0.0034). When a patient was judged on the basis of the adequacy of hemodynamic response to be a dipyridamole "nonresponder" (< 10 mm Hg drop in systolic blood pressure and 10 beats/min increase in heart rate), the only significant predictor was angiotensin-converting enzyme inhibitor intake (p = 0.0025). Inferoposterior hypoperfusion was significantly more frequent in patients with dipyridamole-induced hypotension: 57% (44/77) (p < 0.0001) of those who had hypotension and 89% (8/9) (p = 0.0076) who had severe symptomatic bradyarrhythmias displayed inferoposterior defects on thallium scanning. Caffeine levels were determined in 391 consecutive patients: levels greater than 5 mg/L were observed in only eight patients (2%), suggesting that methylxanthine levels sufficient to alter the hemodynamic response to dipyridamole resulting in suboptimal hyperemic stress are unlikely when patients take nothing by mouth after midnight. CONCLUSION: The risk of serious dipyridamole-induced side effects is very low and is comparable to that reported for exercise testing in a similar patient population.

Adult↗

Northern exposure: nuclear cardiology in the Canadian health care system.

The Canadian health care system may provide valuable insights into the future practice of nuclear cardiology in the United States. Rationing of medical care is not legislated by the Canadian health care system, although resource allocation is required of Canadian physicians and hospital administrators. Canadian nuclear cardiologists and physicians are not restricted in the ordering of diagnostic studies, despite the decreased availability in imaging systems and the centralization of equipment and personnel in Canada. Canadian imaging equipment is, in general, used more with less average idle time per unit. Delays in the performance of nonemergent imaging studies are more common in Canadian imaging laboratories. The number of out-of-hospital nuclear medicine laboratories is not increasing, because of government constraints on licensing and the general requirement that only radiologists or certified nuclear medicine physicians can operate these laboratories. A survey of 71 nuclear cardiology laboratories in the United States and Canada reveal that 21% of all cardiac imaging studies are performed for post-myocardial infarction risk stratification in Canada, compared with only 11% in United States laboratories. Rest and reinjection thallium imaging studies are performed more than twice as often in the United States laboratories. Canadian laboratories perform a higher average number of myocardial perfusion (2123 vs 1789) and ventricular function (773 vs 554) studies as compared with their United States counterparts. No other significant differences in clinical usage patterns were identified. A total of 130,000 nuclear cardiologies were performed in Canada in 1993, with less than 5% growth in the number of Canadian studies projected for 1994. Forty-five percent of Canadian perfusion studies are performed with 99mTc-labeled sestamibi frequently using a 2-day protocol (60%) with electrocardiogram gating (30%). Positron emission tomography (PET) can be performed in only six Canadian cities. Canadian PET centers are government funded, located in university teaching hospitals, and principally used for the purpose of research. Stress echocardiography is not widely performed in Canada because of the heavy clinical volume of standard echocardiographic studies at most hospitals, which reduces the time available for stress echocardiography. No separate billing code is available for stress echocardiography studies in Canada. Canadian cardiologists have accepted the value of rest and stress nuclear studies for the management of their patients and have concluded that it is more time efficient to perform clinical duties in lieu of stress echocardiographic studies. In conclusion, the realities of the Canadian health care system are that universal health care is valuable as long as it is consistent high quality medical care, and that the cost of universal coverage must be borne by the taxpayer using the system. The fact that nuclear cardiology has continued to thrive in the Canadian health care system suggests that future health care modifications in the United States will not exert a significant impact on the practice of nuclear cardiology.

Canada↗

A primer of biostatistic and economic methods for diagnostic and prognostic modeling in nuclear cardiology: Part I.

This review presents a brief overview of existing diagnostic and prognostic methodologies to be used for the evaluation of patients undergoing noninvasive testing. In part I of this review, we will present methods for use of logistic and Cox regression analyses in determining the diagnostic and prognostic value of nuclear imaging techniques. In part II of this review, we will present an outline for the integration of economic evaluations into the clinical decision-making process. This review will document how cost estimates may be defined as well as the differing type of cost analyses (i.e., cost efficiency versus cost-effectiveness).

Coronary Disease↗

Diagnostic utility of tomographic myocardial perfusion imaging with technetium 99m furifosmin (Q12) compared with thallium 201: results of a phase III multicenter trial.

BACKGROUND: Based on physical properties, 99mTc-labeled perfusion agents offer several advantages over 201Tl for myocardial perfusion imaging. The results of in vivo and experimental studies, along with preliminary experience in human subjects, have shown 99mTc-labeled furifosmin to be a promising new perfusion tracer. The purpose of this study was to evaluate the safety of a new myocardial perfusion agent, 99mTc-labeled furifosmin (Q12), and determine the concordance of furifosmin perfusion scintigraphy to 201Tl imaging. In addition, we sought to determine the normalcy rate of myocardial scintigraphy with furifosmin. METHODS AND RESULTS: One hundred fifty patients constituted the study group in this multicenter trial. Patients underwent exercise testing with furifosmin injected at peak exercise, and tomographic imaging was begun 15 to 30 minutes afterward. After a separate injection, resting images were obtained 3 to 4 hours later. Thallium scintigraphy was performed within 2 weeks of the furifosmin scans, after a similar exercise workload. Patients with a low likelihood of coronary artery disease (n = 39) also underwent furifosmin imaging. All images were processed and displayed in uniform manner and interpreted by a panel of readers. No adverse effects or clinically important laboratory alterations were related to furifosmin imaging. Image quality was slightly better with furifosmin than with thallium. The overall concordance between the perfusion studies was 86% (kappa value = 0.669). The normalcy rate for furifosmin scintigraphy was 100%. CONCLUSIONS: 99mTc-labeled furifosmin is a promising new 99mTc-labeled myocardial perfusion agent, providing diagnostic results similar to those obtained with 201Tl.

Coronary Disease↗

Diagnostic accuracy of dipyridamole technetium 99m-labeled sestamibi myocardial tomography for detection of coronary artery disease.

BACKGROUND: The diagnostic accuracy of exercise 99mTc-labeled sestamibi and intravenous dipyridamole 201Tl-labeled myocardial tomography is established. The accuracy of dipyridamole stress 99mTc-labeled sestamibi myocardial tomography for the detection of coronary artery disease has not been reported. METHODS AND RESULTS: Our purpose was to determine the diagnostic accuracy of same-day, rest-dipyridamole stress 99mTc-labeled sestamibi myocardial single-photon emission computed tomography (SPECT) compared with coronary angiography. Two hundred forty-four patients who were unable to exercise adequately underwent both dipyridamole 99mTc-labeled sestamibi SPECT and coronary angiography within 6 months. Dipyridamole was administered intravenously in a standard dose of 0.56 mg/kg for 4 minutes. Cardiac and noncardiac side effects were recorded. The presence of coronary stenoses of 50% or greater diameter reduction in each of the major coronary arteries was compared with imaging data in corresponding myocardial perfusion beds. The patient population was predominately (98.8%) male with a mean age of 63 +/- 9 years (range 33 to 83 years). The majority of patients had stable angina (88%). Eighty-four patients (35%) gave a prior history of myocardial infarction; 44 patients (18%) had a history of congestire heart failure. The principal limitation to exercise stress was peripheral vascular disease in 62 patients (26%). No serious side effects occurred during dipyridamole stress; 14% of patients had chest pain and 8% of patients had 1 mm or greater ST segment depression. Of the 204 patients with documented coronary stenoses, 43 (21%) had single-vessel disease and 161 (79%) had multivessel disease. The sensitivity was 93% (40/43 in patients with single-vessel disease) and 91% (146/161 in patients with multivessel disease). Overall sensitivity was 91%. The specificity was 28% (11/40) in this population with a high prestest probability of coronary artery disease and posttest referral for cardiac catheterization. CONCLUSION: 99mTc-labeled sestamibi myocardial tomography in conjunction with intravenous dipyridamole stress is a safe and sensitive method for the detection of coronary artery disease. The diagnostic accuracy of dipyridamole stress 99mTc-labeled sestamibi SPECT for the detection of coronary artery disease is similar to that reported for exercise stress 99mTc-labeled sestamibi tomography, making this a suitable alternative for the evaluation of patients who are unable to exercise adequately.

Adult↗

Cost analysis of diagnostic testing for coronary artery disease in women with stable chest pain. Economics of Noninvasive Diagnosis (END) Study Group.

BACKGROUND: Seven clinical sites compiled data from 4638 women who were referred directly to coronary angiography (catheterization-first strategy; n = 3375) or who underwent stress myocardial perfusion imaging (MPI) first (n = 1263) followed by coronary angiography if at least one reversible myocardial perfusion abnormality was detected. The study examines the cost minimization potential of these available invasive and noninvasive diagnostic strategies in women with chest pain. METHODS AND RESULTS: Women in both groups were subclassified by the core laboratory as being at low (<0.15), intermediate (0.15 to 0.60), or high (>0.60) pretest likelihood for coronary artery disease (CAD). Among the catheterization-first patients, at least one coronary stenosis >70% was present in 13% of low likelihood patients, 29% of intermediate likelihood patients, and 52% of patients with high CAD likelihood. Perfusion abnormality rates in the MPI-first group were 23% in low likelihood patients, 27% in intermediate likelihood patients, and 34% in high CAD likelihood patients. Of the MPI-first subset, 50%, 55%, and 76%, respectively, underwent catheterization in at least one coronary stenosis >70%. Cardiac death rates ranged from 0.5% to 2.2% in patients with CAD and did not differ from the 2 testing strategies (P = not significant). The composite cost per patient of diagnostic testing plus follow-up medical care over a period of 2.5 +/- 1.5 years (calculated for both strategies from inflation-corrected Medicare charges, adjusted for institutional cost-charge ratios) ranged from $2490 for patients with low likelihood to $3687 for patients with high likelihood with the catheterization-first strategy and from $1587 to $2585 for patients undergoing MPI first (P < .01 between risk subsets and strategies). CONCLUSIONS: In women referred for diagnostic evaluation of stable chest pain, MPI followed by selective coronary angiography in patients with at least 1 perfusion abnormality minimizes the near-term composite cost per patient compared with a direct catheterization-first strategy, regardless of pretest CAD likelihood.

Aged↗