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Biomedical subjects

J K Kahn

Publications and source records attributed to J K Kahn.

89 records · Page 5Linked to original sources

Quantitative rotational tomography with 201Tl and 99mTc 2-methoxy-isobutyl-isonitrile. A direct comparison in normal individuals and patients with coronary artery disease.

We tested the hypothesis that 99mTc 2-methoxy-isobutyl-isonitrile (99mTc MIBI), a new radiopharmaceutical for myocardial perfusion imaging, provides accurate noninvasive detection of coronary artery disease (CAD). Imaging in patients after exercise and at rest with 99mTc MIBI was compared with imaging after exercise and redistribution with 201Tl in 12 normal subjects and 38 patients with angiographic documentation of CAD (greater than or equal to 50% diameter stenosis). We used single-photon emission computed tomography (SPECT) and computer quantitation of regional tracer distribution. The quality of reconstructed images with 99mTc MIBI judged visually was superior to that of 201Tl in 88% of all studies performed and was comparable in the others. With the limits of normal as 2.5 SD below the mean of gender-matched normal volunteers, 201Tl SPECT identified 32 and 99mTc MIBI identified 36 patients with CAD (p = 0.2). 201Tl SPECT identified 45 of 75 (60%) and 99mTc MIBI identified 59 of 75 (79%) stenosed coronary arteries (p less than 0.05). The quantitative severity of perfusion defects was similar for the two tracers. 201Tl SPECT identified 104 reversibly ischemic myocardial segments compared with 134 with 99mTc MIBI (p less than 0.05). Thus, SPECT myocardial perfusion imaging with 99mTc MIBI and computer quantitation provides an accurate method for the noninvasive detection of significant coronary artery disease. Furthermore, image quality is generally superior to 201Tl, and reversibly ischemic myocardial segments may be better identified with 99mTc MIBI.

Adult↗

New radionuclide agents for cardiac imaging: description and application.

The introduction of three new radiopharmaceuticals into clinical research and practice has broadened the potential applications and scope of nuclear cardiology examinations. Technetium-99m labeled isonitrile perfusion agents have excellent imaging characteristics allowing the accurate identification of coronary artery disease. Simultaneous assessments of ventricular function are possible with these agents. Iodine-123 phenylpentadecanoic acid myocardial scintigraphy permits assessments of myocardial perfusion and fatty acid metabolism, and permits investigations of myocardial metabolism with conventional imaging equipment. Iodine-123 meta-iodobenzyl-guanidine serves as an indicator of the functional integrity of the sympathetic nervous system and permits evaluations of the effects of various disease states on catecholamine handling by the heart.

3-Iodobenzylguanidine↗

Quantitation of postexercise lung thallium-201 uptake during single photon emission computed tomography.

To test the hypothesis that analysis of lung thallium uptake measured during single photon emission computed tomography (SPECT) yields supplementary clinical information as reported for planar imaging, quantitative analysis of lung thallium uptake following maximal exercise was performed in 40 clinically normal subjects (Group 1) and 15 angiographically normal subjects (Group 2). Lung thallium uptake was measured from anterior projection images using a ratio of heart-to-lung activities. Seventy subjects with coronary artery disease (CAD) (Group 3) determined by angiography (greater than or equal to 70% luminal stenosis) underwent thallium perfusion SPECT. Thirty-nine percent of these subjects had multivessel and 61% had single vessel CAD. Lung thallium uptake was elevated in 47 of 70 (67%) Group 3 subjects. Group 3 subjects with elevated lung thallium uptake did not differ from Group 3 subjects with normal lung thallium uptake with respect to extent or distribution of coronary artery disease, left ventricular function, or severity of myocardial ischemia as determined by exercise and redistribution thallium SPECT. Thus, the measurement of thallium lung uptake from anterior projection images obtained during SPECT frequently identifies patients with CAD, but it may not provide supplementary information regarding the extent of myocardial ischemia or ventricular dysfunction.

Adult↗

Abnormal I-123 metaiodobenzylguanidine myocardial washout and distribution may reflect myocardial adrenergic derangement in patients with congestive cardiomyopathy.

I-123 metaiodobenzylguanidine (MIBG) is a new radiopharmaceutical with properties that allow the characterization of the sympathetic innervation of several organ systems. In this study, we used MIBG with tomographic imaging to evaluate noninvasively the differences in myocardial sympathetic innervation in 14 healthy volunteers and 16 patients with severe dilated cardiomyopathy (CM). Initial (15-minute) images demonstrated no significant differences in MIBG concentration in the hearts of patients with CM and of healthy volunteers. However, the myocardial retention of MIBG was significantly reduced in the patients with CM. Expressed as the percent washout from 15 to 85 minutes, the patients with CM had a 28 +/- 12% washout rate compared with 6 +/- 8% in the controls (p less than 0.001). A small subset of patients from each group imaged at 4-hour intervals demonstrated even greater disparity in washout rates. In addition, the patients with CM had significantly greater heterogeneity in the MIBG activity distribution within the myocardial images. There was 47 +/- 15% intraimage variability in MIBG distribution in the patients with CM and 22 +/- 9% variation in the controls (p less than 0.001). We conclude from these data that the myocardial distribution and kinetics of MIBG in images obtained from patients with CM differ significantly from those of controls and that the MIBG patterns may be used as a relatively noninvasive means to evaluate the severity of altered adrenergic innervation in the hearts of these patients.

3-Iodobenzylguanidine↗

QT interval prolongation and sudden cardiac death in diabetic autonomic neuropathy.

Alterations in cardiac sympathetic innervation may result in QT interval prolongation and predispose to sudden arrhythmias and death. Sudden cardiac death occurs in diabetic patients who have autonomic neuropathy, but the cause is uncertain. In 30 patients with insulin-dependent diabetes mellitus who had no evidence of ischemic heart disease, cardiac autonomic neuropathy, determined by clinical tests, was found in 17. The corrected QT interval (QTc), measured using Bazett's formula at rest and peak exercise, was prolonged (greater than 440 msec) in 12 of these patients at rest and in 15 at peak exercise. Prolonged QTc intervals were found only in patients who had definite cardiac autonomic neuropathy. As a group, the QTc interval (mean +/- SD) in the diabetic patients with cardiac autonomic neuropathy was prolonged compared to that in patients without cardiac autonomic neuropathy at rest (447 +/- 28 vs. 405 +/- 9 ms; P less than 0.0001) and peak exercise (468 +/- 23 vs. 402 +/- 23 ms; P less than 0.0001). There was a direct linear relationship between the extent of cardiac autonomic neuropathy and the QTc interval (r = 0.71; P less than 0.001). One of the patients with cardiac autonomic neuropathy and prolonged QTc intervals had a nonuniform loss of adrenergic neurons in his heart demonstrated by meta-iodobenzyl-guanidine scintigraphy, indicating sympathetic imbalance; he subsequently died unexpectedly. These data suggest that diabetic cardiac autonomic neuropathy may result in sympathetic imbalance and QTc interval prolongation, predisposing these patients to sudden arrhythmias and death.

Adult↗

Nifedipine-associated acute psychosis.

A 84-year-old man was given nifedipine for control of angina pectoris. Acute psychosis with paranoid ideation developed soon after he began receiving the medication. All symptoms resolved with discontinuation of nifedipine. This is the second reported case of nifedipine-associated acute psychosis. Alternations in calcium-mediated neurotransmitter release, particularly dopamine, may be responsible. Clinicians should consider nifedipine when presented with a patient with acute psychosis.

Aged↗

Plasma levels of immunoreactive atrial natriuretic hormone in patients with diabetes mellitus.

In order to determine whether atrial natriuretic hormone (ANH) secretion is altered in diabetic patients with autonomic neuropathy, plasma immunoreactive ANH (IR-ANH) levels were measured in 23 patients with insulin-dependent diabetes mellitus, 12 of whom had definite cardiac autonomic neuropathy determined by noninvasive maneuvers. Levels were also measured in 31 healthy control subjects. Whereas only one of the 11 diabetics without cardiac autonomic neuropathy had elevated IR-ANH levels, four of the 12 diabetics with cardiac autonomic neuropathy had elevated IR-ANH levels (P = 0.03 compared to control subjects). 24-h urinary sodium excetion was not different among the groups. There was no significant correlation between IR-ANH levels and diabetes control and any of the parameters of autonomic nervous system activity nor between IR-ANH levels and plasma norepinephrine or epinephrine levels. Furthermore, no relationship was observed in the diabetic subjects between IR-ANH levels and left ventricular ejection fraction determined by radionuclide ventriculography. Thus, elevated IR-ANH levels occur with greater frequency in diabetic patients with autonomic neuropathy. These elevations do not appear to be due to alterations in dietary sodium intake or left ventricular dysfunction.

Adult↗

Radionuclide assessment of left ventricular diastolic filling in diabetes mellitus with and without cardiac autonomic neuropathy.

Indexes of left ventricular diastolic filling were measured by radionuclide ventriculography in 28 patients with insulin-dependent diabetes mellitus without evidence of ischemic heart disease. Six patients (21%) had abnormal diastolic filling and differed from diabetic patients with normal filling in their greater severity of cardiac autonomic neuropathy, assessed by noninvasive means, and their lower plasma norepinephrine levels in the supine (131.1 +/- 24.7 versus 356.2 +/- 58.4 pg/ml, p less than 0.01) and upright (224.9 +/- 47.8 versus 673.3 +/- 122.3 pg/ml, p less than 0.005) positions. The diabetic patients determined as having cardiac autonomic neuropathy (n = 15) had depressed left ventricular diastolic filling compared with subjects free of autonomic neuropathy, whether measured as the time to peak filling rate (154.2 +/- 12.0 versus 119.1 +/- 10.6 ms, p less than 0.05) or the time to peak filling rate normalized to the cardiac cycle length (24.3 +/- 2.2 versus 16.2 +/- 1.5%, p less than 0.01). Of the various tests of autonomic nervous system function, the strongest correlate of impaired diastolic filling was orthostasis, measured as the decrease in systolic blood pressure with standing (r = 0.584, p less than 0.001). Thus, in patients with diabetes mellitus, alterations in sympathetic nervous system activity are associated with abnormalities of left ventricular diastolic filling.

Adult↗

Abnormal cardiac function in diabetic patients with autonomic neuropathy in the absence of ischemic heart disease.

To determine if cardiac autonomic neuropathy (CAN) contributes to diabetic cardiomyopathy, left ventricular function was assessed by resting and exercise radionuclide ventriculography (RVG) in 30 patients with long-standing insulin-dependent diabetes mellitus who had no clinical, electrocardiographic, or tomographic thallium scan evidence of heart disease. In 11 of 30 patients (37%), RVG revealed abnormal left ventricular performance. CAN was found in 91% of these patients. RVG was abnormal in 59% of patients with CAN and in only 8% of patients without CAN (P less than 0.005). There were significant reductions in mean (+/- SE) ejection fractions (EF) in patients with CAN at rest (62.8 +/- 2.2% vs. 75.2 +/- 2.5%; P less than 0.001) and with maximal exercise (65.8 +/- 2.6% vs. 80.9 +/- 2.3%; P less than 0.001) compared to patients without CAN. There was an inverse correlation between the autonomic function score and both resting EF (r = -0.53; P less than 0.002) and exercise EF (r = -0.55; P less than 0.002). Systolic function did not correlate with age, sex, duration or control of diabetes, microvascular complications, or plasma norepinephrine levels. Thus, approximately one third of our study population had evidence for depressed left ventricular function in the absence of ischemic heart disease, and the cardiac dysfunction was related to the severity of CAN. CAN may be a contributor to cardiac dysfunction in diabetes mellitus.

Adult↗

Decreased exercise heart rate and blood pressure response in diabetic subjects with cardiac autonomic neuropathy.

Abnormal hemodynamic responses to exercise have been observed in diabetic subjects, but the pathogenesis and significance remain uncertain. We used maximal treadmill exercise to study 32 subjects with long-term insulin-dependent diabetes without clinical evidence of cardiac disease. Two of the 32 had occult ischemic heart disease revealed by stress electrocardiography and myocardial-perfusion scintigraphy and were excluded from subsequent analysis. In the remaining 30 subjects, we compared the responses to exercise of the 17 subjects with cardiac autonomic neuropathy diagnosed by noninvasive maneuvers (group 1) with the 13 without (group 2). At rest, the pressure-rate product (PRP) was higher in group 1 (114.0 +/- 5.7 vs. 95.9 +/- 5.3, P less than .05). With maximal exercise the increase in heart rate (44.6 +/- 4.8 vs. 79.0 +/- 5.4 beats/min, P less than .001), systolic blood pressure (36.8 +/- 5.9 vs. 55.0 +/- 5.8 mmHg, P = .02), and the PRP (102.0 +/- 7.3 vs. 182.0 +/- 8.2, P less than .001) were all lower in group 1 than in group 2, despite similar total treadmill times (631 +/- 47 vs. 587 +/- 40 s, P greater than .1). At each stage of exercise, the increase in heart rate and systolic blood pressure was lower in group 1 patients. The severity of cardiac autonomic neuropathy correlated inversely with the maximal increase in heart rate (r = -.68, P less than .001) and the PRP (r = -.58, P less than .005). Age, duration of diabetes, and the presence and severity of microvascular disease did not correlate with any of the hemodynamic parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗