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Biomedical subjects

R Blumhardt

Publications and source records attributed to R Blumhardt.

At least 19 recordsLinked to original sources

A simple method for producing a technetium-99m-labeled liposome which is stable in vivo.

A new method for labelling preformed liposomes with technetium-99m (99mTc) has been developed which is simple to perform and stable in vivo. Previous 99mTc-liposome labels have had variable labeling efficiencies and stability. This method consistently achieves high labeling efficiencies (greater than 90%) with excellent stability. A commercially available radiopharmaceutical kit--hexamethylpropyleneamine oxime (HM-PAO)--is reconstituted with 99mTcO4- and then incubated with preformed liposomes that encapsulate glutathione. The incubation takes only 30 min at room temperature. Liposomes that co-encapsulate other proteins such as hemoglobin or albumin, in addition to glutathione, also label with high efficiency. Both in vitro and in vivo studies indicate good stability of this label. Rabbit images show significant spleen and liver uptake at 2 and 20 h after liposome infusion without visualization of thyroid, stomach or bladder activity. This labeling method can be used to study the biodistribution of a wide variety of liposome preparations that are being tested as novel drug delivery systems. This method of labeling liposomes with 99mTc may also have applications in diagnostic imaging.

Animals

Demonstration of differential post-stenotic myocardial technetium-99m-teboroxime clearance kinetics after experimental ischemia and hyperemic stress.

The clearance kinetics of the perfusion tracer 99mTc-teboroxime were evaluated in post-stenotic and normal myocardium using dynamic planar gamma camera imaging in pre-instrumented dogs in the control state (n = 9) and following total occlusion (2 min), pharmacologic stress with adenosine [80 and 160 micrograms/kg/min] or dipyridamole, and rapid atrial pacing (220/min). Technetium-99m-teboroxime clearance in normal myocardium was accelerated by adenosine and by dipyridamole compared to the control state (8.9 +/- 1.1 and 9.3 +/- 1.9 min versus 11.9 +/- 1.8 min; p less than 0.05). Post-stenotic 99mTc-teboroxime clearance half-time was most significantly prolonged compared to nonoccluded contralateral perfusion zones by 160 micrograms/kg/min adenosine stress (11.2 +/- 3.7 versus 6.3 +/- 1.5 min) and by complete coronary occlusion (12.1 +/- 3.3 versus 6.6 +/- 1.2 min; both p less than 0.05). Differential tracer clearance from post-stenotic versus nonoccluded zones produced quantitative evidence of relative defect "redistribution" in 71% of maximal stress studies at a mean of 8.8 +/- 2.5 min postinjection. Sensitivity, specificity, and diagnostic accuracy of prolonged regional 99mTc-teboroxime clearance rates for post-stenotic perfusion abnormalities were 62%, 100% and 81% in maximal stress studies. Future clinical trials of exercise and nonexercise stress 99mTc-teboroxime imaging should consider these kinetic characteristics and examine the correlates of perfusion defect "redistribution."

Adenosine

Linear gastric emptying of hyperosmolar glucose solutions.

We performed a total of 12 gastric emptying studies on 6 normal subjects with a hyperosmolar (1.85 mol/l) 400-kcal glucose solution commonly used for diagnosing diabetes and a more dilute (0.62 mol/l) 200-kcal glucose solution. The gastric half-emptying time was greatly prolonged with both glucose solutions; 107 min for the (1.85 mol/l) 400-kcal glucose solution compared to 66 min for the more dilute (0.62 mol/l) 200-kcal glucose solution. Although the 200-kcal glucose solution contained one-half the amount of glucose (50 g) compared to the 400-kcal solution (100 g), the blood glucose values obtained during a 2-hr period were only slightly lower with the former solution. This study demonstrates significantly delayed gastric emptying of glucose solutions in normal subjects and a linear pattern of gastric emptying formerly associated only with solid meals.

Administration, Oral

Acute hemodynamic changes during intravenous dipyridamole thallium imaging early after infarction.

In order to determine the safety and hemodynamic effects of intravenous dipyridamole infusion for thallium-201 scinitigraphy in patients with acute ischemic syndromes, 10 patients with recent uncomplicated myocardial infarction (7 +/- 2 days pre-test) had central pressures and cardiac output values measured serially in a coronary care unit during and after the administration of dipyridamole (0.56 mg/kg over 4 minutes) and following aminophylline reversal (50 to 150 mg intravenously) of dipyridamole effect. Cardiac medications were not discontinued. Double product did not change significantly (8522 +/- 1811 versus 9044 +/- 1701; p = NS). Serious ischemic events did not occur, although 20% of patients had noncardiac side effects and 30% developed greater than or equal to 1 mm ST segment depression with associated angina in one-third of these cases. The peripheral blood pressure and heart rate response did not predict the occurrence of myocardial ischemia. Dipyridamole significantly reduced systemic vascular resistance (1218 +/- 302 to 739 +/- 166 dyne/sec-1/cm-5; p less than 0.05) and increased cardiac index (3.1 +/- 0.7 to 4.7 +/- 1.0 L/min/m2; p less than 0.05) within approximately 10 minutes, in association with a significant increase in pulmonary capillary wedge pressure (13 +/- 5 to 17 +/- 6 mm Hg; p less than 0.05). Three patients developed silent new "V" waves in their pulmonary capillary wedge pressure tracing, associated with anterior thallium redistribution. All three patients with newly elevated wedge pressures (greater than 15 mm Hg) had both thallium-201 redistribution and multivessel coronary disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminophylline

Radionuclide determination of the relationship between left ventricular contractile state and ejection fraction.

To determine whether the relationship between various measures of left ventricular (LV) contractile state and ejection fraction (EF) is linear in man, we studied 30 patients during right atrial pacing over a range of loading conditions. With the use of micromanometer LV pressures and radionuclide LV volumes, pressure-volume (P-V) loops were generated for each loading condition. Then isochronal, instantaneous P-V data points were obtained by linear regression analysis to attain the maximum slope (Emax) of these time-varying isochrones. Other measures of LV end systole were also used to calculate end-systolic P-V relations in a similar fashion, and indirect P-V relations were obtained from the linear regression analysis of brachial artery peak pressure vs minimum LV volume data points. When the slopes of these LV contractile measures were compared to the radionuclide LV EFs, the linear correlation coefficients ranged from 0.53 to 0.67. After natural log transformation of the LV contractile state and EF data, the correlation coefficients for the polynomial curve fits ranged from 0.80 to 0.88. When the correlation coefficients for the polynomial curve fits of the natural log transformed data were compared to those for the linear regression analyses of the raw data, significant improvements were evident (p less than 0.05). Thus the relationship between various measures of LV contractile state and EF obtained with radionuclide angiography is best approximated by a complex, curvilinear relationship that is due, in part, to the wide range of LV contractile states within the relatively narrow normal range of LV ejection fractions.

Adult

Assessment of the radionuclide angiographic left ventricular maximum time-varying elastance calculation in man.

This investigation was designed to determine whether left ventricular (LV) maximum time-varying elastance (Emax) calculations obtained using equilibrium radionuclide angiography (RNA) were comparable to those obtained using biplane contrast cineangiography (CINE), and whether simple, indirect P-V relations might provide reasonable, alternative estimates of Emax. Accordingly, we studied 19 patients with simultaneous high-fidelity micromanometer LV and fluid brachial artery (Ba) pressure recordings, CINE, and RNA under control conditions and during methoxamine and nitroprusside infusions. Emax was defined for CINE and RNA as the maximum slope of the linear relation of isochronal, instantaneous P-V data points obtained from each of the three loading conditions. The indirect P-V relations were similarly obtained from Ba peak (P) pressure versus minimum RNA LV volume (BaP/minV) and Ba dicrotic notch (di) pressure versus minimum RNA LV volume (Badi/minV) data points. The mean heart rates and LV (+)dP/dtmax values were minimally altered during the three loading conditions. The isochronal Emax values ranged from 1.40 to 6.73 mmHg/ml (mean 4.13 +/- 1.99 s.d. mmHg/ml) for CINE and from 1.48 to 7.25 (mean 4.35 +/- 1.81 mmHg/ml) for RNA (p = N.S.). Similarly, the unstressed volumes ranged from -10 to 80 ml (mean 30 +/- 23 ml) for CINE and from -8 to 77 ml (29 +/- 21 ml) for RNA (p = N.S.). The individual, isochronal Emax values by RNA correlated with those by CINE (r = 0.86). In 14 of the 19 patients, the BaP/minV and Badi/minV relations correlated with the isochronal Emax values calculated by RNA (r = 0.83 and 0.82, respectively), and these relations also correlated with the Emax values calculated by CINE (r = 0.82 and 0.78, respectively). The slope and V0 values for the BaP/minV and Badi/minV relations underestimated those for Emax by RNA and CINE (p less than 0.01 and p less than 0.05, respectively, for both). Thus, the isochronal Emax values calculated using RNA are comparable to those obtained using CINE in man. Moreover, indirect P-V relations underestimate these Emax values, but they are linearly related with the isochronal Emax values calculated by RNA and CINE. Consequently, these indirect P-V relations may provide a more simple, alternative estimate of LV contractile function in man.

Adult

Value of tomographic thallium-201 imagining in patients with chest pain following coronary artery bypass grafting.

To determine whether thallium-201 washout profile analysis can detect regional myocardial ischemia caused by coronary artery bypass graft occlusion or progression of disease in nonbypassed coronary arteries, 19 consecutive patients with chest pain following bypass grafting were evaluated with coronary arteriography and thallium-201 scintigraphy. Twenty of the 55 coronary artery regions were perfused by an occluded bypass graft or a significantly stenosed (greater than or equal to 70% diameter narrowing) nonbypassed coronary artery, while 35 coronary regions were perfused by patent bypass grafts or insignificantly diseased coronary arteries. The tomographic thallium-201 washout profile results correlated with the bypass graft and coronary arteriographic findings (k = 0.67, P less than 0.001). The sensitivity of tomographic thallium-201 washout profile abnormalities for arteriographic abnormalities was 75%, while the specificity was 86%. The authors conclude that tomographic thallium-201 washout profile analysis may be very useful in the evaluation of patients with chest pain following coronary artery bypass grafting by detecting regional myocardial ischemia caused by occlusion of specific bypass grafts or progression of disease in nonbypassed coronary arteries.

Adult

Hemodynamically important right ventricular infarction: follow-up evaluation of right ventricular systolic function at rest and during exercise with radionuclide ventriculography and respiratory gas exchange.

The prognosis and recovery of right ventricular systolic function in patients with hemodynamically documented right ventricular myocardial infarction (RVMI) is unclear. Therefore 27 patients who met hemodynamic criteria for RVMI were followed for at least 1 year. Four patients died within 1 year and 23 survived. Postmortem examination performed in three of the four patients showed extensive infarction of the right and left ventricles. Survivors underwent early and late follow-up resting radionuclide ventriculograms and late exercise studies. During long-term follow-up (1 to 4 years) resting radionuclide ventriculography demonstrated a significant improvement in right ventricular ejection fraction (30 +/- 7% to 43 +/- 8%; p less than .001) and right ventricular wall motion index (2.2 +/- 0.4 to 1.5 +/- 0.5; p less than .001) in 18 patients who survived longer than 1 year. Fourteen of these patients underwent upright bicycle exercise while off beta-blocking drugs and peak radionuclide ejection fraction was acquired after anaerobic threshold was achieved. Right ventricular ejection fraction increased significantly from 41 +/- 10% to 47 +/- 12% (p less than .001), as did the left ventricular ejection fraction (55 +/- 15% to 60 +/- 12%; p less than .05). The direction and magnitude of change of the right ventricular ejection fraction correlated significantly with the left ventricular ejection fraction (r = .82, p less than .02). Deviations from this correlation occurred in patients who had a decreased forced expiratory volume in 1 sec and an abnormal ventilatory reserve during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Quantification of left-ventricular regional dyssynergy by radionuclide angiography.

To determine whether variables obtained from Fourier analysis of gated equilibrium radionuclide angiographic (RNA) images can detect and quantify changes in left-ventricular (LV) regional wall motion induced by transient ischemia, 11 chronically instrumented dogs were simultaneously studied with hemodynamic measurements and RNA during control, left circumflex (LCx) coronary artery occlusion, and postocclusion conditions. The dogs were preinstrumented with aortic and LV catheters, electromagnetic aortic and LCx coronary artery flow probes, high-fidelity LV micromanometers, LCx coronary artery occluders, and 4-mm ultrasonic transverse LV diameter and 2-mm regional LV segment crystal pairs. Radionuclide LV regional phase and amplitude variables were calculated for each condition. The absolute changes in LCx region RNA mean, median, and standard deviation of mean phase correlated with the percent changes in LCx segment crystal fractional shortening (r = -0.71, -0.64, and -0.51, respectively; all p less than or equal to 0.01). Similarly, the absolute changes and percent changes in LCx region RNA mean amplitude per pixel correlated with the percent changes in LCx segment crystal fractional shortening (r = 0.89 and 0.94, respectively; both p less than 0.001). When these LCx region RNA phase variables were subgrouped according to mild or severe depression or augmentation in LCx segment crystal fractional shortening, progressive differences were observed between the average values for these subgroups (p less than 0.05 to p less than 0.001). These data, therefore, suggest that these regional RNA phase variables may be able to detect and quantify alterations in LV contraction patterns due to transient ischemia.

Animals

Gallium-67 scintigraphy in well-differentiated lymphocytic lymphoma of the skin.

Skin lymphomas are now divided into "T" or thymic cell lymphomas (mycosis fungoides being the principal type) and "B" cell lymphomas after the bursa of Fabricius. The "T" cell lymphomas all are identified by the thymic or cerebriform cell. Those lymphomas of the skin which do not contain these characteristic cells are derived from the bursa cells and are termed "B" cell lymphomas. A large percentage of these non "T" cell lymphomas have been histologically diagnosed as lymphocytic lymphoma of the skin (1). The authors had an opportunity to scan a patient with histologically proven lymphocytic lymphoma of the skin with Ga-67 and obtained on excellent correlation between gallium accumulation in the skin lesions and histologic confirmation of lymphocytic lymphoma.

Gallium Radioisotopes

Segmental coronary artery disease: detection by rotating slant-hole collimator tomography and planar thallium 201 myocardial scintigraphy.

Normal quantitative circumferential profile limits were established for a 30 degrees bilateral rotating slant-hole (RSH) collimator tomographic system. This system's value in detecting segmental coronary artery disease was assessed in a study evaluating 196 patients by thallium 201 myocardial scintigraphy and coronary arteriography. Profile curves were calculated from images of 20 healthy patients and used to identify significant coronary artery disease (greater than or equal to 70% diameter narrowing) in the left anterior descending (LAD), the right, and the left circumflex (LCx) coronary arteries. In a group of 86 patients, an abnormality on the apical or middle plane optimally identified segmental coronary artery disease. When such abnormalities were prospectively evaluated in a test group of 110 patients, the sensitivity and specificity were 79% and 93% for LAD, 90% and 90% for right, and 83% and 83% for LCx coronary artery disease. Compared with qualitative interpretation of the planar and tomographic images, quantitative tomography significantly improved the sensitivity of T1-201 imaging in detecting LAD, right, and LCx coronary artery disease (P less than .001) in patients with or without previous myocardial infarction.

Adult

Validation of attenuation-corrected equilibrium radionuclide angiographic determinations of right ventricular volume: comparison with cast-validated biplane cineventriculography.

To determine the accuracy of attenuation-corrected equilibrium radionuclide angiographic determinations of right ventricular volumes, we initially studied 14 postmortem human right ventricular casts by water displacement and biplane cineventriculography. Biplane cineventriculographic right ventricular cast volumes, calculated by a modification of Simpson's rule algorithm, correlated well with right ventricular cast volumes measured by water displacement (r = .97, y = 8 + 0.88x, SEE = 6 ml). Moreover, the mean volumes obtained by both methods were no different (73 +/- 28 vs 73 +/- 25 ml). Subsequently, we studied 16 patients by both biplane cineventriculography and equilibrium radionuclide angiography. The uncorrected radionuclide right ventricular volumes were calculated by normalizing background corrected end-diastolic and end-systolic counts from hand-drawn regions of interest obtained by phase analysis for cardiac cycles processed, frame rate, and blood sample counts. Attenuation correction was performed by a simple geometric method. The attenuation-corrected radionuclide right ventricular end-diastolic volumes correlated with the cineventriculographic end-diastolic volumes (r = .91, y = 3 + 0.92x, SEE = 27 ml). Similarly, the attenuation-corrected radionuclide right ventricular end-systolic volumes correlated with the cineventriculographic end-systolic volumes (r = .93, y = - 1 + 0.91x, SEE = 16 ml). Also, the mean attenuation-corrected radionuclide end-diastolic and end-systolic volumes were no different than the average cineventriculographic end-diastolic and end-systolic volumes (160 +/- 61 and 83 +/- 44 vs 170 +/- 61 and 86 +/- 43 ml, respectively). Comparison of the uncorrected and attenuation-corrected radionuclide right ventricular volumes demonstrated narrower 95% confidence intervals for the attentuation-corrected right ventricular volume determinations over a wide range of cineventriculographic volumes. Thus we conclude that: (1) attenuation-corrected radionuclide right ventricular end-diastolic and end-systolic volumes compare closely with those obtained by a cast-validated biplane cineventriculographic method and (2) attenuation-corrected radionuclide right ventricular volumes correspond more closely to determinations of biplane cineventriculographic right ventricular volumes and are thus likely to be more accurate than uncorrected radionuclide right ventricular volumes.

Adolescent

Comparative effects of volume loading, dobutamine, and nitroprusside in patients with predominant right ventricular infarction.

To assess the value of volume loading and to determine the relative efficacy of dobutamine compared with nitroprusside therapy in acute right ventricular infarction (RVMI), 13 patients with clinical, hemodynamic, and radionuclide angiographic evidence of RVMI were evaluated. In 10 patients who had an initial pulmonary arterial wedge pressure less than 18 mm Hg, volume loading did not improve cardiac index (1.9 +/- 0.5 [SD] to 2.1 +/- 0.4 liters/min/m2), despite significant increases in mean right atrial pressure (11 +/- 2 to 15 +/- 2 mm Hg, p less than .001) and pulmonary arterial wedge pressure (10 +/- 4 to 15 +/- 2 mm Hg, p less than .001). Nine patients received dobutamine or nitroprusside in random order, while hemodynamic measurements and radionuclide angiograms were obtained simultaneously. Compared with nitroprusside, dobutamine produced a statistically significant increase in cardiac index (2.0 +/- 0.4 to 2.7 +/- 0.5 vs 2.1 +/- 0.4 to 2.3 +/- 0.5 liters/min/m2, p less than .001), stroke volume index (29 +/- 6 to 36 +/- 8 vs 29 +/- 6 to 30 +/- 6 ml/m2, p = .02), and right ventricular ejection fraction (30 +/- 8% to 42 +/- 7% vs 34 +/- 8% to 37 +/- 4%, p less than .01) by two-way analysis of variance. We conclude that volume loading does not improve cardiac index in patients with acute RVMI despite a rise in cardiac filling pressures and that infusion of dobutamine, after appropriate volume loading, produces a significant improvement in cardiac index and right ventricular ejection fraction over those after infusion of nitroprusside.

Adult