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Biomedical subjects

R Blumhardt

Publications and source records attributed to R Blumhardt.

At least 19 recordsLinked to original sources

Evaluation of [(99m)Tc] liposomes as lymphoscintigraphic agents: comparison with [(99m)Tc] sulfur colloid and [(99m)Tc] human serum albumin.

This study investigates the use of [(99m)Tc] liposomes for the detection of sentinel lymph nodes. A variety of [(99m)Tc] liposome formulations were compared with common lymphoscintigraphic agents including [(99m)Tc] regular-sulfur colloid (SC), [(99m)Tc] 0.22 microfiltered-SC, [(99m)Tc] reduced heating time 0.22 microfiltered-SC, and [(99m)Tc] human serum albumin (HSA) in rabbits. Images were acquired for the first 60 minutes and at 24 hours, followed by tissue biodistribution study. All agents except [(99m)Tc] regular SC demonstrated good migration from the injection site. Agents were retained in the popliteal node at 24 hours to varying degrees as follows: both [(99m)Tc] filtered SC preparations > [(99m)Tc] regular SC > [(99m)Tc] liposomes > [(99m)Tc] HSA. [(99m)Tc] liposome imaging can be used to develop novel liposome compositions with improved lymph node diagnostic and drug delivery characteristics.

Animals↗

Thyroid palpation versus high-resolution thyroid ultrasonography in the detection of nodules.

Detection of thyroid nodules by physical examination and high-resolution ultrasonography was compared using small groups of blinded, experienced physician examiners working with a sample of 2441 persons from Estonia, most of whom were Chernobyl nuclear reactor clean-up workers. A random subsample of 113 (5%) persons was subjected to triple control examinations with both physical examination and high-resolution ultrasonography. Positive high-resolution ultrasonographic findings were considerably more reproducible among different observers than were positive physical examination findings. Agreement between methods was poor. Nodules were found in 169 (6.9%) subjects by physical examination and in 249 (10.2%) subjects by high-resolution ultrasonography. Physical examination found only 53 (21%) of the 249 nodules found by high-resolution ultrasonography. High-resolution ultrasonography did not confirm the existence of 115 (68%) of the 169 nodules found by physical examination. Only 6.4% of nodules less than 0.5 cm in diameter, as based on high-resolution ultrasonographic results, were detected by physical examination. Physical examination detection improved with increasing nodule size but was still only 48.2% for nodules larger than 2 cm. Physical examination was relatively effective in detecting nodules in the isthmus of the thyroid gland but much less so for nodules in the upper pole of the gland. Clinical evaluation and epidemiologic studies of nodular thyroid disease stand to benefit from the greater sensitivity and specificity of ultrasonographic examinations.

Adolescent↗

Rapid objective measurement of gamma camera resolution using statistical moments.

An easy and rapid method for the measurement of the intrinsic spatial resolution of a gamma camera was developed. The measurement is based on the first and second statistical moments of regions of interest (ROIs) applied to bar phantom images. This leads to an estimate of the modulation transfer function (MTF) and the full-width-at-half-maximum (FWHM) of a line spread function (LSF). Bar phantom images were acquired using four large field-of-view (LFOV) gamma cameras (Scintronix, Picker, Searle, Siemens). The following factors important for routine measurements of gamma camera resolution with this method were tested: ROI placement and shape, phantom orientation, spatial sampling, and procedural consistency. A 0.2% coefficient of variation (CV) between repeat measurements of MTF was observed for a circular ROI. The CVs of less than 2% were observed for measured MTF values for bar orientations ranging from -10 degrees to +10 degrees with respect to the x and y axes of the camera acquisition matrix. A 256 x 256 matrix (1.6 mm pixel spacing) was judged sufficient for routine measurements, giving an estimate of the FWHM to within 0.1 mm of manufacturer-specified values (3% difference). Under simulated clinical conditions, the variation in measurements attributable to procedural effects yielded a CV of less than 2% in newer generation cameras. The moments method for determining MTF correlated well with a peak-valley method, with an average difference of 0.03 across the range of spatial frequencies tested (0.11-0.17 line pairs/mm, corresponding to 4.5-3.0 mm bars). When compared with the NEMA method for measuring intrinsic spatial resolution, the moments method was found to be within 4% of the expected FWHM.

Biophysical Phenomena↗

Biodistribution and imaging studies of technetium-99m-labeled liposomes in rats with focal infection.

We have recently developed a procedure to label liposomes containing reduced glutathione (GSH) with 99mTc using the lipophilic chelator, hexamethylpropyleneamine oxime (HMPAO). In the present study, we evaluated the use of 99mTc-liposomes to detect focal infection sites in rats. Rats were infected in the thigh by intramuscular injection with Staphylococcus aureus followed 24 hr later by an intravenous injection of 99mTc-liposomes, 67Ga-citrate, or 99mTc-human serum albumin (HSA). The animals were imaged under a gamma camera and subsequently killed at 4, 24 or 48 hr for tissue biodistribution studies. In contrast to infected rats receiving 67Ga-citrate or 99mTc-HSA, abscesses were prominently localized within 2 hr in rats after 99mTc-liposome injection, and continued to increase in activity up to 24 hr. Abscess-to-muscle ratios calculated from 24-hr biodistribution data obtained from tissue sampling were 35.3 +/- 7.6 for 99mTc-liposomes, 4.1 +/- 0.7 for 67Ga-citrate and 8.0 +/- 1.0 for 99mTc-HSA. These studies show the potential of using 99mTc-liposomes to localize infection.

Animals↗

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↗