Biomedical subjects
Publications and source records attributed to S J Goldsmith.
The appearance of gallium-67 images in bone infarction was studied in nine patients with sickle cell disease and correlated with the bone scan findings. Gallium uptake in acute infarction was decreased or absent with a variable bone scan uptake, and normal in healing infarcts, which showed increased uptake on bone scan. The significance of these findings is discussed.
Pseudomonas otitis externa in elderly diabetics may extend aggressively to adjacent bone, cranial nerves, meninges, and vessels, leading to a clinical diagnosis of "malignant" external otitis. Early diagnosis is necessary for successful treatment. This study compares the findings of initial radiographs, thin-section tomography of temporal bone, CT scans of head and neck, technetium-99m methylene diphosphonate (MDP) and gallium-67 citrate scintigraphy, and single-photon emission computed tomography (SPECT) for detection of temporal bone osteomyelitis in ten patients fulfilling the clinical diagnostic criteria of malignant external otitis. Skull radiographs were negative in all of the eight patients studied. Thin-section tomography was positive in one of the seven patients studied using this modality. CT scanning suggested osteomyelitis in three of nine patients. Both Tc-99m and Ga-67 citrate scintigraphy were positive in 10 of 10 patients. Three patients who were considered to be in clinical remission had positive Tc-99m scans and normal Ga-67 scans. These results suggest that technetium and gallium scintigraphy are more sensitive than radiographs and CT scans for early detection of malignant external otitis. Gallium scintigraphy appears to be more specific for follow-up evaluation of these patients.
The intracarotid infusion of the anti-neoplastic compound, etoposide, has been shown to exert a dose-dependent effect on blood-brain barrier (BBB) permeability. Etoposide, however, is formulated in a complex solvent solution containing alcohol, Tween 80, polyethylene glycol 300, and citric acid. To investigate the contribution of the solvent solution to BBB disruption, the authors studied Sprague-Dawley rats after the internal carotid artery infusion of the solvent solution with and without the addition of etoposide. Experiments were performed at four doses of drug and/or solvent. Disruption of the BBB was evaluated qualitatively by the appearance of the systemically administered dye, Evans blue, in the cerebral hemispheres and quantitatively by the ratio of gamma counts of the technetium-labeled chelate of diethylenetriaminepentaacetic acid (99mTc-DTPA) in the ipsilateral:contralateral hemisphere. Significant barrier opening was obtained in all four groups of animals infused with solvent plus etoposide. In the corresponding groups of rats infused with the solvent solution alone, BBB disruption was markedly lower. Only in the group infused with the largest dose of solvent was the hemispheric ratio of 99mTc-DTPA significantly different from saline-infused animals. Each of the groups with solvent plus etoposide had 99mTc-DTPA ratios significantly different from the control group. Intracarotid infusion and subsequent BBB disruption were well tolerated by the animals receiving either solvent alone or solvent and etoposide. Disruption of the BBB secondary to the intracarotid infusion of etoposide is primarily caused by the drug itself and not by the solvent solution.
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In order to estimate the precision and accuracy of parameters derived from segmental multiharmonic Fourier analysis of gated blood-pool images, a Monte Carlo computer noise simulation was tested on five sample regional time-activity curves. The first three Fourier harmonics were retained and the precision and accuracy of parameters of ventricular function were calculated, varying the ejection fraction, segment size, and framing rate. Precision improved with higher ejection fraction, higher counts per frame, or higher framing rate. There was no change in precision as the framing rate changed at fixed total counts. Accuracy changed little with changing framing rate. Thus, for segmental analysis there is no advantage to using a higher framing rate. Regions five or more pixels in size are recommended for reliable results. This study provides useful information for the optimization of acquisition and processing conditions for regional gated blood-pool analysis.
In order to evaluate the mechanisms which facilitate the transfer of 67Ga from transferrin in plasma to intracellular binding sites, lactoferrin, a glycoprotein with high affinity for 67Ga, was used as a probe to study the effect of protein binding on gallium uptake by tumor cells. The in vivo effect of transferrin and lactoferrin on the biodistribution of 67Ga was studied in nude mice bearing human malignant mesothelioma. Tumor uptake of 67Ga was reduced 30% by transferrin and 57% by lactoferrin compared with 67Ga-citrate alone. Liver uptake of 67Ga, however, was significantly increased by binding to lactoferrin. The in vitro binding of 67Ga to tumor cells (Burkitt's lymphoma) was apparently promoted by the addition of transferrin or lactoferrin to the incubation medium, but this glycoprotein enhancement of gallium uptake by the cells was dependent on the albumin level, decreasing in absolute uptake as the albumin concentration was increased, suggesting nonspecific binding of glycoproteins to cells. Because of the significant amount of nonspecific binding of 67Ga-labeled glycoprotein complexes in cell culture experiments, in vitro experiments should be used with caution in developing a hypothesis on the mechanisms of cellular uptake of radiogallium. In vivo experiments suggest different mechanisms for cellular uptake of 67Ga in neoplastic tissue and in liver.
While evaluating the role of iron-binding glycoproteins on the in vitro uptake of 67Ga and 59Fe by tumor cells, it was observed that these radiometals bind to polystyrene culture tubes in the presence of transferrin or lactoferrin. The amount of 67Ga or 59Fe bound to the tube increases with glycoprotein concentrations up to 20 microgram/ml and decreases thereafter. This biphasic response is a reflection of metal-protein affinity and is greatest for 59Fe-lactoferrin. With 125I-labeled transferrin and lactoferrin, the amount of tube-bound radioactivity was inversely dependent on the glycoprotein concentration suggesting that glycoproteins bind to a limited number of binding sites on the tube wall. Approximately 10(13) glycoprotein molecules were bound per tube with an affinity constant of 1.89 X 10(7) 1/M for transferrin and 1.08 X 10(7) l/M for lactoferrin. These sites are not specific since addition of albumin inhibited the binding of radiolabeled glycoproteins to the tube. In the light of these observations, caution is required in interpreting results of cell culture experiments which have not directed attention to protein-plastic interaction.
This study attempts to determine whether exercise treadmill testing with clinical, electrocardiographic, and thallium-201 myocardial perfusion imaging data can identify which patients have left main or 3-vessel (anatomically high-risk) coronary artery disease (CAD) after their first transmural myocardial infarct (MI). Twelve exercise test criteria for high-risk disease were compared in 40 patients referred for cardiac catheterization; 34 had a history of chest pain and 17 had angiographically defined high-risk CAD. A thallium image defect outside the vascular distribution of the MI was the most reliable criterion to distinguish patients with high-risk CAD (p = 0.00052 for Fisher's exact test of discrimination). Thallium imaging was somewhat more sensitive (92 versus 65%, p = 0.108) when patients with negative thallium imaging criteria who failed to achieve 85% of the age-predicted maximal heart rate were excluded. Failure to achieve 85% of predicted heart rate was by itself a useful criterion for detecting high-risk CAD (p = 0.017), especially in patients not taking propranolol (p = 0.004). Development of positive S-T segment depression at less than 70% predicted heart rate also discriminated left main or 3-vessel disease from less extensive CAD (p = 0.016). Other criteria failed to discriminate significantly between high-risk and less extensive CAD in patients after their first MI (p greater than 0.05). S-T segment depression (p = 0.199) or chest pain (p = 0.577) during exercise testing were particularly unreliable. Further, none of the criteria for high-risk CAD were influenced by irreversible left ventricular dysfunction. It is concluded that patients with thallium imaging defects outside the region of the infarct, decreasing blood pressure during exercise, failure to achieve 85% of predicted heart rate, or S-T depression at less than 70% of predicted heart rate have a high probability of having left main or 3-vessel disease. Patients without these criteria have a very low probability of having high-risk CAD and probably do not need coronary angiography for the purpose of excluding these high-risk coronary lesions after a first MI.
Timing abnormalities of myocardial contractility may occur as inter- or intraventricular asynchrony. Gated blood pool scintigraphy was performed on 21 patients with a normal ejection fraction and the following electrocardiograms: six normal, six with left bundle branch block, four with right bundle branch block and five with right ventricular pacemaker rhythm. A phase and amplitude of the first harmonic of the Fourier transform was obtained for each pixel, and left and right ventricles were trisected. A mean vector phase for each region was obtained by vector summation. Regional and global values were analyzed within each group and compared with normal values. The phase differences between the entire left and right ventricles (mean +/- standard deviation) were: 9 +/- 3 in the normal patients, 38 +/- 8 (p less than 0.01) in patients with left bundle branch block, -6 +/- 7 (p less than 0.05) in patients with right bundle branch block and 15 +/- 9 (difference not significant) in patients with pacemaker rhythm. The phase differences between left ventricular posterolateral and septal regions were -4 +/- 2 in the normal patients, 10 +/- 5 (p less than 0.01) in patients with left bundle branch block, -7 +/- 10 (p less than 0.05) in patients with right bundle branch block and 10 +/- 5 (p less than 0.01) in patients with pacemaker rhythm. Within the right ventricle, phase differences between the apical and septal segments were 14 +/- 9 in the normal patients, 14 +/- 10 (NS) in patients with left bundle branch block, -2 +/- 3 (p less than 0.01) in patients with right bundle branch block and -22 +/- 18 (p less than 0.01) in patients with pacemaker rhythm. Interventricular phase differences were greatest in patients with left bundle branch block and absent or reversed in right bundle branch block.(ABSTRACT TRUNCATED AT 250 WORDS)
An animal model for prolonged reversible blood-brain barrier (BBB) disruption has been developed. The external carotid arteries of Osborn-Mendel rats were catheterized in a retrograde manner. Varying concentrations of sodium dehydrocholate were infused into the internal carotid artery by this technique. BBB disruption was evaluated qualitatively by the appearance in the infused hemisphere of the systemically administered dyes Evans blue and sodium fluorescein and quantitatively by the ratio of counts of the technetium-labeled chelate of diethylenetriaminepentaacetic acid (99mTc-DTPA) in the infused to the noninfused hemisphere. The ability of sodium dehydrocholate to disrupt the BBB was documented with all three markers. As the concentration of the infused dehydrocholate was increased, both the incidence and the degree of BBB disruption increased. Reversibility of BBB disruption was evaluated by the administration of sodium fluorescein and 99mTc-DTPA at varying times after BBB disruption. Depending on the concentration of the infused sodium dehydrocholate, altered BBB permeability can be maintained for over 3 days. This new model of prolonged reversible BBB disruption deserves further investigation both for basic studies of the BBB and for therapeutic studies of drug delivery into the central nervous system.
Three leukemic patients showing minimal bone uptake of Tc-99m pyrophosphate but with good uptake of methylene diphosphonate are described.
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We tested the hypothesis that visualisation of defects on thallium-201 (201Tl) myocardial perfusion images (MPI) depends on the duration of the ischaemic state between 201Tl injection and the time of reperfusion of an occluded coronary artery. Praecordial imaging with a gamma camera was performed in 24 anaesthetised, open-chest dogs with transient coronary occlusion. Results indicated that if the duration of the ischaemic state after 201Tl injection was less than 3 min before reperfusion, then the MPI 5 to 15 min after 201Tl injection was falsely negative (201Tl activity in zone (IZ)/normal zone (NZ)greater than 0.85). Dogs which were ischaemic more than 5 min always had MPI defects 5 to 15 min after 201Tl injection (IZ/NZ201Tl ratio less than 0.85). MPI results (201Tl IZ/NZ) 15 min after 201Tl injection were determined by the duration of the ischaemic state after 201Tl injection (r = -0.86) because prolonged ischaemia allowed 201Tl to distribute from blood to myocardium before reperfusion: 201Tl (IZ/NZ( = 0.356 +/- 1.00 (fraction of total 201Tl remaining in blood at the end of the ischaemic state), r = 0.94.
High-pressure liquid chromatography (HPLC) can be performed with an aqueous size-exclusion column to separate proteins or other macromolecules on the basis of molecular size. An HPLC system with a Spherogel-TSK SW column was modified to detect simultaneously uv absorption and radioactivity. Characteristic retention times (RT) were determined for pure human serum albumin (HSA) (RT = 17 min) and pertechnetate (RT = 28.5 min). When analysis was performed on Tc-99m HSA preparations, Tc-99m radioactivity was resolved into five different peaks, with RT ranging from 10.2 to 28.5 min. Less than 2% radioactivity was associated with the pertechnetate peak, whereas the remaining Tc-99m was protein bound. Most of the activity (90%) corresponded to the albumin peak, and 7% was bound to contaminants of high molecular weight with RTs of 10.2 and 14 min. Rapid separation of various radiochemical components differing in molecular size provides an improved basis for understanding the biodistribution of a Tc-99m HSA preparation. This technique would be useful for the preparation and analysis of various radiolabeled macromolecules such as enzymes, immunoglobulins, and other proteins.
A multicrystal gamma camera has been evaluated for the imaging of 511-keV photons resulting from positron emission. With minor instrument modifications, images of a phantom demonstrating good resolution are obtained. Satisfactory planar images are obtained in animals using fluorine-18 or rubidium-82. These findings establish the feasibility of planar imaging of positron emitters in a clinical setting, and may make possible the more rapid development assessment, and dissemination of positron-emitting radionuclides, thus promoting utilization of tomographic positron imaging techniques.
The use of myocardial perfusion imaging (MPI) to identify obstructive coronary disease of the left anterior descending coronary artery proximal to the first septal perforator (prox LAD) was studied in 60 patients. Perfusion of the septum and anteroapical areas with thallium-201 injected during exercise was compared to results of coronary arteriography. Septal MPI defect was found in 92.3% of patients with obstruction of the proximal LAD, 27.7% of patients with obstruction of LAD distal to first septal perforator, 0% in patients with obstructions involving right or circumflex arteries, and in 10.5% of patients without coronary disease. Anteroapical MPI defects were found with similar frequency in the three groups with obstructive coronary disease. Septal MPI defect had a sensitivity of 92.3% and specificity of 85.4% in the diagnosis of proximal LAD disease. Normal septal perfusion with thallium-201 virtually excluded proximal LAD disease.
Radionuclide gated cardiac blood pool imaging was used to quantify the severity of valve regurgitation in 20 patients, by calculating the ratio of left ventricular to right ventricular stroke counts (end-diastolic minus end-systolic counts in right and left ventricular regions of interest). This ratio (the stroke index ratio) was substantially higher in patients with aortic and mitral regurgitation (3.91 +/- 1.45) than in a control group of 10 patients without regurgitation (1.32 +/- 0.15), p less than 0.001. The stroke index ratio correlated closely (r = 0.947) with measurements of regurgitant fraction derived from simultaneous determinations of total and forward stroke volumes during cardiac catheterization. After aortic and mitral valve replacement in 18 patients, the stroke index ratio decreased from 4.03 +/- 1.46 to 1.38 +/- 0.23 (p less than 0.001), a value not significantly different from that observed in patients without regurgitation. All three patients with residual postoperative regurgitation had a stroke index ratio greater than 2 standard deviations above the mean values for the control group (greater than 1.62), whereas the remaining 15 patients, who had no evidence of regurgitation, had values within the normal range. Therefore, radionuclide gated blood pool scanning provides a noninvasive method of quantifying valve regurgitation and assessing the results of medical or surgical interventions.
A comparison of left ventricular function data derived from a low cost, portable electrocardiographic gated scintillation probe (nuclear stethoscope) with conventional scintiangiographic data was performed in 68 patients. Ejection fraction correlation (r = 0.86, p less than 0.005) was better in patients with uniform wall motion than in those with regional asynergy (r = 0.68 p less than 0.01). Probe variables reflecting systolic emptying rates, diastolic filling rates and timing intervals, and relative volumes analyzed in combination provided 100 percent sensitivity, specificity, and predictive value in detecting abnormal left ventricular performance. The results suggest that radionuclide angiography with an electrocardiographic gated scintillation probe is a sensitive, rapid and relatively inexpensive portable method of screening for cardiac dysfunction with a yield similar to that from the more costly gamma camera derived scintiangiogram.