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Biomedical subjects

D W Seldin

Publications and source records attributed to D W Seldin.

At least 37 records · Page 2Linked to original sources
PubMed1991

Regulation of proximal reabsorption by effective arterial blood volume.

In summary, effective arterial volume is able to regulate the transport of NaCl, NaHCO3, and organic solutes in the proximal tubule. These effects are mediated by changes in renal hemodynamics that secondarily modify proximal tubular transport through changes in interstitial hydrostatic and oncotic pressure, changes in the levels of hormones such as angiotensin II, epinephrine, norepinephrine, dopamine, and atrial natriuretic factor, and changes in renal nerve activity. In addition, there are chronic effects of dietary NaCl, the mechanisms of which have yet to be determined.

Animals↗
PubMed1990

Clinical experience with technetium-99m teboroxime, a neutral, lipophilic myocardial perfusion imaging agent.

Technetium-99m (Tc-99m) teboroxime is a new technetium-based myocardial perfusion imaging agent (investigational code = SQ30217 [Cardiotec, Squibb Diagnostics]). A member of a class of neutral, lipophilic, technetium-containing complexes known as boronic acid adducts of technetium dioxime (BATO) complexes, this agent is chemically very different from the cationic tracer thallium-201 (Tl-201) and from the cationic technetium complex Tc-99m sestamibi (Cardiolite, Du Pont Imaging Agents). Tc-99m teboroxime has high myocardial extraction, rapid blood clearance, little lung uptake and rapid myocardial washout. A biexponential pattern of myocardial washout is demonstrated in animals and in man. Effective half-lives of the 2 washout components in man are 5.2 minutes and 3.8 hours and represent approximately 66 and 33% of the myocardial activity, respectively. The first half-life for the myocardium is approximately 11 minutes. As the agent washes out of the heart, hepatic uptake occurs, peaking at about 5 minutes after injection. The liver is the major organ of excretion and receives, along with the large bowel, the largest radiation dose. Rapid imaging protocols using standard cameras have achieved good myocardial counts from 3 planar views acquired over a 4- to 5-minute period or for single photon emission computed tomography (SPECT) images acquired over a 10-minute period. An entire stress/rest procedure can be completed in 1 hour. Analysis of data from 155 patients from 4 centers using planar or SPECT imaging showed a sensitivity and specificity for blinded readings of 82 and 91%, respectively, when compared against overall clinical impression.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease↗
PubMed1990

Prognostic significance of silent myocardial ischemia on a thallium stress test.

The clinical significance of silent ischemia is not fully known. The purpose of this study was to determine whether the presence or absence of angina during a thallium stress test positive for ischemia was independently predictive of an adverse outcome. Two hundred thirty-four consecutive patients with ischemia on a thallium stress test were identified. Ischemia was defined as the presence of defect(s) on the immediate postexercise scans not in the distribution of prior infarctions that redistributed on 4-hour scans. During the test 129 patients had angina, defined as characteristic neck, jaw, arm, back or chest discomfort, while the remaining 105 patients had no angina. Follow-up ranged from 2 to 8.2 years (mean 5.2 +/- 2.1) and was successfully obtained in 156 patients. Eighty-two of the 156 patients had angina (group A) and 74 had silent ischemia (group S). Group A patients were significantly older (62 +/- 8 vs 59 +/- 8 years, p less than 0.05). There was no significant difference between the 2 groups in terms of sex, history of prior infarction or presence of left main/3-vessel disease. A larger percentage of patients in group A were receiving beta blockers (60 vs 41%, p less than 0.05) and nitrates (52 vs 36%, 0.05 less than p less than 0.10). There was a large number of cardiac events (myocardial infarction, revascularization and death) in both groups (37 of 82 [45%] in group A; 28 of 72 [38%] in group S) but no statistically significant difference between the groups. Similarly, life-table analysis revealed no difference in mortality between the 2 groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed1990

Dual isotope thallium and indium antimyosin SPECT imaging to identify acute infarct patients at further ischemic risk.

Forty-two patients (28 men and 14 women) with acute myocardial infarction (35 Q, seven non-Q wave) were injected with 2.0 mCi indium 111-labeled antimyosin (AM) monoclonal antibody (111In AM) within 48 hours of the onset of chest pain. Forty-eight hours later (72-96 hours after onset of chest pain), patients were injected with 2.2 mCi thallium 201, and two sets of single-photon emission computed tomography (SPECT) images were obtained simultaneously using dual energy windows set for the 247 keV indium photopeak and the 70 keV thallium peak. Seventeen patients had repeat scans at 4 hours. 111In AM uptake and 201Tl defects were localized to one or more of 24 coronal and sagittal segments. Scans with only 201Tl defects and corresponding 111In AM uptake were classified as matches; scans with unmatched 201Tl defects in addition to matching regions corresponding to electrocardiographic infarct location were classified as mismatches; and scans with 201Tl and 111In AM uptake in the same segments were classified as overlap. Scan patterns were correlated with clinical evidence for residual ischemia occurring within 6 weeks of infarct and including infarct extension, recurrent angina, and positive predischarge low-level or 6-week symptom-limited stress tests and with coronary anatomy. Fourteen patients had only matching patterns (group 1), 23 had mismatches (group 2), and five had 201Tl-111In overlap as the predominant pattern. None of the patients in group 1 had previous myocardial infarction; in each, the matched area corresponded to the Q wave location on electrocardiogram, and none had further in-hospital ischemic events or positive stress tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

Measurement of acute Q-wave myocardial infarct size with single photon emission computed tomography imaging of indium-111 antimyosin.

Myocardial infarct size was measured by single photon emission computed tomography (SPECT) following injection of indium-111 antimyosin in 27 patients (18 male and 9 female; mean age 57.4 +/- 10.5 years, range 37 to 75) who had acute transmural myocardial infarction (MI). These 27 patients represent 27 of 35 (77%) consecutive patients with acute Q-wave infarctions who were injected with indium-111 antimyosin. In the remaining 8 patients either tracer uptake was too faint or the scans were technically inadequate to permit infarct sizing from SPECT reconstructions. In the 27 patients studied, infarct location by electrocardiogram was anterior in 15 and inferoposterior in 12. Nine patients had a history of prior infarction. Each patient received 2 mCi of indium-111 antimyosin followed by SPECT imaging 48 hours later. Infarct mass was determined from coronal slices using a threshold value obtained from a human torso/cardiac phantom. Infarct size ranged from 11 to 87 g mean 48.5 +/- 24). Anterior infarcts were significantly (p less than 0.01) larger (60 +/- 20 g) than inferoposterior infarcts (34 +/- 21 g). For patients without prior MI, there were significant inverse correlations between infarct size and ejection fraction (r = 0.71, p less than 0.01) and wall motion score (r = 0.58, p less than 0.01) obtained from predischarge gated blood pool scans. Peak creatine kinase-MB correlated significantly with infarct size for patients without either reperfusion or right ventricular infarction (r = 0.66). Seven patients without prior infarcts had additional simultaneous indium-111/thallium-201 SPECT studies using dual energy windows.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Antimyosin imaging in acute transmural myocardial infarctions: results of a multicenter clinical trial.

Murine monoclonal antimyosin antibody has been shown experimentally to bind selectively to irreversibly damaged myocytes. To evaluate the safety and efficacy of monoclonal antimyosin for identifying acute transmural infarction, 50 patients with acute Q wave myocardial infarction were entered into a phase I/II multicenter trial involving three clinical sites. Indium-111 antimyosin was prepared from an instant kit formulation containing 0.5 mg of diethylene triamine pentaacetic acid (DTPA)-coupled Fab fragment (R11D10) and 1.2 to 2.4 mCi of indium-111. Average labeling efficiency was 92%. Antimyosin was injected 27 +/- 16 h after the onset of chest pain. Planar or tomographic imaging was performed 27 +/- 9 h after injection in all patients, and repeat imaging was done 24 h later in 39 patients. Of the 50 patients entered, 46 showed myocardial uptake of antimyosin (sensitivity 92%). Thirty-one of 39 planar scans performed at 24 h were diagnostic; 8 showed persistent blood pool activity that cleared by 48 h. Focal myocardial uptake of antimyosin corresponded to electrocardiographic infarct localization. No patient had an adverse reaction to antimyosin. In addition, 125 serum samples, including 21 collected greater than 42 days after injection, were tested for human antimouse antibodies, and all samples were assessed as having undetectable titers. Intensity of antimyosin uptake was correlated with infarct location and the presence or absence of collateral vessels. There was a significant correlation between faint uptake and inferoposterior infarct location. In 21 patients who had coronary angiography close to the time of antimyosin injection, there was a significant correlation between faint tracer uptake and closed infarct-related vessel with absent collateral flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

The role of antimyosin antibodies in acute myocardial infarction.

Antimyosin is an Fab fragment of a monoclonal antibody that binds with human myosin exposed in myocytes irreversibly damaged by an ischemic event. Labeled with 111In, the antibody is taken up into acutely necrotic tissue and can be imaged by planar or single photon emission computed tomography (SPECT) techniques. A large, multicenter clinical trial has demonstrated a high degree of both sensitivity for detecting infarction and specificity for excluding a recent ischemic event in patients admitted with chest pain syndrome. No allergic reactions to antibody injection have occurred, nor have there been documented significant increases in human antimouse antibody titers postinjection. Due to relatively slow blood clearance, the optimal imaging time is 24 to 48 hours post-injection. Between 13% and 21% of 24-hour scans are nondiagnostic due to persistent blood pool activity. In two thirds of these patients, 48-hour scans confirm negative tracer uptake. Moderate to intense cardiac uptake occurs in greater than 80% of scans. Faint tracer uptake, which occurs in a small minority of patients, is associated with inferoposterior infarct location and an occluded infarct vessel. Potential clinical uses include both diagnostic and prognostic areas. A negative scan in a patient with chest pain syndrome and no ECG changes rules out a recent significant ischemic event. The extent of antimyosin uptake (infarct size), measured semiquantitatively from planar scans or quantitatively from SPECT reconstructions, has been shown to correlate with future cardiac events. Relative patterns of distribution of indium-antimyosin and 201TI on simultaneous dual isotope SPECT reconstructions may identify patients with residual myocardium at further ischemic risk.

Antibodies, Monoclonal↗
PubMed1989

Myocardial perfusion imaging with technetium-99m SQ30217: comparison with thallium-201 and coronary anatomy.

Myocardial perfusion in ten normal volunteers and 20 patients with coronary artery disease documented by recent coronary arteriography was studied with 99mTc-labeled SQ30217 and 201TI. Plantar 201TI imaging followed standard treadmill exercise and planar SQ30217 imaging followed upright bicycle exercise, performed to angina, or the same double product achieved on the treadmill test. Upright anterior, 30 degrees left anterior oblique, and 60 degrees left anterior oblique images were obtained for 3, 6, and 9 min, respectively, starting 2 min after injection of 15 mCi of 99mTc SQ30217. A second 15-mCi dose was injected at rest approximately 2 hr later, and the same imaging protocol was followed. No adverse reactions or laboratory abnormalities attributable to SQ30217 were observed. All scans on the normal volunteers were interpreted as normal. Qualitative readings of both tests were equally sensitive for detecting patients with coronary disease (SQ30217 - 16/20, TI - 17/20, p = NS) and identifying abnormal vessels (SQ30217 - 19/45, TI - 21/45, p = NS). Both agents were falsely positive in 1/15 vessels. Ten vascular regions showed persistent abnormalities on resting SQ30217 scans; eight of these were distal to stenoses of at least 90% and three were also abnormal on thallium redistribution images. Hepatic uptake of SQ30217 obscured inferoapical segments in some views in 14/20 patients but did not interfere with abnormal vessel identification.

Adult↗
PubMed1988

Dependence of technetium-99m red blood cell labeling efficiency on red cell surface charge.

The mechanisms by which [99mTc]pertechnetate becomes attached to stannous-primed red blood cells are not known in detail. To study the problem further, the effect of red cell surface charge on labeling efficiency was evaluated. Red cell surface charge was reduced by using the enzyme neuraminidase to remove the terminal charge-bearing sialic acid moiety of the membrane glycoprotein. Forty-five blood samples from six volunteers were treated with neuraminidase for varying lengths of time, resulting in the removal of from 11% to 99% of the normal negative surface charge, as determined from electrophoretic mobility measurements. There was excellent linear correlation between labeling efficiency and the remaining red cell surface charge for values down to 20% of normal (r = 0.89). When surface charge was less than 20% of normal, labeling efficiency was constant at 30%. Eleven blood samples from three donors were divided into two groups that were treated with neuraminidase either before or after they were labeled. The labeling efficiency was independent of the order in which the steps were performed. No evidence for shifting of the radiolabel from the cell membrane to hemoglobin was found. The results suggest that clinical conditions associated with a reduction of sialic acid on the erythrocyte membrane may be one cause of decreased red blood cell labeling efficiency, and that increased membrane permeability for reduced technetium species may be responsible for the decrease.

Adult↗
PubMed1988

Evaluation of metastatic melanoma with planar and SPECT scintigraphy using ZME 018 and 96.5 radiolabeled monoclonal antibodies.

To determine the feasibility of using serial injections of monoclonal antibodies (MoAbs; 96.5 and ZME 018) to evaluate metastases of malignant melanoma, 11 patients were studied. Each patient received two injections of antibody 7 days apart and were imaged 7 days after injection. Serum for human antimouse antibody (HAMA) was obtained immediately prior to injection of MoAb and 7-10 days after the second injection. Six patients were evaluated with both planar and single photon emission computed tomography (SPECT) images. Planar imaging alone was compared with SPECT alone and with planar and SPECT imaging in combination. In seven patients with 19 lesions, 96.5 and ZME 018 each identified eight lesions. In no case did one antibody identify a lesion missed by the other. In the six patients on whom SPECT imaging was performed, 14 confirmed and six suspected lesions were identified. Using planar imaging alone, only 12 confirmed and one suspected lesion were identified. HAMA titers rose significantly (0.32 optical density (O.D.) units prior to injection to 1.28 O.D. units on day 14, P less than 0.001). Allergic reactions occurred during the second injection in two patients. One of these demonstrated elevated HAMA titers and one did not. The preliminary data suggest that monoclonal antibody imaging may be aided by SPECT and that a normal HAMA titer does not preclude an allergic reaction.

Adult↗
PubMed1988

Comparison of bone density measurements from different skeletal sites.

Absorptiometric measurements from multiple sites in 212 consecutive patients were examined to determine the interrelationships among bone mineral content values obtained from the lumbar spine, hip, and forearm. Dual photon absorptiometry was used to examine the spine, femoral neck, Ward's triangle, and greater trochanter while the radius and ulna were studied with single photon absorptiometry. All studies were performed on the same day. Concurrent measurements were available for the spine and hip in 197 patients, for the spine and forearm in 151 patients, and at all three sites for 146 patients. Variable degrees of correlation were found among the mineral content values from the six sites, with r values ranging from 0.40 to 0.93. The femoral neck and Ward's triangle showed the highest degree of correlation (r = 0.93); the ulna and lumbar spine demonstrated the poorest correlation (r = 0.40). Relationships between distant anatomic sites exhibited a large amount of variability (large standard error of the estimate) even when highly correlated. Useful predictions of bone mineral content could be obtained only for sites in close proximity. These results suggest that bone mineral content determinations in the upper extremities by single photon absorptiometry may not be useful for predicting mineralization in clinically more significant areas such as the lumbar spine and hip.

Bone and Bones↗
PubMed1987

Imaging of cardiac allograft rejection in dogs using indium-111 monoclonal antimyosin Fab.

The acute rejection of cardiac allografts is currently diagnosed by the presence of myocyte necrosis on endomyocardial biopsy. We evaluated the efficacy of noninvasive scintigraphic imaging with indium-111-labeled anticardiac myosin Fab fragments (indium-111 antimyosin) to detect and quantify cardiac allograft rejection. Six dogs that had intrathoracic heterotopic cardiac allograft transplantation were injected with indium-111 antimyosin and planar and single photon emission computed tomographic (SPECT) images were obtained in various stages of acute and subacute rejection. Four dogs had an allograft older than 8 months and had been on long-term immunosuppressive therapy; two dogs had an allograft less than 2 weeks old and were not on immunosuppressive therapy. Count ratios comparing heterotopic with native hearts were calculated from both SPECT images and in vitro scans of excised and sectioned hearts and were compared with the degree of rejection scored by an independent histopathologic review. Indium-111 antimyosin uptake was not visible in planar or SPECT images of native hearts. Faint diffuse uptake was apparent in cardiac allografts during long-term immunosuppression and intense radioactivity was present in hearts with electrocardiographic evidence of rejection. The heterotopic to native heart count ratios in SPECT images correlated significantly with the count ratios in the excised hearts (r = 0.93) and with the histopathologic rejection score (r = 0.97). The distribution of indium-111 antimyosin activity in right and left ventricles corresponded to areas of histopathologic abnormalities. Immunoperoxidase studies showed deposition of indium-111 antimyosin only in areas of myocyte necrosis. The results demonstrate that indium-111 antimyosin imaging can noninvasively detect the presence, location and severity of canine cardiac allograft rejection.

Animals↗
PubMed1987

Measurement of infarct size and percentage myocardium infarcted in a dog preparation with single photon-emission computed tomography, thallium-201, and indium 111-monoclonal antimyosin Fab.

Single photon-emission tomography (SPECT) and indium 111-labeled monoclonal antimyosin Fab fragments were used to measure myocardial infarct size in 12 dogs, six subjected to balloon catheter-induced coronary artery occlusion for 6 hr (late reperfusion) and six subjected to occlusion with reperfusion at 2 hr (early reperfusion). Tomographic imaging was performed 24 hr after the intravenous injection of labeled Fab fragments with the use of a dual-head SPECT camera with medium-energy collimators. Immediately after the first tomographic scan, thallium-201 was injected into nine of 12 dogs and imaging was repeated. Estimated infarct size in grams was calculated from transaxially reconstructed, normalized, and background-corrected indium SPECT images with the use of a threshold technique for edge detection. Estimated noninfarcted myocardium in grams was calculated from obliquely reconstructed thallium SPECT images by a similar method. The animals were killed and infarct size in grams and true infarct size as a percentage of total left ventricular myocardial volume were measured by triphenyl tetrazolium chloride staining. Estimated infarct size from indium SPECT images showed an excellent correlation with true infarct size (r = .95, SEE = 4.1 g). Estimated percentage myocardium infarcted was calculated by dividing estimated infarct size from indium images by the sum of estimated infarct size plus estimated noninfarcted myocardium obtained from thallium images. Correlation between the estimated percentage of myocardium infarcted and true percentage of myocardium infarcted was excellent (r = .93, SEE = 4.4%). We conclude that dual-isotope SPECT with indium 111-monoclonal antimyosin antibodies and thallium-201 can accurately estimate infarct size and percentage myocardium infarcted.

Animals↗
PubMed1986

Phase analysis of gated blood pool scintigraphic images to localize bypass tracts in Wolff-Parkinson-White syndrome.

The ability of radionuclide techniques to localize bypass tracts in patients with Wolff-Parkinson-White syndrome to sites around the atrioventricular (AV) ring using a three view triangulation method was investigated. In 17 patients with Wolff-Parkinson-White syndrome, phase images were generated from gated blood pool scans using the first Fourier harmonic of the time-activity curve of each pixel. In addition, the difference between left and right ventricular mean phase angles was calculated for each patient and for 13 control subjects. Bypass tracts were localized to one or more sites on a 10 site grid schematically superimposed on the AV ring (Duke grid) by electrophysiologic study in all patients and by intraoperative mapping in 7 of the 17 patients. These same 10 anatomic sites were projected onto three scintigraphic views and the site of earliest ventricular phase angle was located in each view. The 10 sites around the AV ring were divided into two anatomic groups: free wall and septal/paraseptal. Phase image locations correlated with electrophysiologic locations within one grid site in 11 of 11 patients with free wall tracts and were confirmed at surgery in 5 of the 11. In five of six patients with septal/paraseptal tracts, electrophysiologic study could not localize the bypass tract to one site, whereas phase images localized two of the five as free wall adjacent to the septum, one as paraseptal and two as true posteroseptal. One posteroseptal site was confirmed at surgery. In one patient, in whom phase image analysis and electrophysiologic study showed different sites, existence of both tracts was confirmed at surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

Scintigraphic criteria for the diagnosis of renal arteriovenous fistulas.

Visualization of the inferior vena cava (IVC) on renal perfusion imaging occurs in cases of renal arteriovenous (AV) fistulas. A review of consecutive renal scans demonstrated IVC visualization in three of 217 patients without AV fistulas. IVC visualization occurred 3-6 seconds after peak aortic activity in normal patients. With renal AV fistulas, an intrarenal focus of increased activity is seen and IVC visualization occurs coincident with peak aortic activity.

Adolescent↗
PubMed1985

Peak regional acceleration: a method to identify subtle regional ventricular dysfunction from gated blood pool scans at rest in patients with coronary artery disease.

Peak regional acceleration images were obtained from gated blood pool scans at rest in 10 normal subjects, 16 patients who underwent cardiac catheterization for unstable angina or nontransmural infarction and were found to have normal ejection fraction and wall motion and 10 patients with prior infarction and regional dyssynergy. The second derivative of the time-activity curve of each pixel was generated and the maximal systolic value of the derivative for each pixel was displayed as a functional image (peak regional acceleration). Anterior and left anterior oblique views were evaluated for abnormalities and the presence and location of defects were correlated with the coronary anatomy. The scans from the 10 normal subjects were used to establish the normal range for regional second derivative values. Both gated blood pool scans and second derivative images showed regional abnormalities in all 10 patients with prior transmural infarction. Regional abnormalities were present in the second derivative images in the distribution of 17 of the 20 coronary arteries with greater than 50% stenosis; there were no regional abnormalities in the distribution of 7 of the 8 arteries with less than 50% stenosis. In addition, regional second derivative image abnormalities were present in 15 of the 16 patients with unstable angina and normal wall motion and global ejection fraction. These 16 patients showed regional abnormalities on second derivative images in the distribution of 19 of the 23 coronary arteries with significant stenosis and no regional abnormalities in the distribution of 21 of the 23 coronary arteries without significant stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Kr-81m ventilation imaging: clinical utility in suspected pulmonary embolism.

The results of Kr-81m/Tc-99m ventilation-perfusion (VP) lung scintigraphy were correlated with the results of pulmonary angiography for 74 patients suspected of having pulmonary embolism (PE). Among patients having a diagnostic scan, the sensitivity and specificity of scintigraphy were 91% and 94%, respectively. Also, 157 consecutive cases of Kr-81m/Tc-99m VP lung scintigraphy were reviewed, and the frequency of an indeterminate scan was found to be 22%. A similar frequency was found for VP scintigraphy with xenon-133. Of eight patients who had indeterminate scans due to the presence of a single VP mismatch, four were demonstrated to have PE by angiography. Kr-81m is an excellent agent for VP scanning in cases of suspected PE, offering accuracy in diagnosis as well as favorable physical properties.

Humans↗