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Biomedical subjects

S J Goldsmith

Publications and source records attributed to S J Goldsmith.

At least 109 records · Page 6Linked to original sources

Acute radiation nephritis. Its evolution on sequential bone imaging.

Acute radiation nephritis typically affects the kidneys 3-12 months after radiation exposure and may occur with doses as low as 2500 rads. After an initial latent period, the affected portions of the kidneys become swollen and edematous, and develop multiple petechiae. Necrotizing vasculitis and interstitial hemorrhage occur, and the end stage is that of scarring. Two patients are presented in whom localized acute radiation nephritis developed, and whose kidneys demonstrated the characteristic sequential changes of this entity on serial bone imaging.

Adolescent↗

Radiotracers for low density lipoprotein biodistribution studies in vivo: technetium-99m low density lipoprotein versus radioiodinated low density lipoprotein preparations.

In an attempt to characterize the in vivo behavior of [99mTc] low density lipoprotein (LDL), biodistribution studies were performed in normal and hypercholesterolemic (HC) rabbits. In normal rabbits, 24 hr after the injection of [99mTc]LDL, 99mTc activity accumulated mainly in adrenal glands, spleen, liver, and kidney. In HC rabbits, however, there was a marked reduction of 99mTc activity in these organs. In both normal and HC rabbits, less than 17% of 99mTc activity appeared in the 24-hr urine following injection of [99mTc]LDL, suggesting that in vivo, [99mTc]LDL is trapped and accumulated within the tissues. Direct comparison of [99mTc]LDL, 125I-native-LDL and [131I]tyramine cellobiose-LDL (the previously validated trapped radioligand) in normal rabbits, demonstrated that the biodistribution of [99mTc]LDL was similar to that of [131I]tyramine cellobiose-LDL. The adrenal glands, liver, and spleen accumulated significantly greater quantities of 99mTc and 131I activity per gram of tissue than 125I (from native-LDL). In addition, imaging studies in monkeys, showed that the hepatic uptake and retention of [99mTc] LDL was similar to that of [131I]tyramine cellobiose LDL. In contrast, radioiodine from native-LDL was deiodinated in liver with subsequent excretion into the intestine. These results suggest that [99mTc]LDL acts as a trapped ligand in vivo and should therefore, be a good tracer for noninvasive quantitative biodistribution studies of LDL.

Animals↗

Gallium scanning in differentiating malignant from benign asbestos-related pleural disease.

In order to assess the utility of 67gallium citrate in delineating malignant pleural mesothelioma from benign asbestos-related pleural disease, 49 patients with malignant mesothelioma and 16 with benign asbestos-related pleural disease were studied. Seven patients with malignant mesothelioma had no history of asbestos exposure, while the remaining 58 patients were exposed. Forty-three of the 49 patients (88%) with malignant mesothelioma had a positive 67gallium scan including 36 of the 42 (86%) patients with asbestos exposure and all 7 patients without a history of asbestos exposure. Three of 16 patients (19%) with benign asbestos-related pleural disease had a positive scan. 67Gallium radionuclide imaging is nonspecific but may be valuable in noninvasive monitoring of asbestos-exposed populations, which have a high risk for the late development of benign and/or malignant pleural disease.

Asbestosis↗

Studies of the hepatocellular uptake of the hepatobiliary scintiscanning agent 99mTc-DISIDA.

Bilirubin (BR) and organic anionic dyes such as sulfobromophthalein (BSP), indocyanine green (ICG) and rose bengal (RB) enter the hepatocyte by a specific non-sodium-dependent membrane transport system. Two analogous but distinct Na+-dependent transport systems effect the uptake of conjugated bile acids such as taurocholate (TC) and free fatty acids such as oleate, respectively. The mechanism of uptake of the acetanilidoiminodiacetic acid (HIDA) class of biliary scintiscanning agents is unknown. Accordingly, rat hepatocytes were isolated by collagenase perfusion of the liver and differential centrifugation, and incubated with 99mTc-diisopropyl-HIDA (99mTc-DISIDA) alone, or in the presence of various concentrations of BSP, ICG, RB, oleate or TC, with and without bovine serum albumin (BSA). Initial uptake velocity (Vo) was determined from the initial slope of the cumulative radioactivity/time curve. In albumin free media, uptake of 99mTc-DISIDA was temperature- and pH-dependent, with maximal uptake at 37 degrees C. There was virtually no uptake of inorganic 99mTc. In incubations containing 15-1500 microM 99mTc-DISIDA, Vo was saturable, with estimated Vmax = 65 nmoles/min/10(6) hepatocytes, and Km = 1200 microM. In keeping with its weak albumin binding, 99mTc-DISIDA Vo was only minimally influenced by equimolar concentrations of BSA. 99mTc-DISIDA Vo was inhibited by BR, BSP, ICG and RB, as well as by a rabbit antibody to the rat liver plasma membrane BSP/BR binding protein. Surprisingly, Vo was also inhibited by TC and oleate, but not influenced either by ouabain or by substitution of Li+ for Na+ in the medium.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗

Gated blood pool scintigraphic monitoring of doxorubicin cardiomyopathy: comparison of camera and computerized probe results in 101 patients.

Serial gated blood pool scintigraphic monitoring of cardiac function with both a nonimaging scintillation probe and a conventional gamma camera-computer imaging system was performed in 101 patients receiving doxorubicin hydrochloride (Adriamycin) chemotherapy. Comparison of probe- and camera-derived ejection fractions (n = 287) correlated significantly (r = 0.70, p less than 0.005) as did the interstudy (n = 183) change in ejection fraction (r = 0.76, p greater than 0.005). Significant discordance in probe- and camera-derived ejection fraction change occurred in 3 (1.6%) of 183 interstudy intervals. Average intrastudy variability of absolute probe-derived ejection fraction was 2.9%. This variability was unrelated to the level of cardiac function. Thirteen patients (13%) developed clinical cardiotoxicity, including four at cumulative Adriamycin levels less than 450 mg/m2. Mean absolute camera ejection fraction decline for these patients was 21% from baseline evaluation, and mean absolute probe ejection fraction decline was 22%. The minimal absolute ejection fraction decline was 11% for patients with clinical congestive heart failure. Eight asymptomatic patients had therapy terminated before the development of clinical cardiotoxicity after a mean decline in absolute camera ejection fraction of 19 +/- 4% (SD) and in probe ejection fraction of 19 +/- 9% into abnormal ranges (a decline in magnitude equivalent to that in patients developing congestive failure). None of these five asymptomatic patients available for clinical follow-up at 6 months after termination of Adriamycin therapy subsequently developed signs of ventricular dysfunction. The majority of patients (83%) studied at 450 mg/m2 cumulative dose levels did not have a 15% or greater decline from baseline into the abnormal range.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Gaucher's disease type 1: assessment of bone involvement by CT and scintigraphy.

The effectiveness of CT and technetium-99m sulfur colloid (99mTc SC) bone-marrow scans in determining the extent and severity of skeletal involvement in 23 patients with type 1 Gaucher's disease was compared with the effectiveness of conventional radiographic techniques and technetium-99m methylene diphosphonate (99mTc MDP) bone scintigrams. Density measurements obtained by CT proved sensitive in differentiating normal marrow (-50 to -120 H). Scintigrams with the sulfur colloid nuclide demonstrated three distinct patterns of uptake: peripheral expansion of normal marrow (profile B), greater marrow expansion with patchy areas lacking uptake (profile C), and greater loss of uptake with retention of the nuclide in other reticuloendothelial organs and circulation (profile D). CT scans provided greater sensitivity in resolving the extent of marrow involvement in affected areas, while the 99mTc SC scintigrams were more effective in overall assessment of the severity of bone-marrow involvement. Both conventional radiographic techniques and 99mTc MDP bone scans were useful primarily as screening procedures or for evaluating specific involved areas. 99mTc MDP scans were useful in evaluating regional defects (i.e., ischemic necrosis) in certain cases, but no consistent patterns were observed. CT and 99mTc SC scans are useful for determining the extent and severity of Gaucher's disease involvement of bone marrow.

Bone Diseases↗

Indium-111 platelet kinetics in normal human subjects: tropolone versus oxine methods.

The effect of labeling media on the kinetics of[111In]platelets was evaluated by performing a paired crossover study in eight normal human subjects using tropolone and oxine methods. Platelets were labeled in autologous plasma with [111In]tropolone (In-tr) and in ACD-saline with [111In]oxine (In-ox) and reinjected. Starting at 1 hr, ten blood samples were obtained over an 8-day period. The in vivo platelet recovery was higher at 1 hr and throughout the 8 days of study with In-tr and the gamma camera images showed less uptake in liver and spleen than with In-ox. When platelet life-span (PLS) was estimated using all ten samples, only linear regression showed that the platelet life-span was longer with In-tr (10.7 +/- 1.5) than with In-ox (9.5 +/- 0.8). When the PLS was estimated excluding the 1-hr sample point, the life-span of platelets was significantly longer with In-tr than with In-ox based on three out of four models of curve fitting. These results demonstrate that platelets labeled with In-tr in plasma are preserved better in circulation and have equal or longer life-span than platelets labeled with In-ox in ACD-saline.

Adult↗

Etoposide induced blood-brain barrier disruption in rats: duration of opening and histological sequelae.

The intracarotid infusion of the antineoplastic compound etoposide enhances blood-brain barrier (BBB) permeability. In a rat model system, the functional reversibility and anatomic sequelae of etoposide induced BBB disruption were investigated. Etoposide, in a dose range from 3.0 to 22.5 mg/kg, was infused into the left internal carotid artery of Sprague-Dawley rats. BBB disruption was evaluated by the appearance in the infused hemisphere of systemically administered Evans blue dye and quantitatively by the ratio of counts of the technetium labeled chelate of diethylenetriaminepentaacetic acid in the infused to the noninfused hemisphere. Functional reversibility of altered BBB permeability was investigated at three dose levels of etoposide (3.0, 15.0, and 22.5 mg/kg) by the administration of Evans blue dye at the time of etoposide infusion and the administration of the technetium labeled chelate of diethylenetriamine-pentaacetic acid at varying time intervals after etoposide infusion. Fourteen groups of 12 rats each were studied to define the time course of altered BBB permeability at these three doses. The anatomic sequelae of etoposide induced BBB disruption were investigated at varying time intervals (up to 3 weeks) after intracarotid etoposide infusion. Nineteen rats were examined after sacrifice by intracardiac fixation perfusion with 10% formalin. Each brain was sectioned coronally and examined under light microscopy after hematoxylin and eosin staining. Evidence of BBB disruption was seen at all dose levels of etoposide. The degree of BBB disruption increased with increasing doses of etoposide. The duration of altered BBB permeability increased from less than 1 day at 3.0 mg/kg to between 3 and 4 days at 22.5 mg/kg. Histological studies revealed no evidence of parenchymal damage, although at 4 days postdisruption, a mild perivascular lymphocytic infiltration was noted in the infused hemisphere. Etoposide infusion and subsequent BBB disruption were well tolerated by all test animals. In a rat model system the intracarotid infusion of etoposide is capable of producing prolonged reversible BBB disruption.

Animals↗

Characterization and automatic identification of ECG conduction abnormalities using segmental multiharmonic Fourier analysis of gated blood-pool scintigrams.

This study of biventricular segmental timing sequences compared patterns of the first-harmonic phase with those of multiharmonic Fourier-analysis-derived parameters to determine their suitability for the classification of patients using an automatic pattern recognition scheme. The study involved nine patients with normal ECGs, six with left bundle branch block, 4 with right bundle branch block, and 6 with right-ventricular pacemakers; all patients had normal left-ventricular function. The segmental sequence described by the time of end systole was similar to that described by the first-harmonic phase, with a lower correlation using the time of maximum filling rate, and a rather poor correlation of the time of maximum ejection rate with the other parameters. Thus, despite theoretical difficulties, timing patterns described by phase best agreed with those of the time of end systole. Intersegmental timing differences were used as criteria for discriminating between groups by means of a sequential logic tree. Using either phase, time of end systole or time of maximum ejection rate, all patients were correctly classified into the four ECG categories. More intersegmental timing differences were useful as criteria for phase (57) than for the time of end systole (45) or the time of maximum ejection rate (30). The first-harmonic phase was more efficient than the time of end systole for separating patient groups. Sequential biventricular timing disorders can be objectively classified using either first-harmonic or multiharmonic Fourier analysis, and their patterns can be automatically recognized and used for classification.

Bundle-Branch Block↗

Pneumocystis carinii pneumonia studied by gallium-67 scanning.

The validity and reliability of gallium-67 (Ga-67) scanning for diagnosis and follow-up of Pneumocystis carinii pneumonia (PCP) were assessed in 34 patients thought to have pulmonary complications of acquired immunodeficiency syndrome (AIDS). Overall sensitivity was 94% and specificity 74%. Among patients with normal or equivocal chest radiographs at the time of admission, sensitivity was 86% and specificity 85%. The authors consider Ga-67 scanning a valid and reliable adjunct in the diagnosis of PCP in AIDS patients with respiratory symptoms when the chest radiograph is normal or equivocal.

Acquired Immunodeficiency Syndrome↗

Gallium scanning in peritoneal mesothelioma.

Gallium scans in seven cases of pathologically proven primary peritoneal mesothelioma were reviewed and correlated with clinical, radiologic, and surgical findings. Although five patients gave a history of asbestos exposure, only two showed chest film findings typical of asbestosis. Most had abdominal discomfort, ascites, and abdominal masses. Five of the seven had positive gallium scans; three showed a large single focus of uptake and two showed diffuse abdominal uptake. Although these patterns correspond to the two main gross pathologic types described in peritoneal mesothelioma, there was not complete agreement with clinical, radiographic, and surgical findings, and the focal pattern tended to underestimate the extent of the disease. Although gallium uptake can be seen in a variety of other neoplastic and inflammatory conditions, it may be useful in the diagnosis and follow-up of peritoneal mesothelioma.

Adult↗

Effect of intracarotid etoposide on opening the blood-brain barrier.

The effect of an intracarotid artery infusion of etoposide on blood-brain barrier (BBB) integrity was investigated in a rat model system. The external carotid arteries of Sprague-Dawley rats were catheterized in a retrograde manner. Etoposide in a dose range from 3.0 mg/kg to 22.5 mg/kg was 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 dye Evans blue and quantitatively by the ratio of counts of the technetium-labeled chelate of diethylenetriaminepentaacetic acid (99mTc-DTPA) in the infused to the noninfused hemisphere. Evidence of increased BBB permeability was seen at all doses of etoposide. Degree of BBB disruption increased with increasing doses of etoposide. The intracarotid infusion and subsequent BBB disruption were well tolerated. Further clinical trials employing the intracarotid administration of etoposide should be cognizant of the potential for BBB disruption.

Animals↗