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Biomedical subjects

B L Shulkin

Publications and source records attributed to B L Shulkin.

At least 55 records · Page 3Linked to original sources

Lymphoscintigraphy in melanoma: initial evaluation of a low protein dose monoclonal antibody cocktail.

A low protein dose (73 +/- 10 micrograms total) 131I-labeled monoclonal antibody cocktail made of equal microgram quantities of 225.28S (IgG2a) and 763.24T (IgG1) murine monoclonal antibodies, which bind additively to a high molecular weight antigen of melanoma, was evaluated as a lymphoscintigraphic agent in 17 patients with intermediate to thick (mean Breslow depth, 3.39 +/- 0.64 mm) melanomas or clinical Stage II disease scheduled for nodal dissection. Eleven of the patients were clinically Stage I while 6 were clinically Stage II. 131I antibody cocktail, 258 +/- 10 microCi, was administered s.c. at the site of the primary melanoma or its scar following surgical removal. In eight patients, 63 +/- 8 microCi of 125I nonspecific normal sheep IgG was coadministered s.c. Gamma camera imaging was conducted beginning immediately after and continuing for several days following injection. Surgical resection, weighing, and gamma counting of the draining lymph nodes were undertaken in all patients. On gamma scans, early nodal uptake of antibody was most pronounced and of longest duration in the tumor pathologically positive patients (5 of 7 had visible nodal uptake, 4 of 7 visually stable or rising with time), with the t 1/2 of nodal clearance by gamma scan significantly (P less than 0.05) longer than in the negative patients in whom 4 of 10 showed some, although generally transient (0 of 10 stable or rising), nodal uptake. Scans were not easily interpretable when the injection site was very near the draining nodal group, in part due to the detection of scatter activity from the injection site. In several instances the scan was correct and the clinical examination was incorrect as regards nodal disease. Quantitative analysis of the surgically excised draining nodes showed significantly (P less than 0.001) more 131I anti-melanoma antibody uptake in the 21 tumor-involved nodes [0.01217% injected dose (ID)/node median] than in the 512 tumor-negative nodes (0.00051% ID/node median). Median percentage ID/g of anti-melanoma antibody in tumor-involved nodes was significantly greater (P less than 0.01) than in tumor-negative nodes (0.01984 versus 0.003215% ID/g). 125I-labeled nonspecific antibody did not accumulate significantly more in the tumor-involved nodes on a per node or per g basis in the 283 of 533 nodes studied using the dual-label approach (0.0036 versus 0.00092% ID/g). These data demonstrate that by external imaging and by tissue counting that a radiolabeled anti-melanoma monoclonal antibody cocktail can specifically accumulate to melanoma-involved lymph nodes following s.c. administration.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Utility of emission tomography in evaluation of mandibular bone grafts.

Bone scanning, performed within 1 week postoperatively, is valuable in predicting the survival of revascularized composite flap grafts. Conventional planar scintigraphy is limited by a two-dimensional representation of three-dimensional structures. Single photon emission computed tomography (SPECT) is a technique in which a gamma camera rotates around the patient, acquires multiple projections, and with the aid of a computer, reconstructs three-dimensional representations. We wished to evaluate the potential advantages of SPECT in the assessment of mandibular graft viability and to compare it with planar scanning. These noninvasive methods of assessing the vascular supply are critical to patient management in the early postoperative period because the presence of or inability to exclude vascular compromise commands surgical exploration of the anastomosis for graft salvage. Fifteen patients who underwent mandibular reconstruction with revascularized free grafts were studied by both planar and SPECT scintigraphy. Long-term follow-up data were correlated with the outcome predicted by the scanning.

Adult↗

Use of [11C]aminocyclohexanecarboxylate for the measurement of amino acid uptake and distribution volume in human brain.

A quantitative positron emission tomographic (PET) method to measure amino acid blood-brain barrier (BBB) transport rate and tissue distribution volume (DV) has been developed using 11C-labeled aminocyclohexanecarboxylate (ACHC), a nonmetabolized amino acid analogue. Dynamic PET data were acquired as a series of 15 scans covering a total of 60 min and analyzed by means of a two-compartment, two-parameter model. Functional images were calculated for the amino acid transport rate constants across the BBB and the amino acid DV in the brain. Results show [11C]ACHC to have an influx rate constant in gray matter of approximately 0.03-0.04 ml g-1 min-1, indicating a single-pass extraction fraction of approximately 5-7%. The intersubject coefficient of variation was approximately 15% while intrasubject variability of repeat scans was only slightly greater than 5%. Studies were performed in 15 young normal volunteer control subjects, 5 elderly controls, 7 patients with probable Alzheimer's disease, and one patient with phenylketonuria. Results indicate that [11C]-ACHC will serve as the basis of a method for measuring amino acid transport rate and DV in the normal and pathological human brain.

Adult↗

The role of imaging tests in the diagnosis of thyroid carcinoma.

Many noninvasive high-quality imaging tests are widely available to assist in the evaluation of thyroid nodules. These include thyroid scans, computed tomography, ultrasonography, and magnetic resonance imaging. These procedures and other less commonly performed tests are reviewed. Their routine role in the diagnosis of thyroid carcinoma, however, has been, for the most part, obviated by the convenience and accuracy of fine needle aspiration cytology. Special situations in which imaging tests are most useful are discussed.

3-Iodobenzylguanidine↗

Platelet reactivity in human aortic grafts: a prospective, randomized midterm study of platelet adherence and release products in Dacron and polytetrafluoroethylene conduits.

Platelet-related phenomena at the blood-surface interface of randomly placed knitted Dacron (n = 6) and polytetrafluoroethylene (ePTFE) (n = 6) interposition aortic grafts were studied in patients undergoing abdominal aortic aneurysmectomy. Luminal accumulation of platelets was assessed by infusing indium-111-oxine (400 microCi) labeled autologous platelets and imaging grafts at 1 week, 3 months, and 6 months after surgery. Image analysis included an indium ratio technique (comparing aortic graft radioactivity to that of an iliac artery) and a red blood cell technetium subtraction technique (excluding blood pool radioactivity from graft radioactivity, with the heart or iliac artery serving as reference regions). Plasma levels of beta-thromboglobulin and platelet factor 4 were correlated with platelet accumulations on the aortic prostheses. Differences in graft radioactivity or platelet-release products were not evident 1 week after surgery. Three months after implantation, Dacron and ePTFE conduits exhibited 87% and 47% (p less than 0.05) more radioactivity with the indium ratio technique than the iliac artery. Similarly, increased Dacron compared with ePTFE graft radioactivity was noted using technetium subtraction techniques: 71% vs 30% with a heart reference and 26% vs 11% with an iliac artery reference, respectively. Increases in graft radioactivity correlated with increases in both plasma beta-thromboglobulin and platelet factor 4 at 3 months (r = 0.6 to 0.9; p less than 0.05 to 0.001 depending on the imaging technique used). At 6 months, differences did not persist. In fact, technetium subtraction techniques suggested less Dacron conduit reactivity. It is speculated that differences in platelet accumulation and activation associated with different graft substrates may prove clinically important.

Adult↗

Iodine-131 metaiodobenzylguanidine uptake in infantile myofibromatosis.

I-131 MIBG scintigraphy was performed on a neonate who presented with a left neck mass and brachial palsy. Increased uptake of the tracer was apparent in the mass, initially suspected as being a neuroblastoma, but later diagnosed as infantile myofibromatosis. Since MIBG is principally taken up by neuroendocrine tumors, this finding suggests caution be used when interpreting studies in this age group.

3-Iodobenzylguanidine↗

The use of indium-111 oxine platelet scintigraphy and survival studies in pediatric patients with thrombocytopenia.

We have utilized 111In-labeled heterologous platelets to investigate the mechanism of thrombocytopenia in ten children. From the scintigraphic findings, platelet survival times, and clinical information, thrombocytopenia was ascribed to decreased production or to increased destruction. Two patients were found to have bone marrow production defects. Two patients with hemangiomas were studied. In one, the hemangioma was shown not to be the cause of thrombocytopenia. In the second, the hemangioma was proven the source of platelet destruction, but was much more extensive than clinically evident. In both, surgical manipulation of the hemangioma was avoided. Six additional patients had thrombocytopenia due to accelerated destruction. In four, the spleen was shown responsible. In two, however, the spleen was shown not to be responsible for the low platelet counts, and splenectomy was avoided. Thus, 111In-platelet scintigraphy and survival studies are valuable in the classification and management of childhood thrombocytopenia. We believe that this study should be performed, when possible, in any child with thrombocytopenia where the mechanism is unclear or the therapeutic intervention involves splenectomy or resection of a hemangioma.

Adolescent↗

Scintigraphic detection of sinusitis.

Radionuclide scintigraphy is useful in the diagnosis of sinusitis. Three cases are described, using different radionuclide agents (99mTc-MDP, 67Ga-citrate and 111In-leukocytes) in which sinusitis was discovered, though clinically unsuspected. The advantages and limitations of these agents are briefly reviewed.

Adolescent↗

Thyroid hormone analog inhibition of hepatic 5'-iodothyronine deiodinase activity.

Studies using thyroid hormone analogs have provided insight into the structural requirements for thyromimetic activity and for thyroid hormone binding to thyroxine-binding globulin, thyroxine-binding prealbumin, and nuclear T3 receptors. To determine the structural specifications for iodothyronine interaction with 5'-iodothyronine deiodinase (5'-ITD), we examined the ability of 35 thyroid hormone analogs to inhibit hepatic T4 5'-deiodination in vitro. The compounds were incubated in concentrations of 0.1-500 microM with rat liver homogenates, and concentrations producing 50% inhibition of T3 production were calculated. Those iodothyronine analogs which likely serve as substrate for 5'-ITD, e.g.rT3 and 3',5'-T2, and those which have one tyrosyl iodide were the most potent inhibitors of 5'-ITD activity. The presence of tyrosyl iodides enhanced inhibition by compounds with alkyl and halogen substitutions. Inhibition was likely due to direct interaction with the enzyme, since it was readily reversed by DTT. The terminal amino and phenolic hydroxyl groups, as well as the ether linkage, do not appear to be essential components of enzyme interaction.

Animals↗

Dual photon absorptiometry. The importance of clinical correlation.

Dual photon absorptiometry is a reliable method of assessing bone mineral density. However, distortions of bony architecture, which may not be evident from the low-resolution images provided, can complicate the evaluation and lead to misleading findings. A case is presented which describes the importance of clinical and radiographic correlation.

Aged↗

Scintigraphic portrayal of the syndrome of multiple endocrine neoplasia type-2B.

The scintigraphic appearance of the neoplasms in multiple endocrine neoplasia type 2B (MEN-2B) and the interpretations of the image patterns are described. An 18-year-old male patient with the MEN-2B syndrome underwent TI-201 imaging that showed concentrations of TI-201 in the primary medullary thyroid carcinoma (MTC) tumor and in cervical lymph node metastases. After total thyroidectomy and lymph node dissection, the TI-201 image was normal. Catecholamine levels in the blood and urine were only borderline elevated. Yet, greater than normal concentrations of I-131 metaiodobenzylguanidine (I-131 MIBG) were present in both adrenal glands. Computed tomography of the abdomen showed normal adrenal glands. These results were consistent with the diagnosis of adrenal medullary hyperplasia, a precursor of pheochromocytoma. No operation was indicated to remove the adrenal glands. Imaging with TI-201 appears to be useful in identifying sites of MTC in patients with the MEN-2B syndrome. I-131 MIBG imaging, in conjunction with computed tomography of the adrenal glands and appropriate catecholamine measurements, should be performed in patients with the MEN-2B syndrome to determine the status of the adrenal medullae, which then may be classified as normal, hyperplastic, or tumorous with pheochromocytoma.

3-Iodobenzylguanidine↗

Conjugate view gamma camera method for estimating tumor uptake of iodine-131 metaiodobenzylguanidine.

Therapy with [131I]MIBG has produced partial remissions of malignant pheochromocytomas but not all patients respond. Responses correlate with the quantity of radiation delivered. We developed the conjugate-view method of imaging using 131I reference sources of known radioactivity placed on the surface of the patient and standard nuclear medicine equipment (gamma camera and computer), to estimate tumor uptake of [131I]MIBG. Such an estimate is a first step toward calculating radiation absorbed dose. Three different methods of background subtraction were evaluated with an anthropomorphic phantom and in five patients. In phantom results, measured tumor activity decreased exponentially with a half-life in agreement with that of 131I to within 3%. However, in the phantom studies, in which non-tumor activity is zero, no single method of background subtraction is superior. In patients, two background subtraction methods, which take their estimate from regions immediately surrounding or adjacent to the tumor and reference source, are less sensitive to reference source position and appear more accurate than a third method which uses a background region of interest displaced from the tumor. The agreement of the calculated activity concentration (nCi/g) with that measured by counting portions of the excised tumors gives validation to the method.

3-Iodobenzylguanidine↗

Pheochromocytoma, polycythemia, and venous thrombosis.

Polycythemia is rarely associated with pheochromocytoma. A patient with a 22-year history of malignant pheochromocytoma is presented in whom major complications developed as a result of long-standing polycythemia, apparently due to secretion of erythropoietin by the tumors. Despite attempts to reduce tumor burden by surgery, chemotherapy, and large doses of I-131-metaiodobenzylguanidine, polycythemia persisted. Extensive venous thrombosis developed requiring hospitalization and anticoagulation. Thus, polycythemia itself may be a cause of major morbidity in patients with pheochromocytoma, and prophylactic measures may be warranted. Review of the 130 patients with benign and malignant pheochromocytoma studied since the introduction of I-131-metaiodobenzylguanidine in 1980 revealed another six patients with hematocrits over 50 but only one had a hematocrit greater than 55 and required regular phlebotomy. In contrast, anemia (hematocrit less than 35) due to variety of causes was present in 18 cases.

Abdominal Neoplasms↗