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Biomedical subjects

B Shapiro

Publications and source records attributed to B Shapiro.

At least 235 records · Page 13Linked to original sources
PubMed1986

Immunohistochemical localization of epinephrine, norepinephrine, catecholamine-synthesizing enzymes, and chromogranin in neuroendocrine cells and tumors.

The immunohistochemical localization of epinephrine (E), norepinephrine (NE), and chromogranin was analyzed in normal and neoplastic neuroendocrine cells. The immunohistochemical detection of tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), and phenylethanolamine N-methyltransferase (PNMT) was used to distinguish between uptake and biosynthesis of catecholamines. E, NE, chromogranin, TH, DBH, and PNMT were found in the normal human adrenal medulla and in pheochromocytomas. Although many neuroendocrine tissues outside of the adrenal gland contained immunoreactive NE, only a small percentage of these tissues contained DBH. E was found in a few neuroendocrine tissues outside of the adrenal, including cardiac paragangliomas, and the enzyme PNMT was localized in some of these neoplasms. There was very close agreement between the localization of chromogranin and of catecholamines in normal and neoplastic neuroendocrine tissues. These results indicate that the presence of catecholamines and chromogranin in neuroendocrine cells and tumors within the adrenal medulla and in many other sites may be closely related.

Adrenal Medulla↗
PubMed1986

Amount of antibody is critical for immune complex displacement by charge competition from both rabbit glomeruli and anionic beads.

The purpose of this study was to determine the feasibility of displacing cationized bovine serum albumin (CBSA) immune complexes from glomeruli by charge competition. An in vitro model identified protamine as an effective agent for displacing 125I-CBSA from anionic beads (dextran sulfate-coated Sepharose 4B). Anti-CBSA serum prevented displacement of 125I-CBSA from anionic beads in a dose-dependent fashion. When 125I-CBSA was injected intravenously into rabbits 98% of 125I-CBSA disappeared from blood within 5 min, at which time CBSA was visualized by immunofluorescence in glomerular capillary walls but not in liver, muscle, skin, spleen or lung. By 24 h 90% of 125I-CBSA had disappeared from glomeruli. In contrast, injection of anti-CBSA antibody caused persistence of 125I-CBSA in kidney (particularly along glomerular capillary walls) for more than 7 days (detected by counting 125I in kidney, by radionuclide imaging and by immunofluorescence). Protamine administration (50 mg intravenously daily for 6 days) caused significant reduction of 125I-CBSA trapped in kidney only if the amount of anti-CBSA injected was small. Protamine did not significantly displace 125I-CBSA from glomeruli if the anti-CBSA dose was larger. Therefore both in vivo and in vitro displacement of 125I-CBSA by protamine depended upon the amount of antibody. We conclude that although charge dependent displacement of immune complexes from glomeruli is probably feasible using protamine this approach would only work in the presence of small amounts of antibody.

Animals↗
PubMed1986

Metabolism of iodine-131 metaiodobenzylguanidine in patients with metastatic pheochromocytoma.

Iodine-131 metaiodobenzylguanidine ([131I]MIBG) is used to image and treat human pheochromocytoma. As part of a pharmacodynamic study of this agent, we have evaluated its excretion and metabolism in nine pheochromocytoma patients undergoing MIGB therapy. Following diagnostic doses of [131I]MIBG given prior to therapy, 40 to 55% of the administered radioactivity generally appeared in the urine within 24 hr and 70 to 90% was recovered within 4 days. Reverse-phase high performance liquid chromatography was used to identify radioactive metabolites following therapeutic doses of [131I]MIBG. Unaltered [131I]MIBG was the major radioactive urinary component found, representing 75 to 90% of the total in all but one of the nine patients examined. The urine samples from the patient, whose rate of urinary excretion was the lowest of the group, contained [131I]-m-iodohippuric acid ([131I]MIHA) in amounts equal to that of [131I]MIBG, as well as small amounts of [131I]iodide and [131I]-m-iodobenzoic acid ([131I]MIBA). Iodine-131 MIHA and [131I]iodide were also minor components in the urine samples from the other eight patients. Trace quantities of [131I]MIBA and 131I-4-hydroxy-3-iodobenzylguanidine ([131I]HIBG) were also detected in a few of the patient urine samples examined. The 4- to 5-day metabolism profiles varied from patient to patient but were similar for the same patient following therapy doses given 4 mo apart. There was no obvious correlation between the presence of metabolites and the location of the tumors or the plasma or urinary catecholamine levels. Extraction of radioactivity from two pheochromocytomas removed from patients was determined to be primarily MIBG. These studies suggest that [131I]MIBG is a rapidly excreted, relatively stable radiopharmaceutical agent.

3-Iodobenzylguanidine↗
PubMed1985

Tomographic renal cortical scintigraphy: correlation with intravenous urography, computed tomography, ultrasonography, angiography, and nuclear magnetic resonance imaging.

This study evaluates single-photon renal tomoscintigraphy (SPECT) in the evaluation of renal masses and correlates this modality, where indicated, with computed tomography (CT), ultrasonography (US), angiography (ANGIO) and nuclear magnetic resonance imaging (NMR). Eight patients with renal cortical lesions detected on intravenous urography (IVP) were evaluated by SPECT and planar nuclear imaging using Tc-99m glucoheptonate (GH). Three of these patients were felt particularly likely to have renal tumors and were additionally evaluated with US, CT, ANGIO and NMR. The five patients with nodules on IVP that were not particularly suggestive of malignancy had functioning, benign, renal tissue accounting for their IVP lesions. Four of five were found by planar-GH nuclear imaging, five/five by SPECT-GH. In addition, SPECT-GH allowed better "confidence" in the normal renal tissue diagnosis in three/five cases. Of the three renal lesions that were highly suggestive of malignancy, two were hypernephromas and one was hypertrophied functioning cortical tissue. All three were correctly identified prospectively on SPECT-GH; however, one hypernephroma was missed on planar-GH. NMR, CT, and ANGIO detected only one of two hypernephromas prospectively (US detected both); all four modalities incorrectly diagnosed the hypertrophied tissue suggestive of malignancy.

Angiography↗
PubMed1985

Radionuclide diagnosis and therapy of thyroid cancer: current status report.

Thyroid cancer is uncommon, with an incidence of 10,300 new patients each year and a mortality of 1,100 patients each year. Patient survival correlates with many factors, including tumor pathology, age, primary lesion size, distant metastases, extent of surgery, and radioiodine therapy. Deaths from thyroid cancer may occur many years after diagnosis, and such an indolent course has hampered the analysis of the multiple treatment programs advocated. Thyroid imaging continues to play an important role in the initial detection and follow-up management of thyroid cancer, but the search for a specific tracer for the primary lesion continues. The complementary role of serum thyroglobulin and radioiodine in the follow-up of the thyroidectomized patient is discussed. Radioiodine therapy has proven effectiveness in those patients with radioiodine-avid distant metastases and/or regional metastases. Whether radioiodine ablation of residual thyroid bed activity is beneficial remains controversial.

Adenocarcinoma↗
PubMed1985

Radio-iodobenzylguanidine for the scintigraphic location and therapy of adrenergic tumors.

Radioiodinated meta-iodobenzylguanidine, a recently developed radiopharmaceutical, has been shown to permit safe, noninvasive, sensitive, and specific scintigraphic location of pheochromocytomas of all types. The technique is especially efficacious in the case of extraadrenal primary lesions and locally recurrent and metastatic tumors. In addition to being taken up by pheochromocytomas, meta-iodobenzylguanidine may be used to image neuroblastomas, nonfunctioning paragangliomas, and carcinoid tumors. Lesions with high 131I-meta-iodobenzylguanidine uptake may respond to treatment with large doses of this radiopharmaceutical.

3-Iodobenzylguanidine↗
PubMed1985

Pheochromocytoma and the normal adrenal medulla: improved visualization with I-123 MIBG scintigraphy.

The radiopharmaceutical iodine 131 metaiodobenzylguanidine (I-131 MIBG) has been shown to locate pheochromocytomas scintigraphically with a false-negative rate of approximately 13%. To improve image quality and reduce the false-negative rate, I-123 was examined as a radioactive label for MIBG, as it has many advantages over I-131, including superior dosimetry and better detection efficiency. Diagnostic doses of 0.5 mCi (18.5 MBq) I-131 MIBG and 10.0 mCi (370.0 MBq) I-123 MIBG with nearly equivalent radiation dosimetries were compared in 18 patients with known or suspected pheochromocytomas. Images of superior quality were obtained with I-123 MIBG in 18 of 18 patients, and in eight cases lesions not visualized on I-131 MIBG scintigraphy were portrayed. A further advantage of I-123 MIBG is that it permits single photon emission computed tomography (SPECT). This was performed in six cases and provided additional information in three cases. The adrenal medullae were definitely visualized using I-123 scintigraphy in eight of 14 patients still possessing adrenal glands, whereas I-131 MIBG images portrayed the adrenal medulla in only one of 14 cases. Five remaining patients had multiple abdominal tumor deposits that were difficult to differentiate from normal adrenal medullae.

3-Iodobenzylguanidine↗
PubMed1985

Morbid obesity treated by gastroplasty: radionuclide gastric emptying studies.

Mechanisms by which gastroplasty for morbid obesity causes weight loss are poorly understood. We studied the role of altered gastric emptying in 50 patients before surgery, 1-4 weeks after surgery, and 2-24 months after surgery using technetium-99m pentetate in water for liquid meals and a Tc-99m styrene divinylbenzene copolymer resin in oatmeal for semisolid meals. We determined the emptying half-times of the stomach before and after surgery in the proximal and distal compartments. The proximal compartment emptied promptly in the early and late postoperative periods. The distal compartment emptied liquids at rates similar to those before surgery, while the late postoperative emptying of semisolids was significantly faster. The stoma connecting the two compartments thus permits rapid transit of liquids and semisolids without delay of distal compartment emptying. No correlation was seen between the emptying half-times or changes thereof and eventual weight loss. Delayed gastric emptying is therefore not the mechanism for satiety and weight loss after gastroplasty has been performed.

Adult↗
PubMed1985

131I-MIBG--a new agent in diagnosis and treatment of pheochromocytoma.

The newly developed radiopharmaceutical, 131I-metaiodobenzylguanidine (131I-MIBG), has been shown to be efficacious for the location of intra- and extra-adrenal, primary pheochromocytomas and metastatic, malignant pheochromocytomas (11.4% false-negative and 1.8% false-positive in patients with proven pheochromocytomas). Preliminary experience in selected patients with malignant pheochromocytoma suggest that therapy using large doses of 131I-MIBG results in partial tumor regression and improvement in catecholamine hypersecretion in some cases.

3-Iodobenzylguanidine↗
PubMed1985

Usefulness of tumor markers in serum and bronchoalveolar lavage of patients undergoing fiberoptic bronchoscopy.

To evaluate the diagnostic usefulness of simultaneous determinations of 4 tumor markers (carcinoembryonic antigen, calcitonin, creatinine kinase-BB, and DNA), we studied 31 patients with lung cancer, 22 with benign lung disease, and 15 normal volunteers as control subjects. The measurements were made by radioimmunoassay in bronchoalveolar lavage (BAL) and in serum obtained on the same day. The results showed that in serum, only CEA levels were significantly higher in malignancy; in lavage fluids, all 4 markers were abnormally high in cancer patients when compared with control subjects (p less than 0.05); there was no correlation between the levels in lavage and those in the bloodstream. When the mean levels in lavage of the normal control subjects were designated as the limits for a positive test, significant association was found between malignancy and abnormally elevated marker concentration (p less than 0.01). The particular combination of CEA-BAL greater than 35 ng/mg, CEA-serum greater than 4 ng/ml, and calcitonin-BAL greater than 120 pg/mg taken together with the results of bronchoscopy (histologic and cytologic) showed the highest discriminating power between malignant and benign lung disease. The sensitivity of the bronchoscopy procedure increased from 50 to 89%, with at least 2 positive markers, and had a specificity of 71%. When both bronchoscopy and all 3 markers were negative, the results showed a negative predictive value of 100%. We conclude that tumor marker levels in lavage are a useful aid in the diagnosis of malignancy in patients undergoing bronchoscopy.

Adult↗
PubMed1985

Iodine-131 metaiodobenzylguanidine for the locating of suspected pheochromocytoma: experience in 400 cases.

The efficacy of the newly developed pheochromocytoma-seeking radiopharmaceutical, [131I]MIBG, was examined in the first 400 patients (441 studies) investigated for suspected pheochromocytoma at our institution. The results of [131I]MIBG scintigraphy were classified as true positive, false positive, true negative, and false negative. Using this classification the sensitivity was found to be 78.4% in primary, sporadic pheochromocytoma, 92.4% in malignant pheochromocytoma, and 94.3% in familial pheochromocytoma giving an overall sensitivity of 87.4%. The specificity was 98.9% in primary, sporadic pheochromocytoma, 100% in malignant pheochromocytoma, and 100% in familial pheochromocytoma. The overall specificity was 98.9%. Iodine-131 MIBG scintigraphy was thus found to be a safe, noninvasive, and efficacious technique for the location of pheochromocytomas, especially for those arising from nonadrenal sites, recurring postoperatively, and exhibiting malignant metastatic disease. We find that, where available, [131I]MIBG scintigraphy is the study of choice to initiate the location of suspected pheochromocytoma.

3-Iodobenzylguanidine↗
PubMed1985

Limitations of 131I-MIBG scintigraphy in locating pheochromocytomas.

131I-metaiodobenzylguanidine (131I-MIBG) scintigraphy for the location of pheochromocytomas has proved to be a major advance in patient management. In combination with computerized tomographic scanning, nearly all pheochromocytomas can be located before surgery and invasive investigations are now indicated only in exceptional cases. However, there are still lessons to be learned concerning the optimal administration and interpretation of 131I-MIBG scintigraphy. With careful attention to detail and an awareness of isotope distribution, false positive studies should be extremely rare. While the incidence of false negative studies is uncommon, these certainly occur. A patient with sporadic bilateral adrenal medullary hyperplasia, bilateral pheochromocytomas, and additional benign pheochromocytomas arising in paraganglia tissue anterior to the abdominal aorta is presented. The right adrenal pheochromocytoma was not identified on 131I-MIBG imaging. We conclude that even with current locating techniques, the traditional surgical approach to pheochromocytoma should not be abandoned. This involves transabdominal exploration of both adrenal glands and careful examination of all possible sites of extra-adrenal pheochromocytomas.

3-Iodobenzylguanidine↗
PubMed1985

Limited significance of asymmetric adrenal visualization on dexamethasone-suppression scintigraphy.

To assess whether a single measurement of the adrenal uptake of 6 beta-[131I]-iodomethylnorcholesterol (NP-59) on constant dexamethasone suppression would allow discrimination of adenoma from normal and bilateral hyperplasia, the adrenal uptake of 6 beta-[131I]iodomethylnorcholesterol (NP-59) was determined in 50 patients with primary aldosteronism (30 adenoma, 20 hyperplasia) and in 13 with hyperandrogenism (six adenoma, seven hyperplasia). Bilateral adrenal NP-59 activity at 5 days was seen in 14 of 36 patients with adenoma (normal to adenoma ratio of greater than or equal to 0.5), whereas marked asymmetric uptake of NP-59 was seen in six of 27 patients with hyperplasia (uptake ratio of less than or equal to 0.5). Thus the level of adrenal NP-59 uptake does not alone serve to distinguish either adenoma from the normal, contralateral adrenal or the adrenal glands in bilateral hyperplasia in all cases. It appears that the pattern of adrenal imaging, early unilateral or early bilateral NP-59 activity (less than 5 days after NP-59 on 4 mg dexamethasone), best serves to separate adrenal adenoma from bilateral hyperplasia.

19-Iodocholesterol↗
PubMed1985

Phosphorus-32 therapy of cystic Grade IV astrocytomas: technique and preliminary application.

Instillation of [32P]chromic phosphate to cystic brain tumors was performed in six patients. Three patients had craniopharyngioma, two had Grade IV astrocytoma and one had Grade II astrocytoma. The cyst volumes ranged from 2 to 44 cc. A calculated dose of 20,000 rad was delivered to the cyst wall. The [32P]chromic phosphate dose given to achieve this dose ranged from 0.11 mCi to 2.5 mCi. Radionuclide leakage was not detected in either the central nervous system or the reticuloendothelial system by bremsstrahlung scanning. Stereotactic instillation was done in some cases, others had indwelling catheters. The frequency of cyst fluid aspiration in the three patients with craniopharyngioma decreased postinstillation. In the two patients with Grade IV astrocytoma, reductions in both the CT documented cyst size as well as the frequency of cyst aspiration were noted. We conclude that [32P]chromic phosphate installation by stereotactic or indwelling catheter method is a safe and helpful procedure in the management of cystic brain tumors.

Adult↗
PubMed1985

Cardiac paragangliomas. A clinicopathologic and immunohistochemical study of four cases.

Cardiac paragangliomas are extremely rare neoplasms. Four surgically resected tumors were examined by immunohistochemistry and electron microscopy. The patients ranged in age from 18 to 36 years. All patients had hypertension and elevated urine catecholamine levels. Three tumors were located on the posterior left atrium, and one tumor was located in the interventricular groove at the aortic root. The tumors ranged in size from 5 to 7 cm, and they displayed a prominent Zellballen pattern without significant necrosis or mitosis. The tumors were mostly unencapsulated and infiltrated adjacent cardiac tissue in two cases. Immunoperoxidase staining showed that all tumors were positive for chromogranin and neuron-specific enolase. Three tumors were positive for methionine enkephalin. Positive staining for S-100 protein was seen in the sustentacular cells of all tumors but was negative in chromaffin cells. All tumors were negative for insulin, glucagon, gastrin, vasoactive intestinal polypeptide, somatostatin, adrenocorticotropic hormone, calcitonin, serotonin, pancreatic polypeptide, and rat atrial peptide. Ultrastructural studies of all four tumors showed moderate numbers of predominantly norepinephrine-type granules and a few epinephrine-type granules. These results show that cardiac paragangliomas are commonly found in close proximity to the left atrium and have immunohistochemical and ultrastructural features similar to other paragangliomas.

Adolescent↗
PubMed1985

Familial extra-adrenal pheochromocytoma. A new syndrome.

Pheochromocytomas in the same anatomic site, the right renal hilum, occurred in a family over three successive generations. For two patients in the latter two generations, scintigraphy with iodine 131-tagged metaiodobenzylguanidine (MIBG) showed tumors only in the region of the right renal hilum, thus indicating that they were primary lesions. At surgery, except for lymph node metastases noted microscopically in one patient, tumors were found only near the right renal hilum. The adrenal glands seemed normal on inspection, palpation, and computed tomography. In another family, a mother and son had primary pheochromocytomas arising from the urinary bladder. We suggest that primary extra-adrenal pheochromocytoma is a syndrome in which specific genetic abnormalities determine sites of tumor development.

Adolescent↗
PubMed1985

Surgical treatment of cardiac pheochromocytomas.

The development at our institution of the radiopharmaceutical 131-I-metaiodobenzylguanidine has permitted for the first time scintigraphic localization of pheochromocytomas. By the use of this scan in combination with contrast-enhanced computed tomography, intrapericardial pheochromocytomas have been demonstrated in eight patients at our hospital during the past 2 years. Four of these patients have been operated upon by us, and each was found to have a pheochromocytoma arising from the heart (left atrium in three and interventricular groove at the aortic root in one). While in one patient it was possible to "shell" the tumor away from the left atrial wall without cardiopulmonary bypass, in the remaining patients, bypass and cardioplegia were required to resect the pheochromocytomas without inducing life-threatening intraoperative hypertension and cardiac arrhythmias. One patient required coronary artery reconstruction and two, excision of the posterior left atrial wall with pericardial replacement. One of these latter two patients died intraoperatively of uncontrollable hemorrhage. The three remaining patients are well and normotensive after more than 1 year of follow-up. Cardiac pheochromocytomas should not be approached as typical posterior mediastinal tumors, or as they are in the abdomen, with the expectation that they will "shell away" from contiguous structures. Cardiopulmonary bypass should be available, and resection of involved myocardium may be necessary for complete removal.

3-Iodobenzylguanidine↗