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Biomedical subjects

B Shapiro

Publications and source records attributed to B Shapiro.

At least 271 records · Page 15Linked to original sources

Portrayal of pheochromocytoma and normal human adrenal medulla by m-[123I]iodobenzylguanidine: concise communication.

The radiopharmaceutical m-[131I]iodobenzylguanidine (I-131 MIBG), which is readily taken up by adrenergic vesicles, produces scintigraphic images of pheochromocytomas in man but rarely visualizes normal adrenal glands. Iodine-123 has many potential advantages over I-131 as a radiolabel for MIBG, including shorter half-life, freedom from beta emissions, and increased gamma-camera efficiency. In this study, diagnostic doses of MIBG labeled with I-131 and I-123, with nearly equivalent radiation dosimetry, were compared as imaging agents in eight patients with known or suspected pheochromocytoma. Images of superior quality were obtained with I-123 MIBG, and lesions not visualized using I-131 MIBG were portrayed. In addition, the normal adrenal medullae were visualized on the I-123 MIBG scintigrams in six out of eight patients.

3-Iodobenzylguanidine↗

Salivary gland accumulation of meta-[131I]iodobenzylguanidine.

Intense uptake of m-[131I] iodobenzylguanidine (I-131 MIBG ) has been observed in the salivary glands of patients undergoing scintigraphy for the location of suspected pheochromocytomas. This uptake of radioactivity was not due to free I-131 derived from the I-131 MIBG but rather to uptake of I-131 MIBG by sympathetic neuronal elements in the salivary glands. In keeping with this, administration of tricyclic antidepressants reversibly blocked salivary uptake of I-131 MIBG . Furthermore, I-131 MIBG uptake was markedly diminished by the ipsilateral salivary glands in a patient with Horner's syndrome, and was bilaterally diminished in a patient with severe idiopathic sympathetic autonomic neuropathy. The salivary gland uptake of I-131 MIBG may provide a means for the study of sympathetic innervation of these organs, and thus for the study of generalized disorders of autonomic innervation.

3-Iodobenzylguanidine↗

Radiopharmaceutical treatment of malignant pheochromocytoma.

Apart from relieving effects of secreted catecholamines, treatments of malignant pheochromocytoma have achieved little success. When the radiopharmaceutical, meta-[131I] iodobenzylguanidine (I-131 MIBG ), was found to concentrate in some malignant pheochromocytomas, we calculated that this agent could impart therapeutic doses of radiation to these tumors. We therefore treated five patients with two to four doses of I-131 MIBG prepared in high specific activity, 8-11 Ci/mmol. Individual doses were given at 3- to 10-mo intervals and in 97- to 197-mCi amounts. Two patients exhibited subjective and objective benefits. Their tumors declined in size (to 28% and 30% of original volumes) and in hormone secretion (to 50% or less of baseline rates). The other three patients manifested few symptoms before treatment and showed few or no objective improvement afterward. The tumors of the patients who responded to I-131 MIBG (a) appeared to be more rapidly growing, (b) received more cumulative rads, and (c) were more predominantly in soft tissues (in contrast to bone) than those in the patients who obtained little benefit. No toxic effects were encountered during the treatments, and only minor and temporary untoward responses were seen later.

3-Iodobenzylguanidine↗

The location of middle mediastinal pheochromocytomas.

Eight middle mediastinal pheochromocytomas were located by means of 131I- meta- iodobenzylguanidine scintigraphy. The exact anatomic location of the lesions was confirmed by means of dynamic computed tomographic scanning following bolus injection of contrast medium. In all but one case the lesion had not been detected prior to scintigraphy despite extensive investigations including arteriography, venography with sampling, computed tomography with infusion of contrast medium, and in some cases surgical exploration of the abdomen and chest. Accurate anatomic location of the lesion permitted resection of five lesions from the cardiac atria and one from the aortopulmonary window. A sixth case in which an atrial pheochromocytoma was found by coronary angiography was not cured by resection of the primary tumor, and 131I- meta- iodobenzylguanidine scintigraphy revealed extensive metastases. Thus 131I- meta- iodobenzylguanidine scintigraphy has been of considerable value in the location of pheochromocytomas of the middle mediastinum, which may be a more frequent site than previously recognized.

3-Iodobenzylguanidine↗

Determination of circulating DNA levels in patients with benign or malignant gastrointestinal disease.

Previous studies showed that patients with neoplasms of various types and origins have abnormally high concentration of DNA in their serum. The current work compares circulating DNA levels in patients with benign or malignant disease of the gastrointestinal tract and determines the diagnostic value of such measurements. DNA was quantitated by radioimmunoassay capable of detecting 25 ng/ml, and as a simple and noninvasive test, it could be a useful addition to other diagnostic procedures. The GI tract was chosen because it affords a comparison of benign, precancerous, and malignant lesions of the same organ. Of the 386 patients studied prospectively, 48% had benign disease and mean DNA levels (+/- SE) of 118 +/- 14 ng/ml, whereas 52% had malignant disease and 412 +/- 63 ng DNA/ml. The difference was statistically significant (P less than 0.001). The DNA assay showed the highest sensitivity for pancreas carcinoma: 90% of the patients had DNA levels above 100 ng/ml, chosen as the upper normal limit. Simultaneous measurements of both DNA and carcinoembryonic antigen (CEA) resulted in increased sensitivity and specificity, even when either marker alone had low sensitivity (gastric carcinoma). The results indicate that serum DNA concentration is markedly elevated in malignancy, and moderately elevated in benign disease, as compared with normal controls. These findings may have diagnostic and prognostic value.

Carcinoembryonic Antigen↗

Fundamental frequency, language processing, and linguistic structure in Wernicke's aphasia.

Five Wernicke's aphasics and five normal control subjects were tested in order to assess several aspects of fundamental frequency (F0) in speech production. The clinical impression of normal prosody in Wernicke's aphasia is correct inasmuch as these patients generally exhibited F0 declination. However, F0 declination ranged over shorter domains than in normal speech. Moreover, the increased use of F0 continuation rises by the Wernicke's aphasics indicated their inability to maintain a single F0 contour over constituents which are normally integral. The hypermelodic quality of F0 in the speech of Wernicke's aphasics further supported the notion that speech prosody was not strictly normal. F0 attributes tended to be normal when they corresponded to the global linguistic variable of sentence length, while they were abnormal when they corresponded to the processing of syntactic structure. No evidence was found that paraphasias and neologisms directly affected the programming of F0. The results are discussed in terms of speech processing abilities and limitations in Wernicke's aphasia.

Aphasia↗

A role for somatostatin in the control of hamster growth.

Concentrations of somatostatin-like immunoreactivity (SRIF-LI) were measured in cerebral cortex, hippocampus, septum-POA, median eminence, gastric antrum, fundus and pancreas in adult female hamsters to determine whether changes in somatostatin could be related to increased growth hormone (GH) secretion and somatic growth that follow bilateral transections of hippocampus (n = 18; 17 controls). In addition, choline acetyltransferase (CAT) activity was measured in the four brain regions in hippocampectomized (n = 10) and control hamsters (n = 10) to gain insight into the relationship between these two neurotransmitters. Hippocampal transections induced: significant acceleration of somatic growth; increased serum GH concentrations; increased concentrations of SRIF-LI in septum-POA and gastric antrum; reduced concentrations of SRIF-LI in hippocampus and pancreas; and reduced CAT activity in the hippocampus. These results suggest that somatostatinergic and cholinergic projections to hippocampus via fornix suppress GH and somatic growth in adult hamsters and that reduced release of SRIF-LI in the gastric antrum may contribute to the acceleration of somatic growth through facilitated nutrient digestion and entry.

Acetylcholine↗

Mode of action of plastic film in extending life of lemon and bell pepper fruits by alleviation of water stress.

The mechanism by which seal-packaging individual fruit in high density polyethylene film delays deterioration was investigated with lemon (Citrus limon [L.] Burm. f. cv Eureka) and bell pepper (Capsicum annuum L. cv Maor) fruits. Seal-packaging effects were due to the water-saturated atmosphere in the sealed enclosure around the fruit. Softening of fruit was highly correlated with declining water potential of fruit. Sealing drastically inhibited softening as well as changes in cell wall pectins. Sealing also delayed disintegration of membrane as shown by the inhibited leakage of amino acids, in particular, and electrolytes in general. All these effects of sealing were prevented or reduced by including hygroscopic CaCl(2) in the sealed enclosure which reduced the ambient humidity. Furthermore, some of these effects of sealing could be achieved also by maintaining nonsealed fruit in water-saturated atmosphere. Sealing effects could not be related to a possible ;modified atmosphere' mechanism in O(2), CO(2), or ethylene. This work supports the hypothesis that the mode of action of sealing in the polyethylene relates to the alleviation of water stress which exists in harvested fruit.

Journal Article↗

The relationship of adrenal gland iodomethylnorcholesterol uptake to zona glomerulosa function in primary aldosteronism.

Dexamethasone suppression adrenal scintiscans were performed on 37 patients referred for evaluation of primary aldosteronism (PA). Twenty-one had aldosterone-secreting adrenal adenoma (AA) and 16 had bilateral adrenal hyperplasia (BAH). The diagnosis of either AA or BAH was confirmed by adrenalectomy in 19 of 21 subjects with AA and by adrenal venous sampling in 15 of 16 patients with BAH. Biochemical parameters of PA were found in each patient while on both high (150 meq Na) and low salt (10 meq Na) intakes. Urinary aldosterone excretion values were 49.7 +/- 10.2 (+/- SEM) micrograms/day (range, 11.2-103.9) and 44.2 +/- 12.1 micrograms/day (range, 14.3-128.0) in AA patients on high and low salt intakes, respectively. In BAH patients, urinary aldosterone values were 29.1 +/- 2.6 micrograms/day (range, 10.0-55.0) and 47.7 +/- 9.0 micrograms/day (range, 23.0-102.0) on high and low salt intakes, respectively. A semioperator-independent computer algorithm was used to calculate adrenal gland uptake of [131I]6 beta-iodomethyl-19-norcholesterol (NP-59) in PA patients and in 7 patients with essential hypertension. NP-59 adrenal uptake values were 0.20 +/- 0.02%/dose (range, 0.03-0.72), 0.28 +/- 0.04% (range, 0.10-0.65), and 0.14 +/- 0.02%/dose (range, 0.08-0.30) in AA, BAH, and essential hypertension, respectively. A significant correlation was found between adrenal gland uptake of NP-59 and urinary aldosterone excretion in AA (r = 0.93; P less than 0.001) and BAH (r = 0.6; P less than 0.01) patients. These data confirm that adrenal gland accumulation of NP-59 while on dexamethasone suppression can be used to characterize abnormal zona glomerulosa function in PA, in addition to localizing AA and differentiating AA from BAH.

Adenoma↗

Complementary roles of CT and 131I-MIBG scintigraphy in diagnosing pheochromocytoma.

Recently 131I-MIBG (metaiodobenzylguanidine), an adrenergic tissue-localizing radiopharmaceutical, has been used for diagnosis of pheochromocytoma. In a retrospective study of 32 patients with pathologically proved primary, metastatic, or recurrent pheochromocytoma, the roles of 131I-MIBG scintigraphy and computed tomography (CT) in pheochromocytoma detection were compared. The two methods were equally accurate in the identification of primary and recurrent pheochromocytoma. 131I-MIBG scanning was more accurate as the initial examination in patients with extraadrenal tumors. In patients with metastatic disease, scintigraphy was preferable to CT because of its nontomographic nature, which permitted imaging of the entire body. Although a positive MIBG scan is diagnostic of pheochromocytoma, CT of extraadrenal tumors (particularly in the chest) has been very useful in planning appropriate surgical intervention. Furthermore, the roles of 131I-MIBG scintigraphy and CT in the detection of pheochromocytoma are complementary because each method has certain limitations.

3-Iodobenzylguanidine↗

The normal and abnormal distribution of the adrenomedullary imaging agent m-[I-131]iodobenzylguanidine (I-131 MIBG) in man: evaluation by scintigraphy.

The scintigraphic distribution of m-[131I]iodobenzylguanidine (I-131 MIBG), an adrenal medullary imaging agent, was studied to determine the patterns of uptake of this agent in man. The normal distribution of I-131 MIBG includes clear portrayal of the salivary glands, liver, spleen, and urinary bladder. The heart, middle and lower lung zones, and colon were less frequently or less clearly seen. The upper lung zones and kidneys were seldom visualized. The thyroid appeared only in cases of inadequate thyroidal blockade. The "normal" adrenal glands were seldom seen and faintly imaged in 2% at 24 hr after injection and in 16% at 48 hr, in patients shown not to have pheochromocytomas, whereas intra-adrenal, extraadrenal, and malignant pheochromocytomas usually appeared as intense focal areas of I-131 MIBG uptake at 24 through 72 hr.

3-Iodobenzylguanidine↗

A conveniently prepared Tc-99m resin for semisolid gastric emptying studies.

A polystyrene resin, suitable for semi-solid gastric emptying studies, was rapidly (less than 20 min) and conveniently prepared using commercially available reagents. Using the outlined procedure, Chelex-100 resin bound Tc-99m with greater than 98% labeling efficiency. The resulting Tc-99m Chelex-100 resin demonstrated excellent in vitro and in vivo stability. The clinical application of Tc-99m Chelex-100 resin, mixed with oatmeal, was tested in normal subjects and in various patient groups, including diabetic autonomic neuropathy, pyloric obstruction, postoperative dumping syndrome, and morbidly obese patients before and after gastroplasty.

Administration, Oral↗

Inverse relationship between cardiac accumulation of meta-[131I]iodobenzylguanidine (I-131 MIBG) and circulating catecholamines in suspected pheochromocytoma.

Heart intensity (HI) in the 24- and 48-hr images of meta-[131I]iodobenzylguanidine (I-131 MIBG), a pheochromocytoma-seeking guanethidine analog, were compared with concentrations of plasma and urinary catecholamines and their metabolites in nonpheochromocytoma and pheochromocytoma patients. HI was inversely related to plasma concentrations and urinary excretion rates of the hormones. Plasma norepinephrine had the highest inverse correlation with HI (r = -0.73 at 24 hr, -0.63 at 48 hr), and urinary metanephrine the lowest (r = -0.23 at 24 hr, -0.28 at 48 hr). A similar relationship was observed in the intensity of salivary-gland visualization, but with less marked variations. HI was much higher in nonpheochromocytoma patients than in pheochromocytoma patients. HI in an I-131 MIBG image provides useful information in the diagnosis of pheochromocytoma, and may provide a tool for the study of the influence of catecholamines on the heart.

3-Iodobenzylguanidine↗

Treatment of malignant pheochromocytoma with a new radiopharmaceutical.

A new radiopharmaceutical, [131I]metaiodobenzylguandine, concentrates in some malignant pheochromocytomas. Five patients were treated with two to four doses of [131I]MIBG (99-197 mCi/dose). Two patients had substantial subjective and objective responses. [131I]MIBG is the first chemically synthesized radiopharmaceutical of complex molecular structure to reduce cancer.

3-Iodobenzylguanidine↗

Value of bowel preparation in adrenocortical scintigraphy with NP-59.

The use of radiolabeled cholesterol derivatives for functional imaging of the adrenal cortex may be rendered inaccurate or impossible because of the excretion of activity by the liver and its subsequent appearance in the colon. A simple bowel preparation (bisacodyl 5 or 10 mg nightly) significantly reduced bowel background activity during 6 beta-[I-131]iodomethyl-19-norcholesterol (NP-59) adrenal cortical scintigraphy. Activity interfering with image interpretability was present less frequently in patients taking bisacodyl: three days after injection 22% compared with 59%; five days after injection 23% compared with 35%. As bisacodyl acts only on the colon and does not disturb the enterohepatic circulation of cholesterol or bile acids, it is ideal for use with a tracer of cholesterol metabolism.

19-Iodocholesterol↗

Nucleotide sequence of the p21 transforming protein of Harvey murine sarcoma virus.

Harvey murine sarcoma virus is a retrovirus which transforms cells by means of a single virally encoded protein called p21 has. We have determined the nucleotide sequence of 1.0 kilobase in the 5' half of the viral genome which encompasses the has coding sequences and its associated regulatory signals. The nucleotide sequence has identified the amino acid sequence of two additional overlapping polypeptides which share their reading frames and the carboxyl termini with p21 but which contain additional NH2-terminal amino acids.

Amino Acid Sequence↗