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Biomedical subjects

B Shapiro

Publications and source records attributed to B Shapiro.

At least 253 records · Page 14Linked to original sources
PubMed1985

Iodine-131 metaiodobenzylguanidine scintigraphy for the location of neuroblastoma: preliminary experience in ten cases.

Ten patients with histologically proven neuroblastoma were studied by [131I]MIBG scintigraphy. Tumor uptake of the radiopharmaceutical showed a spectrum varying from no uptake in one case, to slight uptake in two, moderate uptake in two and intense uptake in five cases. Iodine-131 MIBG scintigraphy was more effective in demonstrating the extent of neuroblastoma spread than were conventional bone scan and CT in one patient, equal to these modalities in four cases, almost equal in two cases and significantly inferior in three cases. These preliminary results suggest that [131I]MIBG scintigraphy is useful in detecting the presence and delineating the distribution of neuroblastoma and may, in certain cases, have therapeutic potential.

3-Iodobenzylguanidine↗
PubMed1985

Diagnosis and carrier detection of Tay-Sachs disease: direct determination of hexosaminidase A using 4-methylumbelliferyl derivatives of beta-N-acetylglucosamine-6-sulfate and beta-N-acetylgalactosamine-6-sulfate.

4-Methylumbelliferyl-6-sulfo-2-acetamido-2-deoxy derivatives of beta-D glucopyranoside and beta-D-galactopyranoside were prepared by direct sulfation of the commonly used unsulfated derivatives. Both sulfated substrates were highly specific for hexosaminidase A, and in fractionated serum, cells, and tissue preparations, less than 2.5% of these activities were associated with hexosaminidase B and the intermediate isozyme fractions. Serum and leukocytes from patients with infantile Tay-Sachs disease, including a patient with thermolabile hexosaminidase B, had less than 2% of noncarrier activities. Carrier values were clearly separated from those of noncarriers, and no problems were encountered in utilizing sera from pregnant women. The % hexosaminidase A values as derived from the ratio between the activities toward the sulfated and unsulfated substrates in the same specimen were comparable to those obtained by the heat-inactivation method (except for subjects with thermolabile hexosaminidase B) and may be helpful in genotype determination in borderline cases.

Acetylglucosamine↗
PubMed1984

Enhancer elements share local homologous twist-angle variations with a helical periodicity.

Several experiments have shown that some enhancers can be exchanged between different genomes. The transferred enhancers were functional (cf. Levinson, B., Khoury, G., Vande Woude, G. and Gruss, P. (1982) Nature 295, 568-572). This argues that these exchanged fragments are recognized as enhancers and possess some common characteristics which other sequences lack. Extensive comparisons of enhancers yielded only very limited nucleotide sequence homology, which appears to be insufficient for enhancer recognition. We suggest that the enhancers located and sequenced to date have recurring, periodic homologous twist-angle (tg) patterns. This helical periodicity and the symmetric nature of the repeating twist-angle features present a recurring spatial geometry. It also offers a possible explanation of the fact that inverted enhancers are still functional. Regions of large twist, roll or main-chain torsion angle delta deviations from regular B-DNA may facilitate enhancer recognition especially when distant from promoter elements. Tissue specificity may be encoded in additional sequence or structural features.

Animals↗
PubMed1984

DNAase I hypersensitive sites may be correlated with genomic regions of large structural variation.

Helical-twist, roll and torsion-angle variations calculated by the Calladine (1982)-Dickerson (1983) rules were scanned along several nucleotide sequences for which DNAase I cleavage data are available. It has been shown that for short synthetic oligomers DNAase I cuts preferentially at positions of high helical twist (Dickerson & Drew, 1981; Lomonossoff et al., 1981). Our calculations indicate that DNAase I sensitive and hypersensitive sites in chromatin are correlated with regions of successive, large, helical-twist angle variations from regular B-DNA. In many cases these regions exhibit large variations in base-pair roll and backbone torsion angles as well. It has been suggested that DNAase I cuts in the vicinity of cruciforms. However, it was recently demonstrated by Courey & Wang (1983) and Gellert et al. (1983) that such cruciform formation in a negatively supercoiled DNA is kinetically forbidden under physiological conditions. We thus propose that clustering of large twist-angle (and/or roll and backbone torsion angle) variations may be among the conformational features recognized by the enzyme. Specific cuts can then preferentially occur at base-pair steps with high helical twists.

Animals↗
PubMed1984

First-pass left ventricular ejection fraction with 95mAu on a 1/4 in. crystal gamma camera.

First-pass left ventricular ejection fraction was determined in 21 patients using 195mAu. The technical aspects of the application are discussed with particular reference to the thin crystal (1/4 in.) gamma camera. The use of diverse catheter types and combinations were also investigated so that optimal administration of the radionuclide could be achieved.

Cardiac Output↗
PubMed1984

Bilateral pheochromocytomas.

Bilateral pheochromocytomas most often occur as components of well-described syndromes: multiple endocrine neoplasia types 2a and 2b, von Hippel-Lindau disease and neurofibromatosis. We describe 4 patients with isolated bilateral pheochromocytomas; their tumors arose in the absence of stigmata and family history of the syndromes. The manifestations of these 4 individuals are compared with those of 14 other patients who developed pheochromocytomas in both adrenal glands as part of the syndromes. The 4 patients with the isolated pheochromocytomas manifest more rapidly progressing disease: they were 10-14 yrs of age, distinctly younger than those with the syndrome. Three of the 4 exhibited adrenal medullas that were composed entirely of tumor in contrast to the hyperplasia that usually accompanies other bilateral pheochromocytomas. However, malignant transformation of pheochromocytomas was seen both in a non-syndrome patient and in a patient with Lindau's disease.

Adolescent↗
PubMed1984

Scintigraphic localization of adrenal lesions in primary aldosteronism.

Dexamethasone suppression adrenal cortical scintiscanning was performed in 87 patients with primary aldosteronism. Fifty patients had adrenal cortical adenomas and 37 had bilateral adrenal hyperplasia. The diagnosis of adrenal cortical adenoma was confirmed by surgery in 49 of 50, and bilateral adrenal hyperplasia was confirmed by adrenal vein aldosterone sampling in 33 and at operation in four. Dexamethasone suppression adrenal scintigraphy correctly identified the lesion(s) in 82 of the 87 patients. There were three false-negative and two false-positive adrenal cortical scintiscanning results. Computed tomography was performed in 33 patients and correctly identified 14 of 23 patients with adrenal cortical adenomas and two of 10 patients with bilateral adrenal hyperplasia and bilateral enlarged adrenals, whereas the remaining eight were considered to have normal findings. These data indicate that, when properly performed, adrenal cortical scintigraphy is an accurate and efficacious modality for the localization of adrenal cortical adenomas and in the differentiation of adrenal cortical adenoma from bilateral adrenal hyperplasia in primary aldosteronism.

Adenoma↗
PubMed1984

The relationship of I-131 6 beta-iodomethyl-19-norcholesterol (NP-59) adrenal cortical uptake to indices of androgen secretion in women with hyperandrogenism.

Dexamethasone suppression (DS) adrenal cortical scintigraphy has been shown to be useful in the detection of the adrenal pathology in women with hyperandrogenism. However, a relationship between adrenal cortical uptake of I-131 6 beta-iodomethylnorcholesterol (NP-59) and the level of adrenal androgen secretion has not been established. A retrospective analysis of DS adrenal scintiscans has been performed on 39 women with hirsutism and hyperandrogenism. In 14 patients with normal patterns of imaging, in vivo adrenal gland iodocholesterol uptake, calculated using a semi-operator-independent-computer algorithm, did not correlate with the excretion of urinary 17-ketosteroids (17-KS). In contrast, in 20 patients demonstrating abnormal bilateral early imaging patterns, adrenal gland NP-59 uptake correlated significantly with the level of urinary 17-KS excretion (r = 0.65, P less than 0.05). To date seven of these 20 patients have had confirmatory procedures documenting the adrenal glands as contributing sites of androgen secretion. A similar correlation with urinary 17-KS excretion was seen in five other patients with unilateral imaging patterns (r = 0.94, P less than 0.005), due to androgen-secreting adrenal cortical adenomas. No correlation between adrenal NP-59 uptake and plasma testosterone or dehydroepiandrosterone sulphate levels was observed in any of the groups. Thus, adrenal gland uptake of NP-59 under DS reflects a measure of androgen secretion in women with androgen excess.

17-Hydroxycorticosteroids↗
PubMed1984

Computed tomography of pericardial masses: further observations and comparison with echocardiography.

Eight patients with surgically proven primary intrapericardial masses were evaluated over the past 3 years using a variety of radiologic tests. Dynamic CT prospectively identified the masses in all eight patients, esophagography was positive in four of five patients, chest radiography was prospectively positive in one of eight patients, and echocardiography identified a mass in only one of seven patients. Furthermore, precise CT localization of the masses proved important in surgical management of these patients, suggesting in several instances the need for cardiopulmonary bypass. Although echocardiography is the modality of choice in evaluating potential pericardial effusion, CT should be the preferred diagnostic test for suspected intrapericardial mass lesions.

Contrast Media↗
PubMed1984

Constant intrarenal infusion of PGE1 into a canine renal transplant using a totally implantable pump.

A method was devised whereby PGE1 could be administered to a canine renal transplant recipient on a chronic basis. PGE1 was stored in the reservoir of an implantable pump and delivered continuously in high doses directly into the renal transplant artery. In the model studied a contralateral untreated transplant from the same donor served as a control. Sequential renal scans were used to study the effect of intraarterial PGE1 on the rejection process. Continuous delivery of PGE1 into the renal transplant artery did not prevent allograft failure under these conditions; blood flow diminished similarly in both PGE1-treated and untreated transplants. There were, however, striking differences in the histologic appearance of treated and untreated transplants. PGE1 perfusion resulted in the appearance of large numbers of polymorphonuclear leukocytes but few lymphocytes. In the untreated control allograft, however, the findings were typical of lymphocyte-mediated acute rejection. The distinctive differences noted histologically suggested that the local administration of PGE1 influenced the mechanism by which graft failure occurred. The ability to manipulate cell populations infiltrating an allograft represents a potentially important means for modifying the immune response.

Alprostadil↗
PubMed1984

Malignant phaeochromocytoma: clinical, biochemical and scintigraphic characterization.

We have evaluated thirty patients with malignant metastatic phaeochromocytoma with regard to clinical features, indices of catecholamine secretion, histology of lesions and a number of imaging procedures including scintigraphy with the recently developed sympathetic tissue-seeking radiopharmaceutical 131I-metaiodobenzylguanidine (131I-MIBG). The primary tumour was extra-adrenal in 13 cases. The commonest site of metastases was the axial skeleton (20 cases), followed by liver (four cases), lymph nodes (four cases), peritoneum (two cases) and lung (three cases). The malignancies were indolent, the mean time following the initial diagnosis was 9.18 years (range 0 to 33 years) and the mean duration of known metastases 3.71 years (range 0 to 18 years). There was a wide range of abnormalities in plasma and urinary catecholamines which did not correlate with the extent of tumour spread, histological pattern (mitotic index, Zellballen pattern, capsular or vascular invasion pleomorphism or necrosis) or 131I-MIBG uptake by tumour deposits. 131I-MIBG scintigraphy was found to be a useful technique for determining the extent of metastatic disease in most cases (26 of 30) and in some patients (16 of 30) was more sensitive than other radiological procedures. No false positive scans were encountered.

3-Iodobenzylguanidine↗
PubMed1984

The scintigraphic imaging of endocrine organs.

The nuclear medicine approach to the portrayal of endocrine organs is unique; the scintigraphic images provide not only anatomic and localization information, but in many instances allow a quantitative assessment of organ function. The ability to image endocrine glands is based upon the design of radionuclides and radiopharmaceuticals with characteristics to take advantage of many unique and specific biochemical and advantage of many unique and specific biochemical and metabolic functions of these tissues. The recent introduction of new radiopharmaceutical and tracers has provided the consulting endocrinologist with imaging procedures that allow localization and functional characterization not available by other single, noninvasive diagnostic modalities. This review will serve as an update of the available techniques to image and quantitate the function of the endocrine glands using the nuclear medicine approach.

3-Iodobenzylguanidine↗
PubMed1984

Patterns of prolactin secretion in the syndrome of general resistance to thyroid hormones.

The dynamics of TSH and PRL secretion were studied in three patients with incomplete generalized resistance to thyroid hormones. Results in the first patient differed from those in the other two. The first patient had been treated previously with radioiodine but was clinically euthyroid when subsequently treated with supraphysiological quantities of T3 and T4. Increasing doses of T4 from 0.2-0.3 mg/day caused a decline in serum TSH levels and lesser increments in TSH to injected TRH in this patient. The other two patients had not been treated, but had basal TSH levels and TSH responses to TRH similar to those in the first patient. However, the TSH response to injected metoclopramide in the first patient was substantially higher than the responses in the other two patients. The basal levels of PRL in the first patient were elevated at both T4 doses; also, her PRL responses to TRH and metoclopramide were exaggerated and, compared to normal values, disproportionate to her TSH responses to these provocative agents. In contrast, the other two patients had normal basal PRL concentrations and normal or near-normal PRL responses to TRH and metoclopramide. We conclude that within the syndrome of resistance to thyroid hormones, there are heterogeneous patterns of PRL secretion. Dopaminergic tone on thyrotrophs and lactotrophs also differs among patients with the syndrome.

Adolescent↗
PubMed1984

Plasma catecholamines in pheochromocytoma: effect of urographic contrast media.

Hypertensive crises have been provoked in pheochromocytoma patients by the injection of contrast media during angiography and venography. Fear of similar reactions to intravenous urographic contrast medium injection during computed tomography has led to studies without contrast enhancement when pheochromocytoma is suspected. With extraadrenal pheochromocytomas, intravenous contrast enhancement may be essential for tumor location by computed tomography. The catecholamine responses to injection of urographic contrast medium were examined in eight patients with pheochromocytoma and in 12 undergoing computed tomography for other reasons. Plasma norepinephrine concentrations fell in nonpheochromocytoma patients (p less than 0.005), while in pheochromocytoma patients the response was unpredictable, rising in six individuals, although the mean response was not significant (p greater than 0.35). In five patients the magnitude of the increase in norepinephrine concentrations was large enough to have led to a pressor effect had alpha adrenergic blockade not been used. It was concluded that intravenous urographic contrast medium may elevate plasma catecholamines in a significant proportion of patients with pheochromocytoma, but that with adequate alpha adrenergic blockade this should pose no threat.

Contrast Media↗
PubMed1984

An immunohistochemical study of pheochromocytomas.

Twenty -six adrenal pheochromocytomas and four normal adrenal medullae were studied immunohistochemically. These included four malignant tumors with proven metastases, six tumors in patients with neurofibromatosis, nine tumors in patients with multiple endocrine neoplasia type 2, and seven sporadic nonfamilial pheochromocytomas. Immunohistochemical localization of neuron-specific enolase (NSE) was seen in all tumors and in the four normal adrenals. Methionine enkephalin-like immunoreactivity was present in tumors from all four groups and in the normal adrenals. Corticotropinlike immunoreactivity was found focally in two normal adrenal medullae and in four benign pheochromocytomas. Our results indicated that NSE was present in all four major groups of pheochromocytomas, including benign and malignant tumors. This marker aided in distinguishing between adrenal cortical and medullary tumors in unusually difficult cases, since all normal adrenal cortex and adrenal cortical tumors had negative test results for NSE.

14-3-3 Proteins↗
PubMed1984

Diagnosis of adrenal tumors with radionuclide imaging.

The development of radiolabeled cholesterols in 1969 as precursors of adrenocortical steroid production allowed the first noninvasive imaging of the adrenal cortices. FDA-NDA approval in 1984 should allow routine use of these agents in most hospitals. NP-59 is most commonly used in the diagnosis and management of Cushing syndrome; the second most common use is in the diagnosis of primary aldosteronism. It is also helpful in the differential diagnosis of adrenal and ovarian hyperandrogenism and hirsutism, and is the only noninvasive method of detecting unilateral adrenocortical hypofunction. The newest and most popular use is in the differential diagnosis of asymptomatic masses in the region of the adrenal gland discovered incidentally with CT scan ("incidentalomas"). In this situation, the NP-59 scan can define whether the tumor is in the adrenal gland and if it is functional or nonfunctional. We believe that, in the future, radiolabeled enzyme inhibitors might offer better diagnostic imaging of the adrenal cortex, although these agents will probably not be available for routine use for some time. Our development of a radioiodinated guanethidine analog, 131I-MIBG, has allowed differentiation of normal adrenal medullary function from bilateral adrenal medullary hyperplasia before the development of hypertension or tachycardia, diagnostic increases in plasma or urinary catecholamines, or abnormal CT scans. The search for a pheochromocytoma should begin with 131I-MIBG scintigraphy. While over 90% of primary pheochromocytomas occur in the abdomen, neither a survey of the abdomen nor the finding of a single tumor should conclude the search. Whereas the CT scan can only detect a mass, the MIBG scan not only detects the mass but proves whether the mass is a pheochromocytoma. We have detected small or recurrent pheos when all other localizing studies were normal. Present drug and X-ray therapy is relatively ineffective in treating metastatic cancer of the adrenal medulla. Preliminary results in five patients indicate that, for the first time, a complex organic molecule can carry 131I into adrenal neoplasms reproducibly and in therapeutically effective doses of irradiation. We may also be able to select which patients will respond to therapeutic doses of 131I-MIBG and which patients will not respond.

Adenoma↗