Sequestration of platelets in the pulmonary circulation as a consequence of protamine reversal of the anticoagulant effects of heparin.
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Biomedical subjects
Publications and source records attributed to M D Gross.
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I-131-6 beta-iodomethylnorcholesterol (NP-59) was used to localize mineralocorticoid-secreting adrenocortical carcinomas in two patients and functioning metastases in a third patient studied after the removal of the primary tumor. The presence of sufficient NP-59 activity within these lesions for discernable imaging is unusual and would not have been expected based on previous experience with other functioning and nonfunctioning carcinomas of the adrenal cortex. These cases serve to illustrate the variable spectrum of iodocholesterol uptake into adrenocortical malignancies and suggest that scintigraphic studies, preoperatively for localization and postoperatively to confirm the presence of recurrence or metastases, might be useful to identify and characterize these rare neoplasms.
Human kidney L-arginine:glycine amidinotransferase (transamidinase) has been purified to a homogeneous state as defined by native and sodium dodecyl sulfate gel electrophoresis and by ultracentrifugation (sedimentation equilibrium) experiments. The four steps in the isolation procedure were chromatography with DEAE-cellulose, gel filtration with Sephadex G-150, chromatography with phenyl Sepharose, and high-pressure liquid chromatography with hydroxylapatite. The final product represented a 90-fold purification of the enzyme. Human kidney transamidinase is a dimer with a molecular mass of 89,000 Da and subunit masses of 44,000 Da. The Km for arginine and glycine were both 2.5 mM and the Vmax was 0.5 mumol ornithine/min/mg protein. The ultraviolet absorption spectrum, specific activity, and isoelectric points were determined for human kidney transamidinase. Multiple forms of the enzyme were obtained by isoelectric focusing. Human kidney transamidinase cross-reacted with polyclonal antibodies raised to rat kidney transamidinase. All of the properties of human kidney transamidinase that we have examined were similar to those of rat kidney transamidinase. A close evolutionary relationship between the rat and human kidney transamidinase is suggested.
A comparative assessment of regional coronary flow reserve, quantitative percent diameter coronary stenosis and exercise-induced perfusion and wall motion abnormalities was performed in 39 patients with coronary artery disease. Coronary flow reserve was determined by a digital angiographic technique utilizing contrast medium as the hyperemic agent. Percent diameter stenosis was calculated by an automated quantification program applied to orthogonal cineangiograms. Thallium-201 scintigraphy and radionuclide ventriculography were used to assess regional perfusion and wall motion abnormalities, respectively, at rest and during exercise. In Group A, 19 patients without transmural infarction or collateral vessels, coronary flow reserve was inversely related to percent diameter stenosis (r = -0.61, p less than 0.0001), and scintigraphic abnormalities occurred only in vascular distributions with a coronary flow reserve of less than 2.00. There was a strong relation among abnormal regional exercise results, stenoses greater than 50% and reactive hyperemia of less than 2.00. Patients with multivessel disease, however, often had normal exercise scintigrams in regions associated with greater than 50% stenosis and low coronary flow reserve when other regions had a lower coronary flow reserve or higher grade stenosis, or both. In Group B, 20 patients with angiographically visible collateral vessels, 12 of whom had prior myocardial infarction, coronary flow reserve correlated less well with percent diameter stenosis than in Group A (r = -0.47, p less than 0.004). As in Group A patients, there was a significant relation between abnormal exercise test results and stenoses greater than 50%. However, reactive hyperemia values were generally lower than in Group A, and positive exercise stress results were strongly correlated only with highly impaired flow reserves of 1.3 or less. In Group B patients, the coronary flow reserve of vessels with less than 50% stenosis was significantly lower than that of similar vessels in Group A patients (2.40 +/- 0.79 versus 1.56 +/- 0.43; p less than 0.0002). It is concluded that: there is a general relation between quantitative percent diameter stenosis and reactive hyperemia that is not of sufficient precision to allow accurate prediction of coronary flow reserve in individual cases; exercise scintigraphic abnormalities are usually associated with low coronary flow reserve, and the relation between these two functional tests is stronger than the relation between exercise test results and quantitative percent diameter stenosis.(ABSTRACT TRUNCATED AT 400 WORDS)
Detection of gastrointestinal bleeding using Tc-99m labeled RBCs has proven to be clinically useful although false-positive images associated with abnormal vascularity remain problematic. The scintigraphic appearance of a large mesenteric varix is presented, and its potential confusion with gastrointestinal bleeding is discussed. Correlative CT and angiographic images are presented.
The enterohepatic circulation and distribution of 131I-6 beta-iodomethyl-19-norcholesterol (NP-59) was assessed in a rabbit model to examine the relative distribution of NP-59 and its metabolites. Adrenal, bile and serum samples were obtained from seven rabbits at 48 h following NP-59 administration (240 to 570 microCi) and the distribution of 131I radioactivity examined using thin layer chromatography. In serum 71% of the radioactivity circulated as NP-59 and 20% as NP-59 esters. In contrast greater than 90% of the adrenal radioactivity was in the form of NP-59 esters while in bile 70% of the activity was NP-59 with the remainder in the form of bile acids. In another group of animals, adrenal activity was observed 5 days after intragastric administration of NP-59. Thus, we have demonstrated a significant enterohepatic circulation of NP-59 that may have the potential to influence the distribution of and resultant adrenal imaging with NP-59.
The biodistribution of 131I-6 beta-iodomethyl-19-norcholesterol (NP-59) was assessed in hypercholesterolaemic patients and in a rabbit model of HC to examine the alterations in the relative distribution of NP-59 and its metabolites and to explain the changes in the patterns of adrenal cortical imaging in patients with expanded cholesterol pools. Rabbits were rendered hypercholesterolaemic with a diet supplemented with 2% cholesterol for 2 weeks prior to the intravenous administration of 240 to 570 microCi of NP-59. Adrenal, bile and serum samples were obtained from four hypercholesterolaemic rabbits at 48 h following NP-59 administration, and the distribution of 131I radioactivity was compared to that of seven rabbits maintained on a standard laboratory diet. Serum cholesterol levels were 1940 +/- 248 mg dl-1 in the hypercholesterolaemic rabbits as compared to 268 +/- 62 mg dl-1 in the controls. Adrenal cortical uptake of NP-59 was decreased in HC rabbits but no significant differences were observed in the relative proportions of NP-59 or its metabolites in the bile and adrenal tissues of hypercholesterolaemic versus control animals. Hypercholesterolaemic animals did exhibit an increase in NP-59 esters in serum as compared to controls. In three of five patients with hypercholesterolaemia, adrenal uptake of NP-59 was enhanced after successful lowering of serum cholesterol levels, while the remaining two patients who responded inadequately to cholesterol-lowering therapy showed a slight drop in NP-59 uptake.
Using a superconducting magnet operating at 0.35 T, the authors investigated the adrenal tissue characterization potential of magnetic resonance (MR) in 28 patients with 33 adrenal masses. There were 13 adrenal adenomas (12 non-hyperfunctioning, one aldosteronoma), nine adrenal metastases, four pheochromocytomas, two neuroblastomas, two adrenal lymphomas, two myelolipomas, and one adrenal cortical carcinoma. Spin-echo pulse sequences were obtained at TR 0.5, 2.0 sec and TE 28, 56 msec. Both qualitative (visual assessment) and quantitative (absolute signal intensity, intensity ratios, T1, T2) data were used for tissue characterization. The results suggest that non-hyperfunctioning adrenal adenomas can be distinguished from non-adenomas using both qualitative and quantitative data: 16/19 non-adenomas were visually hyperintense compared with liver at TR 2.0 sec, TE 56 msec, while none of the non-hyperfunctioning adenomas was relatively hyperintense at any pulse sequence used. Of the quantitative data, the intensity ratios of adrenal lesion/liver at TR 0.5 sec, TE 56 msec were most useful in diagnosis: all adenomas had ratios less than 0.83, while 19/20 non-adenomas had ratios exceeding this value. It is concluded that MR has considerable promise in adrenal tissue characterization.
Bone is the most common site of metastasis from pheochromocytoma. Now that the effects of hypercatecholaminemia can be adequately controlled with adrenergic blockade, pathologic fractures are becoming an increasingly significant cause of morbidity in patients with metastatic pheochromocytoma. Bone metastases from pheochromocytoma have not been extensively reevaluated since the advent of computed tomography (CT), high-resolution bone scintigraphy, and iodine 131 MIBG scintigraphy. Plain radiographs, CT scans, bone scans, and I-131 MIBG scans of 38 patients with pheochromocytoma bone metastasis were reviewed. The axial skeleton was the most common site of metastasis. Metastases typically appeared expansile and mixed lytic-sclerotic on radiographs. Bone scintigraphy was the most sensitive modality for detecting bone metastasis, with 74% of all alleged lesions being identified. In screening for bone metastasis from pheochromocytoma, bone scanning in conjunction with I-131 MIBG scanning is recommended, followed by scan- and symptom-directed radiography and - where a question still exists - CT.
Creatine is a major component of energy metabolism and enzymes involved in its synthesis have therefore been of considerable interest. L-arginine-glycine amidinotransferase, commonly called transamidinase, catalyzes the first reaction in the biosynthesis of creatine. This first reaction is believed to occur in the kidney because of the high concentration of transamidinase in that tissue. Transamidinase activity is also found in many other tissues of the rat, but its role in these tissues is not known. Immunochemical studies with antisera and monoclonal antibodies were used to confirm and refine our understanding of the presence of transamidinase in rat tissues. Immunofluorescence histochemistry was performed to localize transamidinase immunoreactivity within specific tissues including cells in the proximal tubules of the kidney, hepatocytes of the liver, and alpha cells of the pancreatic islet. Immunochemical studies with monoclonal antibodies confirm localization of transamidinase immunoreactivity in the proximal tubules of the kidney. The localization of such immunoreactivity in specialized cells yields insight into possible physiological role(s) of transamidinase in the rat.
The polycystic ovary syndrome (PCO) is frequently associated with elevated plasma levels of adrenal androgens and/or abnormal adrenal androgen responses to hormonal stimulation and suppression. Because of the overlap in the output of hormones between the adrenal glands and the ovaries, we measured adrenal iodocholesterol accumulation as an index of adrenocortical function in 11 women with PCO confirmed by laparoscopy or culdoscopy. All patients had normal dexamethasone suppression of plasma cortisol or urinary 17-hydroxycorticosteroid excretion. 6 beta-[131I]Iodomethylnorcholesterol (NP-59) adrenal scintiscans showed bilateral and excessive adrenal cortical uptake in PCO patients [0.46 +/- 0.08% (+/- SE) of the administered dose compared to 0.21 +/- 0.01% in a group of normal women; P less than 0.05]. The elevation of adrenal cortical NP-59 uptake in PCO was quantitatively similar to that in women with ACTH-dependent Cushing's syndrome (0.64 +/- 0.11%; P greater than 0.1). These data support the presence of abnormal adrenal cortical function in patients with PCO. The adrenal dysfunction of PCO most likely represents abnormal control of adrenal androgen production/secretion.
Accurate localization of the source of androgen hypersecretion is critical to the appropriate surgical or medical management of women with virilization. Seven patients with virilization and hyperandrogenism of various causes were evaluated with the use of sequential studies: testosterone stimulation and suppression tests; computerized tomography (CT); selective venous catheterization; and 131I-iodomethyl-norcholesterol (NP-59) scintigraphy. Comparison of the diagnostic accuracies of these localization studies with the ultimate diagnoses in this group of virilized women showed that: endocrinologic suppression/stimulation studies are of limited value in tumor localization and helpful only in patients with steroidogenic enzyme deficiencies; both selective catheterization and CT scanning may provide spurious localization data; and NP-59 scintigraphy, by depicting both the anatomic localization and functional androgen hypersecretion, may provide the most significant localization data in the evaluation of patients with virilizing syndromes.
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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.
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Coronary flow reserve, exercise thallium-201 scintigraphy and exercise radionuclide ventriculography were compared in 18 patients with chest pain and angiographically normal coronary arteries. Regional exercise thallium-201 perfusion was abnormal in three patients, regional exercise wall motion was abnormal in three other patients and results of both tests were abnormal in one additional patient. Left ventricular ejection fraction responses were abnormal in five of these seven patients. The coronary flow reserve of arterial distributions with abnormal perfusion or regional dysfunction was significantly lower than that of distributions associated with normal radionuclide results (1.42 +/- 0.23 versus 2.58 +/- 0.83, p less than 0.001). All patients with abnormal scintigraphic results had low coronary flow reserve (less than 1.95) in at least one distribution. Perfusion abnormalities appeared to be more localized in the arterial distributions with the lowest flow reserve. Only two patients had low flow reserve (less than 1.95) with normal scintigraphic results; both were hypertensive. These data suggest that abnormal exercise scintigraphic findings in patients with angiographically normal coronary arteries and chest pain are indicative of true blood flow or perfusion abnormalities.