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J C Sisson

Publications and source records attributed to J C Sisson.

At least 19 recordsLinked to original sources
PubMed1992

131-I-metaiodobenzylguanidine treatment in patients with refractory advanced neuroblastoma.

Fourteen patients with refractory advanced neuroblastoma were treated with 131-I-metaiodobenzylguanidine (131-I-MIBG); all had evidence of progressive disease or recurrent disease following combination chemotherapy. One patient without gross evidence of disease, following surgical resection of recurrent neuroblastoma before therapy with 131-I-MIBG, remains healthy without regrowth of tumor 3.5 years later. Two other patients had minor responses, and one had a mixed response. Two patients remain alive 1,212 and 1,926 days following the initial 131-I-MIBG treatment; the remaining 12 patients died of progressive disease. Moderate myelosuppression was the most notable toxicity observed; mild nausea and vomiting and transient mild liver enzyme elevation were also encountered. Treatment with 131-I-MIBG produced antineoplastic activity in patients with neuroblastoma and was well tolerated. To evaluate dose escalation, alternative dosage schedules, and alternative MIBG-radioconjugates, additional trials of radiolabeled MIBG are indicated.

3-Iodobenzylguanidine↗
PubMed1992

Learning, retention and recall of clinical information.

A representative group of 33 medical students who were entering the junior year clerkships was tested for retention and recall of clinical information 3 months after taking an examination on the same subject. The students were not given an opportunity to review the subject. On 39 identical multiple choice test questions, the students' mean score declined 10 percentile points (P < 0.05) from that on the original examination. On 40 comparable but previously unseen questions, the mean score fell 19 percentile points from that attained 3 months earlier. On open-ended questions of clinical reasoning, a third component of the assessment, the students performed at a level similar to those on the two multiple choice tests, but with greater variability. These assessments give data on retention and recall that have not previously been reported in the literature. Correlations among individual test components were moderate (r = 0.52-0.63). There was inconsistency of individual students in scores on the component tests, and, thus, variability in performance by students was marked. Retention and recall were weakly predicted by results on an initial multiple choice examination. In addition, on a subsequent assessment of knowledge, results from different types of tests were inconsistent, suggesting that these tests evaluate different forms of competence.

Clinical Clerkship↗
PubMed1992

PET scanning with hydroxyephedrine: an approach to the localization of pheochromocytoma.

Pheochromocytomas are potentially curable causes of hypertension. These tumors are currently located by functional imaging with meta-iodobenzylguanidine (MIBG), usually labeled with 131I, or anatomic imaging (computed tomography, magnetic resonance). Hydroxyephedrine (HED) is a newly developed radiotracer that concentrates in adrenergic nerve terminals. When HED is labeled with 11C, its distribution can be mapped in vivo using PET. The purposes of this investigation were to characterize the uptake of 11C-HED in pheochromocytoma and to determine the feasibility and advantages of utilizing this compound as a tumor imaging agent. Ten patients with known or suspected pheochromocytoma were studied. Each patient underwent PET scanning with 11C-HED and conventional scintigraphy with MIBG. Pheochromocytomas were localized by PET scanning in 9 of the 10 patients. Image quality was excellent and superior to that obtained from planar and tomographic MIBG studies. The uptake of 11C-HED into pheochromocytomas was rapid; tumors were evident within 5 min following intravenous injection. All lesions within the field of view that were identified by MIBG scintigraphy were readily apparent. PET scanning with 11C-HED localizes pheochromocytoma using a specifically designed radiotracer and advanced imaging technology. The method has promise for locating the more elusive tumors.

3-Iodobenzylguanidine↗
PubMed1991

Phaeochromocytoma and functioning paraganglioma in childhood and adolescence: role of iodine 131 metaiodobenzylguanidine.

Phaeochromocytomas and functioning paragangliomas are rare tumours in childhood and adolescence. We review our experience of 43 cases (24 men, 19 women) who were first diagnosed at the age of less than or equal to 18 years. All patients were evaluated at some point in their illness with iodine 131 metaiodobenzylguanidine (131I-mIBG) scintigraphy. Eight patients (19%) had bilateral adrenal tumours, 12 (28%) had solitary extra-adrenal tumours, and 8 (19%) had multiple tumours. In 10 patients (23%), the tumours were associated with a familial neurocristopathic syndrome. Thirteen of 24 (54%) unifocal tumours which were initially considered to be benign ultimately proved to be multi-focal and/or malignant. The final prevalence of malignancy was 60%--26 patients, of whom only 15 (57%) had obviously malignant tumours at the time of diagnosis. Primary tumour size greater than or equal to 5 cm was more commonly associated with a malignant course in adrenal but not extra-adrenal tumours. No other clinical, biochemical or morphological characteristic was significantly associated with malignancy. Although the high prevalence of malignancy in this series at least partly reflects referral bias, the need for lifelong follow-up of these patients is underscored. 131I-mIBG scintigraphy was positive in 36 patients (84%), with a somewhat lower false-negative rate (12%) than X-ray computed tomography (20%). Eight patients with malignant tumours received therapeutic doses of 131I-mIBG, with partial tumour responses in 3. Thus, 131I-mIBG is an efficacious, non-invasive, localising agent and may be considered as a palliative therapeutic agent when alternatives have failed.

3-Iodobenzylguanidine↗
PubMed1991

Measuring acute changes in adrenergic nerve activity of the heart in the living animal.

Changes in the function of the adrenergic neurons of the heart may be important indicators of the adaptations of an animal to physiologic stress and disease. Rates of loss of norepinephrine (NE) from the heart were considered to be proportional to NE secretion and to adrenergic function. In rat hearts, yohimbine induced almost identical increases in rates of loss of 3H-NE and of 125I-metaiodobenzylguanidine (MIBG), a functional analog of NE. Clonidine induced decreases in rates of loss of 3H-NE that were also mimicked by those of 125I-MIBG. In the dog heart, pharmacologically-induced increases and decreases in rates of loss of 123I-MIBG could be measured externally; these values were similar to those obtained for 125I-MIBG in the rat heart. Thus acute changes in the adrenergic neuron activity can be measured in the living heart. The method is applicable to man in determining the capacity of the adrenergic system to respond to provocative challenges.

3-Iodobenzylguanidine↗
PubMed1991

The characteristics of early diagnostic hypotheses generated by physicians (experts) and students (novices) at one medical school.

How hypotheses generated at the outset of a physician-patient encounter influence the physician's diagnostic reasoning has received relatively little attention in the literature. Yet, this activity modulates the efficiency and accuracy of the diagnostic process. The authors proposed the theory that physicians (experts) would generate less specific initial diagnostic hypotheses than would students (novices). In 1988 and 1989, the hypotheses generated by 32 practicing physicians and 39 third-year medical students at one medical school were analyzed for number, specificity, and breadth (i.e., range) of diagnoses, and for differences between those generated by the physicians and by the students. The hypotheses were formulated on the basis of the initially available data--chief complaint and its duration, and basic demographic descriptions--from patients in three clinical scenarios. Compared with the physicians, the students generated significantly more hypotheses and significantly more specific hypotheses. There was no significant difference between the groups in the breadths of the hypotheses they selected, that is, the numbers of broad categories of diagnosis covered by individuals' hypotheses.

Analysis of Variance↗
PubMed1991

Scintigraphic portrayal of beta receptors in the heart.

Myocardial beta adrenergic receptors play important roles in physiology and disease, but the receptors have not before been portrayed. The beta antagonist, iodocyanopindolol (ICYP), was used to develop a scintigraphic method for depicting the receptors in the living heart. Labeled with 125I, ICYP bound firmly to beta receptors in the rat heart; the data conformed to a mathematical model. In vivo saturation kinetics indicated binding sites with two affinities. Inhibition of ICYP binding by beta antagonists of different potency and different selectivity for beta-1 and beta-2 receptors produced the expected pharmacologic effects. Inhibition by lipophilic and hydrophilic antagonists gave no evidence that ICYP was appreciably bound to internalized receptors. Fractional binding by tracer quantities of (-) ICYP and (+/-) ICYP demonstrated stereospecificity. Labeled with 123I, ICYP bound to the hearts of intact dogs so that scintigraphic tomographs depicted ventricular myocardium. Small doses of beta antagonists selectively reduced the binding of ICYP to lung enabling better visualization of the heart. Thus, 123I-ICYP appears to portray the beta receptors in the living heart, and the characteristics of binding permit the development of mathematical models and lay the basis for quantifying this receptor binding.

Animals↗
PubMed1990

Linkage of the multiple endocrine neoplasia type 2B gene (MEN2B) to chromosome 10 markers linked to MEN2A.

The syndrome of multiple endocrine neoplasia type 2B (MEN 2B) resembles that of MEN 2A in that both include medullary carcinoma of the thyroid, pheochromocytoma, and autosomal dominant inheritance, but is distinct in that MEN 2B patients have neuromas of the mucous membranes. MEN2A has been linked to RBP3, D10S5, FNRB, D10S15, and D10Z1 near the centromere of chromosome 10. We examined linkage between MEN2B and RFLPs on chromosome 10 in all available members in two or three generations of 14 kindreds. The centromere marker D10Z1 was linked to MEN2B with a peak lod score of 5.42 at theta = 0.02. One possible recombinant was observed between D10Z1 and MEN2B. Multipoint analysis of RFLPs at FNRB, D10Z1, RBP3, and D10S15 gave a peak lod score of 7.12 at the midpoint between D10Z1 and RBP3 on the long arm (band q11). The most likely gene order FNRB-D10Z1-MEN2B was 27 times more likely than MEN2B-FNRB-D10Z1 and 31/2 times more likely than FNRB-MEN2B-D10Z1. Additional data will be required to establish the order of these loci with confidence.

Chromosomes, Human, Pair 10↗
PubMed1990

The reliability of a hypothesis generation and testing task.

The purpose of this paper is to present results of initial experience with a clinical reasoning task which assesses two clearly defined aspects of clinical problem solving. Fourteen senior and 40 junior medical students at the University of Michigan Medical School participated in this study. They were given three clinical reasoning problems--the hypothesis generation and testing tasks (HG & T). As suggested by the name, two specifically defined components of clinical problem-solving, developing the initial hypotheses or differential and then testing hypotheses, were evaluated by these tasks. The findings of this study indicate that hypothesis generation and testing can be reliably evaluated with between seven and ten tasks. The results of this study suggest that reliable assessments of specific components of clinical problem-solving can be developed.

Clinical Competence↗
PubMed1990

Portrayal of adrenergic denervation in the presence of myocardial infarction: a feasibility study.

Myocardial infarction interrupts adrenergic neurons beyond the region of necrosis to give peri-infarct denervation. A method to define the regions of denervation would be a valuable aid in determining the role that loss of adrenergic neurons plays in myocardial infarction and particularly in causing arrhythmias. [123I] meta-iodobenzylguanidine (MIBG) was used to portray scintigraphically the intact neurons in dog hearts. Occlusion of the left circumflex (LCX) or the left anterior descending coronary artery (LAD) produced defects that appeared to be regularly larger in the [123I]MIBG images than in the [201T1]images of the same heart; the differences were considered to be the regions of denervation which were relatively larger after LCX than LAD infarcts. Ex vivo measurements of endogenous norepinephrine and residual [125I]MIBG concentrations gave confirmation of neuronal injury. A computer program to quantify the regions of denervation appeared imprecise, but gave some promise. Scintigraphy of [123I]MIBG offers a method to define patterns of denervation in the living animal and man.

3-Iodobenzylguanidine↗
PubMed1990

Thyrotoxicosis caused by thyroid cancer.

Well-differentiated follicular carcinoma causing thyrotoxicosis is a rare entity. The age and sex distribution is no different from that of other patients with follicular carcinoma, with 87% older than the age of 40 and a female:male ratio of 3:1. The clinical presentation is similar to that of Graves' patients except that evidence of metastatic disease is often present (soft tissue masses, bone pain). The metastases are in the usual locations (bone, lung, mediastinum) and are often bulky. Despite the poor efficiency of iodine uptake and thyroid hormone production, the large tumor mass is capable of producing excessive hormone. Laboratory data confirm the hyperthyroid state, but the occurrence of T3 elevations with normal T4 levels is common, and T3 toxicosis may be missed if only T4 levels are measured. The role of thyroid stimulating immunoglobulins is still evolving, but such stimulators may support the growth of metastatic thyroid carcinoma and promote the development of hyperthyroidism. The treatment of these patients varied. Most had thyroidectomy followed by 131I therapy. Dosimetry allows for the administration of the largest dose of 131I with acceptable side effects. A good response to radioiodine predicted a more favorable outcome. The survival of patients with metastatic thyroid carcinoma causing hyperthyroidism does not differ from euthyroid patients with metastatic follicular disease (10-year survival, 59%).

Adult↗
PubMed1990

Diagnostic accuracy and pitfalls of [iodine-131]6-beta-iodomethyl-19-norcholesterol (NP-59) imaging.

NP-59 concentrates in steroid hormone synthesizing tissues, enabling scintigraphic localization and characterization of endocrine dysfunction in the adrenal cortex and ovary. Studying 108 consecutive cases from 1982 to 1985 and using clinical, biochemical, radiographic, and pathologic data, we performed a rigorous assessment of the accuracy and pitfalls of NP-59 scintigraphy. The evaluation was divided into categories of abnormal hormone secretion: Cushing's syndrome, primary aldosteronism, and hyperandrogenism. Additional categories included euadrenal tumors (without detectable hormone dysfunction) and sites of residual adrenal cortical tissue. The accuracy of NP-59 scintigraphy ranged from 71% in primary aldosteronism and 75% in euadrenal tumors, to 100% for Cushing's syndrome and hyperandrogenism. However, more than in most nuclear medicine studies, NP-59 imaging requires well-defined indications to be met for it to be efficacious, including the fulfillment of clear clinical, biochemical, and radiographic criteria. The high reproducibility of NP-59 scintigraphic interpretation was demonstrated when 40 random cases underwent interinstitutional exchange and through interobserver evaluation at the University of Michigan. Responses of 85/126 medical centers to questionnaires revealed the high level of NP-59 safety.

Adosterol↗
PubMed1990

Iodine-125-MIBG to treat neuroblastoma: preliminary report.

Three children with Stage III neuroblastoma were treated with [125I]MIBG in a phase I toxicity study. Concepts of the treatment were: in small tumors, the absorbed dose of radiation from MIBG labeled with 131I is reduced but the absorbed dose from [125I]MIBG is less affected; and many recurrences of neuroblastoma arise from small tumors. Two patients exhibited only modest thrombocytopenia and leukopenia, the most sensitive indices of radiation toxicity, after receiving 261 and 407 mCi, and 83 and 104 rad of whole-body radiation. One patient died of progressive neuroblastoma; the other two patients have stable disease over 30 mo after treatment. Per millicurie given, [125I]MIBG imparts about one-fourth the radiation dose of [131I]MIBG to the whole body. Iodine-125-MIBG can be given in doses that impart over 100 rad of whole-body radiation and that exceed 400 mCi before toxicity becomes limiting, even in small children.

3-Iodobenzylguanidine↗
PubMed1989

Calculating radiation absorbed dose for pheochromocytoma tumors in 131-I MIBG therapy.

A protocol for calculating radiation absorbed dose to pheochromocytoma tumors during treatment with 131I-labeled metaiodobenzylguanidine (MIBG) is described. The technique calls for (a) obtaining tumor volumes from Computed Tomography and/or Magnetic Resonance Imaging, (b) computing energy absorbed by assuming complete beta-particle absorption and a standard shape for gamma-ray absorption and (c) scaling from tracer to therapy dose rate by the ratio of administered activities. Also a 131I time-activity curve is obtained from planar, Anger-camera, conjugate-view images of the tumor and a known-strength source, both over a series of days. In addition, to correct for any systematic errors in the calculated uptakes, a larger activity of 123I MIBG is administered separately and quantitative Single Photon Emission Computed Tomography (SPECT) is undertaken. A known-strength source also undergoes SPECT to calibrate the tomograms. Correction for Compton scattering is accomplished by the dual-energy-window technique. The subtraction fraction was found to be 0.7 for the 1/2" crystal camera and the mean reduction in tumor counts for seven tumors from Compton correction was 0.76. The normalization factor needed to bring the conjugate-view activities into agreement with the SPECT values ranged from 0.74 to 1.06. A test study on an anthropomorphic phantom indicated that the error in resultant activities might be estimated as +/- 13%. Application of the protocol led to the calculation of real, or potential (when decision was finally made to not administer therapy) radiation absorbed dose to seven tumors in three patients from an administration of about 8 GBq of MIBG. For two metastatic tumors in a 19-year old patient who did not have her primary cancer resected, the calculated radiation absorbed dose was 170 and 180 Gy. For the four metastatic deposits evaluated in two older patients, both of whom had their primary tumor surgically removed, the values ranged from 18 to 31 Gy.

3-Iodobenzylguanidine↗
PubMed1989

Unusual complications of antithyroid drug therapy: four case reports and review of literature.

Two cases of propylthiouracil-associated acute hepatitis, one case of fatal methimazole-associated hepatocellular necrosis and one case of propylthiouracil-associated lupus-like syndrome are described. The literature related to antithyroid drug side effects and the mechanisms for their occurrence are reviewed and the efficacy and complications of thyroidectomy and radioiodine compared to those of antithyroid drugs. It is concluded that in most circumstances 131I is the therapy of choice for hyperthyroidism.

Adult↗
PubMed1989

Medical treatment of benign and malignant thyroid tumors.

This article discusses the multiple types of benign and malignant thyroid tumors. Benign nodules are subclassified as hypofunctioning or functioning and hyperfunctioning, and the management and treatment of these nodules are outlined. The author also discusses in detail the morphologic types, distinctive prognoses, and responses to therapies of the various malignant tumors.

Humans↗
PubMed1989

Labetalol reduces iodine-131 MIBG uptake by pheochromocytoma and normal tissues.

Iodine-131 metaiodobenzylguanidine [131I]MIBG has proven to be an effective radiopharmaceutical for the scintigraphic localization of pheochromocytomas. Uptake of MIBG is inhibited by blockade of the neuronal uptake pathway for catecholamines ("uptake-1") and by depletion of catecholamine storage vesicle contents, but is not significantly affected by conventional alpha- and beta-adrenoreceptor blocking drugs. Labetalol is an antihypertensive agent with combined alpha- and beta-blocking properties that has been used to manage patients with suspected pheochromocytomas. We report eight patients in whom concurrent or recent therapy with labetalol significantly reduced the uptake of [131I]MIBG into salivary glands, liver, spleen, and general body background. Tumor uptake of MIBG was also reduced in two of the three patients who were proven to have pheochromocytomas. In one case, the effect of labetalol persisted for 36 hr after the drug had been discontinued. The inhibitory effect of labetalol on MIBG uptake in sympathomedullary tissues is likely to be a result of the drug's little-known, additional properties of uptake-1 blockade and depletion of storage vesicle contents, rather than its alpha- or beta-blocking effects. Additionally, labetalol would also appear to hasten clearance of MIBG from other tissues. Labetalol therapy should be discontinued for several days (possibly up to 1 wk) before undertaking [131I]MIBG scintigraphy. A comprehensive list of drugs that should be avoided in patients undergoing MIBG scintigraphy is appended.

3-Iodobenzylguanidine↗