Three Endocrine Neoplasms: An Unusual Combination of Pheochromocytoma, Pituitary Adenoma, and Papillary Thyroid Carcinoma

Background: Three endocrine neoplasms?bilateral pheochromocytomas, somatotrophic pituitary adenoma inducing acromegaly, and papillary carcinoma of the thyroid?occurred concurrently in a patient. A genetic mutation was hypothesized. Possible previously described genetic mutations were explored. Methods: Clinical assessments, laboratory data, images of tumors, histopathology, and immunohistochemistry of excised tissues documented the three neoplasms. Clinical assessment of the patient, family history, and a review of the literature sought a familial basis for the disorders. Results: The methods confirmed the presence of three endocrine neoplasms. Each neoplasm was surgically excised and histologically verified. Surgical and 131I treatments reduced the papillary carcinoma, but eventually this tumor progressed to a lethal degree. History, including that of nine siblings, uncovered no familial neoplasms. No similar case was found in the literature, but possible associations with germline mutations were considered. Conclusions: The concurrent development of pheochromocytomas, pituitary somatotrophic adenoma, and papillary thyroid carcinoma appears to be unique. Nevertheless, such tumors, particularly bilateral pheochromocytomas, strongly suggest a de novo germline mutation in a gene not previously associated with multiple endocrine neoplasia syndromes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98488/1/thy%2E2011%2E0345.pd

Rare Clinical Entity: Metastatic malignant struma ovarii diagnosed during pregnancy – Lessons for management

Abstract Background Malignant struma ovarii is an ovarian teratoma containing at least 50% thyroid tissue which has the potential to metastasize and produce thyroid hormone. Given its rarity, management strategies are not well-established. We report a case of metastatic malignant struma ovarii discovered during pregnancy with lessons for evaluation and management. Case presentation A 30-year-old woman who was two months pregnant was discovered to have struma ovarii with over half of the struma comprised of papillary thyroid cancer. Following tumor resection, delivery, and thyroidectomy, she underwent evaluation with stimulated thyroglobulin testing and diagnostic staging sodium iodide-131 scan (I-131), which revealed the presence of skeletal metastases. Following administration of 320 mCi I-131, post-therapy scan also showed miliary pulmonary metastases with improved ability to localize the bony and pulmonary metastases with concurrent SPECT/CT imaging. A second dosimetry-guided I-131 therapy resulted in complete resolution of pulmonary metastases; however, small foci of residual bone disease persisted. Post-therapy scans demonstrated additional findings not shown on diagnostic I-131 scans obtained prior to both her initial and second I-131 therapy. Conclusions SPECT/CT provides accurate anatomic correlation and localization of metastatic foci and can serve as a baseline study to assess interval response to treatment. Post-therapy scans should always be obtained when I-131 treatment is administered, as additional findings may be revealed versus low dose I-131 activity diagnostic scans. This patient had a high metastatic burden that would not have been discovered in a timely fashion with the conservative approach advocated by others. Thyroidectomy followed by a diagnostic staging radioiodine scan and a stimulated thyroglobulin level should be considered in patients with malignant struma ovarii for guiding therapeutic I-131 administration as metastatic risk is difficult to predict based on histopathologic examination.https://deepblue.lib.umich.edu/bitstream/2027.42/144518/1/40842_2018_Article_64.pd

Promotion of retroviral entry in the absence of envelope protein by chlorpromazine

AbstractRetrovirus packaging cell lines that express the Moloney murine leukemia virus gag, pol, and env genes and a retroviral vector genome can produce virus particles that are capable of transducing cells. Normally if the packaging cell line does not produce a functional viral fusion glycoprotein, such as the retroviral envelope protein or a foreign viral glycoprotein, then the viruses will be incapable of transducing cells. We have found that incubating envelope protein-deficient virus particles bound to cells with chlorpromazine leads to transduction. Chlorpromazine (CPZ) is a membrane-active reagent that is commonly used to induce the hemifusion to fusion transition when membrane fusion is mediated by partially defective viral glycoproteins. The concentration and pH dependence of the promotion of transduction by CPZ is consistent with a role for CPZ micelle formation in viral entry. These data indicate that caution is warranted when experiments concerning membrane fusion completion promoted by CPZ are analyzed

Prediction of Therapy Tumor-Absorbed Dose Estimates in I-131 Radioimmunotherapy Using Tracer Data Via a Mixed-Model Fit to Time Activity

Abstract Background: For individualized treatment planning in radioimmunotherapy (RIT), correlations must be established between tracer-predicted and therapy-delivered absorbed doses. The focus of this work was to investigate this correlation for tumors. Methods: The study analyzed 57 tumors in 19 follicular lymphoma patients treated with I-131 tositumomab and imaged with SPECT/CT multiple times after tracer and therapy administrations. Instead of the typical least-squares fit to a single tumor's measured time-activity data, estimation was accomplished via a biexponential mixed model in which the curves from multiple subjects were jointly estimated. The tumor-absorbed dose estimates were determined by patient-specific Monte Carlo calculation. Results: The mixed model gave realistic tumor time-activity fits that showed the expected uptake and clearance phases even with noisy data or missing time points. Correlation between tracer and therapy tumor-residence times (r=0.98; p<0.0001) and correlation between tracer-predicted and therapy-delivered mean tumor-absorbed doses (r=0.86; p<0.0001) were very high. The predicted and delivered absorbed doses were within±25% (or within±75 cGy) for 80% of tumors. Conclusions: The mixed-model approach is feasible for fitting tumor time-activity data in RIT treatment planning when individual least-squares fitting is not possible due to inadequate sampling points. The good correlation between predicted and delivered tumor doses demonstrates the potential of using a pretherapy tracer study for tumor dosimetry-based treatment planning in RIT.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98438/1/cbr%2E2011%2E1053.pd

Biological-Effect Modeling of Radioimmunotherapy for Non-Hodgkins Lymphoma: Determination of Model Parameters

Treatment with Tositumomab and 131I tositumomab anti-CD20 radioimmunotherapy (Bexxar) yields a nonradioactive antibody antitumor response (the so-called cold effect) and a radiation response. Numerical parameter determination by least-squares (LS) fitting was implemented for more accurate parameter estimates in equivalent biological-effect calculations. Methods: One hundred thirty-two tumors in 37 patients were followed using five or six SPECT/CT studies per patient, three each (typical) post-tracer (0.2 GBq) and post-therapy (?3 GBq) injections. The SPECT/CT data were used to calculate position- and time-dependent dose rates and antibody concentrations for each tumor. CT-defined tumor volumes were used to track tumor volume changes. Combined biological-effect and cell-clearance models were fit to tumor volume changes. Optimized parameter values determined using LS fitting were compared to previous fitted values that were determined by matching calculated to measured tumor volume changes using visual assessment. Absorbed dose sensitivity (α) and cold-effect sensitivity (?p) parameters were the primary fitted parameters, yielding equivalent biological-effect (E) values. Results: Individual parameter uncertainties were approximately 10% and 30% for α and ?p, respectively. LS versus previously fit parameter values were highly correlated, although the averaged α value decreased and the averaged ?p value increased for the LS fits compared to the previous fits. Correlation of E with 2-month tumor shrinkage data was similar for the two fitting techniques. The LS fitting yielded improved fit quality and likely improved parameter estimation.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140326/1/cbr.2012.1467.pd

Reduction and reconstruction of stochastic differential equations via symmetries

An algorithmic method to exploit a general class of infinitesimal symmetries for reducing stochastic differential equations is presented and a natural definition of reconstruction, inspired by the classical reconstruction by quadratures, is proposed. As a side result the well-known solution formula for linear one-dimensional stochastic differential equations is obtained within this symmetry approach. The complete procedure is applied to several examples with both theoretical and applied relevance

The smart home: how consumers craft new service networks by combining heterogeneous smart domestic products

Service research suggests homes are becoming increasingly connected as consumers automate and personalize new forms of service provision. Yet large-scale empirical evidence on how and why consumers automate smart domestic products is lacking. To address this knowledge gap we analyze 13,905 consumer-crafted, automated combinations of smart domestic products, totaling 1,144,094 installations, across 253 separate service providers on the Web service IFTTT.com. An exploratory network analysis examines the topology of the network and an interpretive coding exercise reveals how consumers craft different styles of human-computer interaction to co-create value. The results reveal the smart domestic product network is disassortative, imbalanced, has a long-tailed degree distribution, and that popular services have high centrality across all product category combinations. We show that popular combinations of smart domestic products are primarily motivated by utilitarian value seeking enacted through a preference for automated tasks outside of conscious attention, though more individualistic combinations are slightly more likely to be hedonistically inclined. We conclude by showing how these consumer-crafted forms of service provision within domestic environments reveal design redundancy and opportunities for service innovation

Measuring latency distribution of transcallosal fibers using transcranial magnetic stimulation

Background: Neuroimaging technology is being developed to enable non-invasive mapping of the latency distribution of cortical projection pathways in white matter, and correlative clinical neurophysiological techniques would be valuable for mutual verification. Interhemispheric interaction through the corpus callosum can be measured with interhemispheric facilitation and inhibition using transcranial magnetic stimulation. Objective: To develop a method for determining the latency distribution of the transcallosal fibers with transcranial magnetic stimulation. Methods: We measured the precise time courses of interhemispheric facilitation and inhibition with a conditioning-test paired-pulse magnetic stimulation paradigm. The conditioning stimulus was applied to the right primary motor cortex and the test stimulus was applied to the left primary motor cortex. The interstimulus interval was set at 0.1 ms resolution. The proportions of transcallosal fibers with different conduction velocities were calculated by measuring the changes in magnitudes of interhemispheric facilitation and inhibition with interstimulus interval. Results: Both interhemispheric facilitation and inhibition increased with increment in interstimulus interval. The magnitude of interhemispheric facilitation was correlated with that of interhemispheric inhibition. The latency distribution of transcallosal fibers measured with interhemispheric facilitation was also correlated with that measured with interhemispheric inhibition. Conclusions: The data can be interpreted as latency distribution of transcallosal fibers. Interhemispheric interaction measured with transcranial magnetic stimulation is a promising technique to determine the latency distribution of the transcallosal fibers. Similar techniques could be developed for other cortical pathways