An Unlikely Source of Iodine Uptake: A Bronchogenic Cyst Masquerading as Metastatic Thyroid Cancer.

Radioactive iodine therapy and posttreatment scanning are essential components of differentiated thyroid carcinoma treatment and detection of metastatic disease. False-positive results can be seen on an I-131 scan and are important for clinicians to be aware of. Here, we present a case of a 33-year-old female with follicular thyroid carcinoma who was noted to have an area of moderate uptake in the chest on a whole-body scan following remnant ablation with 30 mCi of I-131 (1.11GBq) concerning for a metastatic hilar lymph node. This was determined to be a mediastinal bronchogenic cyst on surgical pathology. It has been previously proposed that the expression of sodium iodide symporters in some bronchogenic cysts could be the mechanism by which iodine uptake is seen within them. We were able to demonstrate positive immunohistochemical staining for both sodium iodide symporter and the associated paired box gene 8 transcription factor in the cyst sample, which supports the proposed theory.

Engaging the Great Circle: a qualitative study of the Confederated Tribes of Grand Ronde's mobile medication unit

BACKGROUND: The Confederated Tribes of the Grand Ronde Community of Oregon began a Mobile Medication Unit (MMU) as part of their Great Circle Recovery Opioid Treatment Program (OTP) to address elevated rates of opioid use disorder (OUD) among American Indians and Alaska Natives in Oregon. The MMU provides methadone or buprenorphine for individuals with OUD, enrolled in the OTP, who are living either on the reservation or in surrounding rural communities. An implementation study describes the service through document review and qualitatively assesses patient and staff experiences and the perceived barriers and facilitators to mobile services. METHODS: Semi-structured qualitative interviews with patients (n = 11), MMU staff (n = 5), and the state opioid treatment authority (n = 1) gathered details on the initiative's development and operations. Provider interviews probed implementation experiences. Patient interviews focused on their experiences with the MMU and staff, changes in quality of life and recommendations for enhancing treatment. Interviews were transcribed and analysed using a Thematic Analysis approach. RESULTS: Staff themes identified two driving forces (i.e. staff desire for an inclusive approach to wellness that is accessible to all community members; the catalysts for the MMU), two steps toward MMU development (i.e. Tribal approvals and support; the construction and maintenance of community relationships) and two perspectives on MMU implementation and impact (i.e. initial implementation barriers; facilitators and observations of how the MMU reduced stigma associated with agonist therapy). Patients' themes noted the MMU's professional and 'caring' environment, accessible rural locations and general suggestions including culturally responsive ancillary services. CONCLUSION: The Great Circle MMU enhanced access to opioid agonist therapy for people with OUD (i.e. American Indians/Alaska Natives, and non-natives) living in rural communities. The Confederated Tribes of Grand Ronde operates the first Tribally owned OTP MMU, grounded in cultural humility and committed to Tribal members and the great circle of the larger community.

MMP-2 regulates Erk1/2 phosphorylation and aortic dilatation in Marfan syndrome.

RATIONALE: Aneurysm and dissection of the ascending thoracic aorta are the main cardiovascular complications of Marfan syndrome (MFS) resulting in premature death. Studies using mouse models of MFS have shown that activation of transforming growth factor-beta (TGF-ß) and the concomitant upregulation of matrix metalloproteinases (MMPs) contribute to aneurysm development. Our previous study showed that doxycycline delayed aneurysm rupture in a mouse model of MFS, Fbn1(mgR/mgR). Losartan has been shown to prevent aneurysms in another mouse model of MFS, Fbn1(C1039G/+), through inhibition of the Erk1/2 pathway. However, the role of MMP-2 in MFS and effect of losartan on the lifespan of MFS mice remain unknown. OBJECTIVE: We investigated the role of MMP-2 in MFS and compared the effects of losartan and doxycycline on aortic dilatation and survival in Fbn1(mgR/mgR) mice. METHODS AND RESULTS: By life table analysis, we found that losartan and doxycycline improved the survival of Fbn1(mgR/mgR) mice. Gelatin zymography and Western blot data showed that only doxycycline inhibited MMP-2 expression, whereas both drugs decreased Erk1/2 phosphorylation. When combined, only one of nine mice died within the 30-week study; aortic histology and diameter were normalized and the effects on Smad2 phosphorylation was additive. To further explore the role of MMP-2 in MFS, we created MMP-2-deficient Fbn1(mgR/mgR) mice. MMP-2 deletion inhibited activation of TGF-ß and phosphorylation of Erk1/2 and Smad2 and prolonged the lifespan of the mice. CONCLUSIONS: These studies demonstrated that inhibition of MMP-2 by doxycycline delayed the manifestations of MFS, in part, through its ability to decrease active TGF-ß and the noncanonical signaling cascade downstream of TGF-ß. This study further suggested that targeting TGF-ß signaling at different points might be a more effective strategy for inhibiting disease progression.

Blocking TNF-alpha attenuates aneurysm formation in a murine model.

Abdominal aortic aneurysm (AAA) is one of a number of diseases associated with a prominent inflammatory cell infiltrate and local destruction of structural matrix macromolecules. This chronic infiltrate is predominately composed of macrophages and T lymphocytes. Activated macrophages produce a variety of cytokines, including TNF-alpha. Elevated levels of TNF-alpha were observed in patients with AAA, suggesting that TNF-alpha may play a role in the pathogenic mechanisms of AAA. In the present study, we investigated the role of TNF-alpha in AAA formation. By studying a murine aneurysm model, we found that both mRNA and protein levels of TNF-alpha were increased in aneurysm tissue compared with normal aortic tissues. Therefore, we tested the response of mice lacking expression of TNF-alpha. These mice were resistant to aneurysm formation. Our results show that TNF-alpha deficiency attenuates matrix metalloproteinase (MMP) 2 and MMP-9 expression and macrophage infiltration into the aortic tissue. These data suggest that TNF-alpha plays a central role in regulating matrix remodeling and inflammation in the aortic wall leading to AAA. In addition, we investigated the pharmacological inhibition of AAA. A Food and Drug Administration-approved TNF-alpha antagonist, infliximab, inhibited aneurysm growth. Our data also show that infliximab treatment attenuated elastic fiber disruption, macrophage infiltration, and MMP-2 and MMP-9 expression in aortic tissue. This study confirms that a strategy of TNF-alpha antagonism may be an important therapeutic strategy for treating AAA.

Inhibition of reactive oxygen species attenuates aneurysm formation in a murine model.

Reactive oxygen species (ROS) are increased in human abdominal aortic aneurysms (AAA). NADPH oxidases are the predominant source of superoxide anion (O(2)(-)) in the vasculature. Inducible nitric oxide synthase (iNOS) produces a significant amount of nitric oxide (NO) during inflammatory processes. We hypothesized that ROS produced by NADPH oxidases and iNOS played an important role in aneurysm formation. We examined this hypothesis using selective blockade of NADPH oxidases and iNOS in a murine model of AAA. Mice, including C57BL/6, iNOS knockout (iNOS(-/-)) mice, and its background matched control (C57BL/6), underwent AAA induction by periaortic application of CaCl(2). Aortic diameter was measured at aneurysm induction and harvest. Beginning 1 week prior to aneurysm induction and continuing to aortic harvest 6 weeks later, one group of the C57BL/6 mice were treated with orally administered apocynin (NADPH oxidase inhibitor). Control mice were given water. The mean diameter and change in diameter of each group were compared with concurrent controls. Aortic levels of the NO metabolite, NO(x) (NO(2) and NO(3)), were significantly increased in CaCl(2)-treated wild type mice. INOS(-/-) mice were partly resistant to aneurysm induction. This was associated with reduced expression of matrix metalloproteinase (MMP)-2 and MMP-9 and decreased production of NO(x) in the aortic tissues. Inhibition of NADPH oxidase by apocynin also blocked aneurysm formation. In conclusion, both iNOS deficiency and NADPH oxidase inhibition suppressed aneurysm formation in association with decreased NO(x) levels. These studies suggest that both NADPH oxidase and iNOS pathways contribute to ROS production and AAA development.

Construction of cDNA libraries from microdissected benign and malignant thyroid tissue.

cDNA libraries were constructed from thyroid epithelial cells gained by laser capture microdissection for gene expression analysis of the progression of thyroid cancer. Six histologically diverse thyroid tissue specimens were used. A mean of 93 ng of total RNA was gained per tissue sample from a mean estimated number of 25,000 microdissected cells per sample. Analysis of randomly selected clones from six libraries showed an average insert size of 600 (range, 300-1500) bp. Preliminary sequencing of clones selected from the six libraries indicates a range of 46% to 62% known genes per library, 4% to 25% anonymous expressed sequence tags per library, and 15% to 43% novel expressed sequence tags per library. Thyroglobulin was found in normal thyroid epithelium and follicular thyroid adenoma, whereas calcitonin precursor transcripts were found in medullary thyroid carcinoma. We demonstrate production of high-quality cDNA libraries of microdissected tissue of the thyroid, which should prove useful for gene expression analysis of human thyroid tumors.