Graves' ophthalmopathy

A 40-year-old woman who recently received a diagnosis of Graves' disease comes for a follow-up visit. She has been taking methimazole, at a dose of 10 mg daily, and is now euthyroid, but for the past 3 months, she has had bothersome eye symptoms, including redness, tearing, grittiness, photophobia, diplopia at the extremes of gaze, and ocular pain with eye movements. She smokes 10 cigarettes per day. Examination reveals exophthalmos, swelling of periorbital tissues, and limitation of eye movements. How should Graves' ophthalmopathy be managed

Risk Factors Associated with the Severity of Thyroid-Associated Orbitopathy in Korean Patients

Risk Factors Associated with the Severity of Thyroid-Associated Orbitopathy in Korean Patientsope

Il ricorso all'art. 28 Stat. lav. nella stagione del dissenso sindacale.

La tesi si propone di comprendere e svelare le dinamiche del conflitto intersindacale una volta trasposto sul piano processuale. In particolare, si cercherà di analizzare, in assenza di regole certe e trascendenti il mero diritto civile, in quale circostanza si possa fare ricorso all’art. 28 per denunciare gli inadempimenti del datore di lavoro rispetto ai diritti inderogabili della libertà e del pluralismo sindacale, soprattutto nel caso in cui il comportamento della parte datoriale sembra costituire “un’opposizione nel conflitto” e non una sua repressione tout court, di cui autorevole dottrina ne ha sostenuto l’indefettibile sussistenza ai fini dell’esperibilità dello strumento processuale in parola. Attraverso la disamina delle pronunce giurisprudenziali che si sono susseguite in epoca recente, potremo dar conto di alcune rilevanti problematiche che si sono riproposte in modo dirompente dopo anni di relativa calma e che hanno trovato origine nel dissenso manifestato da uno dei sindacati maggiormente rappresentativi sul piano nazionale nei confronti delle politiche di revisione delle relazioni industriali intrapreso da Fiat. Scopo della nostra indagine sarà, infatti, quello di esaminare i punti più controversi che sono emersi dopo l’avvento degli accordi separati, con la cui espressione intendiamo, cioè, un contratto collettivo non stipulato da tutte le organizzazioni sindacali storicamente rappresentative. In particolare, cercheremo di verificare l’ambito di efficacia dei contratti sottoscritti in modo non unitario, alla luce della mancata attuazione del IV° comma art. 39 Cost. Inoltre, sarà necessario individuare quali sono i principi che, nel nostro ordinamento, governano le relazioni intercorrenti tra i soggetti antagonisti nella fase negoziale e che orientano, pertanto, il giudizio circa l’antisindacalità di una condotta datoriale. In egual maniera, vaglieremo se e in quali casi l’attuazione di un contratto separato da parte del datore di lavoro possa integrare gli estremi di una condotta antisindacale. Infine, occorre stabilire se, a seguito della mancata stipulazione di un contratto da parte di un sindacato sicuramente rappresentativo, costituisce una condotta illecita l’aver negato il diritto di cittadinanza in azienda a tale organizzazione in forza di quanto dispone l’art. 19 Stat. lav. dopo la sua modifica referendaria del 1995. A tali quesiti cercheremo, pertanto, nel modo più esaustivo possibile, di rispondere nelle pagine che seguiranno anche mediante l’opera di interpretazione fornita sia dalla giurisprudenza che dalla dottrina, la cui soluzione rappresenta, altresì, l’obiettivo di fondo del presente elaborato

The onset time of amiodarone-induced thyrotoxicosis (AIT) depends on AIT type

Objective: Considering the different pathogenic mechanisms of the two main forms of amiodarone-induced thyrotoxicosis (AIT), we ascertained whether this results in a different onset time as well. Design and methods: We retrospectively analyzed the clinical records of 200 consecutive AIT patients (157 men and 43 women; mean age 62.2G12.6 years) referred to our Department from 1987 to 2012. The onset time of AIT was defined as the time elapsed from the beginning of amiodarone therapy and the first diagnosis of thyrotoxicosis, expressed in months. Factors associated with the onset time of AIT were evaluated by univariate and multivariate analyses. Results: The median onset time of thyrotoxicosis was 3.5 months (95% CI 2–6 months) in patients with type 1 AIT (AIT1) and 30 months (95% CI 27–32 months, P!0.001) in those with type 2 AIT (AIT2). Of the total number of patients, 5% with AIT1 and 23% with AIT2 (PZ0.007) developed thyrotoxicosis after amiodarone withdrawal. Factors affecting the onset time of thyrotoxicosis were the type of AIT and thyroid volume (TV). Conclusions:ThedifferentpathogenicmechanismsofthetwoformsofAITaccountfordifferentonsettimesofthyrotoxicosisin the two groups. Patients with preexisting thyroid abnormalities (candidate to develop AIT1) may require a stricter follow-up during amiodarone therapy than those usually recommended. In AIT1, the onset of thyrotoxicosis after amiodarone withdrawal is rare, while AIT2 patients may require periodic tests for thyroid function longer after withdrawing amiodarone

A novel method for assessing adherent single-cell stiffness in tension: design and testing of a substrate-based live cell functional imaging device

Various micro-devices have been used to assess single cell mechanical properties. Here, we designed and implemented a novel, mechanically actuated, two dimensional cell culture system that enables a measure of cell stiffness based on quantitative functional imaging of cell-substrate interaction. Based on parametric finite element design analysis, we fabricated a soft (5kPa) polydimethylsiloxane (PDMS) cell substrate coated with collagen-I and fluorescent micro-beads, thus providing a favorable terrain for cell adhesion and for substrate deformation quantification, respectively. We employed a real-time tracking system that analyzes high magnification images of living cells under stretch, and compensates for gross substrate motions by dynamic adjustment of the microscope stage. Digital image correlation (DIC) was used to quantify substrate deformation beneath and surrounding the cell, leading to an estimate of cell stiffness based upon the ability of the cell to resist the applied substrate deformation. Sensitivity of the system was tested using chemical treatments to both "soften” and "stiffen” the cell cytoskeleton with either 0.5μg/ml Cytochalasin-D or 3% Glutaraldehyde, respectively. Results indicate that untreated osteosarcoma cells (SAOS-2) exhibit a 1.5 ± 0.7% difference in strain from an applied target substrate strain of 8%. Compared to untreated cells, those treated with Cyochalasin-D passively followed the substrate (0.5 ± 0.5%, p < 0.001), whereas Glutaraldehyde enhanced cellular stiffness and the ability to resist the substrate deformation (2.9 ± 1.6%, p < 0.001). Nano-indentation testing showed differences in cell stiffness based on culture treatment, consistent with DIC findings. Our results indicate that mechanics and image analysis approaches do hold promise as a method to quantitatively assess tensile cell constitutive propertie

Continuation of amiodarone delays restoration of euthyroidism in patients with type 2 amiodarone-induced thyrotoxicosis treated with prednisone: a pilot study

Context: Type 2 amiodarone-induced thyrotoxicosis (AIT) is a destructive thyroiditis usually re- sponsive to glucocorticoids. Whether continuation of amiodarone affects treatment outcome is unsettled. Objective: The objective of the study was to compare the outcome of glucocorticoid treatment in type 2 AIT patients who continued or withdrew amiodarone. Design: This was a matched retrospective cohort study. Setting: The study was conducted at a university center. Patients: Eighty-three consecutive patients with untreated type 2 AIT participated in the study. After matching with patients continuing amiodarone (AMIO-ON, n 8), patients interrupting amiodarone were randomly selected in a 4:1 ratio (AMIO-OFF, n 32). Intervention: All patients were treated with oral prednisone. Patients whose thyrotoxicosis re- curred after glucocorticoid withdrawal were treated with a second course of prednisone. Main Outcome Measure: Time and rate of cure were measured. Results: Median time to the first normalization of serum thyroid hormone levels did not signifi- cantly differ in AMIO-ON and AMIO-OFF patients (24 and 31 d, respectively; P 0.326). Conversely, median time for stably restoring euthyroidism was 140 d in AMIO-ON patients and 47 d in AMIO- OFF patients (log rank, P 0.011). In fact, AIT recurred in five of seven AMIO-ON patients (71.4%) and in only three of 32 AMIO-OFF patients (9.4%, P 0.002), requiring readministration of pred- nisone. One AMIO-ON patient never reached thyroid hormone normalization during the study period. Factors associated with glucocorticoid failure were thyroid volume and amiodarone continuation. Conclusions: Prednisone restores euthyroidism in most type 2 AIT patients, irrespective of amio- darone continuation or withdrawal. However, continuing amiodarone increases the recurrence rate of thyrotoxicosis, causing a delay in the stable restoration of euthyroidism and a longer exposure of the heart to thyroid hormone exces

Regulatory T cells in the pathogenesis of graves' disease

Maintaining a delicate balance between the prompt immune response to pathogens and tolerance towards self-antigens and commensals is crucial for health. T regulatory (Treg) cells are pivotal in preserving self-tolerance, serving as negative regulators of inflammation through the secretion of anti-inflammatory cytokines, interleukin-2 neutralization, and direct suppression of effector T cells. Graves' disease (GD) is a thyroid-specific autoimmune disorder primarily attributed to the breakdown of tolerance to the thyroid-stimulating hormone receptor. Given the limitations of currently available GD treatments, identifying potential pathogenetic factors for pharmacological targeting is of paramount importance. Both functional impairment and frequency reduction of Tregs seem likely in GD pathogenesis. Genome-wide association studies in GD have identified polymorphisms of genes involved in Tregs' functions, such as CD25 (interleukin 2 receptor), and Forkhead box protein P3 (FOXP3). Clinical studies have reported both functional impairment and a reduction in Treg frequency or suppressive actions in GD, although their precise involvement remains a subject of debate. This review begins with an overview of Treg phenotype and functions, subsequently delves into the pathophysiology of GD and into the existing literature concerning the role of Tregs and the balance between Tregs and T helper 17 cells in GD, and finally explores the ongoing studies on target therapies for GD