Nestin and vimentin colocalization affects the subcellular location of glucocorticoid receptor in cutaneous melanoma

Aims: Nestin (a neuronal stem cell/progenitor cell marker of central nervous system development), vimentin (which is ubiquitously expressed in mesenchymal cells), and the glucocorticoid receptor (GR, which is involved in the immune response, cell proliferation, and apoptosis) have been shown to interact in embryonic and undifferentiated tissues in modulating cell proliferation. The aim of this study was to analyse nestin, vimentin and GR expression in tumour tissue (melanoma), and their association with clinicopathological variables, to evaluate any effect on tumour progression. Methods and results: Immunohistochemistry, double‐label immunofluorescence and confocal laser scanning microscopy were performed on biopsy specimens of cutaneous melanoma from 81 patients. Fisher’s and Pearson’s tests showed a correlation between nestin, vimentin and subcellular GR location (P = 0.008). Their concomitant expression also correlated with Clark level and thickness (P = 0.02 and P = 0.029, respectively). Kaplan–Meier analysis revealed a poorer outcome for stage III and IV patients with associated expression of nestin, vimentin and cytoplasmic GR in tumour tissue (P = 0.02). Conclusions: These results suggest the presence in melanoma of growth mechanisms involving nestin, vimentin, and GR, similarly to that occurring in embryonic and undifferentiated cells, and may help in understanding tumour biology to provide a molecular basis for clinical therapies.     

Hypothyroid Hashimoto's thyroiditis with scintigraphic and echo-color Doppler features mimicking autonomous adenoma

We investigated a 48-yr-old woman on L-T4 therapy (100 microg/d) for primary autoimmune hypothyroidism, diagnosed 15 yr earlier, presenting a firm oval lump in the right thyroid lobe and symptoms of mild thyrotoxicosis. Free T4, free T3, TSH, anti-thyroperoxidase, anti-TG and anti-thyroid microsomal antibodies were determined. Thyroid US and color flow Doppler sonography (CFDS), 99mTechnetium (99mTc), radioiodine scintiscan and US guided fine needle aspiration cytology (FNAC) were performed. On L-T4 therapy, thyroid function tests showed subclinical hyperthyroidism with high anti-thyroid antibody titers. Thyroid US and CFDS revealed a voluminous hypoechoic hypervascularized nodule with increased peak systolic velocity (type III pattern) in the right lobe; the extranodular tissue volume was markedly reduced and hypoechoic. The presence of an autonomous functioning nodule associated to Hashimoto's thyroiditis (HT) was suspected, L-T4 therapy was temporary withdrawn, and the patient re-evaluated 2 months later. Off L-T4 therapy, thyroid function tests revealed marked primary hypothyroidism, while thyroid US and CFDS were unchanged. 99mTc thyroid scan showed a focal increased uptake corresponding to the nodule in the right lobe with nearly absent uptake in the remaining thyroid tissue. Only a faint, patchy thyroid distribution of 131I was detected by radioiodine scan, and RAIU was very low. Cytological examination by FNAC revealed normal follicular cells and several lymphocytes. The final diagnosis was therefore hypothyroid HT with pseudo-nodular thyroid tissue of the right lobe. To our knowledge, this is the first report of HT mimicking both scintigraphic and CFDS features of an autonomous functioning nodule.     

Italian Society of Hematology practice guidelines for the management of iron overload in thalassemia major and related disorders

New measures of iron accumulation in liver and heart (superconducting quantum inference device and magnetic resonance imaging), and oral iron chelators (deferiprone and deferasirox) are available for managing iron overload in thalassemia major. To assure appropriate use of these new health technologies, the Italian Society of Hematology appointed a panel of experts to produce clinical practice-guidelines for the management of iron overload in thalassemia major and related disorders. The analytical hierarchy process, a technique for multicriteria decision analysis, was applied to relevant key questions in order to identify the alternative strategies, generate explicit criteria for their evaluation, and check how well the alternatives fulfilled the criteria. The result of a comprehensive systematic review of articles released from 1990 to 2007 was used as a source of scientific evidence to compare the decisional options pairwise, and select the final recommendation. Every step in the model was developed from questionnaires and group discussion. The resulting recommendations advise about which examination to carry out in order to plan iron chelation therapy, when to start iron chelation, which iron chelator to choose in regularly transfused patients, how to monitor iron chelation therapy, and when and how to switch standard therapy.     

The usefulness of conventional and echo colour Doppler sonography in the differential diagnosis of toxic multinodular goitres

OBJECTIVE: To assess the potential role of conventional sonography and colour flow Doppler (CFD) sonography (CFDS) in the differential diagnosis of toxic multinodular goitres. SUBJECTS AND METHODS: We investigated 55 patients with untreated hyperthyroidism (24 with typical toxic diffuse goitre of Graves' disease (Group A); 26 with multinodular goitre (Group B); and five with single toxic adenoma (Group C); 22 euthyroid subjects (12 with non-toxic multinodular goitre (Group D) and ten normal subjects (Group E)) were included as controls. In all cases free thyroxine, free tri-iodothyronine, TSH, TSH receptor antibodies (TRAb), anti-thyroperoxidase antibody, anti-thyroglobulin antibodies and anti-thyroid microsomal antibodies were determined and a [(99m)Tc]pertechnetate thyroid scan was performed. RESULTS: Patients with toxic multinodular goitre displayed two different CFDS patterns: 18 patients (Group B-1) had nodules with normal vascularity surrounded by diffuse parenchymal hypoechogenicity with markedly increased CFD signal and maximal peak systolic velocity (PSV) (a pattern similar to Group A patients with Graves' disease); eight patients (Group B-2) had increased intra- and perinodular CFD signal and PSV with normal extranodular vascularity (a pattern similar to that found in Group C patients with single toxic adenoma). Patients of Group B-1 showed a proportion of clinically evident thyroid ophthalmopathy, positive TRAb and other thyroid autoantibodies similar to that observed in Group A patients, while no evidence of thyroid autoimmunity was found in Group B-2. Sixteen out of 18 (89%) patients from Group B-1 displayed a scintiscan pattern of diffuse uneven radionuclide distribution, while seven out of eight (87.5%) of those from Group B-2 had localized uptake in multiple discrete nodules. Taken together, these data strongly suggest that Group B-1 mostly represents patients with the multinodular variant of Graves' disease, while Group B-2 represents patients with non-autoimmune toxic multinodular goitre. CONCLUSIONS: This study shows that combined conventional sonography and CFDS may easily distinguish nodular variants of Graves' disease from non-autoimmune forms of toxic multinodular goitre and confirms the clinical usefulness of this technique in the first-line evaluation of hyperthyroid patients.     

A phase 2 study of the safety, tolerability, and pharmacodynamics of FBS0701, a novel oral iron chelator, in transfusional iron overload

This was a 24-week, multicenter phase-2 study designed to assess safety, tolerability, and pharmacodynamics of FBS0701, a novel oral chelator, in adults with transfusional iron overload. Fifty-one patients, stratified by transfusional iron intake, were randomized to FBS0701 at either 14.5 or 29 mg/kg/d (16 and 32 mg/kg/d salt form). FBS0701 was generally well tolerated at both doses. Forty-nine patients (96%) completed the study. There were no drug-related serious adverse events. No adverse events (AEs) showed dose-dependency in frequency or severity. Treatment-related nausea, vomiting, abdominal pain, and diarrhea were each noted in < 5% of patients. Mean serum creatinine did not change significantly from Baseline or between dose groups. Transaminases wer increased in 8 (16%), three of whom acquired HCV on-study from a single blood bank while five had an abnormal baseline ALT. The 24 week mean change in liver iron concentration (ΔLIC) at 14.5 mg/kg/d was +3.1 mg/g (dw); 29% achieved a decrease in LIC. Mean ΔLIC at 29 mg/kg/d was -0.3 mg/g (dw); 44% achieved a decrease in LIC (P < .03 for ΔLIC between doses). The safety and tolerability profile at therapeutic doses compare favorably to other oral chelators.     

Interaction of child disability and stressful life events in predicting maternal psychological health. Results of an area-based study of very preterm infants at two years corrected age

This study aimed at exploring the relationship between severe neuromotor and/or sensory disability in very preterm infants assessed at 2 years corrected age and their mothers’ psychological health. Data on 581 Italian singletons born at 22–31 weeks of gestation in five Italian regions and their mothers were analyzed. Maternal psychological distress was measured through the General Health Questionnaire short version (GHQ-12). The prevalence of any maternal distress (GHQ scores ≥ 2) and of clinical distress (scores ≥ 5) were 31.3% and 8.1% respectively. At multivariable analysis, we found a statistically significant association between child's disability and mothers’ GHQ scoring ≥5 (OR 3.45, 95% CI 1.07–11.15). Also lower maternal education appeared to increase the likelihood of psychological distress (OR 1.38, 95% CI 1.14–1.66). The impact of child disability was weaker in women who had experienced additional stressful life events since delivery, pointing to the existence of a “ceiling” effect. Maternal psychological assessment and support should be included in follow-up programs targeting very preterm infants.