A somatic mutation in the thyrotropin receptor gene in a patient with an autonomous nodule within a multinodular goiter

Thyrotropin (TSH) is the prime regulator of thyroid cell growth and function and acts through the thyrotropin receptor (TSHR) located on the surface membrane of thyrocytes. Somatic heterozygous mutations that cause TSHR activation in the absence of TSH have been found in toxic adenomas and in hot nodules of multinodular goiters. Clinically and histologically heterogeneous nodules can share common gain-of-function mutations. Mutation prevalence varies greatly and is inversely related to iodine intake of the population. We report a Greek patient presenting with subclinical hyperthyroidism due to a fast-growing autonomous hyperplastic nodule in a long-standing multinodular goiter. Direct DNA sequencing showed that the hot nodule harbored a somatic heterozygous activating TSHR mutation: substitution of glutamine for leucine in the third transmembrane helix. This mutation (L512Q) was recently described in two solitary toxic adenomas. This report expands the spectrum of mutations shared by dissimilar hot nodules, supporting a common mechanism for nonautoimmune thyroid autonomy. The identification of the L512Q substitution demonstrates that gain-of-function TSHR mutations are encountered in Greece, although iodine deficiency has been significantly corrected over the last three decades.     

A morphometric evidence for a hyperfunctioning mesolimbic system in an animal model of ADHD

The hyperfunctioning dopamine hypothesis in the mesocorticolimbic (MCL) system has been addressed by a neurogenetic approach in model systems. Thus, a morphometric analysis was carried out on neurons of origin of Substantia Nigra (SN) and Ventral Tegmental Area (VTA) dopamine systems of the Naples High-Excitability (NHE), Low-Excitability (NLE) and control lines. Male adult rats were tested in a spatial novelty for indices of activity and non-selective attention. Mesencephalic coronal sections were processed for tyrosine hydroxylase (TH) immunohistochemistry and cytochromoxidase (C.O.) histochemistry. Image analysis in the rostro-caudal plane showed (i) a higher neuron size of TH+ elements in the VTA of NHE and NLE, across the entire structure in the NHE, and only in the middle portion in the NLE; (ii) a higher expression of TH in the neuropil of the VTA in NHE; (iii) a lower C.O. activity in both NLE and NHE; (iv) no differences in the SN. The larger neuron size in both NHE and NLE rats as compared with control rats, along with higher TH expression mainly in the NHE, in absence of any relevant alteration in the SN, reveals an unbalance between the two dopamine systems and a subsequent alteration in limbic (reward, motivation, sustained attention) functions. The decreased C.O. activity might be due to reduced feedback inhibition by striatal GABA neurons and interneurons leading to increased DA neuron firing. In conclusion, the increased behavioral activity and impaired attention observed in the NHE rats are associated to hyperfunctioning MCL system in this genetic model of Attention-Deficit Hyperactivity Disorder (ADHD).     

A phase II study of capecitabine plus oxaliplatin (XELOX)

Background: Capecitabine and oxaliplatin are both effective and well-tolerated monotherapies for the treatment of advanced colorectal cancer (CRC). Oxaliplatin has also been shown to be very effective when combined with 5-FU/LV in the first-line setting. Aim of the Study: Assess the efficacy and safety of capecitabine plus oxaliplatin (XELOX) in patients with previously untreated advanced CRC. Methods: Fifty-three patients with measurable disease received capecitabine 1,000 mg/m² twice daily on d 1–14 and oxaliplatin 130 mg/m² on d 1, every 3 wk. Of these, 52 were evaluable for safety and 49 for antitumor response. Results: There was a low rate of grade 1/2 adverse events; grade 3/4 events included leukopenia (10%), neutropenia (6%), thrombocytopenia (2%), nausea/vomiting (4%), and diarrhea (4%). The overall response rate was 39% (95% CI, 25–54%) and median time to disease progression was 7.8 mo. Conclusions: XELOX is an active and well-tolerated first-line treatment for advanced CRC. Randomized phase III studies are ongoing to compare XELOX with FOLFOX in view of the comparable efficacy and safety but superior convenience of XELOX therapy.     

Changing organisations: a study of the context and processes of mergers of health care providers in England

This paper presents findings from a study of the context and processes of provider mergers in the NHS in England. Mergers are an example of organisational restructuring, a key lever for change in the UK health care sector and elsewhere, although it is only one strategy for organisational change. The framework for the study is key themes from the organisational change literature: the complexity of the effects of change; the importance of context; and the role of organisational culture. The drivers for health care mergers and the evidence for these are analysed. Using documentary analysis and in-depth qualitative interviews with internal and external stakeholders, the first part of the paper reports on stated and unstated drivers in nine mergers. This provides the context for four in-depth case studies of the process of merger in the second and third years post-merger. Our study shows that the contexts of mergers, including drivers of change, are important. Merger is a process without clear boundaries, and this study shows problems persisting into the third year post-merger. Loss of management control and focus led to delays in service developments. Difficulties in the merger process included perceived differences in organisational culture and perceptions of 'takeover' which limited sharing of 'good practice' across newly merged organisations. Merger policy was based on simplistic assumptions about processes of organisational change that do not take into account the dynamic relationship between the organisation and its context and between the organisation and individuals within it. Understanding the process of merger better should lead to a more cautious approach to the likely gains, provide understanding of the problems that are likely in the period of change, and anticipate and avoid harmful consequences.     

Fatal Chest Injury with Lung Evisceration during Athletic Games in Ancient Greece

The “Olympic idealism” that dominates modern athletic culture is a myth. The true aims of the athletes in ancient Greece were rewards and life-long appointments to various positions in the military or the city administration. Competitions in the athletic games included, among others, wrestling, boxing, and pangration (a combination of wrestling and boxing). Occasionally, these games resulted in severe trauma or death. Two cases of extreme violence resulting in fatal chest trauma are presented and commented on from both surgical and social points of view.     

Clinical efficacy of distigmine bromide in the treatment of patients with underactive detrusor

Purpose: The aim of this study was to assess the clinical efficacy of distigmine bromide, an anti-cholinesterase agent, deemed to improve detrusor function thereby restoring normal voiding patterns in patients suffering from detrusor underactivity. Materials and methods: A total of 27 patients (11 men and 16 women) with poor detrusor function were included in the study. The diagnosis was established using pressure-flow studies. All patients received distigmine bromide at a dose of 5 mg three times daily for 4 weeks and re-attended for a follow-up urodynamic investigation. The results of baseline pressure-flow studies were compared to those after completion of treatment. Results: Treatment with distigmine bromide resulted in a statistically significant reduction of residual volume and percent residual volume, obviating the need for intermittent self-catheterisation in 11 patients. In addition, maximum flow rate and detrusor pressure at maximum flow increased, although not significantly. The drug was generally well tolerated by the majority of patients. Conclusion: Distigmine bromide shows clinical efficacy in patients with poor detrusor function and may therefore be used alternatively in selected cases.     

Prevalence of overweight and obesity among children and adolescents in Thessaloniki-Greece and Kayseri-Turkey

The aim of this study was to investigate the prevalence of overweight and obesity among children and adolescents in the city of Thessaloniki, Greece and in the Kayseri area of Turkey and compare the results. For this purpose, data concerning the weight and height of 2458 Greek school children aged 6-17 years (1226 6-10 years, 1232 11-17 years) and 3703 Turks (1032 6-10 years, 2671 11-17 years) were collected. BMI was calculated. The prevalence of overweight Greek schoolchildren was 22.2% while that of Turks was 10.6%. The obesity prevalence was 4.1% and 1.6%, respectively (total overweight and obese children 26.3% and 12.2%, respectively). In the analyses, the estimations of the prevalence of overweight and obesity are based on the international BMI percentile curves and cut-off points in subjects aged 2-18 years recently established. A significant gender difference was found, males being more overweight and obese compared to females. Finally, the prevalences for both Greeks and Turks were higher in children when compared to adolescents. In conclusion, Greece (as represented by the Thessaloniki area) has one of the highest prevalences of overweight schoolchildren recorded in Europe while Turkey (as represented by Kayseri area) one of the lowest recorded among developed and developing countries. Differences in lifestyle and socioeconomic status in the two regions are most probably responsible for these results.