A new concurrent chemotherapy with vinorelbine and mitomycin C in combination with radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck

Objective: The purpose of this pilot study was to evaluate the feasibility and toxicity of concurrent chemotherapy with vinorelbine and mitomycin C in combination with accelerated radiotherapy (RT) in patients with locally advanced cancer of the head and neck. Patients and Methods: Between January 2003 and March 2004, 15 patients with T4/N2-3 squamous cell carcinoma (12/15) and with N3 cervical lymph node metastases of carcinoma of unknown primary (3/15) were treated with chemotherapy and simultaneous accelerated RT. Results: 11 patients completed therapy without interruption or dose reduction. Grade 3 - 4 acute mucosal toxicity was observed in 9/15 patients, grade 4 hematologic toxicity in 6/15 patients. At a median follow-up of 7.5 months, 2 patients have died of intercurrent disease, 2 patients have experienced local relapse; 5 patients are alive with no evidence of disease at the primary tumor site. Discussion: The described regimen is highly effective, but led to remarkable side effects

Public transport policy in the Netherlands

Dutch public transport as a part of transport policy.Institute of Transport and Logistics Studies. Faculty of Economics and Business. The University of Sydne

Recurrence of ventricular arrhythmias in ischaemic secondary prevention implantable cardioverter defibrillator recipients: long-term follow-up of the Leiden out-of-hospital cardiac arrest study (LOHCAT)

Aims to assess the long-term rate of mortality and the recurrence of potentially life-threatening ventricular arrhythmias in secondary prevention implantable cardioverter defibrillator (ICD) patients and to construct a model for baseline risk stratification.Methods and resultsSince 1996, all patients with ischaemic heart disease, receiving ICD therapy for secondary prevention of sudden death, were included in the current study. Patients were evaluated at implantation and during long-term follow-up. A total of 456 patients were included in the analysis and followed for 54 ± 35 months. During follow-up, 100 (22) patients died and ICD therapy was noted in 216 (47) patients, of which 138 (30) for fast, potentially life-threatening ventricular arrhythmia. Multivariate analysis revealed a history of atrial fibrillation or flutter (AF), ventricular tachycardia as presenting arrhythmia, and wide QRS and poor left ventricular ejection fraction as independent predictors of life-threatening ventricular arrhythmias. The strongest predictor was AF with a hazard ratio of 2.1 (95 confidence interval 1.3-3.2). On the basis of the available clinical data, it was not possible to identify a group which exhibited no risk on recurrence of potentially life-threatening ventricular arrhythmias.ConclusionIschaemic secondary prevention ICD recipients exhibit a high recurrence rate of potentially life-threatening ventricular arrhythmias. Factors that increase risk can be identified but, even with these factors, it was not possible to distinguish a recurrence-free group

E-Democracy and the European Public Sphere

The chapter starts with an outline of outstanding recent contributions to the discussion of the EU democratic deficit and the so-called “no demos” problem and the debate about European citizenship and European identity—mainly in the light of insights from the EU crisis. This is followed by reflections on the recent discussion on the state of the mass media-based European public sphere. Finally, the author discusses the state of research on the Internet’s capacity to support the emergence of a (renewed) public sphere, with a focus on options for political actors to use the Internet for communication and campaigning, on the related establishment of segmented issue-related publics as well as on social media and its two-faced character as an enabler as well as a distorting factor of the public sphere. The author is sceptic about the capacities of Internet-based political communication to develop into a supranational (European) public sphere. It rather establishes a network of a multitude of discursive processes aimed at opinion formation at various levels and on various issues. The potential of online communication to increase the responsiveness of political institutions so far is set into practice insufficiently. Online media are increasingly used in a vertical and scarcely in a horizontal or interactive manner of communication

Knocking at the brain’s door: intravital two-photon imaging of autoreactive T cell interactions with CNS structures

Since the first applications of two-photon microscopy in immunology 10 years ago, the number of studies using this advanced technology has increased dramatically. The two-photon microscope allows long-term visualization of cell motility in the living tissue with minimal phototoxicity. Using this technique, we examined brain autoantigen-specific T cell behavior in experimental autoimmune encephalitomyelitis, the animal model of human multiple sclerosis. Even before disease symptoms appear, the autoreactive T cells arrive at their target organ. There they crawl along the intraluminal surface of central nervous system (CNS) blood vessels before they extravasate. In the perivascular environment, the T cells meet phagocytes that present autoantigens. This contact activates the T cells to penetrate deep into the CNS parenchyma, where the infiltrated T cells again can find antigen, be further activated, and produce cytokines, resulting in massive immune cell recruitment and clinical disease

Cardiac sodium channelopathies

Cardiac sodium channel are protein complexes that are expressed in the sarcolemma of cardiomyocytes to carry a large inward depolarizing current (INa) during phase 0 of the cardiac action potential. The importance of INa for normal cardiac electrical activity is reflected by the high incidence of arrhythmias in cardiac sodium channelopathies, i.e., arrhythmogenic diseases in patients with mutations in SCN5A, the gene responsible for the pore-forming ion-conducting α-subunit, or in genes that encode the ancillary β-subunits or regulatory proteins of the cardiac sodium channel. While clinical and genetic studies have laid the foundation for our understanding of cardiac sodium channelopathies by establishing links between arrhythmogenic diseases and mutations in genes that encode various subunits of the cardiac sodium channel, biophysical studies (particularly in heterologous expression systems and transgenic mouse models) have provided insights into the mechanisms by which INa dysfunction causes disease in such channelopathies. It is now recognized that mutations that increase INa delay cardiac repolarization, prolong action potential duration, and cause long QT syndrome, while mutations that reduce INa decrease cardiac excitability, reduce electrical conduction velocity, and induce Brugada syndrome, progressive cardiac conduction disease, sick sinus syndrome, or combinations thereof. Recently, mutation-induced INa dysfunction was also linked to dilated cardiomyopathy, atrial fibrillation, and sudden infant death syndrome. This review describes the structure and function of the cardiac sodium channel and its various subunits, summarizes major cardiac sodium channelopathies and the current knowledge concerning their genetic background and underlying molecular mechanisms, and discusses recent advances in the discovery of mutation-specific therapies in the management of these channelopathies

‘Friends call me racist’: Experiences of repercussions from writing comments on newspaper websites

acceptedVersio

State-of-the-art management of locally advanced head and neck cancer

During the past 20 years, treatments for head and neck squamous cell carcinoma (HNSCC) have changed dramatically owing largely to the advent of novel approaches such as combined modality therapy as well as improvements in surgical and radiotherapeutic techniques. Locally advanced disease in particular, which engendered very high recurrence and mortality rates, is now associated with long-term disease-free survival in the majority of cases. This article will focus on locally advanced HNSCC, which frequently remains a clinical challenge, review state-of-the-art therapy, and introduce promising novel therapies. The field continues to evolve rapidly with new evidence during the past year clearly establishing the benefit of adjuvant chemoradiotherapy (CRT), as well as early evidence showing improved survival with the use of an epidermal growth factor receptor inhibitor in combination with radiotherapy. There are varied regimens in use for patients with locally advanced disease, but at the same time the multitude of options can plague the clinician when trying to select the most appropriate one. This article will attempt to put the various approaches into perspective and propose an evidence-based treatment algorithm