Longitudinal changes in magnetisation transfer ratio in secondary progressive multiple sclerosis: data from a randomised placebo controlled trial of lamotrigine.

Sodium blockade with lamotrigine is neuroprotective in animal models of central nervous system demyelination. This study evaluated the effect of lamotrigine on magnetisation transfer ratio (MTR), a putative magnetic resonance imaging measure of intact brain tissue, in a group of subjects with secondary progressive multiple sclerosis (MS). In addition, the utility of MTR measures for detecting change in clinically relevant pathology was evaluated.

Clinical and imaging correlates of the multiple sclerosis impact scale in secondary progressive multiple sclerosis.

The association of pathology and neurological deficit with quality of life (QoL) in multiple sclerosis (MS) is not fully understood. In this study, magnetic resonance imaging (MRI) measures of pathology--T1 and T2 lesion volume and ratio; active T2 lesion number; global and regional brain volume and atrophy; magnetization transfer ratio (MTR) for lesions, normal appearing grey and white matter (NAGM, NAWM); and spinal cord cross-sectional area-and measures of neurological disability (expanded disability status scale, EDSS), deficit (MS functional composite, MSFC) and inflammatory activity (relapse rate) were compared with the MS impact scale (MSIS-29), in participants in a trial of lamotrigine in secondary progressive MS. Data were collected from 118 people (85 female:33 male) aged 30-61 years (mean 50.

Grey matter damage and overall cognitive impairment in primary progressive multiple sclerosis.

Objectives: To identify associations between cognitive impairment and imaging measures in a cross-sectional study of patients with primary progressive multiple sclerosis (PPMS).

Methods: Neuropsychological tests were administered to 27 patients with PPMS and 31 controls. Patients underwent brain conventional magnetic resonance imaging (MRI) sequences, volumetric scans and magnetization transfer (MT) imaging; MT ratio (MTR) parameters, grey matter (GM) and normal-appearing white matter (NAWM) volumes, and WM T2 lesion load (T2LL) were obtained.

Charcot-Marie-Tooth disease associated with recurrent optic neuritis.

The factors precipitating central nervous system (CNS) demyelination, including optic neuritis, remain largely unknown but are likely to represent a complex interplay between the patient's environment and their genetic background. We report the development of sequential demyelinating optic neuritis in a patient with genetically confirmed Charcot-Marie-Tooth disease type 1A, a hereditary neuropathy. This neuropathy is characterized by duplication of peripheral myelin protein 22 (PMP22), which results in structurally abnormal peripheral myelin.

Enhanced surveillance during a large outbreak of bloody diarrhoea and haemolytic uraemic syndrome caused by Shiga toxin/verotoxin-producing Escherichia coli in Germany, May to June 2011.

Germany has a well established broad statutory surveillance system for infectious diseases. In the context of the current outbreak of bloody diarrhoea and haemolytic uraemic syndrome caused by Shiga toxin/ verotoxin-producing Escherichia coli in Germany it became clear that the provisions of the routine surveillance system were not sufficient for an adequate response. This article describes the timeline and concepts of the enhanced surveillance implemented during this public health emergency.

Management of patients pre-, per- and postcatheter ablation procedures: how to minimize complications?

Catheter ablation using radiofrequency energy has become an accepted and safe treatment of cardiac arrhythmias. Nevertheless, it is important to determine the risk-to-benefit ratio of a specific procedure, especially when treating subjects with non-life-threatening cardiac arrhythmias, such as AV-nodal reentrant tachycardia or atrial fibrillation, and efforts have to be made to reduce the incidence of complications associated with these procedures, which are in the vast majority of cases not directly attributable to RF energy application but rather with obtaining peripheral vascular access or intracardiac catheter manipulation. Although complication rates in atrial fibrillation (AF) ablation have decreased with improvements of the ablation technique and a change of ablation concepts since the introduction of this technique, the risk of complication is still considerable and significantly higher compared to ablation procedures of other supraventricular tachycardia, including potentially life-threatening events.

The mesenchymal stem cells in multiple sclerosis (MSCIMS) trial protocol and baseline cohort characteristics: an open-label pre-test: post-test study with blinded outcome assessments.

Background: No treatments are currently available that slow, stop, or reverse disease progression in established multiple sclerosis (MS). The Mesenchymal Stem Cells in Multiple Sclerosis (MSCIMS) trial tests the safety and feasibility of treatment with a candidate cell-based therapy, and will inform the wider challenge of designing early phase clinical trials to evaluate putative neuroprotective therapies in progressive MS. Illustrated by the MSCIMS trial protocol, we describe a novel methodology based on detailed assessment of the anterior visual pathway as a model of wider disease processes--the "sentinel lesion approach".

CD4+ T-cell immunity to the Burkholderia pseudomallei ABC transporter LolC in melioidosis.

Burkholderia pseudomallei causes melioidosis, a disease with a wide range of possible outcomes, from seroconversion and dormancy to sepsis and death. This spectrum of host-pathogen interactions poses challenging questions about the heterogeneity in immunity to B. pseudomallei.

Mortality of 2009 pandemic influenza A(H1N1) in Germany.

The mortality in Germany caused by the 2009 pandemic influenza A(H1N1) seems to have been one of the lowest in Europe. We provide a detailed analysis of all 252 fatal cases of confirmed infection with the pandemic virus notified between 29 April 2009 and 31 March 2010. The overall mortality was 3.

High level of gastrointestinal nosocomial infections in the german surveillance system, 2002-2008.

Objective: Surveillance of nosocomial infections (NIs) is well established in many countries but often does not include gastrointestinal infections. We sought to determine the proportion of NIs among all hospitalized cases for the 4 most prevalent types of gastrointestinal infections in Germany.

Methods: We analyzed all notifications of laboratory-confirmed or epidemiologically linked gastrointestinal infections due to norovirus, rotavirus, Salmonella species, and Campylobacter species reported to the Robert Koch Institute in Berlin, Germany, from 2002 through 2008.

Complementary roles of grey matter MTR and T2 lesions in predicting progression in early PPMS.

Objective: To investigate whether T2 lesion load and magnetisation transfer ratio (MTR) in the normal-appearing white matter (NAWM) and grey matter (GM) at study entry are independent predictors of progression and whether their changes correlate with the accrual of disability, over 5 years in early primary progressive multiple sclerosis (PPMS).

Methods: Forty-seven patients with early PPMS and 18 healthy controls were recruited at baseline and invited to attend clinical 6-monthly assessments for 3 years, and after 5 years. Patients were scored on the Expanded Disability Status Scale and multiple sclerosis functional composite subtests (25-foot timed walk test (TWT), nine-hole peg test and paced auditory serial addition test).

Clinical impact of screening for sleep related breathing disorders in atrial fibrillation.

Objective: The aim of this study was to quantify daytime symptoms in atrial fibrillation (AF) patients with and without sleep related breathing disorders (SRBD).

Background: SRBD are common in patients with AF but little is known about daytime symptoms among those with SRBD.

Methods: Patients with AF admitted to clinics of two tertiary referral hospitals for a variety of different cardiovascular diseases were screened with a trans-nasal airflow measurement device allowing measurement of the apnea-hypopnea-index.

The prognosis of implantable defibrillator patients treated with cardiac resynchronization therapy: comorbidity burden as predictor of mortality.

Aims: Comorbidity, such as myocardial infarction, diabetes, and renal failure, plays a pivotal role in the prognosis of a patient with arrhythmias. However, data on the prognostic impact of comorbiditiy in heart failure patients with cardiac resynchronization therapy and defibrillation (CRT-D) are scarce. The purpose of this study was to determine the impact of comorbidity on survival in CRT-D patients.

Mammalian glucocorticoid metabolites act as androgenic endocrine disruptors in the medaka (Oryzias latipes).

Glucocorticoid metabolites enter the aquatic environment via mammalian excrements. Molecular structures of their C19O3 metabolites strongly resemble the major fish androgen 11-ketotestosterone. Therefore, we tested the hypothesis that the cortisol metabolite 5alpha-androstan-3,11,17-trione acts similarly to 11-ketotestosterone by employing a fish screening assay for endocrine-active substances.

Cryoballoon versus radiofrequency catheter ablation of paroxysmal atrial fibrillation: biomarkers of myocardial injury, recurrence rates, and pulmonary vein reconnection patterns.

Background: Cryoballoon ablation has emerged as a novel treatment strategy for patients with atrial fibrillation (AF).

Objective: The purpose of this study was to compare pulmonary vein isolation (PVI) using cryoballoon ablation versus RF ablation with regard to myocardial injury, pulmonary vein (PV) reconnection patterns, and outcome.

Methods: Fifty patients (age 59 ± 9 years, ejection fraction 0.

Differing effect of modifiable cardiovascular risk factors on intima-media thickening and plaque formation at different sites of the arterial vasculature.

Objective: The effects of cardiovascular risk factors on the vascular anatomy at differing sites of the arterial vasculature have not been well described. The aim of this study was to compare the effect of cardiovascular risk factors on the intima media thickness (IMT) of the wall of the right and left common carotid artery (CCA) at their bifurcation and proximal from their bifurcation, and the effects on the presence of plaque at carotid and femoral arteries.

Design: Cross-sectional population-based study.

An anthrax subunit vaccine candidate based on protective regions of Bacillus anthracis protective antigen and lethal factor.

Studies have confirmed the key role of Bacillus anthracis protective antigen (PA) in the US and UK human anthrax vaccines. However, given the tripartite nature of the toxin, other components, including lethal factor (LF), are also likely to contribute to protection. We examined the antibody and T cell responses to PA and LF in human volunteers immunized with the UK anthrax vaccine (AVP).

Repertoire of HLA-DR1-restricted CD4 T-cell responses to capsular Caf1 antigen of Yersinia pestis in human leukocyte antigen transgenic mice.

Yersinia pestis is the causative agent of plague, a rapidly fatal infectious disease that has not been eradicated worldwide. The capsular Caf1 protein of Y. pestis is a protective antigen under development as a recombinant vaccine.

Hippocampal atrophy in relapsing-remitting and primary progressive MS: a comparative study.

Background: In multiple sclerosis (MS), demyelination and neuroaxonal damage are seen in the hippocampus, and MRI has revealed hippocampal atrophy.

Objectives: To investigate and compare hippocampal volume loss in patients with relapsing-remitting MS (RRMS) and primary progressive MS (PPMS) using manual volumetry, and explore its association with memory dysfunction.

Methods: Hippocampi were manually delineated on volumetric MRI of 34 patients with RRMS, 23 patients with PPMS and 18 controls.

Lamotrigine for neuroprotection in secondary progressive multiple sclerosis: a randomised, double-blind, placebo-controlled, parallel-group trial.

Background: Partial blockade of voltage-gated sodium channels is neuroprotective in experimental models of inflammatory demyelinating disease. In this phase 2 trial, we aimed to assess whether the sodium-channel blocker lamotrigine is also neuroprotective in patients with secondary progressive multiple sclerosis.

Methods: Patients with secondary progressive multiple sclerosis who attended the National Hospital for Neurology and Neurosurgery or the Royal Free Hospital, London, UK, were eligible for inclusion in this double-blind, parallel-group trial.

A serial study of retinal changes following optic neuritis with sample size estimates for acute neuroprotection trials.

Following an episode of optic neuritis, thinning of the retinal nerve fibre layer, which indicates axonal loss, is observed using optical coherence tomography. The longitudinal course of the retinal changes has not been well characterized. We performed a serial optical coherence tomography study in patients presenting with optic neuritis in order to define the temporal evolution of retinal nerve fibre layer changes and to estimate sample sizes for proof-of-concept trials of neuroprotection using retinal nerve fibre layer loss as the outcome measure.

Scanning laser polarimetry quantification of retinal nerve fiber layer thinning following optic neuritis.

Background: Several studies with optical coherence tomography (OCT) have demonstrated thinning of the retinal nerve fiber layer (RNFL) in patients with optic neuritis and multiple sclerosis. Similar studies have not been performed with scanning laser polarimetry (SLP), which relies on different physical phenomena. This study was designed to use SLP to measure axonal loss following a single episode of optic neuritis and to determine if there is a relationship between the degree of axonal loss and the degree of residual visual dysfunction.