Pre-hospital emergency anaesthesia in trauma patients treated by anaesthesiologist and nurse anaesthetist staffed critical care teams.

Background: Pre-hospital tracheal intubation in trauma patients has recently been questioned. However, not only the trauma and patient characteristics but also airway provider competence differ between systems making simplified statements difficult.

Method: The study is a subgroup analysis of trauma patients included in the PHAST study.

Interferon-β corrects massive gene dysregulation in multiple sclerosis: Short-term and long-term effects on immune regulation and neuroprotection.

Background: In multiple sclerosis (MS), immune up-regulation is coupled to subnormal immune response to interferon-β (IFN-β) and low serum IFN-β levels. The relationship between the defect in IFN signalling and acute and long-term effects of IFN-β on gene expression in MS is inadequately understood.

Methods: We profiled IFN-β-induced transcriptome shifts, using high-resolution microarrays on 227 mononuclear cell samples from IFN-β-treated MS Complete Responders (CR) stable for five years, and stable and active Partial Responders (PR), stable and active untreated MS, and healthy controls.

Effect of HLA-DRB1 alleles and genetic variants on the development of neutralizing antibodies to interferon beta in the BEYOND and BENEFIT trials.

Background: Treatment of multiple sclerosis (MS) with interferon β can lead to the development of antibodies directed against interferon β that interfere with treatment efficacy. Several observational studies have proposed different HLA alleles and genetic variants associated with the development of antibodies against interferon β.

Objective: To validate the proposed genetic markers and to identify new markers.

Incidence and course of depression in multiple sclerosis in the multinational BEYOND trial.

Early experience in MS generated concerns that interferon beta treatment might provoke onset or worsening of depression. The objective of the study was to compare depression incidence in relapsing-remitting MS patients receiving interferon beta-1b (IFNB-1b) or glatiramer acetate (GA) in the BEYOND trial. 891/897 (99 %) of English, French, Spanish and Italian speakers among 2244 patients randomized (2:2:1) to receive either IFNB-1b 500 µg, 250 µg, or GA 20 mg QD for 2-3.

Predictors of disease activity in 857 patients with MS treated with interferon beta-1b.

Multiple sclerosis (MS) is a chronic demyelinating neurodegenerative disease of the CNS that requires long-term treatment. The identification of patient characteristics that can help predict disease outcomes could improve care for patients with MS. The objective of this study is to identify predictors of disease activity in patients from the BEYOND trial.

Absence of rapid eye movements during sleep in adult zebrafish.

Sleep is not a uniform phenomenon, but is organized in alternating, fundamentally different states, rapid eye movement sleep and non-rapid eye movement sleep. Zebrafish (Danio rerio) have recently emerged as an excellent model for sleep research. Zebrafish are well characterized in terms of development, neurobiology and genetics.

Effects of inhibitors of the renin-angiotensin system on the efficacy of interferon beta-1b: a post hoc analysis of the BEYOND study.

Background: In experimental autoimmune encephalomyelitis, inhibition of the renin-angiotensin system with angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme (ACE) inhibitors resulted in a significantly ameliorated disease course. We evaluated the effects of ARBs and ACE inhibitors on the efficacy of interferon beta-1b in patients with relapsing-remitting multiple sclerosis (RRMS).

Methods: In this post hoc analysis of the BEYOND (Betaferon Efficacy Yielding Outcomes of a New Dose) study, clinical and MRI end points were compared between patients treated with interferon beta-1b 250 or 500 µg and concomitant ARBs or ACE inhibitors and patients treated with interferon beta-1b 250 or 500 µg only (reference group).

Efficacy and safety of interferon beta-1b sc in older RRMS patients--a posthoc analysis of the BEYOND study.

Evidence of a significant improvement of IFNB-1b in clinical severity in the older population with RRMS has not been established so far. The aim of this exploratory post hoc analysis of the 250 mcg IFNB-1b group of the BEYOND study is to compare the efficacy and safety of older versus younger patients using a cut-off at the age of 50 and at the age of 40, respectively. There was no difference between age groups in adjusted relapse risk (age 50 cut-off: P = 0.

Mechanisms of action of adrenocorticotropic hormone and other melanocortins relevant to the clinical management of patients with multiple sclerosis.

The therapeutic benefits of adrenocorticotropic hormone in multiple sclerosis are usually ascribed to its corticotropic actions. Evidence is presented that adrenocorticotropic hormone, approved for multiple sclerosis relapses, acts via corticosteroid-independent melanocortin pathways to engender down-modulating actions on immune-system cells and the cytokines they synthesize. Immune response-dampening effects are also brought about by agent-induced neurotransmitters that inhibit immunocytes.

Variability in detection and quantification of interferon β-1b-induced neutralizing antibodies.

Background: Interferon-beta (IFNB) therapy for multiple sclerosis can lead to the induction of neutralizing antibodies (NAbs) against IFNB. Various methods are used for detection and quantification of NAbs.

Methods: Blood samples from 125 IFNB-1b-treated patients, which were tested NAb negative or NAb positive after conclusion of a clinical study, were retested three years after first being assessed in four different laboratories that offer routine NAb testing to practicing neurologists.

[Successful resuscitation of a pulseless young woman with pulmonary embolus in rural Iceland].

A 27 year old woman suffered a witnessed cardiac arrest in rural Iceland and regained pulse after one hour's resuscitation. She was transported by an air ambulance to a tertiary medical center in Reykjavik where she was diagnosed with a large pulmonary embolus. After 24 hours therapeutic hypothermia she was rewarmed and extubated two days later.

Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci.

Objective: To perform a 1-stage meta-analysis of genome-wide association studies (GWAS) of multiple sclerosis (MS) susceptibility and to explore functional consequences of new susceptibility loci.

Methods: We synthesized 7 MS GWAS. Each data set was imputed using HapMap phase II, and a per single nucleotide polymorphism (SNP) meta-analysis was performed across the 7 data sets.

Neutralizing antibodies to interferon beta-1b multiple sclerosis: a clinico-radiographic paradox in the BEYOND trial.

Background: The frequency and impact of neutralizing antibodies (NAbs) to interferon beta-1b (IFNβ-1b) on clinical and radiographic outcomes is controversial.

Objective: To assess NAb impact in the BEYOND study.

Methods: 2244 patients were randomized (2:2:1) to receive IFNβ-1b, either 250 or 500 µg, or glatiramer acetate, 20 mg, and observed for 2-3.

Can the functional assessment of multiple sclerosis adapt to changing needs? A psychometric validation in patients with clinically isolated syndrome and early relapsing-remitting multiple sclerosis.

Background: The Functional Assessment of Multiple Sclerosis (FAMS) is widely used in clinical trial programmes; however, it was developed before the rise in trials targeted at early stage multiple sclerosis (MS) and clinically isolated syndrome (CIS).

Objective: The aim of this study was to assess the psychometric properties of the FAMS within two clinically distinct populations, CIS and early relapsing-remitting MS (RRMS), and discern the appropriateness of the FAMS within these populations.

Methods: Secondary analysis was conducted on FAMS data from two clinical trials assessing interferon beta-1b in early RRMS and CIS.

Treatment of infantile spasms: emerging insights from clinical and basic science perspectives.

Infantile spasms is an epileptic encephalopathy of early infancy with specific clinical and electroencephalographic (EEG) features, limited treatment options, and a poor prognosis. Efforts to develop improved treatment options have been hindered by the lack of experimental models in which to test prospective therapies. The neuropeptide adrenocorticotropic hormone (ACTH) is effective in many cases of infantile spasms, although its mechanism(s) of action is unknown.

Tumour Necrosis Factor Neutralization in MS: A Cautionary Tale.

Lenercept, a tumour necrosis factor (TNF) capture molecule, was tested in a double- blind, placebocontrolled Phase II trial in multiple sclerosis (MS). Most patients had relapsing-remitting disease. The code was broken once all patients had been treated for at least 24 weeks.

MS Forum/MS Over the Past 17 Years.

At its final meeting, the MS Forum Executive Committee reviewed highlights of where things stood prior to the immunomodulatory era, and how things have evolved subsequently. What the future might hold was discussed in a second session. Prior to 1990: Genetic predisposition to multiple sclerosis (MS), as determined by human leukocyte antigen expression, was established and an environmental trigger (Epstein-Barr virus?) was suspected, as was lack of sunshine.

Rapid immune responses to a botulinum neurotoxin Hc subunit vaccine through in vivo targeting to antigen-presenting cells.

The clostridial botulinum neurotoxins (BoNTs) are the most potent protein toxins known. The carboxyl-terminal fragment of the toxin heavy chain (Hc) has been intensively investigated as a BoNT vaccine immunogen. We sought to determine whether targeting Hc to antigen-presenting cells (APCs) could accelerate the immune responses to vaccination with BoNT serotype A (BoNT/A) Hc.

Interferon β-1b and glatiramer acetate effects on permanent black hole evolution.

Objective: To compare interferon β-1b (IFNβ-1b) and glatiramer acetate (GA) on new lesion (NL) (gadolinium-enhancing, new T2) evolution into permanent black holes (PBH)--a marker of irreversible tissue damage--in patients with relapsing-remitting multiple sclerosis (RRMS).

Methods: BEYOND was a large, phase III, clinical trial comparing IFNβ-1b 250 μg, IFNβ-1b 500 μg, and GA (2:2:1). Patient scans were reexamined post hoc for PBH in a rater-blinded manner.

Olig1 is expressed in human oligodendrocytes during maturation and regeneration.

Myelin repair is inhibited in multiple sclerosis (MS), ultimately leading to axonal damage and disability. We aimed to understand the transcriptional mechanisms of regeneration in primary human oligodendrocyte cultures isolated from white matter of medically intractable epilepsy patients. Cultures at isolation contained 84% mature oligodendrocytes and 16% oligodendrocyte progenitor cells (OPC).

Immunoglobulin-like transcript 3, an inhibitor of T cell activation, is reduced on blood monocytes during multiple sclerosis relapses and is induced by interferon beta-1b.

Immunoglobulin-like transcripts (ILTs) are immunoregulatory proteins that either activate or inhibit immune responses. ILT3 is inhibitory and is expressed preferentially by antigen-presenting cells. When its extracellular domain binds to an unidentified ligand of activated T cells, the T cell is silenced.

250 microg or 500 microg interferon beta-1b versus 20 mg glatiramer acetate in relapsing-remitting multiple sclerosis: a prospective, randomised, multicentre study.

Background: The aim of the Betaferon Efficacy Yielding Outcomes of a New Dose (BEYOND) trial was to compare the efficacy, safety, and tolerability of 250 microg or 500 microg interferon beta-1b with glatiramer acetate for treating relapsing-remitting multiple sclerosis.

Methods: Between November, 2003, and June, 2005, 2447 patients with relapsing-remitting multiple sclerosis were screened and 2244 patients were enrolled in this prospective, multicentre, randomised trial. Patients were randomly assigned 2:2:1 by block randomisation with regional stratification to receive one of two doses of interferon beta-1b (250 microg or 500 microg) subcutaneously every other day or 20 mg glatiramer acetate subcutaneously every day.

[Can acute renal insufficiency increase the effect of warfarin?].

The use of warfarin is complicated by its narrow therapeutic index. The risk of severe complications in the form of haemorrhage is significantly increased by an elevated degree of anticoagulation. We present a case in which a patient in stable warfarin treatment was admitted with acute renal failure and extremely high international normalized ratio (INR).

Terbutaline in myasthenia gravis: a pilot study.

The objective of this study was to assess the short-term efficacy and safety of terbutaline, a beta2-adrenergic agonist, in patients with myasthenia gravis (MG) in a randomized, double-blind, placebo-controlled, crossover study. The primary endpoint for efficacy was a reduction of at least 3 points in the quantitative MG score (QMGS). Secondary endpoints included changes in the functional disability scale (FDS), forced vital capacity (FVC), grip strength, anti-acetylcholine receptor (AChR) antibody levels and decremental response.