Intravenous immunoglobulin treatment following the first demyelinating event suggestive of multiple sclerosis: a randomized, double-blind, placebo-controlled trial

BACKGROUND: Intravenous immunoglobulin (IVIg) has been reported to reduce disease activity in patients with relapsing-remitting multiple sclerosis. We assessed the effect of IVIg treatment in patients after the first neurological event suggestive of demyelinative disease and evaluated the occurrence of a second attack and dissemination in time demonstrated by brain magnetic resonance imaging within the first year from onset. METHODS: We conducted a randomized, placebo-controlled, double-blind study in 91 eligible patients enrolled within the first 6 weeks of neurological symptoms. Patients were randomly assigned to receive IVIg treatment (2-g/kg loading dose) or placebo, with boosters (0.4 g/kg) given once every 6 weeks for 1 year. Neurological and clinical assessments were done every 3 months, and brain magnetic resonance imaging was performed at baseline and the end of the study. RESULTS: The cumulative probability of developing clinically definite multiple sclerosis was significantly lower in the IVIg treatment group compared with the placebo group (rate ratio, 0.36 [95% confidence interval, 0.15-0.88]; P = .03). Patients in the IVIg treatment group had a significant reduction in the volume and number of T2-weighted lesions and in the volume of gadolinium-enhancing lesions as compared with the placebo group (P = .01, P = .01, and P = .03, respectively). Treatment was well tolerated, compliance was high, and incidence of adverse effects did not differ significantly between groups. CONCLUSIONS: Intravenous immunoglobulin treatment for the first year from onset of the first neurological event suggestive of demyelinative disease significantly lowers the incidence of a second attack and reduces disease activity as measured by brain magnetic resonance imaging.     

Involvement of microparticles in diabetic vascular complications

Type 2 diabetes mellitus (T2DM) is associated with increased coagulability and vascular complications. Circulating microparticles (MPs) are involved in thrombosis, inflammation, and angiogenesis. However, the role of MPs in T2DM vascular complications is unclear. We characterised the cell origin and pro-coagulant profiles of MPs obtained from 41 healthy controls and 123 T2DM patients with coronary artery disease, retinopathy and foot ulcers. The effects of MPs on endothelial cell coagulability and tube formation were evaluated. Patients with severe diabetic foot ulcers expressed the highest levels of MPs originated from platelet and endothelial cells and negatively-charged phospholipid-bearing MPs. MP coagulability, calculated from MP tissue factor (TF) and TF pathway inhibitor (TFPI) ratio, was low in healthy controls and in diabetic retinopathy patients (<0.7) but high in patients with coronary artery disease and foot ulcers (>1.8, p≥0.002). MPs of all T2DM patients induced a more than two-fold increase in endothelial cell TF (antigen and gene expression) but did not affect TFPI levels. Tube networks were longest and most stable in endothelial cells that were incubated with MPs of healthy controls, whereas no tube formation occurred in MPs of diabetic patients with coronary artery disease. MPs of diabetic retinopathy and diabetic foot ulcer patients induced branched tube networks that were unstable and collapsed over time. This study demonstrates that MP characteristics are related to the specific type of vascular complications and may serve as a bio-marker for the pro- coagulant state and vascular pathology in patients with T2DM.     

Glutamate Toxicity to Differentiated Neuroblastoma N2a Cells Is Prevented by the Sesquiterpene Lactone Achillolide A and the Flavonoid 3,5,4′-Trihydroxy-6,7,3′-Trimethoxyflavone from <Emphasis Type="Italic">Achillea fragrantissima</Emphasis>

Glutamate toxicity is a major contributor to the pathophysiology of numerous neurodegenerative diseases including amyotrophic lateral sclerosis and Alzheimer’s disease. Therefore, protecting neuronal cells against glutamate-induced cytotoxicity might be an effective approach for the treatment of these diseases. We have previously purified from the medicinal plant Achillea fragrantissima two bioactive compounds which were not studied before: the sesquiterpene lactone achillolide A and the flavonoid 3,5,4′-trihydroxy-6,7,3′-trimethoxyflavone (TTF). We have shown that these compounds protect astrocytes from oxidative stress-induced cell death and inhibit microglial activation. The current study examined for the first time their effects on differentiated mouse neuroblastoma N2a cells and on glutamate toxicity. We have found that, although these compounds belong to different chemical families, they protect neuronal cells from glutamate toxicity. We further demonstrate that this protective effect might be, at least partially, due to inhibitory effects of these compounds on the levels of reactive oxygen species produced following treatment with glutamate.     

From caring to managing and beyond: an examination of the head nurse's role

AIM: The aim of this study was to depict the essence of what head nurses do, and how they perform their managerial role. METHODS: To achieve this, the work behaviour of 48 head nurses was examined by a semi-structured observation technique for 6 hours each. RESULTS: Results demonstrated that head nurses spent a large proportion of their time in clinical practice, followed by co-ordinating care, operating the unit's functions, and leading staff. Personnel management and quality improvement occupied only a marginal share of head nurses' time. CONCLUSIONS: These results implied that head nurses exhibited a management style orientated to maintenance rather than to re-creation, focusing more on the 'doing' and the 'here and now' aspects of the job than on leading, planning, and proactive problem solving.     

Should ovarian cryopreservation be offered to girls with cancer

Current therapy of childhood cancer makes long-term survival a realistic outcome for most patients. However, some treatment regimens entail a significant risk of infertility. No established method for preservation of female fertility is currently available. Ovarian cryopreservation is an experimental technology that is being offered with increasing frequency to women undergoing cancer therapy. It has not yet been reported in children and adolescent girls. The aim of this review is to stimulate discussion on the possibility of performing ovarian cryopreservation in pre-menarcheal girls in advance of therapies that may induce ovarian failure. We present a multi-disciplinary discussion of the risks and benefits associated with the procedure and propose guidelines for its implementation. We propose that all girls about to receive treatment that has a high risk for infertility be offered consultation about the possibility of ovarian cryopreservation.     

Theta EEG neurofeedback benefits early consolidation of motor sequence learning

Procedural learning is subject to consolidation processes believed to depend on the modulation of functional connections involved in representing the acquired skill. While sleep provides the most commonly studied framework for such consolidation processes, posttraining modulation of oscillatory brain activity may also impact on plasticity processes. Under the hypothesis that consolidation of motor learning is associated with theta band activity, we used EEG neurofeedback (NFB) to enable participants to selectively increase either theta or beta power in their EEG spectra following the acquisition phase of motor sequence learning. We tested performance on a motor task before and after training, right after the NFB session to assess immediate NFB effects, 1 day after NFB to assess interaction between NFB effects and overnight sleep‐dependent stabilization, and 1 week after the initial session, to assess the effects of NFB on long‐term stabilization of motor training. We also explored the extent of the influence of single‐electrode NFB on EEG recorded across the scalp. Results revealed a significantly greater improvement in performance immediately after NFB in the theta group than in the beta group. This effect continued for testing up to 1 week following training. Across participants, post‐NFB improvement correlated positively with theta/beta ratio change achieved during NFB. Additionally, NFB was found to cause widespread band‐power modulation beyond the electrode used for feedback. Thus, upregulating postlearning theta power may yield contributions to the immediate performance and subsequent consolidation of an acquired motor skill.