Antimikrobielle Peptide in induziertem Sputum

Die COPD gilt bezüglich Klinik und Epidemiologie als die bedeutendste und gravierendste Langzeitkomplikation eines langjährigen Nikotinabusus. In der vorliegenden Arbeit wurde untersucht, ob diese Entzündung bereits bei jungen, klinisch noch gesunden Rauchern zu finden ist. Hierzu wurden Nichtraucher als gesunde Kontrollen rekrutiert und mit einer Stichprobe von gesunden Rauchern bezüglich des Diffentialzellbildes, mehrerer Zytokine sowie des antimikrobiellen Peptids LL-37 vergliche

The last animal: cosmopolitanism in The Last Man

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Intramuscular Artesunate for Severe Malaria in African Children: A Multicenter Randomized Controlled Trial.

BACKGROUND: Current artesunate (ARS) regimens for severe malaria are complex. Once daily intramuscular (i.m.) injection for 3 d would be simpler and more appropriate for remote health facilities than the current WHO-recommended regimen of five intravenous (i.v.) or i.m. injections over 4 d. We compared both a three-dose i.m. and a three-dose i.v. parenteral ARS regimen with the standard five-dose regimen using a non-inferiority design (with non-inferiority margins of 10%). METHODS AND FINDINGS: This randomized controlled trial included children (0.5-10 y) with severe malaria at seven sites in five African countries to assess whether the efficacy of simplified three-dose regimens is non-inferior to a five-dose regimen. We randomly allocated 1,047 children to receive a total dose of 12 mg/kg ARS as either a control regimen of five i.m. injections of 2.4 mg/kg (at 0, 12, 24, 48, and 72 h) (n = 348) or three injections of 4 mg/kg (at 0, 24, and 48 h) either i.m. (n = 348) or i.v. (n = 351), both of which were the intervention arms. The primary endpoint was the proportion of children with ≥ 99% reduction in parasitemia at 24 h from admission values, measured by microscopists who were blinded to the group allocations. Primary analysis was performed on the per-protocol population, which was 96% of the intention-to-treat population. Secondary analyses included an analysis of host and parasite genotypes as risks for prolongation of parasite clearance kinetics, measured every 6 h, and a Kaplan-Meier analysis to compare parasite clearance kinetics between treatment groups. A post hoc analysis was performed for delayed anemia, defined as hemoglobin ≤ 7 g/dl 7 d or more after admission. The per-protocol population was 1,002 children (five-dose i.m.: n = 331; three-dose i.m.: n = 338; three-dose i.v.: n = 333); 139 participants were lost to follow-up. In the three-dose i.m. arm, 265/338 (78%) children had a ≥ 99% reduction in parasitemia at 24 h compared to 263/331 (79%) receiving the five-dose i.m. regimen, showing non-inferiority of the simplified three-dose regimen to the conventional five-dose regimen (95% CI -7, 5; p = 0.02). In the three-dose i.v. arm, 246/333 (74%) children had ≥ 99% reduction in parasitemia at 24 h; hence, non-inferiority of this regimen to the five-dose control regimen was not shown (95% CI -12, 1; p = 0.24). Delayed parasite clearance was associated with the N86YPfmdr1 genotype. In a post hoc analysis, 192/885 (22%) children developed delayed anemia, an adverse event associated with increased leukocyte counts. There was no observed difference in delayed anemia between treatment arms. A potential limitation of the study is its open-label design, although the primary outcome measures were assessed in a blinded manner. CONCLUSIONS: A simplified three-dose i.m. regimen for severe malaria in African children is non-inferior to the more complex WHO-recommended regimen. Parenteral ARS is associated with a risk of delayed anemia in African children. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR201102000277177

Neural Adaptations Associated with Interlimb Transfer in a Ballistic Wrist Flexion Task

Cross education is the process whereby training of one limb gives rise to increases in the subsequent performance of its opposite counterpart. The execution of many unilateral tasks is associated with increased excitability of corticospinal projections from primary motor cortex (M1) to the opposite limb. It has been proposed that these effects are causally related. Our aim was to establish whether changes in corticospinal excitability (CSE) arising from prior training of the opposite limb determine levels of interlimb transfer. We used three vision conditions shown previously to modulate the excitability of corticospinal projections to the inactive (right) limb during wrist flexion movements performed by the training (left) limb. These were: (1) mirrored visual feedback of the training limb; (2) no visual feedback of either limb; and (3) visual feedback of the inactive limb. Training comprised 300 discrete, ballistic wrist flexion movements executed as rapidly as possible. Performance of the right limb on the same task was assessed prior to, at the mid point of, and following left limb training. There was no evidence that variations in the excitability of corticospinal projections (assessed by transcranial magnetic stimulation (TMS)) to the inactive limb were associated with, or predictive of, the extent of interlimb transfer that was expressed. There were however associations between alterations in muscle activation dynamics observed for the untrained limb, and the degree of positive transfer that arose from training of the opposite limb. The results suggest that the acute adaptations that mediate the bilateral performance gains realized through unilateral practice of this ballistic wrist flexion task are mediated by neural elements other than those within M1 that are recruited at rest by single-pulse TMS

Antimikrobielle Peptide in induziertem Sputum

Die COPD gilt bezüglich Klinik und Epidemiologie als die bedeutendste und gravierendste Langzeitkomplikation eines langjährigen Nikotinabusus. In der vorliegenden Arbeit wurde untersucht, ob diese Entzündung bereits bei jungen, klinisch noch gesunden Rauchern zu finden ist. Hierzu wurden Nichtraucher als gesunde Kontrollen rekrutiert und mit einer Stichprobe von gesunden Rauchern bezüglich des Diffentialzellbildes, mehrerer Zytokine sowie des antimikrobiellen Peptids LL-37 vergliche

Acetylcholine Receptor Antibody Titers and Clinical Course after Influenza Vaccination in Patients with Myasthenia Gravis: A Double-Blind Randomized Controlled Trial (ProPATIent-Trial)

Background: It is a continuous matter of discussion whether immune activation by vaccination in general and Influenza vaccination in particular increases the risk for clinical deterioration of autoimmune diseases. This prospective study investigated the serological and clinical course of autoimmune Myasthenia gravis (MG) after a seasonal influenza vaccination. Methods: This randomized, placebo-controlled, double-blind study enrolled MG patients with antibodies against acetylcholine-receptors (AChR-ab). They were allocated to receive seasonal influenza vaccine or placebo. The primary endpoint was the relative change of AChR-ab-titer over 12 weeks. A relative increase of 20% was set as non-inferiority margin. Secondary endpoints were clinical changes in the modified Quantitative Myasthenia Gravis Score (QMG), increase of anti-influenza-ELISA-antibodies, and changes of treatment. The study is registered with Clinicaltrialsregister.eu, EudraCT number 2006-004374-27. Findings: 62 patients were included. Mean ± standard deviation (median) in the vaccine and placebo group were AChR-ab-titer changes of −6.0% ± 23.3% (−4.0%) and −2.8% ± 22.0% (−0.5%) and QMG score changes of −0.08 ± 0.27 (0.17) and 0.11 ± 0.31 (0.00), respectively. The difference between groups (Hodges-Lehmann estimate with 95% CI) was - for the AChR-ab-titer change 4·0% [−13.3%, 4.5%] (p = 0.28 for testing a difference, p < 0.0001 for testing non-inferiority) and for the QMG change 0·00 [−0.17, 0.00] (p = 0.79 for testing a difference). The occurrence of 74 adverse events (AE) was comparable between groups. The most common AE was flu-like symptoms. One serious AE (hospitalisation following gastrointestinal haemorrhage) in the verum group was not related to the vaccine. Interpretation: Influenza vaccination in MG is safe. Uprating the potential risk of a severe course of MG exacerbation during influenza infection compared to the 95% CI differences for the endpoints, vaccination is principally indicated in this patient population