Activation of microglia by retroviral infection correlates with transient clearance of prions from the brain but does not change incubation time

Prion diseases are fatal transmissible diseases, where conversion of the endogenous prion protein (PrP^C) into a misfolded isoform (PrP^Sc) leads to neurodegeneration. Microglia, the immune cells of the brain, are activated in neurodegenerative disorders including prion diseases; however, their impact on prion disease pathophysiology is unclear with both beneficial PrP^Sc‐clearing and detrimental potentially neurotoxic effects. Moreover, monocytes entering the brain from the periphery during disease course might add to disease pathophysiology. Here, the degree of microglia activation in the brain of prion infected mice with and without an additional intraperitoneal retrovirus infection was studied. Peripheral murine retrovirus infection leads to activation of parenchymal microglia without recruitment of monocytes. This activation correlated with transient clearance or delay in accumulation of infectious prions specifically from the brain at early time points in the diseases course. Microglia expression profiling showed upregulation of genes involved in protein degradation coinciding with prion clearance. This enforces a concept where microglia act beneficial in prion disease if adequately activated. Once microglia activation has ceased, prion disease reemerges leading to disease kinetics undistinguishable from the situation in prion‐only infected mice. This might be caused by the loss of microglial homeostatic function at clinical prion disease.     

Beta-blocker treatment of chronic systolic heart failure improves prognosis even in patients meeting one or more exclusion criteria of the MERIT-HF study.

AIMS: Improved prognosis of patients with chronic systolic heart failure by treatment with beta-blockers has been shown in several randomized controlled multicentre trials. However, in clinical practice only a part of heart failure patients meet the inclusion criteria of these trials. The present study evaluates whether reduction of mortality by beta-blockers also can be achieved in patients presenting one or more exclusion criteria of the MERIT-HF trial. METHODS AND RESULTS: From the Ludwigshafen Heart Failure Registry 675 patients with chronic systolic heart failure consecutively enrolled between January 1995 and June 2004 were divided in two groups either meeting the inclusion criteria of the MERIT-HF trial ('trial patients': n = 278, 60% treated with beta-blockers) or not ('non-trial patients': n = 397; 51% treated with beta-blockers). The distribution of the MERIT-HF exclusion criteria in the group of 'non-trial patients' was as follows: acute myocardial infarction 9.6%; systolic blood pressure <100 mmHg 7.5%; chronic obstructive lung disease 33.2%; other serious diseases potentially limiting prognosis 16.9%; acutely performed or planned ICD, bypass surgery, PCI, heart transplantation: 17.1, 15.9, 7.8, and 4.8%, respectively. Median follow-up was 31.3 months (upper/lower quartile 16.3/50.0 months). All-cause mortality was significantly reduced by beta-blocker treatment not only in 'trial patients' (adjusted hazard ratio 0.57, 95% CI 0.38-0.86) but also in 'non-trial patients' (adjusted hazard ratio 0.72, 95% CI 0.53-0.97). CONCLUSION: In clinical practice only the smaller part of the population to be treated for chronic systolic heart failure meets the inclusion criteria of the MERIT-HF study. However, beta-blocker treatment is associated with a significantly reduced long-term mortality even in patients meeting one or more exclusion criteria of the MERIT-HF study.     

Leitsymptom Schwindel aus Sicht des Neurologen

In most patients with vertigo, the first and clinically most important question posed to neurologists is whether it is a central or a peripheral syndrome. In more than 90?% of cases, this differentiation is made possible by systematically recording the patient history (asking about the type of vertigo, the duration, triggers and accompanying symptoms) and conducting a physical examination. Particularly in the case of acute vertigo disorders, a five-step procedure has proven useful: 1. A cover test to look for vertical divergence (skew deviation) as a central sign and component of the ocular tilt reaction (OTR); 2. Examination with and without Frenzel goggles to differentiate between peripheral vestibular spontaneous nystagmus and central fixation nystagmus; 3. Examination of smooth pursuit; 4. Examination of the gaze-holding function (particularly gaze-evoked nystagmus beating in the opposite direction to spontaneous nystagmus); 5. The head impulse test to look for a deficit in the vestibulo-ocular reflex (VOR). Considerable advances have been made in the pharmacotherapy of vertigo disorders during the last 10 years, including cortisone for the treatment of acute vestibular neuritis, betahistine as a high-dose long-term treatment for Menière’s disease, carbamazepine to treat vestibular paroxysmia and aminopyridine for down- and upbeat nystagmus and episodic ataxia type 2.     

Weekly Iron and Folic Acid Supplementation As a Tool to Reduce Anemia among Primary School Children in Cambodia

The prevalence of anemia decreased from 62% to 12% and from 57% to 26% in children 5 to 11 years of age in two rural primary schools in Kampot Province, Cambodia, after oral weekly supplementation with iron-folic acid tablets for 20 weeks and with vitamin A and mebendazole twice per year. In 12-to 15-year-old children, success was less marked. The prevalence of hookworm infestation did not change, but the number of eggs in the stool decreased drastically. The intervention had no significant influence on stunting and wasting. An integrated community approach including mass deworming, health education, and multi-micronutrient supplementation was very effective in reducing anemia in Cambodian schoolchildren and should be adopted on a larger scale.     

Cardiac tamponade in a preterm neonate secondary to a chest tube

In a preterm infant, chest tubes were inserted for treatment of bilateral pneumothoraces. Hemorrhagic pericardial effusion with cardiac tamponade developed, probably resulting from traumatic injury by the left chest tube. The infant survived due to timely diagnostic and therapeutic intervention. No recurrence of pericardial effusion was seen and follow-up showed normal psychomotor development.