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  • Exercise limitation of acetazolamide at altitude (3459 m)

    24 October 2018

    Copyright © 2014 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved. OBJECTIVE: To assess the effect of acetazolamide (Az) on exercise performance during early acclimatization to altitude. METHODS: Az (250 mg twice daily) or placebo was administered for 3 days in a double-blind, randomized manner followed by a rapid ascent to 3459 m in the Italian Alps. Twenty healthy adults (age range, 18-67 years) were tested at 60% of sea-level peak power output for 15 minutes on a bicycle ergometer after 16 to 27 hours of altitude exposure. Exercise performance was measured in relation to peripheral oxygen saturations measured from pulse oximetry (Spo2), Lake Louise acute mountain sickness (AMS) score, and perceived difficulty. RESULTS: At altitude, resting Spo2 was higher in the Az group compared with placebo (P < .001). The highest AMS scores were in 4 of the placebo individuals with the lowest resting Spo2 (P < .05). During the exercise test, Spo2 fell in all but 1 subject (P < .001) and was reduced more in the Az group (P < .01). Four Az and 1 placebo subject were unable to complete the exercise test; 4 of these 5 had the largest fall in Spo2. The perception of exercise difficulty was higher in the Az subjects compared with those taking the placebo (P < .01). There was an age relationship with exercise limitation; 4 of the 9 older than 50 years failed to complete the test whereas only 1 of 11 younger than 50 years failed, and there were no failures in the 6 younger than 30 years (P < .05). CONCLUSIONS: In this study group, and despite higher resting Spo2, Az may have compromised exercise at 3459 m altitude during early acclimatization, particularly in older subjects.

  • Functional brain imaging in respiratory medicine

    24 October 2018

    Discordance of clinical symptoms with markers of disease severity remains a conundrum in a variety of respiratory conditions. The breathlessness of chronic lung disease correlates poorly with spirometry, yet is a better predictor of mortality. In chronic cough, symptoms are often evident without clear physical cause. In asthma, the terms over perceivers and under perceivers are common parlance. In all these examples, aberrant brain mechanisms may explain the mismatch between symptoms and pathology. Functional MRI is a non-invasive method of measuring brain function. It has recently become significantly advanced enough to be useful in clinical research and to address these potential mechanisms. This article explains how FMRI works, current understanding from FMRI in breathlessness, cough and asthma and suggests possibilities for future research.

  • Multiple programmed cell death pathways are involved in N-methyl-N-nitrosourea-induced photoreceptor degeneration

    24 October 2018

    © 2015, Springer-Verlag Berlin Heidelberg. Purpose: To identify programmed cell death (PCD) pathways involved in N-methyl-N-nitrosourea (MNU)-induced photoreceptor (PR) degeneration. Methods: Adult C57BL/6 mice received a single MNU i.p. injection (60 mg/kg bodyweight), and were observed over a period of 7 days. Degeneration was visualized by H&E overview staining and electron microscopy. PR cell death was measured by quantifying TUNEL-positive cells in the outer nuclear layer (ONL). Activity measurements of key PCD enzymes (calpain, caspases) were used to identify the involved cell death pathways. Furthermore, the expression level of C/EBP homologous protein (CHOP) and glucose-regulated protein 78 (GRP78), key players in endoplasmic reticulum (ER) stress-induced apoptosis, was analyzed using quantitative real-time PCR. Results: A decrease in ONL thickness and the appearance of apoptotic PR nuclei could be detected beginning 3 days post-injection (PI). This was accompanied by an increase of TUNEL-positive cells. Significant upregulation of activated caspases (3, 9, 12) was found at different time periods after MNU injection. Additionally, several other players of nonconventional PCD pathways were also upregulated. Consequently, calpain activity increased in the ONL, with a maximum on day 7 PI and an upregulation of CHOP and GRP78 expression beginning on day 1 PI was found. Conclusions: The data indicate that regular apoptosis is the major cause of MNU-induced PR cell death. However, alternative PCD pathways, including ER stress and calpain activation, are also involved. Knowledge about the mechanisms involved in this mouse model of PR degeneration could facilitate the design of putative combinatory therapeutic approaches.

  • Controlling Parkinson's disease with adaptive deep brain stimulation

    24 October 2018

    Adaptive deep brain stimulation (aDBS) has the potential to improve the treatment of Parkinson's disease by optimizing stimulation in real time according to fluctuating disease and medication state. In the present realization of adaptive DBS we record and stimulate from the DBS electrodes implanted in the subthalamic nucleus of patients with Parkinson's disease in the early post-operative period. Local field potentials are analogue filtered between 3 and 47 Hz before being passed to a data acquisition unit where they are digitally filtered again around the patient specific beta peak, rectified and smoothed to give an online reading of the beta amplitude. A threshold for beta amplitude is set heuristically, which, if crossed, passes a trigger signal to the stimulator. The stimulator then ramps up stimulation to a pre-determined clinically effective voltage over 250 msec and continues to stimulate until the beta amplitude again falls down below threshold. Stimulation continues in this manner with brief episodes of ramped DBS during periods of heightened beta power. Clinical efficacy is assessed after a minimum period of stabilization (5 min) through the unblinded and blinded video assessment of motor function using a selection of scores from the Unified Parkinson's Rating Scale (UPDRS). Recent work has demonstrated a reduction in power consumption with aDBS as well as an improvement in clinical scores compared to conventional DBS. Chronic aDBS could now be trialed in Parkinsonism. © JoVE 2006-2014. All Rights Reserved.

  • Ecotoxicological risk assessment of hospital wastewater and management recommendations

    24 October 2018

    © 2015, Institut National de la Research Scientifique. All rights reserved. The ecotoxicological risk assessment of hospital effluents is necessary for their management, given their concentrations in pollutants toxic to aquatic organisms, such as disinfectants, detergents, or pharmaceutical residues. To do this, a battery of complementary ecotoxicity tests has been deployed at different sites of the Hospices Civils de Lyon. Monitoring ecotoxicity of effluents during a daily activity showed strong evolution of the latter depending on the activities of the site. Measurement of the ecotoxicity of the particulate fraction of the effluent demonstrated the major contribution of the latter to the total ecotoxicity of the effluent. Parallel to this experimental work, a theoretical study, on all pharmaceuticals consumed in Lyon hospitals, identified to 14 priority medicines to be studied because of their particularly bioaccumulative nature, and their capacity therefore to lead to a significant impact on aquatic organisms and trophic chains. An ecotoxicological risk assessment of these pharmaceuticals was then undertaken, coupling the estimation of their concentration in the receiving medium, and the characterization of their ecotoxicity. This ecotoxicological risk assessment demonstrated the importance of bioaccumulative pharmaceuticals in the overall risk posed by hospital effluents. Based on these results, discussions have been initiated to reduce the risk via different treatments at source and/or pretreatment of these effluents before discharge into the urban sewage network.