622 research outputs found
Cerebral Gaseous Microemboli are Detectable During Continuous Venovenous Hemodialysis in Critically Ill Patients: An Observational Pilot Study
BACKGROUND
Continuous venovenous hemodialysis (CVVHD) may generate microemboli that cross the pulmonary circulation and reach the brain. The aim of the present study was to quantify (load per time interval) and qualify (gaseous vs. solid) cerebral microemboli (CME), detected as high-intensity transient signals, using transcranial Doppler ultrasound.
MATERIALS AND METHODS
Twenty intensive care unit (ICU group) patients requiring CVVHD were examined. CME were recorded in both middle cerebral arteries for 30 minutes during CVVHD and a CVVHD-free interval. Twenty additional patients, hospitalized for orthopedic surgery, served as a non-ICU control group. Statistical analyses were performed using the Mann-Whitney U test or the Wilcoxon matched-pairs signed-rank test, followed by Bonferroni corrections for multiple comparisons.
RESULTS
In the non-ICU group, 48 (14.5-169.5) (median [range]) gaseous CME were detected. In the ICU group, the 67.5 (14.5-588.5) gaseous CME detected during the CVVHD-free interval increased 5-fold to 344.5 (59-1019) during CVVHD (P<0.001). The number of solid CME was low in all groups (non-ICU group: 2 [0-5.5]; ICU group CVVHD-free interval: 1.5 [0-14.25]; ICU group during CVVHD: 7 [3-27.75]).
CONCLUSIONS
This observational pilot study shows that CVVHD was associated with a higher gaseous but not solid CME burden in critically ill patients. Although the differentiation between gaseous and solid CME remains challenging, our finding may support the hypothesis of microbubble generation in the CVVHD circuit and its transpulmonary translocation toward the intracranial circulation. Importantly, the impact of gaseous and solid CME generated during CVVHD on brain integrity of critically ill patients currently remains unknown and is highly debated
Oxygen-sensitive 3He-MRI in bronchiolitis obliterans after lung transplantation
Oxygen-sensitive 3He-MRI was studied for the detection of differences in intrapulmonary oxygen partial pressure (pO2) between patients with normal lung transplants and those with bronchiolitis obliterans syndrome (BOS). Using software developed in-house, oxygen-sensitive 3He-MRI datasets from patients with normal lung grafts (n = 8) and with BOS (n = 6) were evaluated quantitatively. Datasets were acqiured on a 1.5-T system using a spoiled gradient echo pulse sequence. Underlying diseases were pulmonary emphysema (n = 10 datasets) and fibrosis (n = 4). BOS status was verified by pulmonary function tests. Additionally, 3He-MRI was assessed blindedly for ventilation defects. Median intrapulmonary pO2 in patients with normal lung grafts was 146 mbar compared with 108 mbar in patients with BOS. Homogeneity of pO2 distribution was greater in normal grafts (standard deviation pO2 34 versus 43 mbar). Median oxygen decrease rate during breath hold was higher in unaffected patients (−1.75 mbar/s versus −0.38 mbar/s). Normal grafts showed fewer ventilation defects (5% versus 28%, medians). Oxygen-sensitive 3He-MRI appears capable of demonstrating differences of intrapulmonary pO2 between normal lung grafts and grafts affected by BOS. Oxygen-sensitive 3He-MRI may add helpful regional information to other diagnostic techniques for the assessment and follow-up of lung transplant recipients
Endothelin receptor B antagonists decrease glioma cell viability independently of their cognate receptor
Background:
Endothelin receptor antagonists inhibit the progression of many cancers, but research into their influence on glioma has been limited.
Methods:
We treated glioma cell lines, LN-229 and SW1088, and melanoma cell lines, A375 and WM35, with two endothelin receptor type B (ETRB)-specific antagonists, A-192621 and BQ788, and quantified viable cells by the capacity of their intracellular esterases to convert non-fluorescent calcein AM into green-fluorescent calcein. We assessed cell proliferation by labeling cells with carboxyfluorescein diacetate succinimidyl ester and quantifying the fluorescence by FACS analysis. We also examined the cell cycle status using BrdU/propidium iodide double staining and FACS analysis. We evaluated changes in gene expression by microarray analysis following treatment with A-192621 in glioma cells. We examined the role of ETRB by reducing its expression level using small interfering RNA (siRNA).
Results:
We report that two ETRB-specific antagonists, A-192621 and BQ788, reduce the number of viable cells in two glioma cell lines in a dose- and time-dependent manner. We describe similar results for two melanoma cell lines. The more potent of the two antagonists, A-192621, decreases the mean number of cell divisions at least in part by inducing a G2/M arrest and apoptosis. Microarray analysis of the effects of A-192621 treatment reveals up-regulation of several DNA damage-inducible genes. These results were confirmed by real-time RT-PCR. Importantly, reducing expression of ETRB with siRNAs does not abrogate the effects of either A-192621 or BQ788 in glioma or melanoma cells. Furthermore, BQ123, an endothelin receptor type A (ETRA)-specific antagonist, has no effect on cell viability in any of these cell lines, indicating that the ETRB-independent effects on cell viability exhibited by A-192621 and BQ788 are not a result of ETRA inhibition.
Conclusion:
While ETRB antagonists reduce the viability of glioma cells in vitro, it appears unlikely that this effect is mediated by ETRB inhibition or cross-reaction with ETRA. Instead, we present evidence that A-192621 affects glioma and melanoma viability by activating stress/DNA damage response pathways, which leads to cell cycle arrest and apoptosis. This is the first evidence linking ETRB antagonist treatment to enhanced expression of DNA damage-inducible genes
Mutual Regulation of Bcl-2 Proteins Independent of the BH3 Domain as Shown by the BH3-Lacking Protein Bcl-xAK
The BH3 domain of Bcl-2 proteins was regarded as indispensable for apoptosis induction and for mutual regulation of family members. We recently described Bcl-xAK, a proapoptotic splice product of the bcl-x gene, which lacks BH3 but encloses BH2, BH4 and a transmembrane domain. It remained however unclear, how Bcl-xAK may trigger apoptosis
Gravitational clustering of relic neutrinos and implications for their detection
We study the gravitational clustering of big bang relic neutrinos onto
existing cold dark matter (CDM) and baryonic structures within the flat
CDM model, using both numerical simulations and a semi-analytical
linear technique, with the aim of understanding the neutrinos' clustering
properties for direct detection purposes. In a comparative analysis, we find
that the linear technique systematically underestimates the amount of
clustering for a wide range of CDM halo and neutrino masses. This invalidates
earlier claims of the technique's applicability. We then compute the exact
phase space distribution of relic neutrinos in our neighbourhood at Earth, and
estimate the large scale neutrino density contrasts within the local
Greisen--Zatsepin--Kuzmin zone. With these findings, we discuss the
implications of gravitational neutrino clustering for scattering-based
detection methods, ranging from flux detection via Cavendish-type torsion
balances, to target detection using accelerator beams and cosmic rays. For
emission spectroscopy via resonant annihilation of extremely energetic cosmic
neutrinos on the relic neutrino background, we give new estimates for the
expected enhancement in the event rates in the direction of the Virgo cluster.Comment: 38 pages, 8 embedded figures, iopart.cls; v2: references added, minor
changes in text, to appear in JCA
Ultra-High Energy Neutrino Fluxes: New Constraints and Implications
We apply new upper limits on neutrino fluxes and the diffuse extragalactic
component of the GeV gamma-ray flux to various scenarios for ultra high energy
cosmic rays and neutrinos. As a result we find that extra-galactic top-down
sources can not contribute significantly to the observed flux of highest energy
cosmic rays. The Z-burst mechanism where ultra-high energy neutrinos produce
cosmic rays via interactions with relic neutrinos is practically ruled out if
cosmological limits on neutrino mass and clustering apply.Comment: 10 revtex pages, 9 postscript figure
Relic Neutrino Absorption Spectroscopy
Resonant annihilation of extremely high-energy cosmic neutrinos on big-bang
relic anti-neutrinos (and vice versa) into Z-bosons leads to sizable absorption
dips in the neutrino flux to be observed at Earth. The high-energy edges of
these dips are fixed, via the resonance energies, by the neutrino masses alone.
Their depths are determined by the cosmic neutrino background density, by the
cosmological parameters determining the expansion rate of the universe, and by
the large redshift history of the cosmic neutrino sources. We investigate the
possibility of determining the existence of the cosmic neutrino background
within the next decade from a measurement of these absorption dips in the
neutrino flux. As a by-product, we study the prospects to infer the absolute
neutrino mass scale. We find that, with the presently planned neutrino
detectors (ANITA, Auger, EUSO, OWL, RICE, and SalSA) operating in the relevant
energy regime above 10^{21} eV, relic neutrino absorption spectroscopy becomes
a realistic possibility. It requires, however, the existence of extremely
powerful neutrino sources, which should be opaque to nucleons and high-energy
photons to evade present constraints. Furthermore, the neutrino mass spectrum
must be quasi-degenerate to optimize the dip, which implies m_{nu} >~ 0.1 eV
for the lightest neutrino. With a second generation of neutrino detectors,
these demanding requirements can be relaxed considerably.Comment: 19 pages, 26 figures, REVTeX
Methods for specifying the target difference in a randomised controlled trial : the Difference ELicitation in TriAls (DELTA) systematic review
Peer reviewedPublisher PD
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