62 research outputs found
Phenotyping malignant hyperthermia susceptibility by measuring halothane‐induced changes in myoplasmic calcium concentration in cultured human skeletal muscle cells
Background. Malignant hyperthermia (MH) is a potentially lethal disease triggered by volatile anaesthetics and succinylcholine in genetically predisposed individuals. Because of the heterogenetic nature of MH, a simple genetic‐based diagnostic test is not feasible and diagnosis requires an invasive open muscle biopsy followed by the in vitro contracture test (IVCT). Our aim was to establish if measurements of halothane‐induced increases in intracellular calcium ion concentration [Ca2+]i in cultured human skeletal muscle cells can be used to phenotype MH susceptibility and if different mutations in the ryanodine receptor (RYR1) gene affect halothane‐induced increases in [Ca2+]i. Methods. Primary cultures of human skeletal muscle cells were established from 54 individuals diagnosed by the IVCT according to the protocol of the European MH Group as: MH susceptible (n=22), MH negative (n=18) or MH equivocal (n=14). All individuals were screened for the presence of the most common mutations in the RYR1 gene. [Ca2+]i was measured by fluorescent digital microscopy using fura‐2/AM in 10 cells from each patient at five different halothane concentrations. Results. The halothane‐induced increase in [Ca2+]i differed significantly between the three diagnostic groups. Different mutations of the RYR1 gene did not have a specific impact on halothane‐induced increases in [Ca2+]i. Conclusions. Measurements of [Ca2+]i in human skeletal muscle cells can be used to phenotype MH susceptibility; however, we did not observe a specific effect of any mutation in the RYR1 gene on the halothane‐induced increase in [Ca2+]i. Br J Anaesth 2002; 89: 571-
IN VITRO EFFECT OF EPHEDRINE, ADRENALINE, NORADRENALINE AND ISOPRENALINE ON HALOTHANE-INDUCED CONTRACTURES IN SKELETAL MUSCLE FROM PATIENTS POTENTIALLY SUSCEPTIBLE TO MALIGNANT HYPERTHERMIA
SUMMARY We have measured the effects of ephedrine, adrenaline, noradrenaline and isoprenaline on halothaneinduced contractures in muscle biopsies from patients potentially susceptible to malignant hyperthermia (MH). At concentrations of 4-24 mmol litre−1, ephedrine induced in vitro contractures in halothane 0.44 mmol litre−1-prechallenged muscle, whilst adrenaline, noradrenaline and isoprenaline had no effect. There was a shift of the ephedrine concentration-response curve to theleft and an increased maximum muscle contracturein the MH susceptible group compared with the MH negative group (P < 0.001). We conclude that ephedrine increased halothane-induced muscle contractures in vitro either by an unknown pharmacological mechanism or by an adrenergic stimulation which was different from those of the other investigatedadrenoceptoragonists. (Br. J. Anaesth. 1993; 70:76-79
Identification of backgrounds in the EDELWEISS-I dark matter search experiment
This paper presents our interpretation and understanding of the different
backgrounds in the EDELWEISS-I data sets. We analyze in detail the several
populations observed, which include gammas, alphas, neutrons, thermal sensor
events and surface events, and try to combine all data sets to provide a
coherent picture of the nature and localisation of the background sources. In
light of this interpretation, we draw conclusions regarding the background
suppression scheme for the EDELWEISS-II phase
Measurement of the response of heat-and-ionization germanium detectors to nuclear recoils
The heat quenching factor Q' (the ratio of the heat signals produced by
nuclear and electron recoils of equal energy) of the heat-and-ionization
germanium bolometers used by the EDELWEISS collaboration has been measured. It
is explained how this factor affects the energy scale and the effective
quenching factor observed in calibrations with neutron sources. This effective
quenching effect is found to be equal to Q/Q', where Q is the quenching factor
of the ionization yield. To measure Q', a precise EDELWEISS measurement of Q/Q'
is combined with values of Q obtained from a review of all available
measurements of this quantity in tagged neutron beam experiments. The
systematic uncertainties associated with this method to evaluate Q' are
discussed in detail. For recoil energies between 20 and 100 keV, the resulting
heat quenching factor is Q' = 0.91+-0.03+-0.04, where the two errors are the
contributions from the Q and Q/Q' measurements, respectively. The present
compilation of Q values and evaluation of Q' represent one of the most precise
determinations of the absolute energy scale for any detector used in direct
searches for dark matter.Comment: 28 pages, 7 figures. Submitted to Phys. Rev.
Final results of the EDELWEISS-II WIMP search using a 4-kg array of cryogenic germanium detectors with interleaved electrodes
The EDELWEISS-II collaboration has completed a direct search for WIMP dark
matter with an array of ten 400-g cryogenic germanium detectors in operation at
the Laboratoire Souterrain de Modane. The combined use of thermal phonon
sensors and charge collection electrodes with an interleaved geometry enables
the efficient rejection of gamma-induced radioactivity as well as near-surface
interactions. A total effective exposure of 384 kg.d has been achieved, mostly
coming from fourteen months of continuous operation. Five nuclear recoil
candidates are observed above 20 keV, while the estimated background is 3.0
events. The result is interpreted in terms of limits on the cross-section of
spin-independent interactions of WIMPs and nucleons. A cross-section of
4.4x10^-8 pb is excluded at 90%CL for a WIMP mass of 85 GeV. New constraints
are also set on models where the WIMP-nucleon scattering is inelastic.Comment: 23 pages, 5 figures; matches published versio
A search for low-mass WIMPs with EDELWEISS-II heat-and-ionization detectors
We report on a search for low-energy (E < 20 keV) WIMP-induced nuclear
recoils using data collected in 2009 - 2010 by EDELWEISS from four germanium
detectors equipped with thermal sensors and an electrode design (ID) which
allows to efficiently reject several sources of background. The data indicate
no evidence for an exponential distribution of low-energy nuclear recoils that
could be attributed to WIMP elastic scattering after an exposure of 113 kg.d.
For WIMPs of mass 10 GeV, the observation of one event in the WIMP search
region results in a 90% CL limit of 1.0x10^-5 pb on the spin-independent
WIMP-nucleon scattering cross-section, which constrains the parameter space
associated with the findings reported by the CoGeNT, DAMA and CRESST
experiments.Comment: PRD rapid communication accepte
Background studies for the EDELWEISS dark matter experiment
The EDELWEISS-II collaboration has completed a direct search for WIMP dark
matter using cryogenic Ge detectors (400 g each) and 384 kgdays of
effective exposure. A cross-section of pb is excluded at
90% C.L. for a WIMP mass of 85 GeV. The next phase, EDELWEISS-III, aims to
probe spin-independent WIMP-nucleon cross-sections down to a few
pb. We present here the study of gamma and neutron background
coming from radioactive decays in the set-up and shielding materials. We have
carried out Monte Carlo simulations for the completed EDELWEISS-II setup with
GEANT4 and normalised the expected background rates to the measured
radioactivity levels (or their upper limits) of all materials and components.
The expected gamma-ray event rate in EDELWEISS-II at 20-200 keV agrees with the
observed rate of 82 events/kg/day within the uncertainties in the measured
concentrations. The calculated neutron rate from radioactivity of 1.0-3.1
events (90% C.L.) at 20-200 keV in the EDELWEISS-II data together with the
expected upper limit on the misidentified gamma-ray events (), surface
betas (), and muon-induced neutrons (), do not contradict 5
observed events in nuclear recoil band. We have then extended the simulation
framework to the EDELWEISS-III configuration with 800 g crystals, better
material purity and additional neutron shielding inside the cryostat. The
gamma-ray and neutron backgrounds in 24 kg fiducial mass of EDELWEISS-III have
been calculated as 14-44 events/kg/day and 0.7-1.4 events per year,
respectively. The results of the background studies performed in the present
work have helped to select better purity components and improve shielding in
EDELWEISS-III to further reduce the expected rate of background events in the
next phase of the experiment.Comment: 15 pages, 9 figures, to be published in Astroparticle Physic
Muon-induced background in the EDELWEISS dark matter search
A dedicated analysis of the muon-induced background in the EDELWEISS dark
matter search has been performed on a data set acquired in 2009 and 2010. The
total muon flux underground in the Laboratoire Souterrain de Modane (LSM) was
measured to be \,muons/m/d. The
modular design of the muon-veto system allows the reconstruction of the muon
trajectory and hence the determination of the angular dependent muon flux in
LSM. The results are in good agreement with both MC simulations and earlier
measurements. Synchronization of the muon-veto system with the phonon and
ionization signals of the Ge detector array allowed identification of
muon-induced events. Rates for all muon-induced events and of WIMP-like events were extracted. After
vetoing, the remaining rate of accepted muon-induced neutrons in the
EDELWEISS-II dark matter search was determined to be at 90%\,C.L. Based on
these results, the muon-induced background expectation for an anticipated
exposure of 3000\,\kgd\ for EDELWEISS-3 is
events.Comment: 21 pages, 16 figures, Accepted for publication in Astropart. Phy
Axion searches with the EDELWEISS-II experiment
We present new constraints on the couplings of axions and more generic
axion-like particles using data from the EDELWEISS-II experiment. The EDELWEISS
experiment, located at the Underground Laboratory of Modane, primarily aims at
the direct detection of WIMPs using germanium bolometers. It is also sensitive
to the low-energy electron recoils that would be induced by solar or dark
matter axions. Using a total exposure of up to 448 kg.d, we searched for
axion-induced electron recoils down to 2.5 keV within four scenarios involving
different hypotheses on the origin and couplings of axions. We set a 95% CL
limit on the coupling to photons GeV in
a mass range not fully covered by axion helioscopes. We also constrain the
coupling to electrons, , similar to the more
indirect solar neutrino bound. Finally we place a limit on , where is the
effective axion-nucleon coupling for Fe. Combining these results we
fully exclude the mass range keV for DFSZ axions and
keV for KSVZ axions
Final results of the EDELWEISS-I dark matter search with cryogenic heat-and-ionization Ge detectors
The final results of the EDELWEISS-I dark matter search using cryogenic
heat-and-ionization Ge detectors are presented. The final data sample
corresponds to an increase by a factor five in exposure relative to the
previously published results. A recoil energy threshold of 13 keV or better was
achieved with three 320g detectors working simultaneously over four months of
stable operation. Limits on the spin-independent cross-section for the
scattering of a WIMP on a nucleon are derived from an accumulated fiducial
exposure of 62 kg.d.Comment: 42 pages, 16 figures, submitted to Physical Review D, 1 figure and 2
references added, some little changes in the tex
- …