Quantitation using HRMS: A new tool for rapid, specific and sensitive determination of catecholamines and deconjugated methanephrines metanephrines in urine.

Urinary catecholamines and their methylated metabolites are biochemical indicators of pheochromocytoma, paraganglioma and neuroblastoma. A rapid and precise analytical method based on solid-phase extraction (SPE) and liquid chromatography separation coupled to high-resolution mass spectrometry (LC-HRMS) was developed and validated to measure urinary catecholamines (epinephrine (E), norepinephrine (NorE), dopamine (D)) and total methylated metabolites (normetanephrine (NorMN), metanephrine(MN) and 3-methoxytyramine (3-MT)) in a clinical setting. Results of 51 urine specimens measured using this LC-HRMS method were compared with a liquid chromatography assay with electrochemical detection (LC-EC). Urine samples (200 µL) were spiked with an internal standard solution followed by SPE purification. In the case of total methylated metabolites, urine was hydrolyzed before SPE purification. Separation was achieved on an Acclaim Mixed Mode WCX column, with an 8.5 min runtime. All compounds were detected in electrospray positive ionization mode with a parallel reaction monitoring acquisition and quantified with a linear regression (r2 > 0.998) between 2 and 200 µg/L (10.9-1090; 11.8-1182 nmol/L) for E and NorE respectively and between 10 and 1000 µg/L for others (65.2-6520; 50.7-5070; 54.5-5450 ; 59.8-5980 nmol/L for D, M, NorMN and 3-MT, respectively). Overall imprecision and bias did not exceed 15%. No significant matrix effect was observed. Correlation between the two assays was good except for epinephrine. Epinephrine concentrations measured by LC-EC method were slightly higher than values obtained with LC-HRMS method but without impact on clinical decision. This LC-HRMS assay provides a new tool for simultaneous quantitative catecholamine determination and was successfully applied in routine for the screening or follow up of pheochromocytoma, paraganglioma and neuroblastoma. LC-HRMS method offers significant advantages compared to LC-EC with good sensitivity, an unambiguous analyte determination and high sample throughput.

Evidence for a New Compact Symmetric Fission Mode in Light Thorium Isotopes.

Taking benefit of the R3B/SOFIA setup to measure the mass and the nuclear charge of both fission fragments in coincidence with the total prompt-neutron multiplicity, the scission configurations are inferred along the thorium chain, from the asymmetric fission in the heavier isotopes to the symmetric fission in the neutron-deficient thorium. Against all expectations, the symmetric scission in the light thorium isotopes shows a compact configuration, which is in total contrast to what is known in the fission of the heavier thorium isotopes and heavier actinides. This new main symmetric scission mode is characterized by a significant drop in deformation energy of the fission fragments of about 19 MeV, compared to the well-known symmetric scission in the uranium-plutonium region.

Evidence for the Role of Proton Shell Closure in Quasifission Reactions from X-Ray Fluorescence of Mass-Identified Fragments.

The atomic numbers and the masses of fragments formed in quasifission reactions are simultaneously measured at scission in ^{48}Ti+^{238}U reactions at a laboratory energy of 286 MeV. The atomic numbers are determined from measured characteristic fluorescence x rays, whereas the masses are obtained from the emission angles and times of flight of the two emerging fragments. For the first time, thanks to this full identification of the quasifission fragments on a broad angular range, the important role of the proton shell closure at Z=82 is evidenced by the associated maximum production yield, a maximum predicted by time-dependent Hartree-Fock calculations. This new experimental approach gives now access to precise studies of the time dependence of the N/Z (neutron over proton ratios of the fragments) evolution in quasifission reactions.

A simple ultra-high-performance liquid chromatography-high resolution mass spectrometry assay for the simultaneous quantification of 15 antibiotics in plasma.

Antibiotic (ATB) treatment of critically ill patients with pathophysiological injuries remains a challenge due to the constant increase in antimicrobial resistance. Therapeutic drug monitoring (TDM) is advised for ATB dose adjustments to avoid suboptimal concentrations and dose-related adverse effects. Therefore, a single and reliable analytical method for a broad selection of ATBs was developed using a high-resolution mass spectrometry (HRMS) platform for frequent use in intensive care units. An UHPLC assay coupled to high resolution accurate mass acquisition has been developed for the quantification of penicillins (amoxicillin, oxacillin, piperacillin, and ticarcillin), cephalosporines (cefepime, cefotaxime, ceftazidime, and ceftriaxone), carbapenems (ertapenem, imipenem, and meropenem), lincosamide (clindamycin), quinolones (ofloxacin and ciprofloxacin) and tazobactam. Plasma samples (100µL) were spiked with an internal standard solution followed by protein precipitation. Separation was achieved on an Accucore C18 column, which enabled sample analysis every 9min. All compounds were detected in electrospray positive ion mode and quantified with a linear regression between 0.5 and 32mg/L (r2>0.998). Overall precision and accuracy did not exceed 15%. No significant matrix effect was observed for the studied ATBs. Stored stock solutions at -20°C were stable for 6 months, except for amoxicillin and imipenem. Analytes in plasma were stable for 24h under ambient conditions as well as in post-preparation in an autosampler, except for amoxicillin and imipenem. This HRMS assay provides the simultaneous quantification of 15 ATB; it fulfills the usual quality criteria and was successfully applied for routine TDM of ATBs. The method is based on a full scan acquisition, and it would be easy to add other compounds to the present panel in the future, as this assay has already been proven to be efficient for different classes of compounds.

X-ray fluorescence from the element with atomic number Z=120.

An atomic clock based on x-ray fluorescence yields has been used to estimate the mean characteristic time for fusion followed by fission in reactions 238U + 64Ni at 6.6 MeV/A. Inner shell vacancies are created during the collisions in the electronic structure of the possibly formed Z=120 compound nuclei. The filling of these vacancies accompanied by a x-ray emission with energies characteristic of Z=120 can take place only if the atomic transitions occur before nuclear fission. Therefore, the x-ray yield characteristic of the united atom with 120 protons is strongly related to the fission time and to the vacancy lifetimes. K x rays from the element with Z=120 have been unambiguously identified from a coupled analysis of the involved nuclear reaction mechanisms and of the measured photon spectra. A minimum mean fission time τ(f)=2.5×10(-18) s has been deduced for Z=120 from the measured x-ray multiplicity.

Fission time measurements: a new probe into superheavy element stability.

Reaction mechanism analyses performed with a 4pi detector for the systems 208Pb + Ge, 238U + Ni and 238U + Ge, combined with analyses of the associated reaction time distributions, provide us with evidence for nuclei with Z=120 and 124 living longer than 10(-18) s and arising from highly excited compound nuclei. By contrast, the neutron deficient nuclei with Z=114 possibly formed in 208Pb + Ge reactions have shorter lifetimes, close to or below the sensitivity limit of the experiment.

Measurement of a complete set of nuclides, cross sections, and kinetic energies in spallation of 238U 1A GeV with protons.

Spallation residues and fission fragments from 1A GeV 238U projectiles irradiating a liquid hydrogen target were investigated by using the fragment separator at GSI for magnetic selection of reaction products including ray-tracing, energy-loss and time-of-flight techniques. The longitudinal-momentum spectra of identified fragments were analyzed, and evaporation residues and fission fragments could be separated. For 1385 nuclides, production cross sections down to values of 10 microb with a mean accuracy of 15%, velocities in the uranium rest frame and kinetic energies were determined. In the reaction all elements from uranium to nitrogen were found, each with a large number of isotopes.

Evidence for spinodal decomposition in nuclear multifragmentation.

Multifragmentation of a "fused system" was observed for central collisions between 32 MeV/nucleon 129Xe and (nat)Sn. Most of the resulting charged products were well identified due to the high performances of the INDRA 4pi array. Experimental higher-order charge correlations for fragments show a weak but nonambiguous enhancement of events with nearly equal-sized fragments. Supported by dynamical calculations in which spinodal decomposition is simulated, this observed enhancement is interpreted as a "fossil" signal of spinodal instabilities in finite nuclear systems.

Cross sections of spallation residues produced in 1A GeV 208Pb on proton reactions.

Spallation residues produced in 1 GeV per nucleon 208Pb on proton reactions have been studied using the Fragment Separator facility at GSI. Isotopic production cross sections of elements from 61Pm to 82Pb have been measured down to 0.1 mb with a high accuracy. The recoil kinetic energies of the produced fragments were also determined. The obtained cross sections agree with most of the few existing gamma-spectroscopic data. The data are compared with different intranuclear-cascade and evaporation-fission models. Drastic deviations were found for a standard code used in technical applications.

Simultaneous determination of retinyl esters and retinol in human livers by reversed-phase high-performance liquid chromatography.

A high-performance liquid chromatographic method for the simultaneous determination of retinol and retinyl esters in human liver samples is presented. The free retinol and the prevalent retinyl esters (retinyl palmitate, oleate and stearate) are resolved within less than 30 min, using an octasilyl (C8)-substituted column and an isocratic elution with methanol-water as mobile phase. This method allows to determine in duplicate all retinyl ester concentrations in small liver samples (3-10 mg of fresh tissue). The results obtained from thirteen patients without liver disease are described.

[Beta-2 microglobulin in cerebrospinal fluid in neurology]. / La beta 2-microglobuline du liquide céphalorachidien en neurologie.

OBJECTIVES: beta 2-microglobulin (beta 2-m) is a small molecular weight protein (11 800 Daltons) which can transudate into the cerebrospinal fluid (CSF) in the same manner than albumin. Intrathecal synthesis is a sign of local immuno-stimulation and is correlated with immunoglobulin G. The aim of this study was to ascertain the relationship between beta 2-microglobulin levels in the CSF and neurological diseases. METHODS: beta 2-microglobulin was assayed in the CSF and blood using an immunoenzyme method in 64 patients with multiple sclerosis (n = 14), human immunodeficiency virus (HIV) infection (n = 5), meningitis (n = 12) or a peripheral neurological disease (n = 10) and in 7 control subjects. RESULTS: There was no overall correlation between beta 2-m in the CSF and blood levels (r = 0.35). In controls, beta 2-m CSF and blood levels were respectively 0.94 +/- 0.22 and 1.46 +/- 0.83 mg/l. beta 2-m was significantly higher in the CSF of patients with meningitis and in the HIV positive patients (4 +/- 3.5 and 3.69 +/- 2.06 mg/l respectively) (p < 0.05). Type of meningitis (bacterial or non-bacterial) had no effect on the CSF level. For the HIV patients, the CSF/blood ratio for beta 2-m was similar to that in controls due to a rise in both blood and CSF. Finally, in patients with multiple sclerosis, there was no significant change in CSF level of beta 2-m. CONCLUSION: beta 2-microglobulin in cerebrospinal fluid was not found to be correlated with the neurological diseases studied and cannot be used as a diagnostic test.

[Centromuclear myopathy with late clinical manifestations. Clinical, histological and ultrastructural study of a new case]. / Myopathie centro-nucléaire d'expression clinque tardive. Etude clinique, histologique et ultrastructural d'une nouvelle observation

A new case of late-onset centronuclear myopathy is reported. Clinical manifestations only occurred after 27 years age and consisted in diffuse muscle weakness without any ocular involvement. No other case was found in the family. In muscle biopsies the frequence of central nuclei was close to 100 p. 100. With the myofibrillar A.T.Pase reaction, almost all the fibers were type I. Furthermore, the electron microscopic study showed frequent vacuoles and splitting aspects of the muscle fibres, with "en passant" myotendinous junctions. Unusual granular bodies were found near the basement membrane, in particular within the subneural folds of the end-plates.