Safety and Feasibility of Long-term Intravenous Sodium Nitrite Infusion in Healthy Volunteers

BACKGROUND: Infusion of sodium nitrite could provide sustained therapeutic concentrations of nitric oxide (NO) for the treatment of a variety of vascular disorders. The study was developed to determine the safety and feasibility of prolonged sodium nitrite infusion. METHODOLOGY: Healthy volunteers, aged 21 to 60 years old, were candidates for the study performed at the National Institutes of Health (NIH; protocol 05-N-0075) between July 2007 and August 2008. All subjects provided written consent to participate. Twelve subjects (5 males, 7 females; mean age, 38.8±9.2 years (range, 21-56 years)) were intravenously infused with increasing doses of sodium nitrite for 48 hours (starting dose at 4.2 µg/kg/hr; maximal dose of 533.8 µg/kg/hr). Clinical, physiologic and laboratory data before, during and after infusion were analyzed. FINDINGS: The maximal tolerated dose for intravenous infusion of sodium nitrite was 267 µg/kg/hr. Dose limiting toxicity occurred at 446 µg/kg/hr. Toxicity included a transient asymptomatic decrease of mean arterial blood pressure (more than 15 mmHg) and/or an asymptomatic increase of methemoglobin level above 5%. Nitrite, nitrate, S-nitrosothiols concentrations in plasma and whole blood increased in all subjects and returned to preinfusion baseline values within 12 hours after cessation of the infusion. The mean half-life of nitrite estimated at maximal tolerated dose was 45.3 minutes for plasma and 51.4 minutes for whole blood. CONCLUSION: Sodium nitrite can be safely infused intravenously at defined concentrations for prolonged intervals. These results should be valuable for developing studies to investigate new NO treatment paradigms for a variety of clinical disorders, including cerebral vasospasm after subarachnoid hemorrhage, and ischemia of the heart, liver, kidney and brain, as well as organ transplants, blood-brain barrier modulation and pulmonary hypertension. CLINICAL TRIAL REGISTRATION INFORMATION: http://www.clinicaltrials.gov; NCT00103025

Structure specific analysis of the hippocampus in temporal lobe epilepsy

The hippocampus is a major structure of interest affected by temporal lobe epilepsy (TLE). Region of interest (ROI)-based analysis has traditionally been used to study hippocampal involvement in TLE, although spatial variation of structural and functional pathology have been known to exist within the ROI. In this article, structure-specific analysis (Yushkevich et al. (2007) Neuroimage 35:1516–1530) is applied to the study of both structure and function in TLE patients. This methodology takes into account information about the spatial correspondence of voxels within ROIs on left and right sides of the same subject as well as between subjects. Hippocampal thickness is studied as a measure of structural integrity, and functional activation in a functional magnetic resonance imaging (fMRI) experiment in which subjects performed a memory encoding task is studied as a measure of functional integrity. Pronounced disease-related decrease in thickness is found in posterior and anterior hippocampus. A region in the body also shows increased thickness in patients' healthy hippocampi compared with controls. Functional activation in diseased hippocampi is reduced in the body region compared to controls, whereas a region in the tail showing greater right-lateralized activation in controls also shows greater activation in healthy hippocampi compared with the diseased side in patients. Summary measurements generated by integrating quantities of interest over the entire hippocampus can also be used, as is done in conventional ROI analysis. © 2009 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63055/1/20620_ftp.pd

Particle Correlations with Heavy Ions at LHC Energies

The ALICE detector will offer very good conditions to study the space-time characteristics of particle production in heavy-ion collisions at LHC from measurements of the correlation function of identical and non-identical particles at small relative velocities. The correlations - induced by Coulomb and nuclear final-state interactions - of non-identical particles appear to be directly sensitive to the space-time asymmetries of particle production allowing, in particular, a measurement of the mean relative delays in particle emission at time scales as small as few fm/c. The problem of Coulomb interaction of the correlated particles is particularly important in the case of the large effective volumes formed in ultra-relativistic heavy-ion reactions

Influence of temporal lobe epilepsy and temporal lobe resection on olfaction

Although temporal lobe epilepsy (TLE) and resection (TLR) impact olfactory eloquent brain structures, their influences on olfaction remain enigmatic. We sought to more definitively assess the influences of TLE and TLR using three well-validated olfactory tests and the tests’ associations with the volume of numerous temporal lobe brain structures. The University of Pennsylvania Smell Identification Test and an odor detection threshold test were administered to 71 TLE patients and 71 age- and sex-matched controls; 69 TLE patients and controls received an odor discrimination/ memory test. Fifty-seven patients and 57 controls were tested on odor identification and threshold before and after TLR; 27 patients and 27 controls were similarly tested for odor detection/discrimination. Scores were compared using analysis of variance and correlated with pre- and post-operative volumes of the target brain structures. TLE was associated with bilateral deficits in all test measures. TLR further decreased function on the side ipsilateral to resection. The hippocampus and other structures were smaller on the focus side of the TLE subjects. Although post-operative volumetric decreases were evident in most measured brain structures, modest contralateral volumetric increases were observed in some cases. No meaningful correlations were evident pre- or post-operatively between the olfactory test scores and the structural volumes. In conclusion, we demonstrate that smell dysfunction is clearly a key element of both TLE and TLR, impacting odor identification, detection, and discrimination/memory. Whether our novel finding of significant post-operative increases in the volume of brain structures contralateral to the resection side reflects plasticity and compensatory processes requires further study

Phase-space dependence of particle-ratio fluctuations in Pb+Pb collisions from 20A to 158A GeV beam energy

A novel approach, the identity method, was used for particle identification and the study of fluctuations of particle yield ratios in Pb+Pb collisions at the CERN Super Proton Synchrotron (SPS). This procedure allows to unfold the moments of the unknown multiplicity distributions of protons (p), kaons (K), pions ($\pi$) and electrons (e). Using these moments the excitation function of the fluctuation measure $\nu_{\text{\text{dyn}}}$[A,B] was measured, with A and B denoting different particle types. The obtained energy dependence of $\nu_{\text{dyn}}$ agrees with previously published NA49 results on the related measure $\sigma_{\text{dyn}}$. Moreover, $\nu_{\text{dyn}}$ was found to depend on the phase space coverage for [K,p] and [K,$\pi$] pairs. This feature most likely explains the reported differences between measurements of NA49 and those of STAR in central Au+Au collisions

Measurement of event-by-event transverse momentum and multiplicity fluctuations using strongly intensive measures Δ[PT,N]\Delta[P_T, N] and Σ[PT,N]\Sigma[P_T, N] in nucleus-nucleus collisions at the CERN Super Proton Synchrotron

Results from the NA49 experiment at the CERN SPS are presented on event-by-event transverse momentum and multiplicity fluctuations of charged particles, produced at forward rapidities in central Pb+Pb interactions at beam momenta 20$A$, 30$A$, 40$A$, 80$A$, and 158$A$ GeV/c, as well as in systems of different size ($p+p$, C+C, Si+Si, and Pb+Pb) at 158$A$ GeV/c. This publication extends the previous NA49 measurements of the strongly intensive measure $\Phi_{p_T}$ by a study of the recently proposed strongly intensive measures of fluctuations $\Delta[P_T, N]$ and $\Sigma[P_T, N]$. In the explored kinematic region transverse momentum and multiplicity fluctuations show no significant energy dependence in the SPS energy range. However, a remarkable system size dependence is observed for both $\Delta[P_T, N]$ and $\Sigma[P_T, N]$, with the largest values measured in peripheral Pb+Pb interactions. The results are compared with NA61/SHINE measurements in $p+p$ collisions, as well as with predictions of the UrQMD and EPOS models.Comment: 12 pages, 14 figures, to be submitted to PR

Measurement of Production Properties of Positively Charged Kaons in Proton-Carbon Interactions at 31 GeV/c

Spectra of positively charged kaons in p+C interactions at 31 GeV/c were measured with the NA61/SHINE spectrometer at the CERN SPS. The analysis is based on the full set of data collected in 2007 with a graphite target with a thickness of 4% of a nuclear interaction length. Interaction cross sections and charged pion spectra were already measured using the same set of data. These new measurements in combination with the published ones are required to improve predictions of the neutrino flux for the T2K long baseline neutrino oscillation experiment in Japan. In particular, the knowledge of kaon production is crucial for precisely predicting the intrinsic electron neutrino component and the high energy tail of the T2K beam. The results are presented as a function of laboratory momentum in 2 intervals of the laboratory polar angle covering the range from 20 up to 240 mrad. The kaon spectra are compared with predictions of several hadron production models. Using the published pion results and the new kaon data, the K+/\pi+ ratios are computed.Comment: 10 pages, 11 figure

Pion emission from the T2K replica target: method, results and application

The T2K long-baseline neutrino oscillation experiment in Japan needs precise predictions of the initial neutrino flux. The highest precision can be reached based on detailed measurements of hadron emission from the same target as used by T2K exposed to a proton beam of the same kinetic energy of 30 GeV. The corresponding data were recorded in 2007-2010 by the NA61/SHINE experiment at the CERN SPS using a replica of the T2K graphite target. In this paper details of the experiment, data taking, data analysis method and results from the 2007 pilot run are presented. Furthermore, the application of the NA61/SHINE measurements to the predictions of the T2K initial neutrino flux is described and discussed.Comment: updated version as published by NIM

Proton -- Lambda Correlations in Central Pb+Pb Collisions at sqrt(s_{NN}) = 17.3 GeV

The momentum correlation between protons and lambda particles emitted from central Pb+Pb collisions at sqrt(s_{NN}) = 17.3 GeV was studied by the NA49 experiment at the CERN SPS. A clear enhancement is observed for small relative momenta (q_{inv} < 0.2 GeV). By fitting a theoretical model, which uses the strong interaction between the proton and the lambda in a given pair, to the measured data a value for the effective source size is deduced. Assuming a static Gaussian source distribution we derive an effective radius parameter of R_G = 3.02 \pm 0.20$(stat.)^{+0.44}_{-0.16}(syst.) fm.Comment: 14 pages, 9 figures, submitted to Phys. Rev.

Measurements of π±\pi^\pm, K±K^\pm, KS0K^0_S, Λ\Lambda and proton production in proton-carbon interactions at 31 GeV/cc with the NA61/SHINE spectrometer at the CERN SPS

Measurements of hadron production in p+C interactions at 31 GeV/c are performed using the NA61/ SHINE spectrometer at the CERN SPS. The analysis is based on the full set of data collected in 2009 using a graphite target with a thickness of 4% of a nuclear interaction length. Inelastic and production cross sections as well as spectra of $\pi^\pm$, $K^\pm$, p, $K^0_S$ and $\Lambda$ are measured with high precision. These measurements are essential for improved calculations of the initial neutrino fluxes in the T2K long-baseline neutrino oscillation experiment in Japan. A comparison of the NA61/SHINE measurements with predictions of several hadroproduction models is presented.Comment: v1 corresponds to the preprint CERN-PH-EP-2015-278; v2 matches the final published versio