Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis.

BACKGROUND: An open-label study indicated that selective depletion of B cells with the use of rituximab led to sustained clinical improvements for patients with rheumatoid arthritis. To confirm these observations, we conducted a randomized, double-blind, controlled study. METHODS: We randomly assigned 161 patients who had active rheumatoid arthritis despite treatment with methotrexate to receive one of four treatments: oral methotrexate (> or =10 mg per week) (control); rituximab (1000 mg on days 1 and 15); rituximab plus cyclophosphamide (750 mg on days 3 and 17); or rituximab plus methotrexate. Responses defined according to the criteria of the American College of Rheumatology (ACR) and the European League against Rheumatism (EULAR) were assessed at week 24 (primary analyses) and week 48 (exploratory analyses). RESULTS: At week 24, the proportion of patients with 50 percent improvement in disease symptoms according to the ACR criteria, the primary end point, was significantly greater with the rituximab-methotrexate combination (43 percent, P=0.005) and the rituximab-cyclophosphamide combination (41 percent, P=0.005) than with methotrexate alone (13 percent). In all groups treated with rituximab, a significantly higher proportion of patients had a 20 percent improvement in disease symptoms according to the ACR criteria (65 to 76 percent vs. 38 percent, P< or =0.025) or had EULAR responses (83 to 85 percent vs. 50 percent, P< or =0.004). All ACR responses were maintained at week 48 in the rituximab-methotrexate group. The majority of adverse events occurred with the first rituximab infusion: at 24 weeks, serious infections occurred in one patient (2.5 percent) in the control group and in four patients (3.3 percent) in the rituximab groups. Peripheral-blood immunoglobulin concentrations remained within normal ranges. CONCLUSIONS: In patients with active rheumatoid arthritis despite methotrexate treatment, a single course of two infusions of rituximab, alone or in combination with either cyclophosphamide or continued methotrexate, provided significant improvement in disease symptoms at both weeks 24 and 48

Фармакогностический анализ сабельника болотного

АВТОРЕФЕРАТЫ ДИССЕРТАЦИЙБИОЛОГИЧЕСКИ АКТИВНЫЕ ВЕЩЕСТВАЛЕКАРСТВЕННЫЕ СРЕДСТВАРАСТЕНИЯ ЛЕКАРСТВЕННЫЕРАСТИТЕЛЬНОЕ ЛЕКАРСТВЕННОЕ СЫРЬЕСАБЕЛЬНИК БОЛОТНЫЙФАРМАКОГНОЗИЯФАРМАКОЛОГИЯФИТОПРЕПАРАТЫХИМИЯ ФАРМАЦЕВТИЧЕСКА

Controlling shot noise in double-barrier magnetic tunnel junctions

We demonstrate that shot noise in Fe/MgO/Fe/MgO/Fe double-barrier magnetic tunnel junctions is determined by the relative magnetic configuration of the junction and also by the asymmetry of the barriers. The proposed theoretical model, based on sequential tunneling through the system and including spin relaxation, successfully accounts for the experimental observations for bias voltages below 0.5V, where the influence of quantum well states is negligible. A weak enhancement of conductance and shot noise, observed at some voltages (especially above 0.5V), indicates the formation of quantum well states in the middle magnetic layer. The observed results open up new perspectives for a reliable magnetic control of the most fundamental noise in spintronic structures.Comment: 8 pages, 4 figure

Visible photodissociation spectroscopy of PAH cations and derivatives in the PIRENEA experiment

The electronic spectra of gas-phase cationic polycyclic aromatic hydrocarbons (PAHs), trapped in the Fourier Transform Ion Cyclotron Resonance cell of the PIRENEA experiment, have been measured by multiphoton dissociation spectroscopy in the 430-480 nm spectral range using the radiation of a mid-band optical parametric oscillator laser. We present here the spectra recorded for different species of increasing size, namely the pyrene cation (C16H10+), the 1-methylpyrene cation (CH3-C16H9+), the coronene cation (C24H12+), and its dehydrogenated derivative C24H10+. The experimental results are interpreted with the help of time-dependent density functional theory calculations and analysed using spectral information on the same species obtained from matrix isolation spectroscopy data. A kinetic Monte Carlo code has also been used, in the case of pyrene and coronene cations, to estimate the absorption cross-sections of the measured electronic transitions. Gas-phase spectra of highly reactive species such as dehydrogenated PAH cations are reported for the first time

Theory of Dynamic Stripe Induced Superconductivity

Since the recently reported giant isotope effect on T* [1] could be consistently explained within an anharmonic spin-charge-phonon interaction model, we consider here the role played by stripe formation on the superconducting properties within the same model. This is a two-component scenario and we recast its basic elements into a BCS effective Hamiltonian. We find that the stripe formation is vital to high-Tc superconductivity since it provides the glue between the two components to enhance Tc to the unexpectedly large values observed experimentally.Comment: 7 pages, 2 figure

Anomalous Spin and Charge Dynamics of the 2D t-J Model at low doping

We present an exact diagonalization study of the dynamical spin and density correlation function of the 2D t-J model for hole doping < 25%. Both correlation functions show a remarkably regular, but completely different scaling behaviour with both hole concentration and parameter values: the density correlation function is consistent with that of bosons corresponding to the doped holes and condensed into the lowest state of the noninteracting band of width 8t, the spin correlation function is consistent with Fermions in a band of width J. We show that the spin bag picture gives a natural explanation for this unusual behaviour.Comment: Revtex-file, 4 PRB pages + 5 figures attached as uu-encoded ps-files Hardcopies of figures (or the entire manuscript) can also be obtained by e-mailing to: [email protected]

Spin and Charge Texture around In-Plane Charge Centers in the CuO_2 planes

Recent experiments on La_2Cu_{1-x}Li_xO_4 show that although the doped holes remain localized near the substitutional Li impurities, magnetic order is rapidly suppressed. An examination of the spin texture around a bound hole in a CuO_2 plane shows that the formation of a skyrmion is favored in a wide range of parameters, as was previously proposed in the context of Sr doping. The spin texture may be observable by elastic diffuse neutron scattering, and may also have a considerable effect on NMR lineshapes.Comment: 4 pages, postscript file, hardcopy available upon request, to appear in PR

Hole dynamics in generalized spin backgrounds in infinite dimensions

We calculate the dynamical behaviour of a hole in various spin backgrounds in infinite dimensions, where it can be determined exactly. We consider hypercubic lattices with two different types of spin backgrounds. On one hand we study an ensemble of spin configurations with an arbitrary spin probability on each sublattice. This model corresponds to a thermal average over all spin configurations in the presence of staggered or uniform magnetic fields. On the other hand we consider a definite spin state characterized by the angle between the spins on different sublattices, i.e a classical spin system in an external magnetic field. When spin fluctuations are considered, this model describes the physics of unpaired particles in strong coupling superconductors.Comment: Accepted in Phys. Rev. B. 18 pages of text (1 fig. included) in Latex + 2 figures in uuencoded form containing the 2 postscripts (mailed separately