Pharmacokinetics and pharmacodynamics of tiotropium solution and tiotropium powder in chronic obstructive pulmonary disease

The aim of the study was to characterize pharmacokinetics of tiotropium solution 5 µg compared to powder 18 µg and assess dose-dependency of tiotropium solution pharmacodynamics in comparison to placebo. In total 154 patients with chronic obstructive pulmonary disease (COPD) were included in this multicenter, randomized, double-blind within-solution (1.25, 2.5, 5 µg, and placebo), and open-label powder 18 µg, crossover study, including 4-week treatment periods. Primary end points were peak plasma concentration (Cmax,ss ), and area under the plasma concentration-time profile (AUC0-6h,ss ), both at steady state. The pharmacodynamic response was assessed by serial spirometry (forced expiratory volume in 1 second/forced vital capacity). Safety was evaluated as adverse events and by electrocardiogram/Holter. Tiotropium was rapidly absorbed with a median tmax,ss of 5-7 minutes postdosing for both devices. The gMean ratio of solution 5 µg over powder 18 µg was 81% (90% confidence interval, 73-89%) for Cmax,ss and 76% (70-82%) for AUC0-6h,ss , indicating that bioequivalence was not established. Dose ordering for bronchodilation was observed. Powder 18 µg and solution 5 µg were most effective, providing comparable bronchodilation. All treatments were well tolerated with no apparent relation to dose or device. Comparable bronchodilator efficacy to powder18 µg at lower systemic exposure supports tiotropium solution 5 µg for maintenance treatment of COPD

Review: ‘Gimme five’: future challenges in multiple sclerosis. ECTRIMS Lecture 2009

This article is based on the ECTRIMS lecture given at the 25th ECTRIMS meeting which was held in Düsseldorf, Germany, from 9 to 12 September 2009. Five challenges have been identified: (1) safeguarding the principles of medical ethics; (2) optimizing the risk/benefit ratio; (3) bridging the gap between multiple sclerosis and experimental autoimmune encephalitis; (4) promoting neuroprotection and repair; and (5) tailoring multiple sclerosis therapy to the individual patient. Each of these challenges will be discussed and placed in the context of current research into the pathogenesis and treatment of multiple sclerosis

Effects of interactions on the relaxation processes in magnetic nanostructures

Controlling the relaxation of magnetization in magnetic nanostructures is key to optimizing magnetic storage device performance. This relaxation is governed by both intrinsic and extrinsic relaxation mechanisms and with the latter strongly dependent on the interactions between the nanostructures. In the present work we investigate laser induced magnetization dynamics in a broadband optical resonance type experiment revealing the role of interactions between nanostructures on the relaxation processes of granular magnetic structures. The results are corroborated by constructing a temperature dependent numerical micromagnetic model of magnetization dynamics based on the Landau-Lifshitz-Bloch equation. The model predicts a strong dependence of damping on the key material properties of coupled granular nanostructures in good agreement with the experimental data. We show that the intergranular, magnetostatic and exchange interactions provide a large extrinsic contribution to the damping. Finally we show that the mechanism can be attributed to an increase in spin-wave degeneracy with the ferromagnetic resonance mode as revealed by semianalytical spin-wave calculations

Capillary buckling of a thin film adhering to a sphere

We present a combined theoretical and experimental study of the buckling of a thin film wrapped around a sphere under the action of capillary forces. A rigid sphere is coated with a wetting liquid, and then wrapped by a thin film into an initially cylindrical shape. The equilibrium of this cylindrical shape is governed by the antagonistic effects of elasticity and capillarity: elasticity tends to keep the film developable while capillarity tends to curve it in both directions so as to maximize the area of contact with the sphere. In the experiments, the contact area between the film and the sphere has cylindrical symmetry when the sphere radius is small, but destabilises to a non-symmetric, wrinkled configuration when the radius is larger than a critical value. We combine the Donnell equations for near-cylindrical shells to include a unilateral constraint with the impenetrable sphere, and the capillary forces acting along a moving edge. A non-linear solution describing the axisymmetric configuration of the film is derived. A linear stability analysis is then presented, which successfully captures the wrinkling instability, the symmetry of the unstable mode, the instability threshold and the critical wavelength. The motion of the free boundary at the edge of the region of contact, which has an effect on the instability, is treated without any approximation

Nonequilibrium Magnetization Dynamics of Nickel

Ultrafast magnetization dynamics of nickel has been studied for different degrees of electronic excitation, using pump-probe second-harmonic generation with 150 fs/800 nm laser pulses of various fluences. Information about the electronic and magnetic response to laser irradiation is obtained from sums and differences of the SHG intensity for opposite magnetization directions. The classical M(T)-curve can be reproduced for delay times larger than the electron thermalization time of about 280 fs, even when electrons and lattice have not reached thermal equilibrium. Further we show that the transient magnetization reaches its minimum approx. 50 fs before electron thermalization is completed.Comment: 8 pages, 5 figures, revte

Co-occurrence of two cases of progressive multifocal leukoencephalopathy in a natalizumab ``infusion group''

We observed two cases of progressive multifocal leukoencephalopathy (PML) that occurred in the same infusion group. The group consisted of four patients with relapsing-remitting multiple sclerosis (RRMS) who had been treated with natalizumab (NAT) in the same medical practice for more than four years at the same times and in the same room, raising concerns about viral transmission between members of the infusion group. DNA amplification and sequence comparison of the non-coding control region (NCCR) of JC virus (JCV) present in cerebrospinal fluid (CSF) samples from PML patients #1 and #2 revealed that the amplified JCV sequences differed from the JCV archetype. The NCRR of the viral DNA was unique to each patient, arguing against the possibility of viral transmission between patients. Statistical considerations predict that similar co-occurrences of PML are likely to happen in the future

Ursinus College Alumni Journal, Winter 1947

An auspicious beginning for a worthwhile project • President\u27s page • Committees plan new position at college • Status of the war memorial campaign • 964 students enrolled at Ursinus • Miss Moll resumes duties at Ursinus • General Arnold Founders\u27 Day speaker • Three faculty promotions, one appointment announced • New gymnasium nearing completion • Questionnaires outstanding from 900 alumni • Sports: football, soccer, hockey • The shape of things to come? • The attack on illiteracy in British Guiana • News around town • News about ourselves • Faculty members complete laboratory manual • Necrologyhttps://digitalcommons.ursinus.edu/alumnijournal/1029/thumbnail.jp

Co-occurrence of two cases of progressive multifocal leukoencephalopathy in a natalizumab ``infusion group''

We observed two cases of progressive multifocal leukoencephalopathy (PML) that occurred in the same infusion group. The group consisted of four patients with relapsing-remitting multiple sclerosis (RRMS) who had been treated with natalizumab (NAT) in the same medical practice for more than four years at the same times and in the same room, raising concerns about viral transmission between members of the infusion group. DNA amplification and sequence comparison of the non-coding control region (NCCR) of JC virus (JCV) present in cerebrospinal fluid (CSF) samples from PML patients #1 and #2 revealed that the amplified JCV sequences differed from the JCV archetype. The NCRR of the viral DNA was unique to each patient, arguing against the possibility of viral transmission between patients. Statistical considerations predict that similar co-occurrences of PML are likely to happen in the future