Time of interferon-beta 1a injection and duration of treatment affect clinical side effects and acute changes of plasma hormone and cytokine levels in multiple sclerosis patients.

During initiation of interferon-beta (IFN-beta) therapy, many multiple sclerosis (MS) patients experience systemic side effects which may depend on the time point of IFN-beta injection. We investigated the time course of plasma hormone-, cytokine- and cytokine-receptor concentrations after the first injection of IFN-beta either at 8.00 a.m. (group A) or at 6.00 p.m. (group B) and quantified clinical side effects within the first 9 h in 16 medication free patients with relapsing-remitting MS. This investigation was repeated after 6-month IFN-beta therapy. Plasma ACTH and cortisol concentrations followed their physiological rhythms, with lower levels in the evening compared to the morning, but raised earlier and stronger in group B after IFN-beta administration. IFN-beta injection in the evening led to a prompter increase of plasma IL-6 concentrations and temperature during the first hours and correlated to more intense clinical side effects compared to group A. Plasma IL-10 concentrations increased more in group A compared to group B, but sTNF-RI and sTNF-RII concentrations raised 7 h after IFN-beta injection only in group B. Acute effects on plasma hormone and cytokine concentrations adapted after 6-month IFN-beta treatment, while diurnal variations were still present. Baseline sTNF-RII concentrations were elevated after 6-month IFN-beta therapy only in group A. Our results show that time point of IFN-beta injection has differential effects on acute changes of plasma hormone and cytokine concentrations and is related to systemic side effects. This may have implications on the tolerability and effectiveness of IFN-beta therapy.

Relevance of C1 and C2 epitopes for hemopoietic stem cell transplantation: role for sequential acquisition of HLA-C-specific inhibitory killer Ig-like receptor.

Killer Ig-like receptors (KIR) and HLA class I ligands were studied in unrelated hemopoietic stem cell transplantation for chronic myeloid leukemia (n = 108). Significantly improved overall survival was observed in patients, which were homozygous for HLA-C-encoded group 1 (C1) ligands compared with those with group 2 (C2) ligands. Favorable outcome in the former patient group was an early effect that was highly significant in patients transplanted with G-CSF-mobilized peripheral blood and patients with advanced disease stages. In contrast, presence of C1 ligands in the donor was associated with significantly reduced patient survival. The differential roles of the two HLA-C ligands are explained in the context of a biased NK cell reconstitution, which is generally dominated by the presence of C1- but absence of C2-specific NK cells. The clinical observations are corroborated by in vitro experiments showing that NK cells derived from hemopoietic progenitor cells generally acquire the C1-specific inhibitory KIR2DL2/3 at earlier time points and with higher frequency than the C2-specific KIR2DL1. These findings define a novel determinant for understanding the role of NK cells in clinical hemopoietic stem cell transplantation.

Closed-loop class E transcutaneous power and data link for microimplants.

Magnetic transcutaneous coupling is frequently used for power and data transfer to implanted electronic devices. The proposed development of MicroImplants, small enough to be injected through a hypodermic needle suggest the need for a high-efficiency magnetic transcutaneous link. This paper describes the use of a multifrequency transmitter coil driver based upon the Class E topology. The development of a "high-Q approximation" which simplifies the design procedure is presented. A closed-loop controller to compensate for transmitter and receiver variations, and a method of data modulation, using synchronous frequency shifting are described. The closed-loop Class E circuit shows great promise, especially for circuits with unusually low coefficients of coupling. Currents of several amperes, at radio frequencies, can easily and efficiently be obtained.

Class E driver for transcutaneous power and data link for implanted electronic devices.

Magnetic transcutaneous coupling is frequently used for power and data transfer to implanted electronic devices. The paper describes a transmitter/coil driver based on the class E topology. The development of a 'high-Q approximation' simplifies the design procedure. A method of data modulation using synchronous frequency shifting is described. The class E circuit shows great promise, especially for circuits with unusually low coefficients of coupling. Transmitter coil currents of several amperes, at radio frequencies, with relatively low active device power dissipation, can easily be obtained.