Pilot trial of fk 506 in the management of steroid-resistant nephrotic syndrome

Seven patients with steroid-resistant nephrotic syndrome were treated with FK 506 monotherapy. Four patients were children with focal sclerosing glomerulonephritis (FSGS). Three of these had evldence for chronic progressive renal disease consisting of interstitial fibrosis and tubular atrophy on pretreatment renal biopsies. Two patients had also failed cyclosporin A (CsA), two cyclophosphamide, and one chlorambucil prior to treatment with FK 506. Three patients were adults wlth mesangial proliferative. membranoproliferative, and membranous glomerulonephritis. Three patterns of response were noted: (1) a reduction in proteinuria to normal levels, (2) partial response (50% reduction) or; (3) no improvement. All patients except one experienced at least a 50% reduction in protein excretion at some time during FK 506 therapy. Two of the children and one adult reduced protein excretion to essentially normal values. One patient had no sustained reduction In Droteln excretion and is considered to be a treatment fallure, although her protein excretion was approximately 50% of pretreatment values intermittently. The drug was generally well tolerated. The most common side-effect was nephrotoxlclty, whlch was reversible. These encouraging results suggest that FK 506 monotherapy may be effective in controlling the proteinuria of somc patlents with steroid-resistant nephrotic syndrome The use of this drug may extend our understanding of the role of T lymphocytes and cytokines in the pathogenesls of glomerulonephritis. Further study of this agent In a larger population of patlents is warranted. © 1993 European Dialysis and Transplant Assoiation-European Renal Association

Positronium emission from mesoporous silica studied by laser-enhanced time-of-flight spectroscopy

The use of mesoporous silica films for the production and study of positronium (Ps) atoms has become increasingly important in recent years, providing a robust source of free Ps in vacuum that may be used for a wide variety of experiments, including precision spectroscopy and the production of antihydrogen. The ability of mesoporous materials to cool and confine Ps has also been utilized to conduct measurements of Ps–Ps scattering and Ps2 molecule formation, and this approach offers the possibility of making a sufficiently dense and cold Ps ensemble to realize a Ps Bose–Einstein condensate. As a result there is great interest in studying the dynamics of Ps atoms inside such mesoporous structures, and how their morphology affects Ps cooling, diffusion and emission into vacuum. It is now well established that Ps atoms are initially created in the bulk of such materials and are subsequently ejected into the internal voids with energies of the order of 1 eV, whereupon they rapidly cool via hundreds of thousands of wall collisions. This process can lead to thermalisation to the ambient sample temperature, but will be arrested when the Ps deBroglie wavelength approaches the size of the confining mesopores. At this point diffusion through the pore network can only proceed via tunneling, at a much slower rate. An important question then becomes, how long does it take for the Ps atoms to cool and escape into vacuum? In a direct measurement of this process, conducted using laser-enhanced positronium time-of-flight spectroscopy, we show that cooling to the quantum confinement regime in a film with approximately 5 nm diameter pores is nearly complete within 5 ns, and that emission into vacuum takes ~10 ns when the incident positron beam energy is 5 keV. The observed dependence of the Ps emission time on the positron implantation energy supports the idea that quantum confined Ps does not sample all of the available pore volume, but rather is limited to a subset of the mesoporous network