Tacrolimus rescue therapy for renal allograft rejection - Five-year experience

Over the 5 year period from 7/14/1989 until 5/24/1994, we have attempted graft salvage with tacrolimus conversion in a total of 169 patients (median age 33 years, range 2-75 years) with ongoing rejection on baseline CsA immunosuppression after failure of high dose corticosteroids and/or antilymphocyte preparations to reverse rejection. The indications for conversion to tacrolimus were ongoing, biopsy confirmed rejection in all patients. The median interval to tacrolimus conversion was 2 months (range 2 days to 55 months; mean 4.3±2.6 months) after transplantation. All patients had failed high dose corticosteroid therapy and 144 (85%) of the 169 patients had received at least one course of an antilymphocyte preparation plus high dose corticosteroid therapy prior to conversion. Twenty-eight patients (17%) were dialysis-dependent at the time of conversion owing to the severity of rejection. With a mean follow-up of 30.0±2.4 months (median 36.5 months, range 12-62 months), 125 of 169 patients (74%) have been successfully rescued and still have functioning grafts with a mean serum creatinine (SCR) of 2.3±1.1 mg/dl. Of the 144 patients previously treated with antilymphocyte preparations, 117 (81%) were salvaged. Of the 28 patients on dialysis at the time of conversion to tacrolimus, 13 (46%) continue to have functioning grafts (mean SCR 2.15±0.37 mg/dl) at a mean follow-up of 37.3±16.7 months. In the 125 patients salvaged, prednisone doses have been lowered from 28.0±9.0 mg/d (median 32, range 4-60 mg/d) preconversion to 8.5±4.1 mg/d (median 12 mg/d, range 2.5-20 mg/d) postconversion. Twenty-eight patients (22.4%) are currently receiving no steroids. This 5 year experience demonstrates that tacrolimus has sustained efficacy as a rescue agent for ongoing renal allograft rejection. Based on these data, we recommend that tacrolimus be used as an alternative to the conventional drugs used for antirejection therapy in renal transplantation

Strategies for High-Temperature Corrosion Simulations of Fe-Based Alloys Using the Calphad Approach: Part I

The environmental degradation of materials at high temperatures limits the useful life of different industrial components and hinders the development of more economical and environmentally friendly processes for the energy production. Despite the importance of this phenomena, a model to predict lifetime of materials that degrade due to high-temperature corrosion has up till now been lacking due to limitations of the computational possibilities and the complex nature of oxidation. In the present work we develop some strategies to model high-temperature corrosion in Fe-based alloys using the Calphad (Calculation of Phase Diagrams) approach. It is proposed that kinetic-based simulations for oxidation of Al and Cr can accurately represent the lifetime of the protective layers in FeCrAl and FeCr alloys at different temperatures in air. The oxide systems are in addition investigated by equilibrium calculations. The corrosion mechanisms of FeCr and FeCrAl alloys are discussed based on theoretical and experimental knowledge

Diagnosis and neurosurgical treatment of glossopharyngeal neuralgia: clinical findings and 3-D visualization of neurovascular compression in 19 consecutive patients

Glossopharyngeal neuralgia is a rare condition with neuralgic sharp pain in the pharyngeal and auricular region. Classical glossopharyngeal neuralgia is caused by neurovascular compression at the root entry zone of the nerve. Regarding the rare occurrence of glossopharyngeal neuralgia, we report clinical data and magnetic resonance imaging (MRI) findings in a case series of 19 patients, of whom 18 underwent surgery. Two patients additionally suffered from trigeminal neuralgia and three from additional symptomatic vagal nerve compression. In all patients, ipsilateral neurovascular compression syndrome of the IX cranial nerve could be shown by high-resolution MRI and image processing, which was confirmed intraoperatively. Additional neurovascular compression of the V cranial nerve was shown in patients suffering from trigeminal neuralgia. Vagal nerve neurovascular compression could be seen in all patients during surgery. Sixteen patients were completely pain free after surgery without need of anticonvulsant treatment. As a consequence of the operation, two patients suffered from transient cerebrospinal fluid hypersecretion as a reaction to Teflon implants. One patient suffered postoperatively from deep vein thrombosis and pulmonary embolism. Six patients showed transient cranial nerve dysfunctions (difficulties in swallowing, vocal cord paresis), but all recovered within 1 week. One patient complained of a gnawing and burning pain in the cervical area. Microvascular decompression is a second-line treatment after failure of standard medical treatment with high success in glossopharyngeal neuralgia. High-resolution MRI and 3D visualization of the brainstem and accompanying vessels as well as the cranial nerves is helpful in identifying neurovascular compression before microvascular decompression procedure

Assessing MWCNT-graphene surface energy through in situ SEM peeling

Carbon nanotubes (CNTs) are envisioned as ideal filaments for next-generation nanocomposites due to their high strength-to-weight ratios. However, while individual nanotubes are strong, interfaces between tubes cannot bear significant load due to the weak van der Waals forces that govern their behavior. Premature interfacial failure could thus counteract the inherent strength of carbon nanotubes and, in turn, prevent CNT-based composites from achieving optimal mechanical performance. To increase the load bearing capacity of these interfaces, interlayer crosslinking schemes have been proposed using chemical functionalization. For instance, introduction of hydrogen bonds or additional van der Waals bonds between tubes could improve load transfer between CNTs. While introducing chemical groups on CNT surfaces may enhance intermolecular interactions at these interfaces, a means of quantitatively evaluating changes in interlayer adhesion as a result of to these treatments needs to be defined. In addition, as sizes of CNTs will inherently vary within a composite, it is important that such energy measurements be normalized irrespective of tube dimensions. Here we report an experimental peeling technique that can be used to measure the adhesion energy between multiwalled carbon nanotubes (MWCNTs) and graphene. Peeling tests conducted in situ a scanning electron microscope allow direct visualization of the nanoscale peeling process which, in turn, enables adhesion energy to be estimated through classical fracture analysis. The applicability of this analysis is validated by finite element simulations with boundary conditions derived from experiments. The effective contact width between tubes and graphene is estimated via atomistic simulations, providing a means to normalize interaction energy per unit area. The surface energies of bare MWCNT-graphene interfaces found in this study compare favorably with theoretical and experimental values reported for graphite. This method can serve as a foundation for evaluating the enhancements afforded by chemical functionalization, which is a critical step toward the development of strong, lightweight composites that effectively utilize the full mechanical potential of CNTs

Conformational changes of calmodulin upon Ca2+ binding studied with a microfluidic mixer

A microfluidic mixer is applied to study the kinetics of calmodulin conformational changes upon Ca2+ binding. The device facilitates rapid, uniform mixing by decoupling hydrodynamic focusing from diffusive mixing and accesses time scales of tens of microseconds. The mixer is used in conjunction with multiphoton microscopy to examine the fast Ca2+-induced transitions of acrylodan-labeled calmodulin. We find that the kinetic rates of the conformational changes in two homologous globular domains differ by more than an order of magnitude. The characteristic time constants are ≈490 μs for the transitions in the C-terminal domain and ≈20 ms for those in the N-terminal domain of the protein. We discuss possible mechanisms for the two distinct events and the biological role of the stable intermediate, half-saturated calmodulin

Report of the GDR working group on the R-parity violation

This report summarizes the work of the "R-parity violation group" of the French Research Network (GDR) in Supersymmetry, concerning the physics of supersymmetric models without conservation of R-parity at HERA, LEP, Tevatron and LHC and limits on R-parity violating couplings from various processes. The report includes a discussion of the recent searches at the HERA experiment, prospects for new experiments, a review of the existing limits, and also theoretically motivated alternatives to R-parity and a brief discussion on the implications of R-parity violation on the neutrino masses.Comment: 60 pages, LaTeX, 22 figures, 2 table