Current and Emerging Pharmacotherapies for Primary CNS Lymphoma

Primary central nervous system lymphoma (PCNSL) constitutes a rare group of extranodal non-Hodgkin’s lymphoma (NHL) primarily of B cell origin. It occurs in both immuno-competent and immune-compromised patients. High dose m ethotrexate (HD-MTX) based chemotherapy is the standard therapy. Chemotherapy with whole brain radiation therapy (WBRT) improves response rates and survival compared with WBRT alone. However, due to the increased risk for neurotoxicity with WBRT, recent studies have focused on using chemotherapy alone. Methotrexate based multi-agent chemotherapy without WBRT is associated with similar t reatment rates and survival compared with regimens that include WBRT although controlled trials have not been performed. Because of the low incidence of this disease, it is difficult to conduct randomized controlled trials. In this article we have discussed about the past, present and emerging treatment options in patients with PCNSL

Analytical form of current-voltage characteristic of parallel-plane, cylindrical and spherical ionization chambers with homogeneous ionization

The elementary processes taking place in the formation of charged particles and their flow in parallel-plane, cylindrical and spherical ionization chambers are considered. On the basis of particles and charges balance a differential equation describing the distribution of current densities in the ionization chamber volume is obtained. As a result of the differential equation solution an analytical form of the current-voltage characteristic of an ionization chamber with homogeneous ionization is obtained. For the parallel-plane case the comparison with experimental data is performed.Comment: 20 pages, 6 figures, 2 tables; changed conten

Bevacizumab for the Treatment of Recurrent Glioblastoma

Despite advances in upfront therapy, the prognosis in the great majority of patients with glioblastoma (GBM) is poor as almost all recur and result in disease-related death. Glioblastoma are highly vascularized cancers with elevated expression levels of vascular endothelial growth factor (VEGF), the dominant mediator of angiogenesis. A compelling biologic rationale, a need for improved therapy, and positive results from studies of bevacizumab in other cancers led to the evaluation of bevacizumab in the treatment of recurrent GBM. Bevacizumab, a humanized monoclonal antibody that targets VEGF, has been shown to improve patient outcomes in combination with chemotherapy (most commonly irinotecan) in recurrent GBM, and on the basis of positive results in two prospective phase 2 studies, bevacizumab was granted accelerated approval by the US Food and Drug Administration (FDA) as a single agent in recurrent GBM. Bevacizumab therapy is associated with manageable, class-specific toxicity as severe treatment-related adverse events are observed in only a minority of patients. With the goal of addressing questions and controversies regarding the optimal use of bevacizumab, the objective of this review is to provide a summary of the clinical efficacy and safety data of bevacizumab in patients with recurrent GBM, the practical issues surrounding the administration of bevacizumab, and ongoing investigations of bevacizumab in managing GBM

The Origin of Mercury

Mercury’s unusually high mean density has always been attributed to special circumstances that occurred during the formation of the planet or shortly thereafter, and due to the planet’s close proximity to the Sun. The nature of these special circumstances is still being debated and several scenarios, all proposed more than 20 years ago, have been suggested. In all scenarios, the high mean density is the result of severe fractionation occurring between silicates and iron. It is the origin of this fractionation that is at the centre of the debate: is it due to differences in condensation temperature and/or in material characteristics (e.g. density, strength)? Is it because of mantle evaporation due to the close proximity to the Sun? Or is it due to the blasting off of the mantle during a giant impact? In this paper we investigate, in some detail, the fractionation induced by a giant impact on a proto-Mercury having roughly chondritic elemental abundances. We have extended the previous work on this hypothesis in two significant directions. First, we have considerably increased the resolution of the simulation of the collision itself. Second, we have addressed the fate of the ejecta following the impact by computing the expected reaccretion timescale and comparing it to the removal timescale from gravitational interactions with other planets (essentially Venus) and the Poynting–Robertson effect. To compute the latter, we have determined the expected size distribution of the condensates formed during the cooling of the expanding vapor cloud generated by the impact. We find that, even though some ejected material will be reaccreted, the removal of the mantle of proto-Mercury following a giant impact can indeed lead to the required long-term fractionation between silicates and iron and therefore account for the anomalously high mean density of the planet. Detailed coupled dynamical–chemical modeling of this formation mechanism should be carried out in such a way as to allow explicit testing of the giant impact hypothesis by forthcoming space missions (e.g. MESSENGER and BepiColombo)