110 research outputs found
Emergency reversal of antiplatelet agents in patients presenting with an intracranial hemorrhage: A clinical review
Abstract
Objective: Prehospital use of antiplatelet agents has been associated with an increased risk for ICH as well as a secondary increase in ICH volume after the initial hemorrhage. Strategies to reestablish platelet aggregation are used in clinical practice, but without any established guidelines or recommendations. This article serves to evaluate the literature regarding βreversalβ of antiplatelet agents in neurosurgical populations.
Methods: PUBMED and MEDLINE databases were searched for publications from 1966 to 2009 relating to intracranial hemorrhage and antiplatelet agents. The reference sections of recent articles, guidelines and reviews were reviewed and pertinent articles identified. Studies were classified by two broad subsets; those describing intracranial hemorrhage relatable to a traumatic mechanism and those with a spontaneous intracranial hemorrhage. Two independent auditors recorded and analyzed study design and the reported outcome measures.
Results: For the spontaneous intracranial hemorrhage group, 9 reports assessing antiplatelet effects on various outcome measures were identified. Eleven studies evaluating the use of prehospital antiplatlets prior to a traumatic intracranial hemorrhage were examined.
Conclusion: The data assessing the relationship between outcome and prehospital antiplatelet agents in the setting of ICH is conflicting in both the trauma and the stroke literature. Only one retrospective review specifically addressed outcomes after attempted reversal with platelet transfusion. Further study is needed to determine whether platelet transfusion ameliorates hematoma enlargement and/or improves outcome in the setting of acute ICH
Incidence, risk factors, and impact on hospital mortality of status epilepticus after subdural hemorrhage in the United States
In-Vivo T-Cell Depletion Using Thymoglobulin (Thymo) Allows Successful Allogeneic Stem Cell Transplantation (Allo-SCT) From Mismatched, Unrelated Donors (MM-URD): Potential Influence Of Graft Source On Outcome
Prediction of inter-particle adhesion force from surface energy and surface roughness
Fine powder flow is a topic of great interest to industry, in particular for the pharmaceutical industry; a major concern being their poor flow behavior due to high cohesion. In this study, cohesion reduction, produced via surface modification, at the particle scale as well as bulk scale is addressed. The adhesion force model of Derjaguin-Muller-Toporov (DMT) was utilized to quantify the inter-particle adhesion force of both pure and surface modified fine aluminum powders (βΌ8 ΞΌm in size). Inverse Gas Chromatography was utilized for the determination of surface energy of the samples, and Atomic Force Microscopy was utilized to evaluate surface roughness of the powders. Surface modification of the original aluminum powders was done for the purpose of reduction in cohesiveness and improvement in flowability, employing either silane surface treatment or dry mechanical coating of nano-particles on the surface of original powders. For selected samples, the AFM was utilized for direct evaluation of the particle pull-off force. The results indicated that surface modification reduced the surface energy and altered the surface nano-roughness, resulting in drastic reduction of the inter-particle adhesion force. The particle bond number values were computed based on either the inter-particle adhesion force from the DMT model or the inter-particle pull-off force obtained from direct AFM measurements. Surface modification resulted in two to three fold reductions in the Bond number. In order to examine the influence of the particle scale property such as the Bond number on the bulk-scale flow characterization, Angle of Repose measurements were done and showed good qualitative agreements with the Bond number and acid/base surface characteristics of the powders. The results indicate a promising method that may be used to predict flow behavior of original (cohesive) and surface modified (previously cohesive) powders utilizing very small samples
A human brainstem glioma xenograft model enabled for bioluminescence imaging
Despite the use of radiation and chemotherapy, the prognosis for children with diffuse brainstem gliomas is extremely poor. There is a need for relevant brainstem tumor models that can be used to test new therapeutic agents and delivery systems in pre-clinical studies. We report the development of a brainstem-tumor model in rats and the application of bioluminescence imaging (BLI) for monitoring tumor growth and response to therapy as part of this model. Luciferase-modified human glioblastoma cells from five different tumor cell sources (either cell lines or serially-passaged xenografts) were implanted into the pontine tegmentum of athymic rats using an implantable guide-screw system. Tumor growth was monitored by BLI and tumor volume was calculated by three-dimensional measurements from serial histopathologic sections. To evaluate if this model would allow detection of therapeutic response, rats bearing brainstem U-87 MG or GS2 glioblastoma xenografts were treated with the DNA methylating agent temozolomide (TMZ). For each of the tumor cell sources tested, BLI monitoring revealed progressive tumor growth in all animals, and symptoms caused by tumor burden were evident 26β29Β days after implantation of U-87 MG, U-251 MG, GBM6, and GBM14 cells, and 37β47Β days after implantation of GS2 cells. Histopathologic analysis revealed tumor growth within the pons in all rats and BLI correlated quantitatively with tumor volume. Variable infiltration was evident among the different tumors, with GS2 tumor cells exhibiting the greatest degree of infiltration. TMZ treatment groups were included for experiments involving U-87 MG and GS2 cells, and in each case TMZ delayed tumor growth, as indicated by BLI monitoring, and significantly extended survival of animal subjects. Our results demonstrate the development of a brainstem tumor model in athymic rats, in which tumor growth and response to therapy can be accurately monitored by BLI. This model is well suited for pre-clinical testing of therapeutics that are being considered for treatment of patients with brainstem tumors
Clinical Trials in Head Injury
Traumatic brain injury (TBI) remains a major public health problem globally. In the United States the incidence of closed head injuries admitted to hospitals is conservatively estimated to be 200 per 100,000 population, and the incidence of penetrating head injury is estimated to be 12 per 100,000, the highest of any developed country in the world. This yields an approximate number of 500,000 new cases each year, a sizeable proportion of which demonstrate signficant long-term disabilities. Unfortunately, there is a paucity of proven therapies for this disease. For a variety of reasons, clinical trials for this condition have been difficult to design and perform. Despite promising pre-clinical data, most of the trials that have been performed in recent years have failed to demonstrate any significant improvement in outcomes. The reasons for these failures have not always been apparent and any insights gained were not always shared. It was therefore feared that we were running the risk of repeating our mistakes. Recognizing the importance of TBI, the National Institute of Neurological Disorders and Stroke (NINDS) sponsored a workshop that brought together experts from clinical, research, and pharmaceutical backgrounds. This workshop proved to be very informative and yielded many insights into previous and future TBI trials. This paper is an attempt to summarize the key points made at the workshop. It is hoped that these lessons will enhance the planning and design of future efforts in this important field of research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63185/1/089771502753754037.pd
The role of tenascin-C in tissue injury and tumorigenesis
The extracellular matrix molecule tenascin-C is highly expressed during embryonic development, tissue repair and in pathological situations such as chronic inflammation and cancer. Tenascin-C interacts with several other extracellular matrix molecules and cell-surface receptors, thus affecting tissue architecture, tissue resilience and cell responses. Tenascin-C modulates cell migration, proliferation and cellular signaling through induction of pro-inflammatory cytokines and oncogenic signaling molecules amongst other mechanisms. Given the causal role of inflammation in cancer progression, common mechanisms might be controlled by tenascin-C during both events. Drugs targeting the expression or function of tenascin-C or the tenascin-C protein itself are currently being developed and some drugs have already reached advanced clinical trials. This generates hope that increased knowledge about tenascin-C will further improve management of diseases with high tenascin-C expression such as chronic inflammation, heart failure, artheriosclerosis and cancer
Posterior fossa and spinal gangliogliomas form two distinct clinicopathologic and molecular subgroups
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