3 resultados para Neoplasms, unknown primary

em Aston University Research Archive


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Magnetoencephalography (MEG) can be used to reconstruct neuronal activity with high spatial and temporal resolution. However, this reconstruction problem is ill-posed, and requires the use of prior constraints in order to produce a unique solution. At present there are a multitude of inversion algorithms, each employing different assumptions, but one major problem when comparing the accuracy of these different approaches is that often the true underlying electrical state of the brain is unknown. In this study, we explore one paradigm, retinotopic mapping in the primary visual cortex (V1), for which the ground truth is known to a reasonable degree of accuracy, enabling the comparison of MEG source reconstructions with the true electrical state of the brain. Specifically, we attempted to localize, using a beanforming method, the induced responses in the visual cortex generated by a high contrast, retinotopically varying stimulus. Although well described in primate studies, it has been an open question whether the induced gamma power in humans due to high contrast gratings derives from V1 rather than the prestriate cortex (V2). We show that the beanformer source estimate in the gamma and theta bands does vary in a manner consistent with the known retinotopy of V1. However, these peak locations, although retinotopically organized, did not accurately localize to the cortical surface. We considered possible causes for this discrepancy and suggest that improved MEG/magnetic resonance imaging co-registration and the use of more accurate source models that take into account the spatial extent and shape of the active cortex may, in future, improve the accuracy of the source reconstructions.

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BACKGROUND: Community pharmacies are at the forefront of primary care providers and have an important role in the referral of patients to a medical practitioner for review when necessary. Chronic cough is a common disorder in the community and requires medical assessment. The proficiency of community pharmacy staff to refer patients with chronic cough is currently unknown. OBJECTIVE: To assess the ability of community pharmacy staff to recognize and medically refer patients with a chronic nonproductive cough. METHODS: Following ethics approval, a simulated patient study of 156 community pharmacies in Perth, Western Australia, was conducted over a 3-month period. Simulated patients presented to the pharmacy requesting treatment for a cough. The simulated patient required a referral based on a designated scenario. Demographic details, assessment questions, and advice provided were recorded by the simulated patient immediately postvisit. A logistic regression analysis was performed, with referral for medical assessment as the dependent variable. RESULTS: Of the 155 community pharmacies included in the analysis, 38% provided appropriate medical referral. Cough suppressants were provided as therapy in 72% of all visits. Predictors of medical referral were assessment of symptom duration, medical history, current medications being taken, frequency of reliever use, and the position of the pharmacy staff member conducting the consultation. A third of community pharmacies provided appropriate primary care by recommending medical referral advice to patients with chronic cough. The majority of pharmacy staff members acquired information from the patient that suggested a need for medical referral, yet did not provide referral advice. CONCLUSIONS: Appropriate medical referral is more likely when adequate assessment is undertaken and when a pharmacist is directly involved in the consultation. This highlights the need for pharmacies to ensure that processes are in place for patients to access the pharmacist.

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Objective: There is evidence to suggest a beneficial role for growth factors, including vascular endothelial growth factor (VEGF), in tissue repair and proliferation after injury within the lung. Whether this effect is mediated predominantly by actions on endothelial cells or epithelial cells is unknown. This study tested the hypothesis that VEGF acts as an autocrine trophic factor for human adult alveolar epithelial cells and that under situations of pro-apoptotic stress, VEGF reduces cell death. Design: In vitro cell culture study looking at the effects of 0.03% H2O2 on both A549 and primary distal lung epithelial cells.Measurement and Main Results: Primary adult human distal lung epithelial cells express both the soluble and membrane-associated VEGF isoforms and VEGF receptors 1 and 2. At physiologically relevant doses, soluble VEGF isoforms stimulate wound repair and have a proliferative action. Specific receptor ligands confirmed that this effect was mediated by VEGF receptor 1. In addition to proliferation, we demonstrate that VEGF reduces A549 and distal lung epithelial cell apoptosis when administered after 0.03% H2O2 injury. This effect occurs due to reduced caspase-3 activation and is phosphatidylinositol 3′–kinase dependent. Conclusion: In addition to its known effects on endothelial cells, VEGF acts as a growth and anti-apoptotic factor on alveolar epithelial cells. VEGF treatment may have potential as a rescue therapy for diseases associated with alveolar epithelial damage such as acute respiratory distress syndrome.