181 research outputs found

    Variations in the management of acute illness in children with congenital adrenal hyperplasia: An audit of three paediatric hospitals

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    Objective: Episodes of acute adrenal insufficiency (AI)/adrenal crises (AC) are a serious consequence of congenital adrenal hyperplasia (CAH). This study aimed to assess morbidity from acute illness in CAH and identify factors associated with use of IV hydrocortisone, admission and diagnosis of an AC. Method: An audit of acute illness presentations among children with CAH to paediatric hospitals in New South Wales, Australia, between 2000 and 2015. Results: There were 321 acute presentations among 74 children with CAH. Two thirds (66.7%, n=214) of these resulted in admission and 49.2% (n=158) of the patients received intravenous (IV) hydrocortisone. An AC was diagnosed in (9.0%). Prior to presentation, 64.2% (n=206) had used oral stress dosing and 22.1% (n=71) had been given intramuscular (IM) hydrocortisone. Vomiting was recorded in 61.1% (n=196), 32.7% (n=64) of whom had used IM hydrocortisone. Admission, AC diagnosis, and use of stress dosing varied significantly between hospitals. IM use varied from 7.0% in one metropolitan hospital to 45.8% in the regional hospital. Children aged up to 12 months had the lowest levels of stress dosing and IV hydrocortisone administration. A higher number of prior hospital attendances for acute illness was associated with increased use of IM hydrocortisone. Conclusion: Pre-hospital and in-hospital management of children with CAH can vary between health services. Children under 12 months have lower levels of stress dosing prior to hospital than other age groups. Experience with acute episodes improves self-management of CAH in the context of acute illness in educated patient populations

    LAI based trees selection for mid latitude urban developments: A microclimatic study in Cairo, Egypt

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    To study the leaf area index, LAI, based thermal performance in distinguishing trees for Cairo's urban developments, ENVI-met plants database was used as platform for a foliage modeling parameter, the leaf area density, LAD. Two Egyptian trees: Ficus elastica. and Peltophorum pterocarpum were simulated in 2 urban sites with one having no trees, whilst the second is having Ficus nitida trees. Trees LAD values were calculated using flat leaves' trees LAI definition to produce maximum ground solid shadow at peak time. An empirical value of 1 for LAI is applied to numerically introduce LAD values for ENVI-met. Basically, different meteorological records showed improvements for pedestrian comfort and ambient microclimate of the building using E elastica. About 40-50% interception of direct radiation, reductions in surfaces' fluxes around trees and in radiant temperature T-mrt in comparison to base cases gave preferability to E elastica. The lack of soil water prevented evapotranspiration to take place effectively and the reduced wind speeds concluded negligible air temperature differences from both base cases except slightly appeared with the F elastica. Results show that a flat leaves tree if does not validate LAI of 1, the ground shading would not fulfill about 50% direct radiation interception and this value can be used as a reference for urban trees selection. Further simulations were held to investigate LAI value of maximum direct radiation interception. Performing additional simulations, F elastica of LAI of 3 intercepted almost 84% of direct radiation and revealed implications about urban trees in practice and its actual LAI. (C) 2009 Elsevier Ltd. All rights reserved

    P2X7 in Cancer: From Molecular Mechanisms to Therapeutics

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    P2X7 is a transmembrane receptor expressed in multiple cell types including neurons, dendritic cells, macrophages, monocytes, B and T cells where it can drive a wide range of physiological responses from pain transduction to immune response. Upon activation by its main ligand, extracellular ATP, P2X7 can form a nonselective channel for cations to enter the cell. Prolonged activation of P2X7, via high levels of extracellular ATP over an extended time period can lead to the formation of a macropore, leading to depolarization of the plasma membrane and ultimately to cell death. Thus, dependent on its activation state, P2X7 can either drive cell survival and proliferation, or induce cell death. In cancer, P2X7 has been shown to have a broad range of functions, including playing key roles in the development and spread of tumor cells. It is therefore unsurprising that P2X7 has been reported to be upregulated in several malignancies. Critically, ATP is present at high extracellular concentrations in the tumor microenvironment (TME) compared to levels observed in normal tissues. These high levels of ATP should present a survival challenge for cancer cells, potentially leading to constitutive receptor activation, prolonged macropore formation and ultimately to cell death. Therefore, to deliver the proven advantages for P2X7 in driving tumor survival and metastatic potential, the P2X7 macropore must be tightly controlled while retaining other functions. Studies have shown that commonly expressed P2X7 splice variants, distinct SNPs and post-translational receptor modifications can impair the capacity of P2X7 to open the macropore. These receptor modifications and potentially others may ultimately protect cancer cells from the negative consequences associated with constitutive activation of P2X7. Significantly, the effects of both P2X7 agonists and antagonists in preclinical tumor models of cancer demonstrate the potential for agents modifying P2X7 function, to provide innovative cancer therapies. This review summarizes recent advances in understanding of the structure and functions of P2X7 and how these impact P2X7 roles in cancer progression. We also review potential therapeutic approaches directed against P2X7
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