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| 1 | Molecular targets in the treatment of alcoholic hepatitis显示文摘Alcohol related costs to health and society are high. One of the most serious complications of alcohol misuse to the individual is the development of alcoholic hepatitis (AH), a clinical syndrome of jaundice and progressive inflammatory liver injury in patients with a history of recent heavy alcohol use. It has a poor outcome and few existing successful therapies. The use of glucocorticoids in patients with severe AH is still controversial and there remains a group of patients with glucocorticoid-resistant disease. However, as our understanding of the pathogenesis of the condition improves there are opportunities to develop new targeted therapies with specific actions to control liver inflammation without having a detrimental effect on the immune system as a whole. In this article we review the molecular mechanisms of AH concentrating on the activation of the innate and adaptive immune response. We consider existing treatments including glucocorticoids, anti-tumor necrosis factor therapy and pentoxifylline and their limitations. Using our knowledge of the disease pathogenesis we discuss possible novel therapeutic approaches. New targets include pro-inflammatory cytokines such as interleukin (IL)-17, chemokines and their receptors (for example IL-8, CXCL9 and CXCR3) and augmentation of anti-inflam- matory molecules such as IL-10 and IL-22. And there is also future potential to consider combination therapy to selectively modulate the immune response and gain control of disease. | Ashwin D Dhanda Richard WL Lee Peter L Collins C Anne McCune | 2012 | World Journal of Gastroenterology2012，18，39： | 9 |
| 2 | Is liver biopsy necessary in the management of alcoholic hepatitis?显示文摘Acute alcoholic hepatitis(AAH)is characterised by deep jaundice in patients with a history of heavy alcohol use,which can progress to liver failure.A clinical diagnosis of AAH can be challenging to make in patients without a clear alcohol history or in the presence of risk factors for other causes of acute liver failure.Other causes of acute on chronic liver failure such as sepsis or variceal haemorrhage should be considered.Liver biopsy remains the only reliable method to make an accurate diagnosis.However,there is controversy surrounding the use of liver biopsy in patients with AAH because of the risks of performing a percutaneous biopsy and limitations in access to transjugular biopsy.We review the existing literature and find there are few studies directly comparing clinical and histological diagnosis of AAH.In the small number of studies that have been conducted the correlation between a clinical and histological diagnosis of AAH is poor.Due to this lack of agreement together with difficulties in accessing transjugular liver biopsy outside tertiary referral centres and research institutions,we cannot advocate universal biopsy for AAH but there remains a definite role for liver biopsy where there is clinical diagnostic doubt or dual pathology.Italso adds value in a clinical trial context to ensure a homogeneous trial population and to further our understanding of the disease pathology.Further prospective studies are required to determine whether non-invasive markers can be used to accurately diagnose AAH. | Ashwin D Dhanda Peter L Collins C Anne McCune | 2013 | World Journal of Gastroenterology2013，19，44： | 4 |
| 3 | Planer negative refractive index media using periodically L - CLoaded transmission lines 显示文摘 | George V Eleftheriades Ashwin K lyer Peter C Kremer | 2004 | IEEE Trans Micro TheoTech2004，50，12： | 1 |
| 4 | Planar negative refractive index media using periodically L- C loaded transmission lines 显示文摘 | George V Eleftheriades Ashwin K lyer Peter C Kremer | 2002 | IEEE Transactions on Microwave Theory and Techniques2002，50，12： | 1 |
| 5 | Calculation of the periodic spectral components in a chaotic DC-DC converter 显示文摘 | Deane J H B Ashwin Peter Hamill D C | 1999 | IEEE Transactions on Circuits and Systems-1:Fundamental Theory and Applications1999，46，11： | 1 |
| 6 | Selecting High Quality Protein Structures from Diverse Conformational Ensembles显示文摘 | Ashwin Subramani Peter A. DiMaggio Christodoulos A. Floudas | 2009 | Biophysical Journal2009，，6： | 1 |
| 7 | Infection does not increase long-term mortality in patients with acute severe alcoholic hepatitis treated with corticosteroids显示文摘AIM To determine whether infection in patients with acute severe alcoholic hepatitis(AAH) treated with corticosteroids is associated with increased mortality.METHODS Consecutive patients with AAH were treated with steroids and recruited to the study. Clinically relevant infections(body temperature > 38 ℃ or < 36 ℃ for more than 4 h, ascitic neutrophil count > 0.25 ×109/L, consolidation on chest radiograph or clinically relevant positive microbiological culture of bodily fluid) were recorded prospectively. Clinical and laboratory parameters were recorded and survival at 90 d and 6 mo was determined. Univariate analysis of factors associated with 90-d mortality was performed and significant variables included in a multivariate analysis.RESULTS Seventy-two patients were included in the final analysis(mean age 47.9 years, 26% female, mean discriminant function 53.0). Overall mortality in the group occurred in 15(21%), 23(32%) and 31(43%) at day 28, day 90 and 1 year respectively. 36(50%) had a clinically relevant infection during their hospitalisation(23 after initiation of steroids). The median time to development of incident infection after commencement of steroids was 10 d. The commonest site of infection was ascites(31%) and bacteraemia(31%) followed by urinary tract(19%) and respiratory tract(8%). Forty-one separate organisms were isolated in 33 patients; the most frequent genus was Escherichia(22%) and Enterococcus(20%). Infection was not associated with 90-d or 1 year mortality but was associated with higher creatinine, model for end-stage liver disease and Lille score. Baseline urea was the only independent predictor of 90-d mortality.CONCLUSION Clinically relevant infections are common in patients with AAH but are not associated with increased 90-d or 1 year mortality. | Ashwin D Dhanda Ashish Sinha Vicky Hunt Sarah Saleem Matthew E Cramp Peter L Collins | 2017 | World Journal of Gastroenterology2017，23，11： | 1 |
| 8 | Planar negative refractive index media using periodically L - C loaded transmission lines 显示文摘 | Eleflheriades George V Iyer Ashwin K Kremer Peter C | 2002 | IEEE transactions on microwave theory and techniques2002，50，12： | 1 |
| 9 | Relationship of plant density to fruit yield of 'Sweet Charlie' strawberry grown in a pine bark soilless medium in a high-roof passively ventilated greenhouse显示文摘 | Ashwin V Paranjpe Daniel J Cantliffe Peter J Stoffella | 2008 | Scientia Horticulturae2008，115，2： | 1 |
| 10 | Calculation of the periodic spectral components in a chaotic dc-dc converter显示文摘 | Jonathan H B Deane Peter Ashwin Senior Member | 1999 | IEEE Transactions on Circuits and Systems-1:Fundamental Theory and Applications1999，46，11： | 1 |
| 11 | Alpha-B crystalline gene(CRYAB) mutation causes dominant congenital posterior polar cataract in humans显示文摘 | Vanita B Peter F Ashwin M | 2001 | Am J Hum Genet2001，69，： | 1 |
| 12 | Planer negative refractive index media u- sing periodically L-C loaded transmission lines 显示文摘 | ELEFTHERIADES George V LYER Ashwin K KRE- MER Peter C | 2004 | IEEE Trans Microw Theory Tech2004，50，12： | 1 |
| 13 | Immune dysfunction in acute alcoholic hepatitis显示文摘Acute alcoholic hepatitis(AAH) is a serious complication of alcohol misuse and has high short term mortality. It is a clinical syndrome characterised by jaundice and coagulopathy in a patient with a history of recent heavy alcohol use and is associated with profound immune dysfunction with a primed but ineffective immune response against pathogens. Here, we review the current knowledge of the pathogenesis and immune defects of AAH and identify areas requiring further study. Alcohol activates the immune system primarily through the disruption of gut tight junction integrity allowing the escape of pathogenassociated molecular particles(PAMPs) into the portal venous system. PAMPs stimulate cells expressing toll-like receptors(mainly myeloid derived cells) and initiate a network of intercellular signalling by secretion of many soluble mediators including cytokines and chemokines. The latter coordinates the infiltration of neutrophils, monocytes and T cells and results in hepatic stellate cell activation, cellular damage and hepatocyte death by necrosis or apoptosis. On the converse of this immune activation is the growing evidence of impaired microbial defence. Neutrophils have reduced phagocytic capacity and oxidative burst and there is recent evidence that T cell exhaustion plays a role in this. | Ashwin D Dhanda Peter L Collins | 2015 | World Journal of Gastroenterology2015，21，42： | 0 |
| 14 | Delayed inflammatory pulmonary syndrome: A distinct clinical entity in the spectrum of inflammatory syndromes in COVID-19 infection?显示文摘BACKGROUND During the second wave of the coronavirus disease 2019(COVID-19)pandemic,a subset of critically ill patients developed delayed respiratory deterioration in the absence of new infection,fluid overload or extra-pulmonary organ dysfunction.AIM To describe the clinical and laboratory characteristics,outcomes,and management of these patients,and to contrast this entity with other post COVID-19 immune dysregulation related inflammatory disorders.METHODS This was a retrospective observational study of adult patients admitted to the medical intensive care unit of a 2200-bed university affiliated teaching hospital,between May and August 2021,who fulfilled clearly defined inclusion and exclusion criteria.Outcome was assessed by a change in PaO_(2)/FiO_(2) ratio and levels of inflammatory markers before and after immunomodulation,duration of mechanical ventilation after starting treatment,and survival to discharge.RESULTS Five patients developed delayed respiratory deterioration in the absence of new infection,fluid overload or extrapulmonary organ dysfunction at a median interquartile range(IQR)duration of 32(23-35)d after the onset of symptoms.These patients had elevated inflammatory markers,required mechanical ventilation for 13(IQR 10-23)d,and responded to glucocorticoids and/or intravenous immunoglobulin.One patient died(20%).CONCLUSION This delayed respiratory worsening with elevated inflammatory markers and clinical response to immunomodulation appears to contrast the well described Multisystem Inflammatory Syndrome–Adults by the paucity of extrapulmonary organ involvement.The diagnosis can be considered in patients presenting with delayed respiratory worsening,that is not attributable to cardiac dysfunction,fluid overload or ongoing infections,and associated with an increase in systemic inflammatory markers like C-reactive protein,inteleukin-6 and ferritin.A good response to immunomodulation can be expected.This delayed inflammatory pulmonary syndrome may represent a distinct clinical entity in the spectrum of inflammatory syndromes in COVID-19 infection. | Prithviraj Bose Binila Chacko Ashwin Oliver Arul Leena Robinson Vimala Balamugesh Thangakunam George M Varghese Mohan Jambugulam Audrin Lenin John Victor Peter | 2023 | World Journal of Critical Care Medicine2023，12，4： | 0 |
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