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| 1 | Pyogenic liver abscess:An audit of 10 years’experience显示文摘AIM:To describe our own experience with pyogenic liver abscesses over the past 10 years and investigate the risk factors associated with failure of initial percutaneous therapy.METHODS:A retrospective study of records of 63 PLA patients presenting between 1998 and 2008 to Australian tertiary referral centre,were reviewed.Amoebic and hydatid abscesses were excluded.Demographic,clinical,radiological,and microbiological characteristics,as well as surgical/radiological interventions,were recorded.RESULTS:Sixty-three patients(42 males,21 females) aged 65(±14) years[mean±(SD) ]had prodromal symptoms for a median(interquartile range;IQR) of 7(5-14) d.Only 59%of patients were febrile at presentation;however,the serum C-reactive protein was elevated in all 47 in whom it was measured.Liver function tests were non-specifically abnormal.67%of patients had a solitary abscess,while 32%had>3 abscesses with a median(IQR) diameter of 6.3(4-9) cm.Causative organisms were:Streptococcus milleri 25%,Klebsiella pneumoniae 21%,and Escherichia coli 16%.A presumptive cryptogenic cause was most common (34%).Four patients died in this series:one from sepsis,two from advanced cancer,and one from acute myocardial infarction.The initial procedure was radiological aspiration±drainage in 54 and surgery in two patients.17%underwent surgical management during their hospitalization.Serum hypoalbuminaemia[mean (95%CI) :32(29-35) g/L vs 28(25-31) g/L,P=0.045] on presentation was found to be the only factor related to failure of initial percutaneous therapy on univariate analysis.CONCLUSION:PLA is a diagnostic challenge,because the presentation of this condition is non-specific.Intravenous antibiotics and radiological drainage in the first instance allows resolution of most PLAs;However,a small proportion of patients still require surgical drainage. | Tony CY Pang Thomas Fung Jaswinder Samra Thomas J Hugh Ross C Smith | 2011 | World Journal of Gastroenterology2011，17，12： | 46 |
| 2 | Celiac disease:Prevalence,diagnosis,pathogenesis and treatment显示文摘Celiac disease(CD) is one of the most common diseases,resulting from both environmental(gluten) and genetic factors [human leukocyte antigen(HLA) and nonHLA genes].The prevalence of CD has been estimated to approximate 0.5%-1% in different parts of the world.However,the population with diabetes,autoimmune disorder or relatives of CD individuals have even higher risk for the development of CD,at least in part,because of shared HLA typing.Gliadin gains access to the basal surface of the epithelium,and interact directly with the immune system,via both trans-and para-cellular routes.From a diagnostic perspective,symptoms may be viewed as either 'typical' or 'atypical'.In both positive serological screening results suggestive of CD,should lead to small bowel biopsy followed by a favourable clinical and serological response to the gluten-free diet(GFD) to confirm the diagnosis.Positive anti-tissue transglutaminase antibody or antiendomysial antibody during the clinical course helps to confirm the diagnosis of CD because of their over 99% specificities when small bowel villous atrophy is present on biopsy.Currently,the only treatment available for CD individuals is a strict life-long GFD.A greater understanding of the pathogenesis of CD allows alternative future CD treatments to hydrolyse toxic gliadin peptide,prevent toxic gliadin peptide absorption,blockage of selective deamidation of specific glutamine residues by tissue,restore immune tolerance towards gluten,modulation of immune response to dietary gliadin,and restoration of intestinal architecture. | Naiyana Gujral Hugh J Freeman Alan BR Thomson | 2012 | World Journal of Gastroenterology2012，18，42： | 19 |
| 3 | Relationship between Fusobacterium nucleatum,inflammatory mediators and microRNAs in colorectal carcinogenesis显示文摘AIM To examine the effect of Fusobacterium nucleatum(F. nucleatum) on the microenvironment of colonic neoplasms and the expression of inflammatory mediators and microRNAs(miRNAs).METHODS Levels of F. nucleatum DNA, cytokine gene mRNA(TLR2, TLR4, NFKB1, TNF, IL1 B, IL6 and IL8), and potentially interacting miRNAs(miR-21-3p, miR-22-3p, mi R-28-5p, miR-34a-5p, miR-135b-5p) were measured by quantitative polymerase chain reaction(qPCR) TaqMan? assays in DNA and/or RNA extracted from the disease and adjacent normal fresh tissues of 27 colorectal adenoma(CRA) and 43 colorectal cancer(CRC) patients. KRAS mutations were detected by direct sequencing and microsatellite instability(MSI) status by multiplex PCR. Cytoscape v3.1.1 was used to construct the postulated miRNA:mRNA interaction network.RESULTS Overabundance of F. nucleatum in neoplastic tissue compared to matched normal tissue was detected in CRA(51.8%) and more markedly in CRC(72.1%). We observed significantly greater expression of TLR4, IL1 B, IL8, and miR-135 b in CRA lesions and TLR2, IL1 B, IL6, IL8, mi R-34 a and miR-135 b in CRC tumours compared to their respective normal tissues. Only two transcripts for miR-22 and miR-28 were exclusively downregulated in CRC tumour samples. The mRNA expression of IL1 B, IL6, IL8 and miR-22 was positively correlated with F. nucleatum quantification in CRC tumours. The mRNA expression of miR-135 b and TNF was inversely correlated. The miRNA:mRNA interaction network suggested that the upregulation of miR-34 a in CRC proceeds via a TLR2/TLR4-dependent response to F. nucleatum. Finally, KRAS mutations were more frequently observed in CRC samples infected with F. nucleatum and were associated with greater expression of miR-21 in CRA, while IL8 was upregulated in MSI-high CRC.CONCLUSION Our findings indicate that F. nucleatum is a risk factor for CRC by increasing the expression of inflammatory mediators through a possible mi RNA-mediated activation of TLR2/TLR4. | Marcela Alcantara Proenca Joice Matos Biselli Maysa Succi Fábio Eduardo Severino Gustavo Noriz Berardinelli Alaor Caetano Rui Manuel Reis David J Hughes Ana Elizabete Silva | 2018 | World Journal of Gastroenterology2018，24，47： | 15 |
| 4 | Accuracy of clinical diagnosis of idiopathic Parkinson's disease:a clinicopathologic study of 100 cases显示文摘 | Hughes A J Daniel SE Kilford L | 1992 | J Neurol Neurosurg Psychiatry1992，55，3： | 10 |
| 5 | One hundred and seventy-eight consecutive pancreatoduodenectomies without mortality:role of the multidisciplinary approach显示文摘BACKGROUND:Pancreatoduodenectomy offers the only chance of cure for patients with periampullary cancers.This,however,is a major undertaking in most patients and is associated with a significant morbidity and mortality.A multidisciplinary approach to the workup and follow-up of patients undergoing pancreatoduodenectomy was initiated at our institution to improve the diagnosis,resection rate,mortality and morbidity.We undertook the study to assess the effect of this approach on diagnosis,resection rates and short-term outcomes such as morbidity and mortality.METHODS:A prospective database of patients presenting with periampullary cancers to a single surgeon between April 2004 and April 2010 was reviewed.All cases were discussed at a multidisciplinary meeting comprising surgeons,gastroenterologists,radiologists,oncologists,radiation oncologists,pathologists and nursing staff.A standardized investigation and management algorithm was followed.Complications were graded according to the Clavien-Dindo classification.RESULTS:A total of 295 patients with a periampullary lesion were discussed and 178 underwent pancreatoduodenectomy (resection rate 60%).Sixty-one patients (34%) required either a vascular or an additional organ resection.Eighty-nine patients experienced complications,of which the commonest was blood transfusion (12%).Thirty-four patients (19%) had major complications,i.e.grade 3 or above.There was no in-hospital,30-day or 60-day mortality.CONCLUSIONS:Pancreatoduodenectomy can safely be performed in high-volume centers with very low mortality.The surgeon's role should be careful patient selection,intensive preoperative investigations,use of a team approach,and an unbiased discussion at a multidisciplinary meeting to optimize the outcome in these patients. | Jaswinder S Samra Raul Alvarado Bachmann Julian Choi Anthony Gill Michael Neale Vikram Puttaswamy Cameron Bell Ian Norton Sarah Cho Steven Blome Ritchie Maher Sivakumar Gananadha Thomas J Hugh | 2011 | Hepatobiliary & Pancreatic Diseases International2011，10，4： | 8 |
| 6 | Three-dimensional perfused human in vitro model of nonalcoholic fatty liver disease显示文摘AIM To develop a human in vitro model of non-alcoholic fatty liver disease(NAFLD), utilising primary hepatocytes cultured in a three-dimensional(3D) perfused platform. METHODS Fat and lean culture media were developed to directly investigate the effects of fat loading on primary hepatocytes cultured in a 3D perfused culture system. Oil Red O staining was used to measure fat loading in the hepatocytes and the consumption of free fatty acids(FFA) from culture medium was monitored. Hepatic functions, gene expression profiles and adipokine release were compared for cells cultured in fat and lean conditions. To determine if fat loading in the system could be modulated hepatocytes were treated with known anti-steatotic compounds. RESULTS Hepatocytes cultured in fat medium were found to accumulate three times more fat than lean cells and fat uptake was continuous over a 14-d culture. Fat loading of hepatocytes did not cause any hepatotoxicity and significantly increased albumin production. Numerous adipokines were expressed by fatty cells and genes associated with NAFLD and liver disease were upregulated including: Insulin-like growth factorbinding protein 1, fatty acid-binding protein 3 and CYP7A1. The metabolic activity of hepatocytes cultured in fatty conditions was found to be impaired and the activities of CYP3A4 and CYP2C9 were significantlyreduced, similar to observations made in NAFLD patients. The utility of the model for drug screening was demonstrated by measuring the effects of known antisteatotic compounds. Hepatocytes, cultured under fatty conditions and treated with metformin, had a reduced cellular fat content compared to untreated controls and consumed less FFA from cell culture medium.CONCLUSION The 3D in vitro NAFLD model recapitulates many features of clinical NAFLD and is an ideal tool for analysing the efficacy of anti-steatotic compounds. | Tomasz Kostrzewski Terri Cornforth Sophie A Snow Larissa Ouro-Gnao Cliff Rowe Emma M Large David J Hughes | 2017 | World Journal of Gastroenterology2017，23，2： | 6 |
| 7 | Osteoprotegerin: A Novel Secreted Protein Involved in the Regulation of Bone Density显示文摘 | W.S Simonet D.L Lacey C.R Dunstan M Kelley M.-S Chang R Lüthy H.Q Nguyen S Wooden L Bennett T Boone G Shimamoto M DeRose R Elliott A Colombero H.-L Tan G Trail J Sullivan E Davy N Bucay L Renshaw-Gegg T.M Hughes D Hill W Pattison P Campbell S Sander G Van | 1997 | Cell1997，，2： | 6 |
| 8 | c-Met signaling in the development of tumorigenesis and chemoresistance: Potential applications in pancreatic cancer显示文摘Pancreatic ductal adenocarcinoma is the 4th leading cause of cancer deaths in the United States.The majority of patients are candidates only for palliative chemotherapy,which has proven largely ineffective in halting tumor progression.One proposed mechanism of chemoresistance involves signaling via the mesenchymalepithelial transition factor protein(MET),a previously established pathway critical to cell proliferation and migration.Here,we review the literature to characterize the role of MET in the development of tumorigenesis,metastasis and chemoresistance,highlighting the potential of MET as a therapeutic target in pancreatic cancer.In this review,we characterize the role of c-Met in the development of tumorigenesis,metastasis and chemoresistance,highlighting the potential of c-Met as a therapeutic target in pancreatic cancer. | Daniel Delitto Eva Vertes-George Steven J Hughes Kevin E Behrns Jose G Trevino | 2014 | World Journal of Gastroenterology2014，20，26： | 6 |
| 9 | Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial显示文摘 | David N Krag Stewart J Anderson Thomas B Julian Ann M Brown Seth P Harlow Joseph P Costantino Takamaru Ashikaga Donald L Weaver Eleftherios P Mamounas Lynne M Jalovec Thomas G Frazier R Dirk Noyes André Robidoux Hugh MC Scarth Norman Wolmark | 2010 | Lancet Oncology2010，，10： | 3 |
| 10 | 全科医生工作困难和压力应对能力及复原力:一项定性研究显示文摘背景'新自由主义'工作策略、工作环境艰苦、英国医疗服务体系(NHS)重组及工作量的增加,造成全科医生职业倦怠及数量短缺,诸如此类的报道越来越多。目的本文旨在探讨全科医生工作上的困难和压力以及其应对策略,尤其是最近NHS要求改变工作环境给全科医生造成的影响。设计与场所本研究为定性研究。研究数据来自两个讨论组的访谈及7个'一对一'电话访谈资料。方法采用方便抽样方法选择研究对象。对研究对象进行半结构化讨论组访谈及'一对一'电话访谈,调查当前英国全科医生的执业情况。对访谈数据进行主题分析。结果共22例全科医生参与研究,其中15例参与讨论组讨论,7例参与电话采访。受访者谈到全科医生正承受着前所未有的强大压力,这种压力与工作环境有关,因为工作环境使得其觉得应该做个'好'医生。许多研究报道了全职全科医生压力太大:工作压力引起情绪改变,导致睡眠不良,焦虑增加,与亲人之间关系紧张。有些人尝试通过减少工作量来改善这种状况。工作环境的变化使得全科医生几乎没有时间采取措施来提高复原力以做到工作与生活之间平衡良好以及更好地与同事相处。尽管有些全科医生能更有效地应对压力,但是其也承认,自己已经尽了最大努力来应对工作压力。结论 NHS诸多因素造成了全科医生在感情生活及工作压力上的明显改变。为促进全科医生提供有效的医疗服务,其复原力的构建应不仅局限于改善全科医生个人情况,还应包括系统地解决其工作上的困难与压力。 | CHESHIRE A RIDGE D HUGHES J 本刊编辑部 | 2017 | 中国全科医学2017，20，21： | 3 |
| 11 | Use of the tumor necrosis factor-blockers for Crohn's disease显示文摘The use of anti-tumor necrosis factor-therapy for inflammatory bowel disease represents the most important advance in the care of these patients since the publication of the National Co-operative Crohn's disease study thirty years ago.The recommendations of numerous consensus groups worldwide are now supported by a wealth of clinical trials and several meta-analyses.In general,it is suggested that tumor necrosis factor-blockers(TNFBs) are indicated(1) for persons with moderately-severe Crohn's disease or ulcerative colitis(UC) who have failed two or more causes of glucocorticosteroids and an acceptably long cause(8 wk to 12 wk) of an immune modulator such as azathioprine or methotrexate;(2) non-responsive perianal disease;and(3) severe UC not responding to a 3-d to 5-d course of steroids.Once TNFBs have been introduced and the patient is responsive,therapy given by the IV and SC rate must be continued.It remains open to definitive evidence if concomitant immune modulators are required with TNFB maintenance therapy,and when or if TNFB may be weaned and discontinued.The supportive evidence from a single study on the role of early versus later introduction of TNFB in the course of a patient's illness needs to be confirmed.The risk/benefit profile of TNFB appears to be acceptable as long as the patient is immunized and tested for tuberculosis and viral hepatitis before the initiation of TNFB,and as long as the long-term adverse effects on the development of lymphoma and other tumors do not prone to be problematic.Because the rates of benefits to TNFB are modest from a population perspective and the cost of therapy is very high,the ultimate application of use of TNFBs will likely be established by cost/benefit studies. | Alan BR Thomson Milli Gupta Hugh J Freeman | 2012 | World Journal of Gastroenterology2012，18，35： | 3 |
| 12 | Glaciers显示文摘 | Michael Hambrey Jürg Alean Dr. Philip Hughes | 2006 | Episodes2006，29，1： | 3 |
| 13 | Pancreatic endocrine and exocrine changes in celiac disease显示文摘Although there is a great deal of information on celiac disease and associated involvement of other non-intestinal sites,data on concomitant changes in the structure and function of the pancreas is limited. The present review critically examines pancreatic endocrine changes that have been well documented in the literature,including insulin-dependent diabetes mellitus. Pancreatic exocrine alterations may also occur,and if severe,marked malnutrition with pancreatic failure and ductal calcification have been observed. Finally,other pancreatic disorders have been recorded with celiac disease. | Hugh J Freeman | 2007 | World Journal of Gastroenterology2007，13，47： | 2 |
| 14 | Technical outcomes of sentinel-lymph-node resection and conventional axillary-lymph-node dissection in patients with clinically node-negative breast cancer: results from the NSABP B-32 randomised phase III trial显示文摘 | David N Krag Stewart J Anderson Thomas B Julian Ann M Brown Seth P Harlow Takamaru Ashikaga Donald L Weaver Barbara J Miller Lynne M Jalovec Thomas G Frazier R Dirk Noyes André Robidoux Hugh MC Scarth Denise M Mammolito David R McCready Eleftherios P Mamo | 2007 | Lancet Oncology2007，，10： | 2 |
| 15 | On drilling degrees of freedom显示文摘 | Hughes T J R Brezzi F | 1989 | Computer Methods in Applied Mechanics and Engineering1989，72，： | 2 |
| 16 | Endoscopic excision of a prolapsing malignant polyp which caused intermittent gastric outlet obstruction显示文摘A 69-year-old male with chronic lymphocytic leukemia presented with iron deficiency anemia and post-prandial abdominal fullness. Endoscopy showed a large polyp on a stalk, protruding through the pylorus into the duodenum causing intermittent gastric outlet obstruction. While prolapsing gastric antral polyps are usually benign and hyperplastic, inflammatory or regenerative in type, excisional snare polypectomy here led to complete resolution of his symptoms, but showed a malignant polyp. | Hugh J Freeman | 2005 | World Journal of Gastroenterology2005，11，33： | 2 |
| 17 | Second order elastic deformation of solids显示文摘 | HUGHES D S KELLY J L | 1953 | Physical Review1953，92，5： | 1 |
| 18 | Quantum key distribution over a 48 km optical fiber network显示文摘 | | 2000 | Journal of Modern Opticals2000，47，23： | 1 |
| 19 | Fetal health surveillance in labour显示文摘 | Crane J Hughes O | 2002 | Obstet Gynaecol Can2002，24，4： | 1 |
| 20 | Finite element modeling of blood flow in arteries 显示文摘 | Thomas J R Hughes Zarins C K | 1998 | Computer Methods in Applied Mechanics and Engineering1998，158，： | 1 |
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