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Gastroenterology Report 2022年第1期10卷 612-614页

作者： Lotte Lindgreen Eriksen Simon Mark Dahl Baunwall Peter Lykke Eriksen Kirstine Petrea Bak-Fredslund Jens Erik Nielsen Jens Frederik Dahlerup karen louise thomsen Hendrik Vilstrup Christian Lodberg Hvas Department of Hepatology and Gastroenterology Aarhus University HospitalAarhus NDenmark Department of Hepatology and Gastroenterology Randers Regional HospitalRandersDenmark Department of Radiology Aarhus University HospitalAarhus NDenmark

Introduction Fecal microbiota transplantation(FMT)is highly effective and potentially life-saving for recurrent Clostridioides difficile infection(CDI)[1].Recent pilot trials also reported the use of FMT to revert hepatic encephalopathy(HE)in patients with decompensated liver cirrhosis without infectious colitis[2,3].Intestinal microbiota-driven hyperammonemia is central to HE development and most treatments aim to reduce ammonia levels by modulating the intestinal ***,FMT might lead to increased intestinal ammonia production,as we describe here.

关键词： hepatic infection encephalopathy

Preserved liver regeneration capacity after partial hepatectomy in rats with non-alcoholic steatohepatitis

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World Journal of Hepatology 2018年第1期10卷 8-21页

作者： David Haldrup Sara Heeboll karen louise thomsen Kasper Jarlhelt Andersen Michelle Meier Frank Viborg Mortensen Jens Randel Nyengaard Stephen Hamilton-Dutoit Henning Gronbaek Department of Hepatology and Gastroenterology Aarhus University HospitalAarhus C DK-8000Denmark Department of Internal Medicine Randers Regional HospitalRanders NO DK-8930Denmark Department of Surgical Gastroenterology Aarhus University HospitalAarhus C DK-8000Denmark Stereology and Electron Microscopy Laboratory Centre for Stochastic Geometry and Advanced BioimagingAarhus University HospitalAarhus C DK-8000Denmark Institute of Pathology Aarhus University HospitalAarhus C DK-8000Denmark

AIM To evaluate the liver regeneration capacity(LRC) after partial hepatectomy(PH) in experimental non-alcoholic steatohepatitis(NASH).METHODS Fifty-four female rats were fed a high-fat, high-cholesterol diet(HFCD, 65% fat, 1% cholesterol) or standard diet(STD) for 16 wk. A 70% PH was performed and the animals were euthanised before PH or 2 or 5 d postPH. LRC was evaluated using: The total number of Ki-67 positive hepatocytes in the caudate lobe, N(Ki-67, lobe) evaluated in a stereology-based design, the regenerated protein ratio(RPR), prothrombin-proconvertin ratio(PP), and m RNA expression of genes related to *** The HFCD NASH model showed significant steatosis with ballooning and inflammation, while no fibrosis was present. Mortality was similar in HFCD and STD animals following PH. HFCD groups were compared to respective STD groups and HFCD animals had a significantly elevated alanine transaminase at baseline(P < 0.001), as well as a significantly elevated bilirubin at day 2 after PH(P < 0.05). HFCD animals had a higher N(Ki-67, lobe) at baseline,(P < 0.0001), day 2 after PH(P = 0.06) and day 5 after PH(P < 0.025). We found no significant difference in RPR or PP neither 2 or 5 d post-PH. Expression of liver regeneration genes(e.g., hepatic growth factor) was higher at both day 2 and 5 post-PH in HFCD groups(P < 0.05).CONCLUSION NASH rats had a preserved LRC after hepatectomy when compared to STD rats. The methods and models of NASH are essential in understanding and evaluating LRC.

关键词： Rat Non-alcoholic fatty liver Non-alcoholic steatohepatitis Liver regeneration Hepatectomy Ki-67 Gene expression

Effects of resveratrol in experimental and clinical non-alcoholic fatty liver disease

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World Journal of Hepatology 2014年第4期6卷 188-198页

作者： Sara Heebll karen louise thomsen Steen B Pedersen Hendrik Vilstrup Jacob George Henning Grnbk Department of Hepatology and Gastroenterology Aarhus University Hospital Department of Endocrinology Aarhus University Hospital Storr Liver Unit Westmead Millennium InstituteWestmead Hospital and University of Sydney

The prevalence of obesity and related conditions like non-alcoholic fatty liver disease(NAFLD) is increasing worldwide and therapeutic options are *** treatment options are therefore intensively sought *** interesting candidate is the natural polyphenol resveratrol(RSV) that activates adenosinmonophosphate-activated protein kinase(AMPK) and silent information regulation-2 homolog 1(SIRT1).In addition,RSV has known anti-oxidant and anti-inflammatory ***,we review the current evidence for RSVmediated effects on NAFLD and address the different aspects of NAFLD and non-alcoholic steatohepatitis(NASH) pathogenesis with respect to free fatty acid(FFA) flux from adipose tissue,hepatic de novo lipogenesis,inadequate FFA β-oxidation and additional intra- and extrahepatic inflammatory and oxidant *** review the in vivo evidence from animal studies and clinical *** abundance of animal studies reports a decrease in hepatic triglyceride accumulation,liver weight and a general improvement in histological fatty liver changes,along with a reduction in circulating insulin,glucose and lipid *** studies document AMPK or SIRT1 activation,and modulation of relevant markers of hepatic lipogenesis,inflammation and oxidation ***,AMPK/SIRT1-independent actions are also *** trials are scarce and have primarily been performed with a focus on overweight/obese participants without a focus on NAFLD/NASH and histological liver *** clinical studies with appropriate design are needed to clarify the true impact of RSV treatment in NAFLD/NASH patients.

关键词： Non-alcoholic fatty liver disease Nonalcoholic steatohepatitis Steatosis Resveratrol AMPactivated protein kinase Silent information regulation-2 homolog 1 Anti-oxidants Anti-inflammatory agents Animal studies Clinical trial

Anti-CD163-dexamethasone conjugate inhibits the acute phase response to lipopolysaccharide in rats

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World Journal of Hepatology 2016年第17期8卷 726-730页

作者： karen louise thomsen Holger Jon Moller Jonas Heilskov Graversen Nils E Magnusson Soren K Moestrup Hendrik Vilstrup Henning Gronbaek Department of Hepatology and Gastroenterology Aarhus University Hospital Department of Clinical Biochemistry Aarhus University Hospital Affinicon Aps Incuba Science Park Institute of Molecular Medicine University of Southern Denmark Department of Clinical Medicine Faculty of HealthMedical Research LaboratoryAarhus University Department of Biomedicine University of Aarhus

AIM: To study the effect of a new anti-CD163-dexamethasone conjugate targeting activated macrophages on the hepatic acute phase response in rats. METHODS: Wistar rats were injected intravenous with either the CD163 targeted dexamethasone-conjugate(0.02 mg/kg) or free dexamethasone(0.02 or 1 mg/kg) 24 h prior to lipopolysaccharide(LPS)(2.5 mg/kg intraperitoneal). We measured plasma concentrations of tumour necrosis factor-a(TNF-a) and interleukin 6(IL-6) 2 h post-LPS and liver m RNAs and serum concentrations of the rat acute phase protein a-2-macroglobulin(a-2-M) 24 h after LPS. Also, plasma concentrations of alanine aminotransferase and bilirubin were measured at termination of the study. Spleen weight served as an indicator of systemic steroid ***: The conjugate halved the a-2-M liver m RNA(3.3 ± 0.6 vs 6.8 ± 1.1, P < 0.01) and serum protein(201 ± 48 μg/mL vs 389 ± 67 μg/mL, P = 0.04) after LPS compared to low dose dexamethasone treated animals, while none of the free dexamethasone doses had an effect on liver m RNA or serum levels of a-2-M. Also, the conjugate reduced TNF-a(7208 ± 1977 pg/mL vs 21583 ± 7117 pg/mL, P = 0.03) and IL-6(15685 ± 3779 pg/mL vs 25715 ± 4036 pg/mL, P = 0.03) compared to the low dose dexamethasone. The high dose dexamethasone dose decreased the spleen weight(421 ± 11 mg vs 465 ± 12 mg, P < 0.05) compared to controls, an effect not seen in any other ***: Low-dose anti-CD163-dexamethasone conjugate effectively decreased the hepatic acute phase response to LPS. This indicates an anti-inflammatory potential of the conjugate in vivo.

关键词： Acute phase response Dexamethasone Endotoxin Hemoglobin scavenger receptor CD163 Cytokines Inflammation Rats

Bariatric surgery in patients with non-alcoholic fatty liver disease-from pathophysiology to clinical effects

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World Journal of Hepatology 2019年第2期11卷 138-149页

作者： Tea L Laursen Christoffer A Hagemann Chunshan Wei Konstantin Kazankov karen L thomsen Filip K Knop Henning Grønbæk Department of Hepatology and Gastroenterology Aarhus University Hospital Gubra ApS Clinical Metabolic Physiology Steno Diabetes Center CopenhagenGentofte Hospital Department of Clinical Medicine Faculty of Health and Medical SciencesUniversity of Copenhagen Department of Hepatology Shenzhen Traditional Chinese Medicine Hospitalthe Fourth Clinical Medical College of Guangzhou University of Chinese Medicine Novo Nordisk Foundation Center for Basic Metabolic Research Faculty of Health and Medical SciencesUniversity of Copenhagen

Non-alcoholic fatty liver disease(NAFLD) is increasingly recognized as a significant liver disease,and it covers the disease spectrum from simple steatosis with a risk of development of non-alcoholic steatohepatitis(NASH) to fibrosis,subsequent cirrhosis,end-stage liver failure,and liver cancer with a potential need for liver *** and NASH are closely related to obesity,metabolic syndrome,and type 2 diabetes(T2 D).The role of gut hormones,especially glucagon-like peptide 1(GLP-1),is important in *** surgery has the potential for inducing great weight loss and may improve the symptoms of metabolic syndrome and T2 *** data demonstrated significant effects of bariatric surgery on GLP-1 and other gut hormones and important lipid metabolic and inflammatory abnormalities in the pathophysiology of ***,bariatric surgery may reverse the pathological liver changes in NAFLD and NASH *** the present review,we describe NAFLD and NASH pathophysiology and the primary effects of bariatric surgery on metabolic *** performed a systematic review of the beneficial and harmful effects and focused on changes in liver disease severity in NAFLD and NASH *** specific focus was liver histopathology as assessed by the invasive liver ***,we reviewed several non-invasive methods used for the assessment of liver disease severity following bariatric surgery.

关键词： Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis Bariatric surgery Insulin resistance,Gut hormones Glucagon-like peptide 1 Steatosis Inflammation Fibrosis

MRI of the Bladder in Patients Suspected of Bladder Tumors

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Open Journal of Radiology 2014年第2期4卷 207-214页

作者： karen Lind Gandrup Jorgen Nordling Henrik S.thomsen Department of Diagnostic Radiology Copenhagen University Hospital HerlevCopenhagenDenmark Department of Urology Copenhagen University Hospital HerlevCopenhagenDenmark

Objective: To prospectively evaluate the use of MRI for the detecting of bladder tumors and the T- stage using T2W, T1W and diffusion-weighted images (DWI). Material and methods: Twenty-eight consecutive patients (21 men, 7 women;age range, 20 - 82 years;mean age, 62.8 years) suspected of bladder tumors underwent MRI, flexible cystoscopy and transurethral resection (TURB). The presence of bladder tumor was confirmed by histopathology in 21 patients;18 patients had pTa, one pT1 and two pT2. The images were reviewed by two uroradiologists. They assigned the presence of a bladder tumor and whether the tumor was non-muscle invasive (Ta and T1) or muscle- invasive (T2, T3 or T4). Results: Compared to the histopathological results, the accuracy for identifying a bladder tumor was 60.7% and 53.7% for reviewer A and B, respectively. The sensitivity and specificity were 66.7%/61.9% and 57.1%/42.9%. Positive predictive values were 82.6%/ 76.5%. The overall staging was correct in 47.6%/52.5%, but improved on stage-by-stage up to 50%/66.7%. The agreement between the reviewers was moderate in the detecting, staging and location of the tumor (Kappa = 0.47 - 0.57). Conclusion: A simple MRI using no contrast media, but DWI, cannot replace flexible cystoscopy in the detection of new or recurrent bladder tumors.

关键词： Urography Diagnostic Imaging Hematuria Magnetic Resonance Imaging Cystoscopy

Current Techniques and Practices for Myocardial Stress Testing—A Comparative Survey between Malta and International Nuclear Medicine Centres

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Open Journal of Clinical Diagnostics 2014年第4期4卷 217-226页

作者： karen Borg Grima Desiree O’Leary Paul Bezzina louise Rainford Department of Radiography Faculty of Health Sciences University of Malta Msida Malta Diagnostic Imaging UCD School of Medicine and Medical Science University College Dublin Dublin Ireland

Objectives: The study compared cardiac scintigraphy stress scanning practices applied in a National Maltese Nuclear Medicine centre and in international centres. This was achieved through the design of an online survey which investigated participant knowledge of stress testing, and current procedural practice. Methods: An online survey comprising 12 questions was prepared using Survey Monkey. Professional Nuclear Medicine groups such as the Medical-Physics-Engineering community and Virtual Radiopharmacy were targeted. Access to the survey remained open for eight months during which a periodic reminder was sent to optimise the response rate. Forty-three members responded from across Europe and Australasia. Chi-square tests and comparisons between multiple responses using IBM SPSS 20 were used to evaluate the results. Information related to Maltese practice was collated separately for review and comparative purposes. Results: The online survey participants comprised United Kingdom [72%], other European countries [18%] and Australasia [9%]. The majority of respondents [n = 39] reported pharmacological stress testing as being performed either alone or in conjunction with exercise stress testing as the preferred option. Most participants [60%] were aware of local stress test protocols but had limited knowledge in relation to guidelines designed for cases where patients were not suitable for pharmacological stress testing. Conclusion: The survey provided information about procedures within participating centres for scintigraphic cardiac stress scanning. Differences were identified with regards to the preferred radiopharmaceutical tracers and procedural protocols. Further investigation of examination techniques is warranted, with the aim of increasing standardisation of protocol compliance and the application of more suitable practice.

关键词： Nuclear Medicine Cardiology Myocardial Stress Test Coronary Artery Disease Cardiac Tracers Pharmacological Stress Agents

A systematic review of metabolism of methionine sources in animals:One parameter does not convey a comprehensive story

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Animal Nutrition 2023年第2期13卷 31-49页

作者： Philippe Becquet Mercedes Vazquez-Anon Yves Mercier karen Wedekind Tahir Mahmood Dolores I.Batonon-Alavo Frances Yan International Methionine Analogue Association Regus Brussels City CentreStephanie SquareAvenue Louise65B-1050 BrusselsBelgium Novus International Inc. 20 Research Park DriveSaint CharlesMissouri 63304USA Adisseo France SAS Antony Parc II10 Place Du General de GaulleAntony 92160France

The goal of this review article,based on a systematic literature search,is to critically assess the state of knowledge and experimental methodologies used to delineate the conversion and metabolism of the 2 methionine(Met)sources DL-methionine(DL-Met)and DL-2-hydroxy-4-(methylthio)butanoic acid(HMTBa).The difference in the chemical structures of HMTBa and DL-Met indicates that these molecules are absorbed and metabolized differently in *** review explores the methodologies used to describe the 2-step enzymatic conversion of the 3 enantiomers(D-HMTBa,L-HMTBa and D-Met)to L-Met,as well as the site of conversion at the organ and tissue *** work was published documenting the conversion of HMTBa and D-Met into L-Met and,consequently,the incorporation into protein using a variety of in vitro techniques,such as tissue homogenates,cell lines,primary cell lines,and everted gut sacs of individual *** studies illustrated the role of the liver,kidney,and intestine in the con-version of Met precursors into L-Met.A combination of in vivo studies using stable isotopes and infusions provided evidence of the wide conversion of HMTBa to L-Met by all tissues and how some tissues are net users of HMTBa,whereas others are net secreters of L-Met derived from *** of D-Met to L-Met in organs other than the liver and kidney is poorly *** methodology cited in the literature to determine conversion efficiency ranged from measurements of urinary,fecal,and respiratory excretion to plasma concentration and tissue incorporation of isotopes after intraperitoneal and oral *** observed between these methodologies reflect differences in the metabolism of Met sources rather than differences in conversion *** factors affecting conversion efficiency are explored in this paper and are mostly associated with extreme dietary conditions,such as noncommercial crystalline diets that are very deficient in total sulfur amino a

关键词： DL-Methionine Hydroxy-analog of methionine 2-Hydroxy-4-(methylthio)butanoic acid Conversion Metabolism Methodology

Long-term follow-up of cervical abnormalities among women screened by HPV testing and cytology-results from the Hammersmith Study

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Long-term follow-up of cervical abnormalities among women sc...

基于家庭的早期干预对2岁儿童体质指数的影响：随机对照试验

24th International Papillomavirus Conference and Clinical Workshop

作者： Jack Cuzick Anne Szarewski David Mesher louise Cadman Janet Austin karen Perryman Linda Ho George Terry Peter Sasieni William Pat Soutter Wolfson Institute of Preventive Medicine Wolfson Institute of Preventive Medicine Wolfson Institute of Preventive Medicine Wolfson Institute of Preventive Medicine Wolfson Institute of Preventive Medicine Department of Gynaecological Oncology Wolfson Institute of Preventive Medicine Wolfson Institute of Preventive Medicine Wolfson Institute of Preventive Medicine Department of Gynaecological Oncology

＜正＞Background:Several studies have shown that HPV testing is substantially more sensitive than cytology for primary cervical ***,little data exist concerning the duration of i°protectioni±afforded by a negative HPV test compared to a normal cytotogic *** we report the long-term findings from the Hammersmith HPV screening study in women aged 35 or more.

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英国医学杂志中文版 2012年第5期15卷 305-305页

作者： Li Ming Wen louise A Baur Judy M Simpson karen Wardle Victoria M Flood 付晓霞(译) school of Public Health Sydney Medical School University of Sydney Sydney NSW 2006 Australia Health Promotion Service South Western Sydney and Sydney Local Health Districts NSW 21150 Discipline of Paediatrics and Child Health Sydney Medical School University of Sydney NSW 2145 School of Health Sciences Faculty of Health and Behavioural Sciences University of Wollongong NSW 2522 中华儿科杂志编辑部

目的评估基于家庭的早期干预对2岁儿童体质指数（BMI）的影响。设计随机对照试验。背景健康开端项目（Healthy Beginnings Trial）实施时间是2007至2010年，地点是澳大利亚悉尼社会和经济落后地区。

关键词：随机对照试验体质指数早期干预儿童家庭经济落后地区澳大利亚