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1H nuclear magnetic resonance spectroscopy-basedmetabonomic study in patients with cirrhosis and hepaticencephalopathy

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World Journal of Hepatology 2015年第12期7卷 1701-1707页

作者： Konstantinos John Dabos John Andrew Parkinson Ian Howard Sadler John Nicholas Plevris peter clive hayes Centre of Liver and Digestive Disorders Royal Infirmary of Edinburgh Department of Chemistry University of Strathclyde Department of Chemistry University of Edinburgh

AIM: To identify plasma metabolites used as biomarkers in order to distinguish cirrhotics from controls and ***: A clinical study involving stable cirrhotic patients with and without overt hepatic encephalopathy was designed. A control group of healthy volunteers was used. Plasma from those patients was analysed using 1H- nuclear magnetic resonance spectroscopy. We used the Carr Purcell Meiboom Gill sequence to process the sample spectra at ambient probe temperature. We used a gated secondary irradiation field for water signal suppression. Samples were calibrated and referenced using the sodium trimethyl silyl propionate peak at 0.00 ppm. For each sample 128 transients(FID's) were acquired into 32 K complex data points over a spectral width of 6 KHz. 30 degree pulses were applied with an acquisition time of 4.0 s in order to achieve better resolution, followed by a recovery delay of 12 s, to allow for complete relaxation and recovery of the magnetisation. A metabolic profile was created for stable cirrhotic patients without signs of overt hepatic encephalopathy and encephalopathic patients as well as healthy controls. Stepwise discriminant analysis was then used and discriminant factors were created to differentiate between the three ***: Eighteen stabled cirrhotic patients, eighteen patients with overt hepatic encephalopathy and seventeen healthy volunteers were recruited. Patients with cirrhosis had significantly impaired ketone body metabolism, urea synthesis and gluconeogenesis. This was demonstrated by higher concentrations of acetoacetate(0.23 ± 0.02 vs 0.05 ± 0.00, P < 0.01), and b-hydroxybutarate(0.58 ± 0.14 vs 0.08 ± 0.00, P < 0.01), lower concentrations of glutamine(0.44 ± 0.08 vs 0.63 ± 0.03, P < 0.05), histidine(0.16 ± 0.01 vs 0.36 ± 0.04, P < 0.01) and arginine(0.08 ± 0.01 vs 0.14 ± 0.02, P < 0.03) and higher concentrations of glutamate(1.36 ± 0.25 vs 0.58 ± 0.04, P < 0.01), lactate(1.53 ± 0.11 vs 0.42 ± 0.05, P < 0.01),

关键词： Ketone bodies Branch chain amino acids Glutamine Glycolysis

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Hepatic angiotensin-converting enzyme 2 expression in metabolic dysfunction-associated steatotic liver disease and in patients with fatal COVID-19

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World Journal of Gastroenterology 2024年第31期30卷 3705-3716页

作者： Angus K Jacobs Steven D Morley Kay Samuel Katie Morgan Lyndsey Boswell Timothy J Kendall David A Dorward Jonathan A Fallowfield peter C hayes John N Plevris Hepatology Laboratory University of EdinburghEdinburgh EH164SBUnited Kingdom Scottish National Blood Transfusion Service Jack Copland CentreEdinburgh EH144BEUnited Kingdom Institute for Regeneration and Repair University of EdinburghEdinburgh EH164UUUnited Kingdom Edinburgh Pathology University of EdinburghEdinburgh EH164SBUnited Kingdom

BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),characterised by hepatic lipid accumulation,causes inflammation and oxidative stress accompanied by cell damage and *** injury(LI)is also frequently reported in patients hospitalised with coronavirus disease 2019(COVID-19),while preexisting MASLD increases the risk of LI and the development of COVID-19-associated *** of injury at the cellular level remain unclear,but it may be significant that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)which causes COVID-19,uses angiotensin-converting expression enzyme 2(ACE2),a key regulator of the‘anti-inflammatory’arm of the renin-angiotensin system,for viral attachment and host cell *** To determine if hepatic ACE2 levels are altered during progression of MASLD and in patients who died with severe *** ACE2 protein levels and localisation,and histological fibrosis and lipid droplet accumulation as markers of MASLD were determined in formalin-fixed liver tissue sections across the MASLD pathological spectrum(isolated hepatocellular steatosis,metabolic dysfunction-associated steatohepatitis(MASH)+/-fibrosis,end-stage cirrhosis)and in post-mortem tissues from patients who had died with severe COVID-19,using ACE2 immunohistochemistry and haematoxylin and eosin and picrosirius red staining of total collagen and lipid droplet areas,followed by quantification using machine learning-based image pixel *** ACE2 staining is primarily intracellular and concentrated in the cytoplasm of centrilobular hepatocytes and apical membranes of bile duct ***,ACE2 protein levels are elevated in non-fibrotic MASH compared to healthy controls but not in the progression to MASH with fibrosis and in ***2 protein levels and histological fibrosis are not associated,but ACE2 and liver lipid droplet content are significantly correlated across the MASLD *** A

关键词： Metabolic dysfunction-associated steatotic liver disease Angiotensin-converting enzyme 2 Immunohistochemistry COVID-19 COVID-19-associated cholangiopathy

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Primary lateral sclerosis:more than just an upper motor neuron disease

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Neural Regeneration Research 2024年第9期19卷 1881-1882页

作者： Ee Ling Tan Jasmin Lope peter Bede Computational Neuroimaging Group(CNG) School of MedicineTrinity College DublinIreland Department of Neurology St James’s HospitalDublinIreland

Advances in clinical care and recent research achievements:Primary lateral sclerosis(PLS)has traditionally been regarded as a pure upper motor neuron condition,a view perpetuated by most medical textbooks.

关键词： sclerosis clinical traditionally

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Sedation reversal trends at outpatient ambulatory endoscopic center vs in-hospital ambulatory procedure center using a triage protocol

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World Journal of Gastrointestinal Endoscopy 2024年第7期16卷 413-423页

作者： Saqib Walayat peter Stadmeyer Azfar Hameed Minahil Sarfaraz Paul Estrada Mark Benson Anurag Soni Patrick Pfau Paul hayes Brittney Kile Toni Cruz Deepak Gopal Department of Gastroenterology University of IllinoisPeoriaIL 61605United States Department of Gastroenterology University of WisconsinMadisonWI 53792United States Department of Internal Medicine Texas Health DentonDentonTX 76201United States Department of Internal Medicine Allama Iqbal Medical CollegeLahore 042Pakistan Department of Gastroenterology Texas Tech University Health Services CenterEl PasoTX 79911United States Department of Gastroenterology and Hepatology University of WisconsinMadisonWI 53705United States Finance Business Partners UW Health University of WisconsinMadisonWI 53792United States UW Health Digestive Health Center Endoscopy University of WisconsinMadisonWI 53792United States Division of Gastroenterology and Hepatology Department of MedicineUniversity of Wisconsin Hospitals and ClinicsMadisonWI 53705United States

BACKGROUND Routine outpatient endoscopy is performed across a variety of outpatient settings.A known risk of performing endoscopy under moderate sedation is the potential for over-sedation,requiring the use of reversal *** needs to be reported on rates of reversal across different outpatient *** academic tertiary care center utilizes a triage tool that directs higher-risk patients to the in-hospital ambulatory procedure center(APC)for their ***,we report data on outpatient sedation reversal rates for endoscopy performed at an inhospital APC vs at a free-standing ambulatory endoscopy digestive health center(AEC-DHC)following risk stratification with a triage *** To observe the effect of risk stratification using a triage tool on patient outcomes,primarily sedation reversal *** We observed all outpatient endoscopy procedures performed at AEC-DHC and APC from April 2013 to September *** were stratified to their respective sites using a triage *** evaluated each procedure for which sedation reversal with flumazenil and naloxone was *** and characteristics recorded include patient age,gender,body mass index(BMI),American Society of Anesthesiologists(ASA)classification,procedure type,and reason for sedation *** There were 97366 endoscopic procedures performed at AEC-DHC and 22494 at the APC during the study *** these,17 patients at AEC-DHC and 9 at the APC underwent sedation reversals(0.017%vs 0.04%;P=0.06).Demographics recorded for those requiring reversal at AEC-DHC vs APC included mean age(53.5±21 vs 60.4±17.42 years;P=0.23),ASA class(1.66±0.48 vs 2.22±0.83;P=0.20),BMI(27.7±6.7 kg/m^(2) vs 23.7±4.03 kg/m^(2);P=0.06),and female gender(64.7%vs 22%;P=0.04).The mean doses of sedative agents and reversal drugs used at AEC-DHC vs APC were midazolam(5.9±1.7 mg vs 8.9±3.5 mg;P=0.01),fentanyl(147.1±49.9μg vs 188.9±74.1μg;P=0.10),flumazenil(0.3±0.18μg vs 0.17±0.17μg;P=0.13)and naloxo

关键词： Ambulatory care Conscious sedation Endoscopy Colonoscopy Risk assessment Risk factors

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Human thrombin for the treatment of gastric and ectopic varices

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World Journal of Gastroenterology 2012年第41期18卷 5912-5917页

作者： Norma C McAvoy John N Plevris peter C hayes Department of Hepatology University of EdinburghRoyal Infirmary of EdinburghEdinburgh EH16 4SAUnited Kingdom

AIM:To evaluate the efficacy of human thrombin in the treatment of bleeding gastric and ectopic ***:Retrospective observational study in a Tertiary Referral *** January 1999-October 2005,we identified 37 patients who were endoscopically treated with human thrombin injection therapy for bleeding gastric and ectopic *** details including age,gender and aetiology of liver disease/segmental portal hypertension were *** thrombin was obtained from the Scottish National Blood Transfusion Service and prepared to give a solution of 250 IU/mL which was injected via a standard injection *** patient case notes were reviewed and the total dose of thrombin given along with the number of endoscopy sessions was *** haemostasis rates,rebleeding rates and mortality were catalogued along with the incidence of any immediate complications which could be attributable to the thrombin *** duration of follow up was also *** study was conducted according to the United Kingdom research ethics ***:Thirty-seven patients were included.33 patients(89%) had thrombin(250 U/mL) for gastric varices,2(5.4%) for duodenal varices,1 for rectal varices and 1 for gastric and rectal varices.(1) Gastric varices,an average of 15.2 mL of thrombin was used per ***-bleeding occurred in 4 patients(10.8%),managed in 2 by a transjugular intrahepatic portosystemic shunt(TIPSS)(one unsuccessfully who died) and in other 2 by a distal splenorenal shunt;(2) Duodenal varices(or type 2 isolated gastric varices),an average of 12.5 mL was used per patient over 2-3 endoscopy ***-bleeding occurred in one patient,which was treated by TIPSS;and(3) Rectal varices,an average of 18.3 mL was used per patient over 3 endoscopy *** re-bleeding occurred in this ***:Human thrombin is a safe,easy to use and effective therapeutic option to control haemorrhage from gastric and ectopic varices.

关键词： Variceal haemorrhage Ectopic Varices Gastric varices, Portal hypertension Thrombin

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Update of endoscopy in liver disease:More than just treating varices

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World Journal of Gastroenterology 2012年第5期18卷 401-411页

作者： Christoforos Krystallis Gail S Masterton peter C hayes John N Plevris Centre for Liver and Digestive Disorders The Royal InfirmaryUniversity of EdinburghEdinburgh EH16 4SAUnited Kingdom

The management of complications in liver disease is often complex and *** has undergone a period of rapid expansion with numerous novel and specialized endoscopic modalities that are of increasing value in the investigation and management of the patient with liver *** this review,relevant literature search and expert opinions have been used to provide a brief overview and update of the current endoscopic management of patients with liver disease and portal *** main areas covered are safety of endoscopy in patients with liver disease,the use of standard endoscopy for the treatment of varices and the role of new endoscopic modalities such as endoscopic ultrasound,esophageal capsule,argon plasma coagulation,spyglass and endomicroscopy in the investigation and treatment of liver-related gastrointestinal and biliary *** is clear that the role of the endoscopy in liver disease is well beyond that of just treating *** the technology in endoscopy expands,so does the role of the endoscopist in liver disease.

关键词： Cirrhosis Portal hypertension Varices En-doscopic ultrasound Esophageal capsule Endoscopicretrograde cholangiopancreatography Endomicros-copy Spyglass

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Immunohistochemical assessment of NY-ESO-1 expression in esophageal adenocarcinoma resection specimens

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World Journal of Gastroenterology 2014年第14期20卷 4011-4016页

作者： Stephen J hayes Keng Ngee Hng peter Clark Fiona Thistlethwaite Robert E Hawkins Yeng Ang Department of Histopathology Salford Royal NHS Foundation Trust Faculty of Medical and Human Sciences University of Manchester Department of Gastroenterology Salford Royal NHS Foundation Trust Department of Medical Oncology The Christie NHS Foundation Trust Department of Medical Oncology Paterson Institute of Cancer ResearchUniversity of Manchester

AIM: To assess NY-ESO-1 expression in a cohort of esophageal adenocarcinomas.

关键词： Esophageal adenocarcinoma Immunohistochemistry NY-ESO-1 Stem cells Vesicle trafficking

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Impaired gluconeogenesis in a porcine model of paracetamol induced acute liver failure

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World Journal of Gastroenterology 2011年第11期17卷 1457-1461页

作者： Konstantinos J Dabos Henry R Whalen Philip N Newsome John A Parkinson Neil C Henderson Ian H Sadler peter C hayes John N Plevris Liver Cell Biology Laboratory Department of HepatologyUniversity of EdinburghEdinburghEH16 4SAUnited Kingdom Gastroenterology Unit Ioannina General Hospital Hatzikosta450-01 IoanninaGreece Gastroenterology Department Hatzikosta General HospitalLeoforos Makrygianni450-01 IoanninaGreece Department of Chemistry University of EdinburghEdinburghEH16 6AAUnited Kingdom

AIM:To investigate glucose homeostasis and in particular gluconeogenesis in a large animal model of acute liver failure(ALF).METHODS:Six pigs with paracetamol induced ALF under general anaesthesia were studied over 25 *** samples were withdrawn every five hours from a central *** animals were used as controls and were maintained under anaesthesia *** 1 H NMR spectroscopy we identified most gluconeogenic amino acids along with lactate and pyruvate in the animal plasma ***:No significant changes were observed in the concentrations of the amino acids studied in the animals maintained under anaesthesia *** we look at the ALF animals,we observed a statistically significant rise of lactate(P<0.003)and pyruvate(P<0.018) at the end of the *** also observed statistically significant rises in the concentrations of alanine(P<0.002),glycine(P<0.005),threonine(P< 0.048),tyrosine(P<0.000),phenylalanine(P<0.000) and isoleucine(P<0.01).Valine levels decreased significantly(P<0.05).CONCLUSION:Our pig model of ALF is characterized by an altered gluconeogenetic capacity,an impaired tricarboxylic acid(TCA)cycle and a glycolytic state.

关键词： Lactate Pyruvate Branch chain amino acids Aromatic amino acids

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Exploring Compositional Space in Metallurgical Slag Systems

Exploring Compositional Space in Metallurgical Slag Systems

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Ninth International Conference on Molten Slags,Fluxes and Salts(MOLTEN12)

作者： peter hayes Evgueni Jak Pyrometallurgy Research Centre（PYROSEARCH） The University of QueenslandBrisbaneAustralia

Critical to our understanding of the relative stabilities of metallurgical reaction systems is knowledge of equilibrium phase chemistry,and how the phases and their chemical compositions might change as functions of key process *** the extensive research that has been undertaken to determine the thermodynamic properties of slagforming systems there is still much more that needs to be done to Improve the accuracy of existing data,Describe the behaviour of complex multi-component,multi-phase systems,and Characterise new combinations of elements arising from the manufacture of new materials The main themes that will be examined include:A review of some of the modern experimental and modeling tools that are available to characterize the elements and phases present in high temperature slag systems,How complex multi-component systems can be described in understandable and useful forms,and how these approaches can be used to systematically explore the sequences of phase changes during processing,Identifying critical experimental data,and the development of research strategies to accurately and optimally determine phase equilibria,What lies ahead? Future challenges and directions.

关键词： phase diagrams slags liquidus

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APPLICATION OF EXPERIMENTAL AND THERMODYNAMIC MODELLING STUDIES IN LEAD AND ZINC SMELTING INDUSTRY （THE SYSTEM PbO-ZnO-FeO-Fe2O3-CaO-SiO2）

APPLICATION OF EXPERIMENTAL AND THERMODYNAMIC MODELLING STUD...

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21世纪重有色金属冶金高新技术及新材料国际会议

作者： Evgueni Jak peter C.hayes PYROSEARCH Pyrometallurgy Research Centre School of Engineering The University of Queensland St Lucia Queensland 4072 Australia PYROSEARCH Pyrometallurgy Research Centre School of Engineering The University of Queensland St Lucia Queensland 4072 Australia

A'comprehensive research program focused on characterisation of phase equilibria and thermodynamics of zinc and lead smelting slags and sinters has resulted in the development of a thermodynamic database of the system *** measurements of the liquidus and solidus have been undertaken under oxidising and reducing conditions using equilibration, quenching, and electron probe X-ray microanalysis. Data have been obtained for thermodynamic model development as well as for experimental pseudo-ternary liquidus diagrams, which can be used directly by process operators. All new and previously existing experimental data for the six-component system PbO-ZnO-FeO-Fe2O3-CaO-SiO2 have been used to develop a self-consistent thermodynamic database. The thermodynamic modelling is carried out using the computer system F*A*C*T which contains thermodynamic databases with over 5000 compounds as well as evaluated solution models. The F*A*C*T package is used for calculation of slag / solid / gas / matte / metal / salt multi-phase equilibria in multi-component systems of industrial *** thermodynamic database is now used to assist in a number of important industrial issues. Example of practical applications of the thermodynamic database to lead and zinc smelting industrial processes are presented in the paper.

关键词： PbO APPLICATION OF EXPERIMENTAL AND THERMODYNAMIC MODELLING STUDIES IN LEAD AND ZINC SMELTING INDUSTRY THE SYSTEM PbO-ZnO-FeO-Fe2O3-CaO-SiO2 ZnO FeO CaO SiO

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