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Portal hypertensive gastropathy:A systematic review of thepathophysiology,clinical presentation,natural history andtherapy

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World Journal of Hepatology 2016年第4期8卷 231-262页

作者： Mihajlo Gjeorgjievski mitchell s Cappell Division of Gastroenterology and Hepatology William Beaumont HospitalRoyal OakMI 48073United States Oakland University William Beaumont school of Medicine Royal OakMI 48073United States

AIM: To describe the pathophysiology, clinical presentation, natural history, and therapy of portal hypertensive gastropathy(PHG) based on a systematic literature ***: Computerized search of the literature was performed via Pub Med using the following medical subject headings or keywords: "portal" and "gastropathy"; or "portal" and "hypertensive"; or "congestive" and "gastropathy"; or "congestive" and "gastroenteropathy". The following criteria were applied for study inclusion: Publication in peer-reviewed journals, and publication since 1980. Articles were independently evaluated by each author and selected for inclusion by consensus after discussion based on the following criteria: Well-designed, prospective trials; recent studies; large study populations; and study emphasis on PHG. REsULTs: PHG is diagnosed by characteristic endoscopic findings of small polygonal areas of variable erythema surrounded by a pale, reticular border in a mosaic pattern in the gastric fundus/body in a patient with cirrhotic or non-cirrhotic portal hypertension. Histologic findings include capillary and venule dilatation, congestion, and tortuosity, without vascular fibrin thrombi or inflammatory cells in gastric submucosa. PHG is differentiated from gastric antral vascular ectasia by a different endoscopic appearance. The etiology of PHG is inadequately understood. Portal hypertension is necessary but insufficient to develop PHG because many patients have portal hypertension without *** increases in frequency with more severe portal hypertension, advanced liver disease, longer liver disease duration, presence of esophageal varices, and endoscopic variceal obliteration. PHG pathogenesis is related to a hyperdynamic circulation, induced by portal hypertension, characterized by increased intrahepatic resistance to flow, increased splanchnic flow, increased total gastric flow, and most likely decreased gastric mucosal flow. Gastric mucosa in PHG shows increased susceptibilit

关键词： Portal hypertensive gastropathy Congestivegastropathy Portal hypertension Cirrhosis Cirrhotic Chronic liver disease Nonvariceal upper gastrointestinalbleeding Esophageal varices Hepatic fibrosis

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Primary biliary cirrhosis: Pathophysiology, clinical presentation and therapy

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World Journal of Hepatology 2015年第7期7卷 926-941页

作者： Treta Purohit mitchell s Cappell Division of Gastroenterology and Hepatology William Beaumont Hospital Oakland University William Beaumont school of Medicine

Primary biliary cirrhosis(PBC) is an autoimmune, slowly progressive, cholestatic, liver disease characterized by a triad of chronic cholestasis, circulating anti-mitochondrial antibodies(AMA), and characteristic liver biopsy findings of nonsuppurative destructive cholangitis and interlobular bile duct destruction. About 10% of PBC patients, however, lack AMA. A variant, called PBC-autoimmune hepatitis(AIH) overlap, is characterized by the above findings of PBC together with findings of elevated serum alanine aminotransferase, elevated serum immunoglobulin G, and circulating anti-smooth muscle antibodies, with liver biopsy demonstrating periportal or periseptal, lymphocytic, piecemeal necrosis. PBC is hypothesized to be related to environmental exposure in genetically vulnerable individuals. It typically occurs in middle-aged females. Prominent clinical features include fatigue, pruritis, jaundice, xanthomas, osteoporosis, and dyslipidemia. The Mayo Risk score is the most widely used and best prognostic system. Ursodeoxycholic acid is the primary therapy. It works partly by reducing the concentration and injury from relatively toxic bile acids. PBC-AIH overlap syndrome is treated with ursodeoxycholic acid and corticosteroids, especially budesonide. Obeticholic acid and fibrate are promising new, but incompletely tested, therapies. Liver transplantation is the definitive therapy for advanced disease, with about 70% 10-year survival after transplantation. Management of pruritis includes local skin care, dermatologist referral, avoiding potential pruritogens, cholestyramine, and possibly opioid antagonists, sertraline, or rifaximin. Management of osteoporosis includes life-style modifications, administration of calcium and vitamin D, and alendronate. statins are relatively safe to treat the osteopenia associated with PBC. Associated sjogren's syndrome is treated by artificial tears, cyclosporine ophthalmic emulsion to stimulate tear production; and saliva substitutes, c

关键词： Primary biliary cirrhosis Ursodeoxycholicacid Cirrhosis Liver transplantation Cholestatic liverdisease

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Reply to Letter by Dr. Christoph Kupferschmid： Commentary on ＂Countries with high circumcision prevalence have lower prostate cancer mortality＂

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Asian Journal of Andrology 2016年第6期18卷 950-951页

作者： mitchell s Wachtel shengping Yang Brian J Morris Texas Tech University Health sciences Center Lubbock Texas USA school of Medical sciences University of Sydney Sydney New South Wales Australia

Dear Editor, We thank Dr. Kupferschmid for his interest in our study, which examined male circumcision （MC） and prostate cancer mortality〉2 Considerable strong evidence has been accumulated since 1951.3 Most of his references4-10 do not address MC and the risk of death from prostate cancer. That is a different question than MC and the risk of developing prostate cancer, which none of his references validly assess. One reference addressed bacterial colonization,6 not prostate cancer. Another7 concerned sexually transmitted infections and prostate cancer.

关键词： @@

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True polar wander in the Earth system

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science China Earth sciences 2023年第6期66卷 1165-1184页

作者： Chong WANG Ross N.mitchell state Key Laboratory of Lithospheric Evolution Institute of Geology and GeophysicsChinese Academy of SciencesBeijing 100029China College of Earth and Planetary sciences University of Chinese Academy of SciencesBeijing 100049China

True polar wander(TPW),or planetary reorientation,is the rotation of solid Earth(crust and mantle)about the liquid outer core in order to stabilize Earth’s rotation due to mass *** TPW is well-documented on Earth presently with satellites and for multiple planets and moons in the solar system,the prevalence of TPW in Earth history remains *** a history of controversy,both the physical plausibility of TPW on Earth and an empirical basis for it are now *** resistance to the old idea likely stems from the fact that,like plate tectonics,TPW may influence much of the Earth system,thus acknowledging its existence requires rethinking how many different datasets are *** review summarizes the development of TPW as a concept and provides a framework for future research that no longer regards TPW like a ghost process that may or may not exist,but as an integral part of the Earth system that can relate shallow and deep processes that are otherwise only mysteriously ***,we focus on the temporal regularity of large TPW,and discuss its relationship with the supercontinent-megacontinent cycle based on previous *** suggest the assembly of megacontinents has a close linkage to large ***,supercontinent tenure and breakup have a close linkage to fast *** effects of TPW on sea level changes,paleoclimate,biological diversity,and other facets of the Earth system are presented and require interdisciplinary tests in the future.

关键词： True polar wander(TPW) Planetary reorientation Apparent polar wander(APW) Mantle convection supercontinent cycle Megacontinent

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sphincter of Oddi dysfunction and pancreatitis

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World Journal of Gastroenterology 2007年第47期13卷 6333-6343页

作者： MT McLoughlin RMs mitchell Department of Gastroenterology Belfast City HospitalNorthern Ireland

sphincter of Oddi dysfunction (sOD) is a term used to describe a group of heterogenous pain syndromes caused by abnormalities in sphincter contractility. Biliary and pancreatic sOD are each sub-classified as typeⅠ,Ⅱ or Ⅲ,according to the Milwaukee classification. sOD appears to carry an increased risk of acute pancreatitis as well as rates of post ERCP pancreatitis of over 30%. Various mechanisms have been postulated but the exact role of sOD in the pathophysiology of acute pancreatitis is unknown. There is also an association between sOD and chronic pancreatitis but it is still unclear if this is a cause or effect relationship. Management of sOD is aimed at sphincter ablation,usually by endoscopic sphincterotomy (Es). Patients with typeⅠsOD will benefit from Es in 55%-95% of cases. sphincter of Oddi manometry is not necessary before Es in typeⅠ sOD. For patients with types Ⅱ and Ⅲ the benefit of Es is lower. These patients should be more thoroughly evaluated before performing Es. some researchers have found that manometry and ablation of both the biliary and pancreatic sphincters is required to adequately assess and treat sOD. In pancreatic sOD up to 88% of patients will benefit from sphincterotomy. Therefore,there have been calls from some quarters for the current classification system to be scrapped in favour of an overall system encompassing both biliary and pancreatic types. Future work should be aimed at understanding the mechanisms underlying the relationship between sOD and pancreatitis and identifying patient factors that will help predict benefit from endoscopic therapy.

关键词： sphincter of Oddi dysfunction Pancreatitis, Post-ERCP pancreatitis, sphincter of Oddi manometry Endoscopic sphincterotomy

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Acute liver failure secondary to severe systemic disease from fatal hemophagocytic lymphohistiocytosis:Case report and systematic literature review

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World Journal of Hepatology 2018年第9期10卷 629-636页

作者： mitchell s Cappell Ismail Hader Mitual Amin Division of Gastroenterology and Hepato-logy William Beaumont Hospital Department of Medicine Oakland University William Beaumont School of Medicine Department of Medicine William Beaumont Hospital Department of Pathology William Beaumont Hospital Department of Pathology Oakland University William Beaumont School of Medicine

AIM To systematically review liver disease associated with hemophagocytic lymphohistiocytosis(HLH),propose reasonable contraindications for liver transplantation for liver failure in HLH,and report an illustrative *** systematic review according to PRIsMA guidelines of hepatic manifestations of HLH using computerizedliterature search via PubMed of articles published since 1980 with keywords("hemophagocytic lymphohistiocytosis" or "HLH") AND("liver" or "hepatic"). Two authors independently performed literature search and incorporated articles into this review by consensus. Illustrative case report presented based on review of medical chart,and expert re-review of endoscopic photographs,radiologic images,and pathologic slides. REsULTs A 47-year-old Caucasian male,was hospitalized with high-grade pyrexia,rash,total bilirubin = 45 g/dL,moderately elevated hepatic transaminases,ferritin of 3300 ng/dL,leukopenia,and profound neutropenia(absolute neutrophil count s/mm3). Viral serologies for hepatitis A,B,and C were negative. Abdominal computed tomography scan and magnetic resonance imaging revealed no hepatic or biliary abnormalities. Pathologic analysis of liver biopsy revealed relatively well-preserved hepatic parenchyma without lymphocytic infiltrates or macrophage invasion,except for sparse,focal hepatocyte necrosis. Bone marrow biopsy and aspirate revealed foamy macrophages engulfing mature and precursor erythrocytes,consistent with HLH. Interleukin-2 receptor(CD25) was highly elevated,confirming diagnosis of HLH according to Histiocytic society criteria. Patient initially improved after high-dose prednisone therapy. Patient was judged not to be a liver transplant candidate despite model for end stage liver disease(MELD) score = 33 because liver failure was secondary to severe systemic disease from HLH,including septic shock,focal centrilobular hepatocyte necrosis from hypotension,bone marrow failure,and explosive immune activation from HLH. The pa

关键词： Hemophagocytic lymphohistiocytosis Acute liver failure Liver injury Liver transplantation Acquired immune hyperactivation Pancytopenia

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salt Accumulation and Physiology of Naturally Occurring Grasses in saline soils in Australia

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Pedosphere 2015年第4期25卷 501-511页

作者： Mohammad s.I.BHUIYAN Anantanarayanan RAMAN Dennis s.HODGKINs David mitchell Helen I.NICOL soil Research Group Charles Sturt University Graham Centre for Agricultural Innovation Orange Agricultural Institute NSW Department of Primary Industries

salinity is a major soil contamination problem in Australia. To explore salinity remediation, we evaluated the concentrations of sodium （Na）, potassium （K）, magnesium （Mg）, and calcium （Ca） in roots and shoots and in the supporting soil of the naturally occurring grasses, Cynodon dactylon and Thinopyrurn ponticum, at two salt-affected sites, Gumble and Cundumbul in central-western New south Wales, Australia. The physiological parameters of the two grass species, including net photosynthetic rate （Pn）, stomatal conductance （gs）, and intercellular CO2 concentration （Ci）, were investigated using one mature leaf from C. dactylon and T. ponticum populations. Increasing salinity levels in the topsoil had a significant influence on Ci and gs, whereas no significant effect occurred on Pn in C. dactylon and T. ponticum. The Pn values in C. dactylon and T. ponticum were greater at Cundumbul than at Gumble. The greater Mg concentration facilitated greater Pn in C. dactylon and T. ponticum populations at Cundumbul than Gumble. With increasing salinity levels in the soil, Na accumulation increased in C. dactylon and T. ponticum. The ratio between K and Na was ~ 1 in roots and shoots of both populations irrespective of the sites. Bioaccumulation factor （BF） and translocation factor （TF） results revealed that K and Na translocations were significantly higher in T. ponticum than in C. dactylon, whereas Ca and Mg translocations were significantly higher in C. dactylon than in T. ponticum. Accumulation of Na, K, Mg, and Ca ions was higher in T. ponticum than in C. dactylon; therefore, we suggest that T. ponticum as a greater salt accumulator than C. dactylon could be used for revegetation and phytoremediation of the salt-affected soils.

关键词： bioaccumulation factor intercellular CO2 concentration net photosynthetic rate phytoremediation revegetation soilcontamination stomatal conductance translocation factor

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selective androgen receptor modulators for the treatment of late onset male hypogonadism

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Asian Journal of Andrology 2014年第2期16卷 256-261,I0009页

作者： Christopher C Coss Amanda Jones Michael L Hancock mitchell s steiner James T Dalton GTx Inc. Memphis Tennessee USA.

several testosterone preparations are used in the treatment of hypogonadism in the ageing male. These therapies differ in their convenience, flexibility, regional availability and expense but share their pharmacokinetic basis of approval and dearth of long-term safety data. The brevity and relatively reduced cost of pharmacokinetic based registration trials provides little commercial incentive to develop improved novel therapies for the treatment of late onset male hypogonadism. selective androgen receptor modulators （sARMs） have been shown to provide anabolic benefit in the absence of androgenic effects on prostate, hair and skin. Current clinical development for sARMs is focused on acute muscle wasting conditions with defined clinical endpoints of physical function and lean body mass. similar regulatory clarity concerning clinical deficits in men with hypogonadism is required before the beneficial pharmacology and desirable pharmacokinetics of sARMs can be employed in the treatment of late onset male hypogonadism.

关键词： hypogonadism late onset hypogonadism selective androgen receptor modulators testosterone

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Brains, bacteria and behaviors: the role of interferon-gamma in the pathogenesis of pneumococcal meningitis

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Neural Regeneration Research 2021年第1期16卷 125-126页

作者： Lay Khoon Too Andrew mitchell Molecular Immunopathology Unit Bosch Institute and School of Medical SciencesSave Sight InstituteFaculty of Medicine and HealthUniversity of SydneySydneyNSWAustralia Materials Characterisation and Fabrication Platform Department of Chemical EngineeringThe University of MelbourneMelbourneVictoriaAustralia

of bacterial meningitis that occurs following brain infection by the Gram-positive cocci streptococcus *** only does it cause acute mortality,but pneumococcal meningitis also accounts for the highest proportion of survivors living with neurological sequelae,including behavioral disorders,cognitive deficits,hearing loss,motor impairment and *** than 90 distinct pneumococcal serotypes have been identified worldwide based on their capsular compositions and serological *** replacement continually poses great challenge to costly vaccination programs in developed countries(Koelman et al.,2020),this has therefore emphasized the need to develop new treatment strategies in addition to improving vaccine coverage.

关键词： meningitis epilepsy mortality

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Evolution of X-pinch loads for pulsed power generators with current from 50 to 5000 kA

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Matter and Radiation at Extremes 2018年第6期3卷 267-277页

作者： T.A.shelkovenko s.A.Pikuz I.N.Tilikin M.D.mitchell s.N.Bland D.A.Hammer Cornell University IthacaNY14850USA P.N.Lebedev Institute Moscow119991Russia Blackett Laboratory Imperial College LondonLondonSW72AZUK University of Evansville EvansvilleINUSA

A review of X-pinches of various configurations and of different materials as an X-ray source for various applications is presented. Theadvantages and disadvantages of different designs of X-pinches as a load for generators with a wide range of output parameters and as a sourceof X-ray radiation for X-ray point-projection imaging were analyzed.

关键词： X-pinch X-ray source X-ray point-projection imaging

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