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Crypt region localization of intestinal stem cells in adults

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World Journal of Gastroenterology 2008年第47期14卷 7160-7162页

作者： Hugh James freeman Department of Medicine(Gastroen-terology) University of British ColumbiaVancouver V6T 1W5Canada

The intestinal epithelial lining plays a central role in the digestion and absorption of nutrients,but exists in a harsh luminal environment that necessitates continual *** renewal process involves epithelial cell proliferation in the crypt base and later cell migration from the crypt base to the luminal *** process is dependent on multi-potent progenitor cells,or stem cells,located in each *** are about 4 to 6 stem cells per crypt,and these stem cells are believed to generate distinct end-differentiated epithelial cell types,including absorptive cells,goblet cells,enteroendocrine cells and Paneth cells,while also maintaining their own progenitor cell *** studies suggested that intestinal stem cells were located either in the crypt base interspersed between the Paneth cells [*** base columnar(CBC) cell model] or at an average position of 4 cells from the crypt base [***-retaining cells(LRC +4) model].Recent studies have employed biomarkers in the in vivo mammalian state to more precisely evaluate the location of these progenitor cells in the intestinal *** notable of these novel markers are Lgr5,a gene that encodes a G-protein-coupled receptor with expression restricted to CBC cells,and Bmi 1,which encodes a chromatin remodeling protein expressed by *** studies raise the possibility that there may be separate stem cell lines or different states of stem cell activation involved in the renewal of normal mammalian intestinal tract.

关键词： Crypt base columnar cells Intestinal epithelial cell renewal Lgr5 gene Polycomb bmil protein Progenitor cells Stem cells +4 stem cellmodel

Multifocal stenosing ulceration of the small intestine

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World Journal of Gastroenterology 2009年第39期15卷 4883-4885页

作者： Hugh James freeman Department of Medicine University of British ColumbiaUBC Hospital

Several reports have described an apparently uncommon clinicopathological disorder that is characterized by multifocal stenosing small-intestinal *** to Crohn's disease,the ulcers are not transmural and typically remain shallow,and involve only the mucosa and *** disorder seems to be localized in the jejunum and proximal ileum only,and not the distal ileum or *** nonspecif ic inflammatory changes are present without giant cells or other typical features of granulomatous *** patients present clinically with recurrent obstructive events that usually respond to steroids,surgical resection,or *** the development of newer imaging modalities to visualize the small-intestinal mucosa,such as double-balloon enteroscopy,improved understanding of the long-term natural history of this apparently distinctive disorder should emerge.

关键词： Ulcer Stenosis Intestinal diseases Small intestine Crohn's disease

Endoscopic excision of a prolapsing malignant polyp which caused intermittent gastric outlet obstruction

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World Journal of Gastroenterology 2005年第33期11卷 5245-5247页

作者： Hugh J freeman Department of Medicine (Gastroenterology) University of British Columbia Vancouver BC V6T 1W5 Canada Correspondence to:Dr.Hugh J FreemanGastroenterologyUBC Hospital2211 Wesbrook MallVancouverBCV6T 1W5

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.

关键词： Gastric adenoma Gastric carcinoma Endoscopic polypectomy Neoplastic gastric polyps

Tropheryma whipplei infection

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World Journal of Gastroenterology 2009年第17期15卷 2078-2080页

作者： Hugh James freeman Department of Medicine (Gastroen-terology) University of British Columbia Vancouver V6T 1W5 Canada

Whipple's disease was initially described in 1907. Over the next century, the clinical and pathological features of this disorder have been better appreciated. Most often, weight loss, diarrhea, abdominal and joint pain occur. Occasionally, other sites of involvement have been documented, including isolated neurological disease, changes in the eyes and culture-negative endocarditis. In the past decade, the responsible organism Tropheryma whipplei has been cultivated, its genome sequenced and its antibiotic susceptibility defined. Although rare, it is a systemic infection that may mimic a wide spectrum of clinical disorders and may have a fatal outcome. If recognized, prolonged antibiotic therapy may be a very successful form of treatment.

关键词： Tropheryma whipplei Small intestinalmalabsorption Abdominal lymphadenopathy Periodicacid-Schiff staining Whipple's disease

Recent developments on the role of Clostridium difficile in inflammatory bowel disease

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World Journal of Gastroenterology 2008年第18期14卷 2794-2796页

作者： Hugh James freeman Department of Medicine (Gastroenterology) University of British Columbia Vancouver V6T 1W5Canada

Clostridium difficile (CD), specifically its toxins, have been implicated as a risk factor for exacerbation of the inflammatory process in up to 5% of patients with ulcerative colitis or Crohn’s disease. Typical evidence of colonic changes with CD infection, including pseudomembranous exudate, are often not present; however, a severe clinical course may result, including precipitation of toxic colitis and toxic megacolon. Recently, hypervirulent CD strains have been reported raising concern for a more severe disease process in patients with underlying inflammatory bowel ***, small bowel involvement or CD enteritis has been increasingly described, usually in those with a history of a prior colectomy or total proctocolectomy for prior severe and extensive inflammatory bowel disease. Finally, refractory or treatment-resistant pouchitis may occur with CD infection.

关键词： Crohn's disease Ulcerative colitis Antibiotic-associated colitis Cytotoxin Enterotoxin Pseudomembranous colitis Clostridium difficile colitis

Intraductal papillary mucinous neoplasms and other pancreatic cystic lesions

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World Journal of Gastroenterology 2008年第19期14卷 2977-2979页

作者： Hugh James freeman Department of Medicine (Gastroen-terology) University of British Columbia

Pancreatic cystic neoplasms are being increasingly recognized, even in the absence of symptoms, in large part, due to markedly improved imaging modalities such as magnetic resonance imaging (MRI)/magnetic resonance cholangio pancreatography (MRCP) and computer tomography (CT) scanning. During the past 2 decades, better imaging of these cystic lesions has resulted in definition of different types, including pancreatic intraductal papillary mucinous neoplasms (IPMN). While IPMN represent only a distinct minority of all pancreatic cancers, they appear to be a relatively frequent neoplastic form of pancreatic cystic neoplasm. Moreover, IPMN have a much better outcome and prognosis compared to pancreatic ductal adenocarcinomas. Therefore, recognition of this entity is exceedingly important for the clinician involved in diagnosis and further evaluation of a potentially curable form of pancreatic cancer.

关键词： Pancreatic cancer Pancreatic intraductal papillary mucinous neoplasms Mucinous cystic neoplasm of pancreas Serous cystadenoma Pancreatic cysticlesions

Long-term natural history of Crohn’s disease

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World Journal of Gastroenterology 2009年第11期15卷 1315-1318页

作者： Hugh James freeman Department of Medicine (Gastroen-terology) University of British Columbia Vancouver V6T 1W5 Canada

Crohn’s disease is a chronic inflammatory granulomatous process that usually involves different sites in the intestinal tract. Genetic and environmental factors are thought to play a role in its etiology and pathogenesis. The disorder has a heterogeneous clinical expression and data from tertiary care settings have documented its female predominance, occasional familial nature, and high rate of stricture formation and penetrating disease. It may appear from early childhood to late adulthood, although over 80% are currently diagnosed before age 40 years, usually with terminal ileal and colonic involvement. Several studies have now shown differences in phenotypic clinical expression depending on the initial age at diagnosis, with pediatric-onset disease being more severe and more extensive with more involvement of the upper gastrointestinal tract compared to adult-onset disease. In addition, long- term studies from these tertiary care settings have documented that the disorder may evolve with time into a more complex disease with stricture formation and penetrating disease complications (i.e. fistula and abscess). Although prolonged remission with no evidence of inflammatory disease may occur, discrete periods of symptomatic and active granulomatous inflammatory disease may re-appear over many decades. Long-term studies on the natural history have also suggested that discrete events (or agents) may precipitate this granulomatous inflammatory process.

关键词： Natural history Crohn's disease Age-dependent phenotypes Clinical behavior Granulomatous inflammation

Adult autoimmune enteropathy

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World Journal of Gastroenterology 2008年第8期14卷 1156-1158页

作者： Hugh James freeman Department of Medicine (Gastroenterology) University of British Columbia Vancouver BC Canada

Recent reports have suggested that autoimmune enteropathy involving the small bowel may occur in adults as well as in children. Apparently, the endoscopic and histological changes are similar to celiac disease before treatment, but these are not altered by any form of dietary restriction, including a gluten-free diet. As in celiac disease, histologic changes in gastric and colonic biopsies have also been recorded. Anti-enterocyte antibodies detected with immunofluorescent methods have been reported by a few laboratories, but these antibodies appear not to be specific and may simply represent epiphenomena. A widely available, reproducible and quantitative anti-enterocyte antibody assay is needed that could be applied in small bowel disorders that have the histological appearance of celiac disease, but fail to respond to a gluten-free diet.

关键词： Celiac disease Autoimmune enteropathy Anti-enterocyte antibodies Anti-goblet cell antibodies Antibodies in celiac disease

Adult eosinophilic gastroenteritis and hypereosinophilic syndromes

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World Journal of Gastroenterology 2008年第44期14卷 6771-6773页

作者： Hugh James freeman Department of Medicine (Gastroen-terology) University of British ColumbiaVancouver V6T 1W5Canada

Eosinophilic gastroenteritis (EGE) in the adult is a distinctive pathologically-based disorder characterized by an eosinophil-predominant mucosal inflammatory process. Most often,the disorder is detected during endoscopic investigation for abdominal pain or diarrhea. Other causes of gastric and intestinal mucosal eosinophilia require exclusion,including parasitic infections and drug-induced causes. Occasionally,the muscle wall or serosal surface may be involved. EGE appears to be more readily recognized,in large part,due to an evolution in the imaging methods used to evaluate abdominal pain and diarrhea,in particular,endoscopic imaging and mucosal biopsies. Def inition of EGE,however,may be diffi cult,as the normal ranges of eosinophil numbers in normal and abnormal gastric and intestinal mucosa are not well standardized. Also,the eosinophilic inflammatory process may be either patchy or diffuse and the detection of the eosinophilic infiltrates may vary depending on the method of biopsy fixation. Treatment has traditionally focused on resolution of symptoms,and,in some instances,eosinophil quantification in pre-treatment and post-treatment biopsies. Future evaluation and treatment of EGE may depend on precise serological biomarkers to aid in defi nition of the long-term natural history of the disorder and its response to pharmacological or biological forms of therapy.

关键词： Eosinophils Eosinophilic gastroenteritis Eosinophilic gastritis Eosinophilic enteritis