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Adult celiac disease in the elderly

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World Journal of Gastroenterology 2008年第45期14卷 6911-6914页

作者： Hugh james Freeman Department of Medicine (Gastroentero-logy) University of British Columbia

There is an increased awareness that celiac disease may occur in the elderly although presentations with either diarrhea, weight loss or both may be less common causing delays in diagnosis for prolonged periods. Higher detection rates also seem evident owing to active case screening, largely through serodiagnostic measures. In some elderly patients who are genetically predisposed, it has been hypothesized that celiac disease might be precipitated late in life by an antigen, possibly from an infectious agent. As a result, peptide mimicry or other poorly-defined mechanisms may precipitate an autoimmune gluten-dependent clinical state. Although diarrhea and weight loss occur, only isolated iron deficiency anemia may be present at the time of initial diagnosis. In addition, the risk of other autoimmune disorders, particularly autoimmune thyroiditis, and bone disease, are increased. Osteopenia may also be associated with an increased risk of fractures. Finally, elderly celiacs have an increased risk of malignant intestinal disease, especially lymphoma.

关键词： Celiac disease Elderly Lymphoma Silentceliac disease

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

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

Heterogeneity of colorectal adenomas, the serrated adenoma, and implications for screening and surveillance

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World Journal of Gastroenterology 2008年第22期14卷 3461-3463页

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

Current algorithms for screening and surveillance for colon cancer are valuable, but may be limited by the underlying nature of the targeted neoplastic lesions. Although part of the success of adenoma removal relates to interruption of so-called "adenoma-carcinoma sequence", an alternate serrated pathway to colon cancer may pose difficulties with the ultimate results achieved by traditional colonoscopic methods. The endpoint carcinoma in this unique pathway may be derived from a dysplastic serrated adenoma. These tend to be located primarily in the right colon, especially in females, and are frequently associated with co-existent colon cancer. Unfortunately, however, there are few, if any, other identifiable risk factors, including age or family history of colon polyps or colon cancer. Moreover, this alternate serrated pathway may itself also be quite biologically heterogeneous as reflected in sessile serrated adenomas (SSA) with virtually exclusive molecular signatures defined by the presence of either BRAF or KRAS mutations. Screening algorithms in the future may need to be modified and individualized, depending on new information that likely will emerge on the natural history of these biologically heterogeneous lesions that differs from traditional adenomatous polyps.

关键词： Colorectal adenomas Serrated polyps Polyp Heterogeneity Colonoscopy Screening Colorectal Cancer

Reproductive changes associated with celiac disease

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World Journal of Gastroenterology 2010年第46期16卷 5810-5814页

作者： Hugh james Freeman Department of Medicine (Gastroenterology) University of British Columbia Hospital

Celiac disease is a mucosal disorder of the small intestine that may be triggered by dietary exposure to gluten in genetically-susceptible *** disorder is often associated with diarrhea,malabsorption and weight loss along with other extra-intestinal *** changes have been described,including impaired fertility and adverse pregnancy outcomes possibly related to immune-mediated mechanisms or nutrient *** possible pathogenetic factors that may alter placental function include maternal celiac disease autoantibodies binding to placental transglutaminase,and genetic mutations that may facilitate microthrombus *** noting activation during pregnancy or the puerperium may be important,and suggest that celiac disease may also be hypothetically precipitated by maternal exposure to one or more fetal antigens.

关键词： Celiac disease Infertility Pregnancy Post-partum celiac disease Fetal outcome

Risk factors in familial forms of celiac disease

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World Journal of Gastroenterology 2010年第15期16卷 1828-1831页

作者： Hugh james Freeman Department of Medicine University of British Columbia Hospital

Celiac disease has been reported in up to 2% of some European populations. A similar risk has been identified in the America and Australia where immigration of Eu-ropeans has occurred. Moreover, an increasing number of celiac disease patients are being identified in many Asian countries, including China and India. Finally, celiac disease has also been detected in Asian immigrants and their descendants to other countries, such as Canada. Within these so-called "general" celiac populations, however, there are specific high risk groups that have an even higher prevalence of celiac disease. Indeed, the single most important risk factor for celiac disease is having a first-degree relative with already-defined celiac disease, particularly a sibling. A rate up to 20% or more has been noted. Risk is even greater if a specific family has 2 siblings affected, particularly if a male carries the human leukocyte antigen-DQ2. Both structural changes in the small bowel architecture occur along with func-tional changes in permeability, even in asymptomatic first-degree relatives. Even if celiac disease is not evident, the risk of other autoimmune disorders seems significantly increased in first-degree relatives as well as intestinal lymphoma. Identification of celiac disease is important since recent long-term studies have shown that the mortality of celiac disease is increased, if it is unrecognized and untreated.

关键词： Celiac disease Screening Risk factors Fa-milial disease Human leukocyte antigen-DQ2 Genome-wide association studies Genomewide linkage studies

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

Complications of collagenous colitis

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World Journal of Gastroenterology 2008年第11期14卷 1643-1645页

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

Microscopic forms of colitis have been described, including collagenous colitis. This disorder generally has an apparently benign clinical course. However, a number of gastric and intestinal complications, possibly coincidental, may develop with collagenous colitis. Distinctive inflammatory disorders of the gastric mucosa have been described, including lymphocytic gastritis and collagenous gastritis. Celiac disease and collagenous sprue （or collagenous enteritis） may occur. Colonic ulceration has been associated with use of nonsteroidal anti-inflammatory drugs, while other forms of inflammatory bowel disease, including ulcerative colitis and Crohn＇s disease, may evolve from coUagenous colitis. Submucosal ＂dissection＂, colonic fractures or mucosal tears and perforation from air insufflation during colonoscopy may occur and has been hypothesized to be due to compromise of the colonic wall from submucosal collagen deposition. Similar changes may result from increased intraluminal pressure during barium enema contrast studies. Finally, malignant disorders have also been reported, including carcinoma and lymphoproliferative disease.

关键词： Colonic fractures Colonic perforation Celiac disease Collagenous gastritis Collagenous sprue Cat scratch colon Colon cancer Microscopic colitis

Colorectal cancer risk in Crohn's disease

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World Journal of Gastroenterology 2008年第12期14卷 1810-1811页

作者： Hugh james Freeman Department of Medicine (Gastro-enterology) University of British Columbia UBC Hospital Vancouver BC Canada

There is recognized increased risk for colorectal cancer in patients with inflammatory bowel disease, particularly in long-standing and extensive ulcerative colitis. There also appears to be an increased rate of intestinal cancer in Crohn's disease, including both colon and small bowel sites. In Crohn's disease, evidence suggests that detection of colorectal cancer may be delayed with a worse progno-sis. Some risk factors for cancer in Crohn's disease include the extent of inflammatory change within the colon and the presence of bypassed or excluded segments, inclu-ding rectal "stump" cancer. In addition, the risk for other types of intestinal neoplasms may be increased in Crohn's disease, including lymphoma and carcinoid tumors. Earlier detection of colorectal cancer based on colonoscopy scre-ening and surveillance may be achieved but, to date, this has not translated into a positive survival benefit. Moreo-ver, newer staining methods and evolving micro-endos-copic techniques show promise, but have not significantly altered management. Future research should focus on development of molecular or other bio-markers that might predict future dysplasia or cancer development in Crohn's disease.

关键词： Colon cancer Crohn's disease Surveillance Small bowel cancer