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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

Segmental colitis associated with diverticulosis syndrome

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World Journal of Gastroenterology 2008年第42期14卷 6442-6443页

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

An inflammatory process that involves the sigmoid colonic segment associated with diverticular disease(SCAD) appears to be a distinct clinical and pathological *** has been described in older adults,often presenting with rectal *** of the patients seem to respond to treatment only with a 5-aminosalicylate,but some spontaneously resolve with no *** evaluation usually shows a non-specific inflammatory process localized in the sigmoid colon alone that may resolve completely with histologically normal colonic *** symptomatic events with discrete episodes of segmental colitis may occur,but most patients have an entirely benign clinical *** of the underlying molecular events that occur with SCAD may be critically important in understanding the critical elements present in a colonic inflammatory process that can completely resolve without pharmacological or biological treatment.

关键词： Segmental colitis Diverticulosis Crohn'sdisease Natural history Ulcerative colitis Colon cancer

Pancreatic endocrine and exocrine changes in celiac disease

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World Journal of Gastroenterology 2007年第47期13卷 6344-6346页

作者： Hugh J freeman Department of Medicine (Gastroenterology) University of British ColumbiaVancouverBCCanada

Although there is a great deal of information on celiac disease and associated involvement of other non-intestinal sites,data on concomitant changes in the structure and function of the pancreas is limited. The present review critically examines pancreatic endocrine changes that have been well documented in the literature,including insulin-dependent diabetes mellitus. Pancreatic exocrine alterations may also occur,and if severe,marked malnutrition with pancreatic failure and ductal calcification have been observed. Finally,other pancreatic disorders have been recorded with celiac disease.

关键词： Celiac disease Gluten-sensitive enteropathy Diabetes mellitus Chronic pancreatitis Pancreatic function

Mesenteric lymph node cavitation syndrome

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World Journal of Gastroenterology 2010年第24期16卷 2991-2993页

作者： Hugh James freeman Department of Medicine (Gastroenter-ology) University of British Columbia Hospital

The mesenteric lymph node cavitation syndrome consists of central necrosis of mesenteric lymph nodes and may occur with either celiac disease or a sprue-like intestinal disease that fails to respond to a gluten-free diet. Splenic hypofunction may also be present. The cause is not known but its development during the clinical course of celiac disease is usually indicative of a poor prognosis for the intestinal disorder, a potential for signif icant compli-cations including sepsis and malignancy, particularly T-cell lymphoma, and signif icant mortality. Modern abdominal imaging modalities may permit earlier detection in celiac disease so that earlier diagnosis and improved under-standing of its pathogenesis may result.

关键词： Mesenteric lymph node Celiac disease Yersinia infection Tuberculosis kikuchi disease Hyposplenism Lymphoma

Predictors of visual outcome in eyes with choroidal neovascularization secondary to age related macular degeneration treated with intravitreal bevacizumab monotherapy

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International Journal of Ophthalmology(English edition) 2013年第1期6卷 62-66页

作者： Jay Chhablani Jae Sukkim william R freeman Igor kozak Hai-Yan Wang Lingyun Cheng Jacob's Retina Center at Shiley Eye Center University of California L V Prasad Eye Institute Department of Ophthalmology Sanggye Paik Hospital Inje University

AIM:To evaluate the predictors of visual improvement in eyes with naive choroidal neovascularization secondary to age-related macular degeneration (CNV -AMD) treated with intravitreal bevacizumab (IVB) monotherapy. METHODS:Fifty eyes with naive CNV-AMD with pretreatment best-corrected visual acuity (BCVA) better than 20/200 and treated with IVB monotherapy were evaluated. Several variables including age, sex, pre-treatment BCVA, CNV type and lesion size on fluorescein angiogram as well as SD-OCT parameters including pre-treatment central macular thickness (CMT), inner-segment/outer-segment (IS/OS) junction integrity, and external limiting membrane (ELM) integrity were analyzed to predict visual ***:On univariate regression, pretreatment ELM damage was associated with less visual improvement after treatment (P =0.0145). However, ELM damage predicted only 10% of the visual outcome. On multivariate regression, pretreatment BCVA, IS/OS junction, and ELM integrity on SD-OCT were the significant predictors for the treatment effect and together predicted 37% of visual improvement. CONCLUSION:Pretreatment BCVA, ELM and IS/OS junction integrity on SD-OCT are of significant value inpredicting the visual improvement in naive wet AMD patients treated with IVB monotherapy.

关键词： external limiting membrane age-related macular degeneration choroidal neovascularization avastin

The ubiquitin ligase Siah2 is revealed as an accomplice of the androgen receptor in castration resistant prostate cancer

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Asian Journal of Andrology 2013年第4期15卷 447-448页

作者： Michael R freeman Research Division of Cancer Biology and Therapeutics Departments of Surgery Medicine and BiomedicalSciences Cancer Biology Program Samuel OschinComprehensive Cancer Institute Los Angeles CA90048 USA

The androgen receptor （AR） remains the primary molecular target forprostate cancer （PCa） treatment and for development of novel therapies. Profiling and other analyses of human prostate adenocarcinoma have shown that the AR is still functional during latestage disease in the absence of circulating hormone fol lowing castration therapy. The molecular mechanisms that operate during this ＇cas tration resistant＇ phase are still not well understood. Qi et al. have now implicated the ubiquitin ligase Siah2 as an important mediator of AR action in castration resis tant prostate cancer （CRPC）. Siah2 was found to target repressed AR chromatin complexes for degradation, resulting in activation of ARregulated genes involved in tumor cell proliferation, cell motility and lipid metabolism. The authors show a requirement for Siah2 activity for PCa cell growth under conditions of low androgen, and also that targeting Siah2 results in tumor growth suppression under castrate conditions. These findings identify a new mechanism of AR regulation in progressing disease as well as a novel enzymatic target for therapeutic intervention. The AR is a wellstudied hormone receptor that belongs to the large nuclear receptor gene superfamily. AR is activated by androgen binding （principally 5：~dihydrotestosterone, 5DHT）, which elicits changes in AR resident cytosolic complexes, translocation of the receptor to cell nuclei, formation of multiprotein transcriptional complexes onchromatin, and activation or repression of gene expression. Experiments with in vivo model systems have provided evidence that virtually all physiologic processes affected by androgens require the AR as a mediator of molecular effects at the gene level.1 AR is widely expressed beyond the reproductive systems and is believed to play important roles in several nonreproductive tissues, including muscle and brain. The fact that PCa growth is initially dependent on the pre sence of androgens in the circulation, and that prostat

关键词： ligase revealed accomplice

Proton pump inhibitors and an emerging epidemic of gastric fundic gland polyposis

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World Journal of Gastroenterology 2008年第9期14卷 1318-1320页

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

Fundic gland polyps are now commonly recognized during endoscopy. These polyps are benign, often multiple and usually detected in the gastric body and fundus. In the past, these polyps were sometimes associated with familial adenomatous polyposis. In recent years, it has become evident that increasing numbers of these polyps are being detected during endoscopic studies, particularly in patients treated with proton pump inhibitors for prolonged periods. In some, dysplastic changes in these polyps have also been reported. Recent studies have suggested that there may be no increase in risk of colon cancer with long-term proton pump inhibitor therapy. While temporarily reassuring, ongoing vigilance, particularly in those genetically predisposed to colon cancer, is still warranted.

关键词： Gastric polyps Fundic gland polyposis Gastric dysplasia Gastric cancer Colon polyps Familial polyposis coli Adenomatous polyposis coli gene mutation

Use of the Crohn's disease activity index in clinical trials of biological agents

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World Journal of Gastroenterology 2008年第26期14卷 4127-4130页

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

The Crohn＇s disease activity index （CDAI） has been commonly used to assess the effects of treatment with different agents in Crohn＇s disease （CD）. However, these studies may be compromised, if the results compared to a placebo or standard therapy group （in the absence of a placebo） substantially differ from the expected response. In addition, significant concerns have been raised regarding the reliability and validity of the CDAI. Reproducibility of the CDAI may be limited as significant inter-observer error has been recorded, even if measurements are done by experienced clinicians with expertise in the diagnosis and treatment of CD. Finally, many CDAI endpoints are open to subjective interpretation and have the potential for manipulation. This is worrisome as there is the potential for significant financial gain, if the results of a clinical trial appear to provide a positive result. Physicians caring for patients should be concerned about the positive results in clinical trials that are sponsored by industry, even if the trials involve respected centers and the results appear in highly ranked medical journals.

关键词： Crohn's disease Crohn's disease activity index Clinical trials Infliximab Adalimumab Corticosteroids Azathioprine

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