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Biomedical subjects

Peter H R Green

Publications and source records attributed to Peter H R Green.

13 recordsLinked to original sources

Risk of malignancy in patients with celiac disease.

PURPOSE: Studies from Europe have demonstrated an increased risk of malignancy, especially non-Hodgkin's lymphoma, in patients with celiac disease. However, there are no data on the risk for similar patients in the United States. Our aim was to estimate the risk of malignancy in a cohort of patients with celiac disease compared with the general U.S. population and to determine if a gluten-free diet is protective. METHODS: Patients with celiac disease seen between July 1981 and January 2000 at a referral center were included. Standardized morbidity ratios (SMRs) (ratio of observed to expected) and corresponding 95% confidence intervals (CI) were calculated, using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. RESULTS: Forty-three (11%) of 381 celiac disease patients had a diagnosis of cancer; 9 were after the diagnosis of celiac disease, 7 were simultaneous (during same month or admission), and 27 were before the diagnosis. The standardized morbidity ratio for all cancers combined was 1.5 (95% CI: 0.3 to 7.5), with significantly increased values for small bowel cancer (SMR = 34; 95% CI: 24 to 42), esophageal cancer (SMR = 12; 95% CI: 6.5 to 21), non-Hodgkin's lymphoma (SMR = 9.1; 95% CI: 4.7 to 13), and melanoma (SMR = 5.0; 95% CI: 2.1 to 12). Following the diagnosis of celiac disease, patients were at increased risk of non-Hodgkin's lymphoma only (SMR = 6.2; 95% CI: 2.9 to 14), despite adherence to a gluten-free diet. The non-Hodgkin's lymphoma included both T-cell and B-cell types and occurred in both gastrointestinal (n = 5) and extraintestinal sites (n = 4). CONCLUSION: In this cohort of patients with celiac disease, we observed increased risks of small intestinal adenocarcinoma, esophageal cancer, melanoma, and non-Hodgkin's lymphoma. The risk of non-Hodgkin's lymphoma persisted despite a gluten-free diet.

Adult↗

Coeliac disease.

Coeliac disease is a genetically-determined chronic inflammatory intestinal disease induced by an environmental precipitant, gluten. Patients with the disease might have mainly non-gastrointestinal symptoms, and as a result patients present to various medical practitioners. Epidemiological studies have shown that coeliac disease is very common and affects about one in 250 people. The disease is associated with an increased rate of osteoporosis, infertility, autoimmune diseases, and malignant disease, especially lymphomas. The mechanism of the intestinal immune-mediated response is not completely clear, but involves an HLA-DQ2 or HLA-DQ8 restricted T-cell immune reaction in the lamina propria as well as an immune reaction in the intestinal epithelium. An important component of the disease is the intraepithelial lymphocyte that might become clonally expanded in refractory sprue and enteropathy-associated T-cell lymphoma. Study of the mechanism of the immune response in coeliac disease could provide insight into the mechanism of inflammatory and autoimmune responses and lead to innovations in treatment.

Celiac Disease↗

Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study.

BACKGROUND: Celiac disease (CD) is an immune-mediated enteropathic condition triggered in genetically susceptible individuals by the ingestion of gluten. Although common in Europe, CD is thought to be rare in the United States, where there are no large epidemiologic studies of its prevalence. The aim of this study was to determine the prevalence of CD in at-risk and not-at-risk groups in the United States. METHODS: Serum antigliadin antibodies and anti-endomysial antibodies (EMA) were measured. In EMA-positive subjects, human tissue transglutaminase IgA antibodies and CD-associated human leukocyte antigen DQ2/DQ8 haplotypes were determined. Intestinal biopsy was recommended and performed whenever possible for all EMA-positive subjects. A total of 13 145 subjects were screened: 4508 first-degree and 1275 second-degree relatives of patients with biopsy-proven CD, 3236 symptomatic patients (with either gastrointestinal symptoms or a disorder associated with CD), and 4126 not-at-risk individuals. RESULTS: In at-risk groups, the prevalence of CD was 1:22 in first-degree relatives, 1:39 in second-degree relatives, and 1:56 in symptomatic patients. The overall prevalence of CD in not-at-risk groups was 1:133. All the EMA-positive subjects who underwent intestinal biopsy had lesions consistent with CD. CONCLUSIONS: Our results suggest that CD occurs frequently not only in patients with gastrointestinal symptoms, but also in first- and second-degree relatives and patients with numerous common disorders even in the absence of gastrointestinal symptoms. The prevalence of CD in symptomatic patients and not-at-risk subjects was similar to that reported in Europe. Celiac disease appears to be a more common but neglected disorder than has generally been recognized in the United States.

Adolescent↗

Refractory sprue.

Celiac disease is a T cell-mediated disorder that results from intolerance to gluten. The major cause of failure to respond to a gluten-free diet is continuing gluten ingestion. In poorly responsive patients diagnosis of refractory sprue can be established after exclusion of a limited number of conditions. Refractory sprue may occur after an initial response to the diet or without evidence of preexisting celiac disease. The detection of aberrant, clonally expanded, intraepithelial lymphocytes has led to better definition and classification of patients with refractory sprue. Only a few series of patients with well-characterized refractory sprue have been reported in the literature. The prognosis is poor, though some patients respond to corticosteroids and immunosuppressive agents. The presence of an aberrant clonal intraepithelial T-cell population has led to the designation of refractory sprue as a cryptic intestinal T-cell lymphoma.

Celiac Disease↗

Giardiasis.

Explore the source record for details and available documents.

Animals↗

Changing presentation of adult celiac disease.

The mode of presentation of celiac disease in the United States is not known. We investigated the demographic and clinical features of 227 patients with biopsy-proven celiac disease and determined if there had been changes over time. The patients had been entered into a database; those seen prior to 1990 were retrospectively entered while those seen subsequently were prospectively entered. A "symptomatic" presentation described the "classical" presentation of celiac disease with prominent gastrointestinal symptoms: diarrhea and weight loss. Females were younger and had a longer duration of symptoms compared to males. The modes of presentation were symptomatic (62%), anemia or reduced bone density (15%), screening first-degree relatives (13%), and incidental diagnosis at endoscopy (8%). We compared those diagnosed before and after 1993 (when serologic testing was first used), and noted a reduction in those presenting with diarrhea, 73% vs 43% (P = 0.0001) and a reduction in the duration of symptoms, from 9.0 +/- 1.1 years to 4.4 +/- 0.6 years (P < 0001). In conclusion, the percentage of celiac disease patients presenting with diarrhea has decreased, probably related to the more widespread use of serologic testing for celiac disease.

Adolescent↗

Duodenal histology in patients with celiac disease after treatment with a gluten-free diet.

BACKGROUND: The diagnosis of celiac disease requires characteristic histopathologic changes in an intestinal biopsy with clinical improvement in response to a gluten-free diet. Endoscopy with procurement of biopsy specimens is often performed to document response to the diet, but there are little data on the appearance of treated celiac disease. This study examined the endoscopic and histopathologic appearance of the duodenum of patients with celiac disease whose diet was gluten-free. METHODS: A cohort of 39 adult patients (mean age 52 years, range 20-74 years) with biopsy-proven celiac disease was retrospectively reviewed. All had responded clinically to a gluten-free diet that they had maintained for a mean of 8.5 years (range 1-45 years). The endoscopic and histopathologic appearances of the duodenal mucosa were reviewed. Blinded review of the diagnostic (initial) and post-treatment biopsy specimens was also performed to assess response of individual patients to the diet. RESULTS: The endoscopic appearance was normal in 23%, reduced duodenal folds were present in 46%, scalloping of folds in 33%, mucosal fissures in 44%, and nodularity in 33%. There was more than 1 abnormality present in 46%. Histology was normal in only 21%. The remainder had villous atrophy (69% partial, 10% total). Paired (diagnostic and follow-up) biopsy specimens were reviewed blindly for 12 patients. The mean (SD) intraepithelial lymphocyte count fell from 61 (22) to 38 (17) (normal <30 per 100 epithelial cells) and the crypt-to-villous ratio improved although it did not normalize. CONCLUSIONS: Despite a good clinical response, abnormal endoscopic and histopathologic appearances persist in the majority of patients with celiac disease treated with a gluten-free diet.

Adult↗

Ganglioside reactive antibodies in the neuropathy associated with celiac disease.

We tested patients with celiac disease (CD) for the presence of serum anti-ganglioside antibodies. Six of twenty-seven patient sera were reactive against brain gangliosides by an agglutination immunoassay. Neurological examination in all six revealed the presence of distal sensory loss, consistent with the diagnosis of peripheral neuropathy. When tested by ELISA for antibodies to isolated GM1, GM2, GD1a, GD1b, GT1b, and GQ1b gangliosides, all six were positive for IgG antibodies to at least one. The neuropathy of celiac disease may be autoimmune and associated with anti-ganglioside antibodies. The presence of IgG reactivity furthermore implicates a T cell-mediated response to ganglioside antigens.

Adult↗

Celiac disease and other precursors to small-bowel malignancy.

Small-intestinal malignancies are rare. Major risk factors for the development of these malignancies include celiac disease, which predisposes to both carcinoma and lymphoma. Crohn's disease patients have an increased risk of the development of adenocarcinoma, as do the inherited polyposis syndromes, FAP, and Peutz-Jehgers syndrome. Each of these conditions provides unique models for the development of malignancy.

Adenomatous Polyposis Coli↗