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Biomedical subjects

H J Freeman

Publications and source records attributed to H J Freeman.

At least 37 records · Page 2Linked to original sources

Prevalence of celiac disease in collagenous and lymphocytic colitis.

Both collagenous and lymphocytic colitis have been described in patients with celiac disease, suggesting an association between the conditions. Over the past few years, the availability, sensitivity and specificity of serological markers for celiac disease have improved - the most recent advancement being the description of tissue transglutaminase as the major antigen for endomysium antibody. A quantitative ELISA was used to measure titres of immunoglobulin A (IgA) antibody to tissue transglutaminase (tTG) along with an immunofluorescent technique for IgA endomysium antibody (EmA) in 15 patients with lymphocytic colitis and eight with collagenous colitis to determine whether celiac disease latency could be detected. One patient with lymphocytic colitis demonstrated both elevated titres of tTG antibody and positive EmA, and small bowel biopsy confirmed celiac disease. One patient with collagenous colitis had a slightly elevated titre of tTG antibody with a negative EmA, and results of a small bowel biopsy were normal. Three other patients with lymphocytic colitis were already treated for previously diagnosed celiac disease. The prevalence of celiac disease occurring in lymphocytic colitis was found to be 27%, but no cases of celiac disease in association with collagenous colitis were found.

Adult↗

Prevalence of IgA antibodies to endomysium and tissue transglutaminase in primary biliary cirrhosis.

The association between celiac disease and primary biliary cirrhosis has been described in several case reports and small screening studies, with varying prevalence rates. Stored sera from 378 patients with primary biliary cirrhosis were tested for immunoglobulin (Ig) A endomysium and tissue transglutaminase antibodies. Ten patients were positive for both antibodies (2.6%); five of these patients had had small bowel biopsies confirming celiac disease. A further 44 patients (11.6%) had raised titres of IgA tissue transglutaminase antibody but were negative for IgA endomysium antibody. The increased prevalence of celiac-related antibodies in patients with primary biliary cirrhosis suggests that the two conditions are associated, although the reason for the association remains unclear. Patients with primary biliary cirrhosis should be considered to be at high risk for celiac disease. Although liver biochemistry does not improve when these patients are fed a gluten-free diet, the complications of untreated celiac disease warrant the identification and treatment of the condition in this population.

Celiac Disease↗

Prevalence rates and an evaluation of reported risk factors for osteonecrosis (avascular necrosis) in Crohn's disease.

Avascular necrosis (osteonecrosis) occurs in Crohn's disease, but the rate of this particular complication is not known. Over 20 years, 877 patients with Crohn's disease, 492 women (56.1%) and 385 men (43.9%), were evaluated with patient follow-up data available for a mean of 7.8 years. In this group, four men were seen with osteonecrosis. No woman was affected. All patients had typical radiological, magnetic resonance imaging or pathological changes of osteonecrosis involving the femoral heads, while two also had superimposed avascular necrosis involving the humeral heads. Patient ages ranged from 19 to 36 years at the time of diagnosis of their Crohn's disease, and all were white. In one patient, disease was confined to the colon, while three patients had disease involving the terminal ileum and colon. Disease behaviour in two patients was classified as penetrating because of concomitant ischiorectal abscesses, while one patient developed a metastatic colon carcinoma. Ankylosing spondylitis was present in two patients, but no other extraintestinal manifestations developed. Two patients received corticosteroids as well as parenteral nutrition during the course of their disease. Two patients did not receive corticosteroids or parenteral nutrition. Of 877 patients with Crohn's disease, 484 (55. 1%) received corticosteroids during the course of the disease, 196 (22.4%) received at least one course of parenteral nutrition, and 125 (14.3%) received both corticosteroids and parenteral nutrition. A total of 311 patients (35.5%) had at least one small intestinal resection. The overall rate of avascular necrosis in Crohn's disease was less than 0.5% but for men with Crohn's disease was about 1%. In this series, risk of osteonecrosis could not be attributed to corticosteroid use, parenteral nutrition or both forms of therapy administered together. Small intestinal resection with loss of small intestinal absorptive area was not a risk factor for the development of osteonecrosis. Avascular necrosis (or osteonecrosis) is a very rare extraintestinal osseous complication that may occur in Crohn's disease, independent of previously reported risk factors, including corticosteroids or parenteral nutrition with lipid emulsions.

Adult↗

Small intestinal mucosal biopsy for investigation of diarrhea and malabsorption in adults.

The use of small intestinal biopsy for diagnosis in diarrhea and suspected malabsorption depends on an optimal interaction between the clinician-endoscopist and the pathologist. This necessitates open and interactive communication between involved physicians and an appreciation for correct tissue handling and biopsy orientation in the endoscopy unit and the pathology laboratory. Classification of biopsy changes on the basis of architectural abnormalities in the small intestinal biopsy may be helpful in defining the diagnosis and include severe (flat) or variably severe (mild or moderate) abnormalities. For some small intestinal disorders that are characterized by diarrhea or malabsorption, the biopsy findings may be distinctive and lead to a specific diagnosis. For others, like celiac disease, the changes are less specific, and it has become better recognized that an increasing number of conditions can produce similar histopathologic changes. Definition of typical gluten-sensitive biopsy changes in this disorder is critical.

Adult↗

Serological testing in screening for adult celiac disease.

Assays for celiac-related antibodies are becoming widely available, and the present review aims to clarify the use of these investigations in the diagnosis of, management of and screening for adult celiac disease. The sensitivities and specificities of various antibody tests are discussed, along with their clinical use as an adjunct to small bowel biopsy, and as a first-line investigation for patients with atypical symptoms of celiac disease or patients at high risk of developing sprue.

Adult↗

Hyposplenism, antiendomysial antibodies and lymphocytic colitis in collagenous sprue.

A 66-year-old woman was seen repeatedly over a decade to remove recurrent colonic adenomas and investigate episodes of watery diarrhea. Although the diarrhea was believed to be due to lymphocytic colitis, she developed weight loss, hypoproteinemia and hyposplenism that resulted in further studies, specifically to exclude celiac disease. Small intestinal biopsies, however, showed severely 'flattened' villous architecture with trichrome-positive subepithelial collagenous deposits, characteristic of collagenous sprue. Antiendomysial antibodies, known serological markers of celiac disease, were also detected. While collagenous sprue has been considered a distinct small intestinal disorder, the constellation of clinical and pathological findings in this patient suggests a close link with adult celiac disease.

Aged↗

Survey of gastroenterologists on the diagnosis and treatment of adult patients with celiac disease in British Columbia.

A recent survey of physician specialists from New York City suggested that few patients with celiac disease are seen and that management experience is limited. The present study, using a survey similar to that of the New York City investigation, evaluated the diagnostic and management experience of specialists for adult celiac disease patients in British Columbia. Four hundred and four patients were reported in the combined clinical practice experience of the responding physicians. Of these, 59, or 15%, were diagnosed in the prior year. Although each physician diagnosed an average of 2.4 new celiac disease patients per year in their entire practice experience, an average of over 4.0 new celiac disease patients were detected in the past year. Most patients presented with diarrhea, weight loss, anemia or nutrient deficiency, but about 14% were asymptomatic or diagnosed by an incidental small intestinal biopsy done at upper gastrointestinal endoscopy. Specialist physicians in British Columbia usually refer patients to their family physicians, dietitians and patient support groups for continued care and appear to rarely rely on serological assays, including antibody tests, for detection of celiac disease in adults. An associated or complicating lymphoma was detected in 16 of 404 patients (4%). Recognition of biopsy-defined celiac disease appears to be increasing in British Columbia.

Adult↗

Disappearance of Helicobacter without antibiotics in 12 patients with gastritis.

Detection of Helicobacter pylori in endoscopic gastric biopsies has been associated with a variety of diseases, including ulcers and gastritis. Although the natural history of H pylori in the gastric mucosa is unknown, antibiotic regimens have been used for eradication. Gastric biopsies from 6050 endoscopic procedures done by a single gastroenterologist from 1981 to 1994 were evaluated. Of these, 2860 from April 1, 1991 to September 30, 1994 had silver-stained biopsies to facilitate H pylori detection, and at least two upper endoscopic procedures were done with gastric biopsies in 188 patients. Twelve of the 188 patients with an initially positive H pylori gastric biopsy became H pylori-negative without antibiotic treatment for H pylori or other infection, 10 received omeprazole and two received no drug treatment. In two of the 12 patients recurrent H pylori in the gastric mucosa was also documented. These findings indicate that H pylori may disappear and reappear in the gastric mucosa with no specific antibiotic eradication regimen, although omeprazole may eradicate H pylori in vivo in some patients. The natural history of H pylori in gastric biopsies is poorly understood. Improved understanding, especially regarding the pathogenesis of upper gastrointestinal ulcerative and inflammatory disease processes, is essential before recommendations for specific antibiotic eradication regimens can be made.

Adult↗

Osteomyelitis and osteonecrosis in inflammatory bowel disease.

Osteomyelitis and osteonecrosis are skeletal disorders seen in patients with inflammatory bowel disease (IBD). Osteomyelitis usually occurs in the pelvic bones, especially in complicated Crohn's disease, presumably by direct extension from a pelvic inflammatory mass, abscess or fistulous tract. Diagnosis of osteomyelitis may be difficult and can lead to spinal extension of the septic process with a resultant neurological deficit, including paraplegia. Osteonecrosis or avascular necrosis has been reported in patients with either ulcerative colitis or Crohn's disease, often, but not exclusively, during or following steroid treatment. The disease is often multifocal, but its natural history is unknown, especially if diagnosed early with modern imaging methods, such as magnetic resonance. In IBD patients, the relationship between osteonecrosis and steroid use is unknown. An adverse steroid effect on bones, especially the femoral heads, may develop in some patients with IBD but, to date, this hypothesis remains unproven. Critical evaluation of published data reveals no consistent association between osteonecrosis and steroid treatment in IBD patients.

Animals↗

Endogenous antioxidant status in neoplastic and adjacent tissues in 1,2-dimethylhydrazine-induced colon cancer in rats: effects of olsalazine.

There is much evidence suggesting a possible role of reactive oxygen-derived substances in the pathogenesis of both ulcerative colitis and colon cancer. The antioxidant effects of 5-aminosalicylic acid (the active moiety of olsalazine) on induction of colon cancer in an experimental model using 1,2-dimethylhydrazine were studied in male Wistar rats. The levels of reduced glutathione were significantly (P < 0.01) decreased (by approximately 50%) in neoplastic tissues of rats receiving 1,2-dimethylhydrazine alone and olsalazine treatment significantly (P < 0.01) reduced the extent of this alteration. Adjacent tissues from rats receiving either carcinogen alone or carcinogen and olsalazine showed comparable levels of glutathione and these were significantly (P < 0.01) lower than corresponding control values and higher than corresponding values from neoplastic tissues. Activity of the glutathione regenerating enzyme glutathione reductase was significantly (P < 0.01) decreased (by approximately 40%) in neoplastic colonic tissue and this alteration was unaffected by olsalazine treatment. Neither carcinogen nor olsalazine treatment caused alterations in activity of glutathione reductase in adjacent tissue as compared with corresponding control values. Activity of the glutathione utilizing enzyme glutathione peroxidase was significantly (P < 0.01) increased (almost doubled) in neoplastic tissue of rats treated with carcinogen alone. Olsalazine treatment significantly (P < 0.01) reduced the elevation in glutathione peroxidase activity in neoplastic tissues of rats treated with the carcinogen. Glutathione peroxidase showed comparable activity in adjacent tissue from rats treated with either carcinogen alone or a combination of carcinogen and olsalazine and these values were significantly (P < 0.01) lower than corresponding control values. Colonic neoplastic tissues from all experimental groups of animals showed a small, but statistically significant (P < 0.05), decrease in superoxide dismutase activity compared with that in corresponding tissues from control animals.

1,2-Dimethylhydrazine↗

Immune thrombocytopenic purpura in three patients with preexisting ulcerative colitis.

Ulcerative colitis (UC) is associated with extraintestinal diseases in numerous target tissues. Associated immune-mediated hematological diseases, however, are rarely described. We report three Caucasian adult patients with UC and immune thrombocytopenic purpura (ITP). Platelet-associated antibodies (IgG) were positive in two patients, and bone marrow examinations in two patients revealed normal to increased megakaryocyte numbers. ITP was treated with corticosteroids in all patients. Two patients eventually received intravenous immune gamma-globulin, and one patient required surgical splenectomy. Of particular interest, UC preceded the onset of ITP in all patients (by from 1 to 19 yr). This suggests that ITP in these patients is causally associated with UC, possibly secondary to immunostimulation from lumenal antigens and altered immunoregulation.

Adult↗

T cell receptor gene expression and genotypes in celiac disease.

Celiac disease (CD) occurs as a result of an abnormal immune response, within the mucosa of the small bowel, to dietary gliadin peptides. To further characterize the intramucosal lymphocytes in patients with untreated CD, we compared T cell receptor (TCR) variable region gene expression in small bowel biopsies from patients with CD to that of normal small bowel. We also assessed TCR genotypes, using restriction fragment length polymorphisms (RFLPs) spanning the V beta gene locus, comparing 59 CD patients to 64 normals. The abnormal immune response in CD is polyclonal, without evidence of restriction or significantly increased expression of any TCR variable region gene families, compared to normal small bowel. No significant association was found between TCR genotypes, as defined by TCR V beta RFLPs, and CD.

Adult↗