Anna B. Pulimood

Endoscopic mucosal biopsies are useful in distinguishing granulomatous colitis due to Crohn's disease from tuberculosis

BACKGROUND Intestinal tuberculosis and Crohn’s disease are chronic granulomatous disorders that are difficult to differentiate histologically. AIMS To characterise distinctive diagnostic features of tuberculosis and Crohn’s disease in mucosal biopsy specimens obtained at colonoscopy. METHODS Selected histological parameters were evaluated retrospectively in a total of 61 biopsy sites from 20 patients with tuberculosis and 112 biopsy sites from 20 patients with Crohn’s disease. The patients were chosen on the basis of clinical history, colonoscopic findings, diagnostic histology, and response to treatment. RESULTS The histological parameters characteristic of tuberculosis were multiple (mean number of granulomas per section: 5.35), large (mean widest diameter: 193 μm), confluent granulomas often with caseating necrosis. Other features were ulcers lined by conglomerate epithelioid histiocytes and disproportionate submucosal inflammation. The features characteristic of Crohn’s disease were infrequent (mean number of granulomas per section: 0.75), small (mean widest diameter: 95 μm) granulomas, microgranulomas (defined as poorly organised collections of epithelioid histiocytes), focally enhanced colitis, and a high prevalence of chronic inflammation, even in endoscopically normal appearing areas. CONCLUSIONS The type and frequency of granulomas, presence or absence of ulcers lined by epithelioid histiocytes and microgranulomas, and the distribution of chronic inflammation have been identified as histological parameters that can be used to differentiate tuberculosis and Crohn’s disease in mucosal biopsy specimens obtained at colonoscopy.

Surgical stress and the small intestine: role of oxygen free radicals.

BACKGROUND Any surgical procedure can be associated with altered intestinal function. The mechanism involved in these changes at the cellular level during surgical stress has not been worked out. This study looked at the biochemical and functional alterations, along with ultrastructural changes, in the intestine during surgical stress in a simple rat model. METHODS Surgical stress was induced by opening the abdominal wall and handling the intestine as during laparotomy. The effect of oxidative stress on the enterocyte and altered intestinal permeability as well as the ultrastructural changes to the mucosa were studied. RESULTS Surgical stress results in oxidative stress on enterocytes, as evidenced by increased xanthine oxidase and decreased catalase activity along with altered thiol redox status. This was associated with increased intestinal permeability and widened intercellular spaces. These changes were prominent at 60 minutes after laparotomy and returned to normal by 24 hours. CONCLUSIONS Mild intestinal handling is capable of inducing oxidative stress in enterocytes; this could be one of the mechanisms by which intestinal mucosal alterations occur during surgical stress.

Segmental colonoscopic biopsies in the differentiation of ileocolic tuberculosis from Crohn's disease

Background and Aim:  The differentiation between Crohns disease (CD) and tuberculosis (TB) of the intestine can be difficult in areas where both diseases occur. The present study examined histological criteria that would enable the diagnosis in mucosal biopsies.

Oxidative stress in the development of liver cirrhosis: a comparison of two different experimental models.

Background/Aims:  Oxidative stress has been implicated in liver cirrhosis. Carbon tetrachloride and thioacetamide are the most widely used models to develop cirrhosis in rats and the present study compares oxidative stress in the liver induced by these compounds at different stages of cirrhosis development.

Probiotic administration alters the gut flora and attenuates colitis in mice administered dextran sodium sulfate

Background:  Probiotics are used in the therapy of inflammatory bowel disease. This study aimed to determine whether prior administration of probiotic lactobacilli and bifidobacteria would prevent disease and change gut flora in an animal model of colitis.

Differentiation of Crohn's disease from intestinal tuberculosis in India in 2010

Differentiating intestinal tuberculosis from Crohns disease (CD) is an important clinical challenge of considerable therapeutic significance. The problem is of greatest magnitude in countries where tuberculosis continues to be highly prevalent, and where the incidence of CD is increasing. The final clinical diagnosis is based on a combination of the clinical history with endoscopic studies, culture and polymerase chain reaction for Mycobacterium tuberculosis, biopsy pathology, radiological investigations and response to therapy. In a subset of patients, surgery is required and intraoperative findings with pathological study of the resected bowel provide a definitive diagnosis. Awareness of the parameters useful in distinguishing these two disorders in each of the different diagnostic modalities is crucial to accurate decision making. Newer techniques, such as capsule endoscopy, small bowel enteroscopy and immunological assays for Mycobacterium tuberculosis, have a role to play in the differentiation of intestinal tuberculosis and CD. This review presents currently available evidence regarding the usefulness and limitations of all these different modalities available for the evaluation of these two disorders.

In Situ PCR for Mycobacterium tuberculosis in Endoscopic Mucosal Biopsy Specimens of Intestinal Tuberculosis and Crohn Disease

Tuberculosis and Crohn disease are granulomatous disorders affecting the intestinal tract with similar clinical manifestations and pathologic features. We evaluated the use of in situ polymerase chain reaction (PCR) using Mycobacterium tuberculosis complex-specific primers for IS 6110 to differentiate these 2 disorders in archival mucosal biopsy specimens. In situ PCR was positive in 6 of 20 tuberculosis biopsy specimens and 1 of 20 Crohn disease biopsy specimens. Staining was localized to a site of granulomatous inflammation in 3 of the tuberculosis specimens and in the Crohn disease specimen. In the other tuberculosis biopsy specimens, positive staining was localized to inflammatory granulation tissue and to a focus of intact mucosa without granulomatous inflammation. The presence of M tuberculosis DNA in Crohn disease could be due to coexisting latent tuberculosis or indicate a role for these bacteria in triggering an abnormal immune response. Therefore, in situ PCR is potentially useful to differentiate intestinal tuberculosis from Crohn disease, if the sensitivity is improved.

Collagenous gastritis and collagenous colitis: a report with sequential histological and ultrastructural findings

The case is reported of a young adult man with collagenous gastritis, an extremely rare disorder with only three case reports in the English literature, who subsequently presented with collagenous colitis. Sequential gastric biopsies showed a notable increase in thickness of the subepithelial collagen band. Ultrastructural study of gastric and rectal mucosa showed the characteristic subepithelial band composed of haphazardly arranged collagen fibres, prominent degranulating eosinophils, and activated pericryptal fibroblasts.

Indomethacin-induced free radical-mediated changes in the intestinal brush border membranes.

Nonsteroidal anti-inflammatory drugs (NSAIDs) cause small intestinal damage but the pathogenesis of this toxicity is not well established. Our earlier work has shown that villus enterocytes are most susceptible to the effects of indomethacin, a commonly used NSAID. This study looked at the acute effect of indomethacin on brush border membranes (BBM), which are present mainly in the villus cells and are in immediate contact with the contents of the small intestinal lumen. Evidence of oxidative stress was found in the mucosa of the small intestine of rats dosed with indomethacin, as indicated by increased activity of xanthine oxidase with corresponding decrease in the levels of several free radical scavenging enzymes. These changes were associated with an increase in peroxidation parameters in the BBM and a fall in the level of alpha-tocopherol. These BBM also exhibited impairment in glucose transport. Significant changes were seen in the lipid composition of these membranes, with upregulation of an 85kDa isoform of phospholipase A(2). Pretreatment of animals with allopurinol, arginine or zinc protected against these effects of indomethacin. Thus this study suggests that in an acute model of indomethacin dosing there is impairment in structure and function of the BBM in enterocytes, with the effects possibly mediated by free radicals and phospholipases.

How reliable an indicator of inflammation is myeloperoxidase activity

BACKGROUND Myeloperoxidase (MPO) and interleukin-6 (IL-6) are often used as markers of inflammation. The aim of this study was to ascertain whether MPO activity is as reliable as IL-6 as an indicator of inflammation. METHODS Inflammation was induced in mice, using either turpentine or indomethacin. Duodenal tissue was removed from these animals at various time periods ranging from 6 h to 7 days later. Concentrations of IL-6 and MPO activity were estimated in the tissue. Histopathological examination was also carried out at some of the time periods to determine the presence of neutrophil infiltration in turpentine-treated mice. RESULTS Concentrations of IL-6 and MPO activity were significantly higher in tissue that had been treated with the agents used, at all the time periods studied, when compared with corresponding control tissue. Fold-increases in MPO activity were higher than fold-increases in IL-6. Concentrations of the 2 parameters showed significant positive correlation. Histopathological examination did not show significantly higher numbers of neutrophils infiltrating the tissue in response to turpentine, at the time periods studied. CONCLUSIONS Estimation of MPO activity is a reliable indicator of inflammation, being more sensitive than histopathological examination of tissue and as good as measurement of IL-6 concentrations.