Matthew McKinley

Increased oxidative stress and decreased antioxidant defenses in mucosa of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation whose cellular components are capable of oxidative respiratory bursts that may result in tissue injury. Mucosal biopsies were analyzed for protein carbonyl content (POPs), DNA oxidation products [8-hydroxy-2′-deoxyguanosine (8-OHdG)], reactive oxygen intermediates (ROIs), trace metals (copper, zinc, and iron) and superoxide dismutase (Cu-Zn SOD). In Crohns disease biopsies, there was an increase in ROIs, POPs, 8-OHdG, and iron, while decreased copper and Cu-Zn SOD activity were found in inflamed tissues compared to controls. For ulcerative colitis, there was an increase in ROIs, POPs, and iron in inflamed tissue compared to controls, while decreased zinc and copper were observed. An imbalance in the formation of reactive oxygen species and antioxidant micronutrients may be important in the pathogenesis and/or perpetuation of the tissue injury in IBD and may provide a rationale for therapeutic modulation with antioxidants.

Sclerosing cholangitis, chronic pancreatitis, and sjogren's syndrome: A syndrome complex

The disease complex of chronic pancreatitis, sclerosing cholangitis, and Sjogrens syndrome seems to be a well-defined entity with an autoimmune cause similar to that which occurs in primary biliary cirrhosis. Treatment depends on the component of primary sclerosing cholangitis and, more particularly, on the degree of extrahepatic involvement.

Crohn's disease is accompanied by changes in the CD4+, but not CD8+, T cell receptor BV repertoire of lamina propria lymphocytes

To identify disease-specific T cell changes that occur in Crohns disease (CD), the T cell receptor (TCR) BV repertoires of lamina propria lymphocytes (LPL) isolated from the diseased colon of seven CD patients and eight controls were determined by semiquantitative polymerase chain reaction (qPCR). As an internal control for the effects of HLA and other genes on the TCR repertoire, the BV repertoires of peripheral blood lymphocytes (PBL) from the same individuals were similarly determined and used for comparison. It was observed that the BV repertoires of LPL and PBL within the same individual were very different in both the CD and control groups. However, the CD4+, but not CD8+, repertoires of LPL and PBL differed to a much greater extent in the CD group than in the control group. Furthermore, in each CD patient there was a unique pattern of BV segments which were increased in the CD4+ LPL repertoire relative to that in PBL. These observations suggest that the inflammatory process in CD involves responses by specific CD4+ T cells to specific antigens. The isolation of such inflammation-specific CD4+ T cells may make it possible to identify the antigens which are responsible for the inflammatory process in CD and provide a better understanding of its pathogenesis.

Ogilvie's syndrome associated with herpes zoster infection.

Acute colonic pseudo-obstruction that occurs in the setting of an underlying medical condition is known as Ogilvies syndrome. The etiology of Ogilvies syndrome is unknown, and associated medical illnesses are varied and often extra-abdominal. While herpes zoster infection has been reported to cause constipation and hypomotility, the association with massive colonic distention has not so far been described. We present a patient with Ogilvies syndrome in the setting of herpes zoster infection. There was no evidence of other active illnesses, and the patient has continued to do well since the resolution of the zoster. We believe that this is the first reported association of Ogilvies syndrome and herpes zoster infection.

CD4+ Cell Oligoclonality in Crohn's Disease: Evidence for an Antigen-Specific Response

To identify disease-specific T cell changes that occur in Crohns disease (CD) the T-cell receptor (TCR) BV repertoires of lamina propria lymphocytes (LPL) from both disease-active and disease-inactive colonic tissue of three CD patients were compared by a quantitative polymerase chain reaction (qPCR) and CDR3 length analysis. It was observed that the BV repertoires of LPL isolated from the disease-active and disease-inactive parts of the colon of the same individual were different, and most of the differences occurred in CD4+ LPL with very few differences in the CD8+ populations of LPL. Although the pattern of BV segments that was increased in disease-active relative to disease-inactive tissue was different for all three CD patients, there was an increase in the levels of BV11, 13S2, 15, 16, and 17 segments in the disease-active tissue of all three patients. Standard CDR3 length analysis of BV11, 13S2, 15, 16, and 17 segments revealed that in two of the three CD patients there was a striking degree of TCR oligoclonality in the disease-active tissue that was absent from disease-inactive tissue of the same individual. Additional differences between the disease-active and disease-inactive tissues were observed using a more refined method of CDR3 length analysis, which employs BV- and BJ-specific primers. These observations suggest that at least some of the inflammation in CD is the result of responses by CD4+ T cells to specific antigens.

Volumetric laser endomicroscopy can target neoplasia not detected by conventional endoscopic measures in long segment Barrett's esophagus.

Methods and study aims: The incidence of esophageal cancer is rising despite increased surveillance efforts. Volumetric laser endomicroscopy (VLE) is a new endoscopic imaging tool that can allow for targeted biopsy of neoplasia in Barrett’s esophagus. We report a series of 6 patients with long-segment Barrett’s esophagus ( > 3 cm), who underwent a session of endoscopy with volumetric laser endomicroscopy, after a separate prior session of standard high-definition endoscopy with narrow band imaging (NBI) and random biopsies that did not reveal neoplasia. In all six patients, the first endoscopy was the index endoscopy diagnosing the Barrett’s esophagus. All VLE exams were performed within 6 months of the previous endoscopy. In five patients, VLE-targeted biopsy resulted in upstaged disease/diagnosed dysplasia that then qualified the patient for endoscopic ablation therapy. In one patient, VLE localized a focus of intramucosal cancer that allowed for curative endoscopic mucosal resection. This case series shows that endoscopy with VLE can target neoplasia that cannot be localized by high-definition endoscopy with NBI and random biopsies.

The value of MRI in evaluating perirectal and pelvic disease

MRI of the perirectal region is facilitated by the superb soft tissue contrast, multiplanar imaging capability, lack of respiratory motion artifact and absence of clip artifact which can hamper visualization by CT scan. MRI provides distinct advantages over CT scanning without the need for ionizing radiation or the injection of intravenous contrast material. This study reviews the findings in 18 consecutive patients with a variety of perirectal pathologies including rectal carcinoma (3), gynecologic neoplasm (8), sacral lesions (2), pelvic arteriovenous malformations (2), inflammatory bowel disease (2), and a pelvic kidney (1). In the perirectal region, MR was useful to show normal tissue planes, benign processes which can mimic neoplasm, intrapelvic extension of malignancy and adenopathy.

Flow cytometry: a new technique in the diagnosis of malignant ascites

The diagnosis of peritoneal carcinomatosis is often dependent on the finding of malignant cells in ascitic fluid analysis by a trained cytologist. Other methods are needed to increase the current diagnostic yield of 60-90%. Abnormal DNA content is characteristic of most malignancies. In an attempt to detect aneuploidy, we used high-resolution DNA histogram analysis with fluorescent DNA-specific stains and flow cytometry to evaluate 33 ascitic fluid samples. Of 13 patients with malignant ascites, aneuploidy was demonstrated in 10. Six patients with proven peritoneal carcinomatosis and normal cytologic examination had abnormal DNA histograms. DNA quantitation and cytologic examination agreed in 24 of 33 cases. These findings suggest that flow cytometry is a rapid and useful technique in the diagnosis of malignant ascites. The presence of aneuploidy in cells from ascitic fluid is highly suspicious for peritoneal carcinomatosis and suggests the need for further evaluation for malignancy.

Going with the flow: a perspective on flow cytometry in gastroenterology.

In this perspective on the applications of flow cytometry in gastroenterology are described the use of flow cytometry in the study of normal physiology, in normal anatomy, and in premalignant and malignant conditions of the digestive tract. The basic principles and applications for cell counting, sorting, cell cycle analysis, and quantitation of cellular characteristics are addressed to emphasize the great potential and availability of flow cytometry.

High grade dysplasia in Crohn's colitis characterized by flow cytometry.

A patient with Crohns ileocolitis had high grade dysplasia. Preoperative evaluation of colonoscopic biopsies by flow cytometry demonstrated aneuploidy, a marker of malignancy. In the surgical specimen, however, carcinoma was not demonstrated despite extensive sampling. The detection of abnormal DNA content in this premalignant lesion suggests a useful role for this technique in selecting those patients with inflammatory bowel disease at risk for carcinoma.