摘要:

The abundant literature on gastroesophageal reflux disease (GERD) in 1994 was again mainly focused on the underlying pathophysiologic mechanisms of this disorder and its treatment. Dysfunction of the lower esophageal sphincter and hiatal hernia are well-established mechanisms in the pathogenesis of GERD. Motility disturbances of the esophageal body are clearly present in patients with GERD; however, whether they result from a primary esophageal motor disorder or are secondary to reflux esophagitis remains unclear. Apparently, traction force measurement seems more appropriate than conventional manometry to study motility disturbances in (mild forms of) GERD. There is increasing interest in the detection of bile reflux and its relationship to severity of esophagitis and the development of Barrett's esophagus. In addition, a new technique was introduced allowing investigation of the esophagosalivary reflex and illustrating the importance of saliva as a defense mechanism against gastroesophageal reflux. Attention was also focused on the association between GERD and respiratory symptoms, with conflicting results. New diagnostic techniques for gastroesophageal reflux, such as electrical impedance tomography and ultrasonography, were introduced, whereas the importance of radiology was reevaluated. For research purposes, ambulatory 24-hour pH-metry recordings were increasingly combined with measurement of pressure and bile reflux and with electrocardiography, obviating computer-assisted analysis. Finally, many studies, including very large prospective randomized studies, illustrated the superiority of omeprazole to H2blockers in the initial treatment and long-term maintenance therapy of complicated GERD. Further safety follow-up, however, remains warranted. Although follow-up is still rather limited, positive results were published on laparoscopic Nissen antireflux surgery for GERD. Controlled studies comparing it with medical treatment and conventional Nissen antireflux surgery are crucial.

ISSN:0267-1379    

出版商:OVID    

年代:1995

数据来源: OVID

ISSN:0267-1379    

出版商:OVID    

年代:1995

数据来源: OVID

ISSN:0267-1379    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Although considerable progress has been made in the identification of pathophysiologic mechanisms of ulcerative colitis and Crohn's disease, the etiology and pathogenesis of these diseases remain elusive. Numerous observations implicate genetic factors in the development of these inflammatory bowel diseases and this review discusses recent advances in the major research areas in the field of inflammatory bowel disease genetics: epidemiologic studies, studies on genetic markers in inflammatory bowel disease-associated cancer, genetic marker studies, and subclinical marker studies. Finally, the exciting opportunities for further insight into the genetics of inflammatory bowel diseases provided by animal models with spontaneously developing colitis will be highlighted. Despite important advances in the past year, it seems that the literature raises more questions than it answers.

ISSN:0267-1379    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Recent studies in the immunology of inflammatory bowel disease (IBD) have focused on several areas: definition of pathogenic mechanisms, discovery of etiologic agents, development or refinement of new diagnostic tests, and identification of targets for immunologically based therapy. The repertoire of T lymphocytes is different in the gut compared with the peripheral blood in both healthy control subjects and patients with IBD. There is as yet, however, no evidence that activation of these cells is due to a single antigen or superantigen, and it is not clear whether this activation is specific for IBD. Bacterial peptidoglycan-polysaccharide complexes have been found within the gut wall in patients with Crohn's disease, and these antigens produce a higher T-lymphocyte proliferative response in this group compared with control subjects. B-cell function is also altered in IBD, in the classes and subclasses of immunoglobulin secretion. Lower HLA class II antigen expression by monocytes is also seen in IBD, and preliminary studies suggest that this correlates with poor outcome. Further characterization of the antineutrophil cytoplasmic antibody has been done within different populations, but the exact target of this antibody within the neutrophil remains unknown. Another autoantibody targeting colonic epithelial cells in patients with ulcerative colitis has also been shown to bind to epitopes of epithelial cells in the biliary tract, ciliary cells in the eye, and chondrocytes in the joint space. Adhesion molecules continue to be studied, but no specific alterations have been found in IBD compared with bowel inflammation from other causes.

ISSN:0267-1379    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Cytokines have now been established as critical mediators in the cascade of inflammatory events associated with inflammatory bowel disease (IBD). Research performed in the past few years has contributed much to the identification of individual cytokines involved in the inflammatory process and to the characterization of their biologic properties. Pro-inflammatory cytokines, including interleukin-1, interleukin-6, and tumor necrosis factor, as well as chemotactic cytokines, such as interleukin-8 and other related chemokines, have been detected in inflamed tissues from IBD patients; this has provided even more evidence that these mediators are intimately involved in the pathophysiology of ulcerative colitis and Crohn's disease. More recently, interest has been directed at understanding how these cytokines interact with each other as well as with other intestinal mucosal and immune cells. Whereas past research was aimed at determining the key events in the initiation and promotion of inflammation, current studies have focused on elucidating the processes of down-regulation and possible dysregulation of the inflammatory events that may be important in the pathogenesis of IBD. Even more provocative are studies investigating the genetic association between cytokine polymorphisms and IBD. Because cytokine research in IBD has progressed at such a rapid pace, this review will attempt to highlight some of the new and exciting discoveries published in the past year.

ISSN:0267-1379    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

In 1994 the greatest progress in the development of animal models of human inflammatory bowel disease occurred in the characterization of the roles of specific subsets of immune cells and specific microbial agents in colitis. The reconstitution of scid mice with specific subsets of CD4+lymphocytes causes colitis, a finding that has underscored the potential importance of balance between T-helper 1 and 2 lymphocyte subsets as a determining factor in the development of colitis. The demonstration that the germ-free state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats suggests that reconstitution of germ-free animals with specific bacterial strains may provide an approach to determine the differential effect of specific bacteria on the development of inflammation in animal models of colitis.

ISSN:0267-1379    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Patients with ulcerative colitis are at a higher risk for colorectal cancer compared with the normal population, although pharmacologic therapy seems to be able to modify the risk. Additionally, an elevated risk for colorectal cancer appears to be present in those with Crohn's disease, a disease also associated with an increased risk for small bowel cancer. There is still no consensus on how to lower the mortality in colorectal cancer among patients with ulcerative colitis and Crohn's disease. Although the benefit of colonoscopy surveillance programs remains to be proven, such programs are still the only way to detect asymptomatic carcinomas or high-grade dysplasia in these patient groups. Molecular pathogenesis of dysplasia and its progression to carcinoma has been proposed as one way to identify high-risk patient groups but it is still too early to include such methods in standard surveillance programs.

ISSN:0267-1379    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The medical armamentarium for inflammatory bowel diseases continues to expand despite the uncertain etiologies of Crohn's disease and ulcerative colitis. To date, almost all of the medications in use have multiple sites of activity or are regarded as nonspecific suppressants of the chronic intestinal inflammatory response. Newer agents, such as cyclosporine, offer more focused, single-mediator activity, which still influence many “down-stream” cascades of inflammatory compounds. Whereas prior attempts to control these diseases have relied on corticosteroids, antibiotics, sulfasalazine, and dietary manipulations, these approaches have left many patients either resistant to, or intolerant of steroids while exposed to their long-term sequelae. The immunomodulatory agents offer new therapeutic options to many of these patients. Azathioprine, 6-mercaptopurine, cyclosporine, and methotrexate have all shown efficacy in Crohn's disease or ulcerative colitis, although in some cases the onset of action is slow, or potential side effects preclude generalized use outside of experienced centers. The success in achieving and maintaining remission in patients when other agents have failed, in reducing or eliminating steroids, and in avoiding surgery have made these agents important therapeutic alternatives. The spectrum of aminosalicylate formulations has already improved the quality of life for patients while similar advances in the site-specific delivery of novel steroids can be expected to improve the short-and long-term clinical outcomes. Novel agents continue to be applied to inflammatory bowel disease in hopes of both improving the therapeutic response and delineating pathogenic mechanisms.

ISSN:0267-1379    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The clinical course of inflammatory bowel disease and the impact of therapies on the disease process have traditionally been assessed using composite activity indices. These indices are variably composed of subjective symptoms, endoscopic appearance, histology of mucosal biopsy specimens, and blood, urine, or tissue levels of acute-phase reactants or soluble mediators of inflammation. More recently, health-related quality of life (HRQOL, also calledfunctional status), a subjective measurement of physical, emotional, and social function and perception has become a key element in the assessment of health status in inflammatory bowel disease. Both disease activity and functional status may change with time and specific treatment depending on disease-related features. HRQOL, however, is also affected by disease-independent features. Each index assessing disease activity or HRQOL should be tailored to the study population (eg Crohn's disease, ulcerative colitis, pouchitis, pediatric patients) and research questions of the study. To adequately gauge disease severity and health status, both cross-sectional and prospective studies are critical.

ISSN:0267-1379    

出版商:OVID    

年代:1995

数据来源: OVID