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PubMed2006

The complexity and challenges of genetic counseling and testing for inflammatory bowel disease.

Inflammatory bowel disease (IBD) is an umbrella term referring to two chronic idiopathic intestinal diseases: ulcerative colitis (UC) and Crohn's disease (CD). Both UC and CD are characterized by immune activation that leads to symptoms, but the location, severity and behavior of the inflammation varies among individuals and in characteristic ways between UC and CD. A majority of patients with IBD are diagnosed in young adulthood, but the response to therapy is variable and difficult to predict, with some patients demonstrating a prompt and effective remission while others have continuous symptoms that do not respond to existing medical options. Surgery remains a frequent and necessary occurrence among patients with IBD, but in UC it is considered curative, while in CD only temporizing. Clinical observations, epidemiological studies, and molecular genetics have provided strong evidence that both genetic and environmental factors are important determinants for disease susceptibility. In recent years, a number of genes have been identified that associate with CD and UC, although the clinical utility of these discoveries in patients or in susceptible family members has not been determined. Nonetheless, it is hoped that these fundamental advances in our understanding of IBD will lead to better therapies for patients and prevention strategies for those who are susceptible. Effective incorporation of clinical genetic testing for IBD into practice will require appropriate education and counseling.

Crohn Disease↗

PubMed2003

Advances in clinical laboratory tests for inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a generic term that refers to Crohn's disease and chronic ulcerative colitis (UC). The CD and UC are considered to be distinct forms of IBD; but there is a subgroup of CD with a UC-like presentation. The genetic factors play a significant role in IBD. IBD is associated with a strong familial pattern. Recent studies support the hypothesis that IBD patients have a dysregulated immune response to endogenous bacteria in the gastrointestinal tract. The serologic responses seen in Crohn's disease include antibodies to Saccharomyces cerevisiae, mycobacteria, bacteroides and E. coli. The pANCA antibody seen in UC and CD has been demonstrated to react with epitopes of H1 histone, Bacteroides caccae (Ton-B linked outer membrane protein), Pseudomonas fluorescens-associated bacterial protein I-2, mycobacterial histone 1 homologue called Hup B. In recent years, several serologic markers have been found to be useful for the diagnosis and differentiation of CD and UC. These markers include the following antibodies: (a) pANCA, (b) ASCA, (c) anti-pancreatic antibody, (d) OmpC antibody and (e) I-2 antibody and antibodies to anaerobic coccoid rods. The application of a panel of markers with the use of an algorithm (i.e. IBD First Step) can identify specific subtypes of IBD that have different clinical courses and progression of the diseases. The serologic markers are useful for the diagnosis and management of CD and UC patients.

Antibodies↗

PubMed2003

Recent indications and methods of surgery for inflammatory bowel disease.

Inflammatory bowel disease, notably ulcerative colitis (UC) or Crohn disease (CD), is basically benign, but sometimes develops into serious or fatal cancer. While the primary therapies are medical, such as pharmacotherapy and dietetic modification, intractable, serious, and cancerous cases can require surgical intervention. Surgery represents only one of the treatment options, but prediction of whether UC and CD are likely to progress to serious conditions and determination of when to undertake surgery is essential. Various surgical procedures have been developed over time, and the postoperative results are now generally good. Regarding laparoscopic surgeries, relatively few cases have been accumulated, and addressing the indications and limitations is premature at this point. However, this procedure is likely to fulfill a central role in surgical treatment strategies and represent a major benefit to patients. This paper discusses surgical treatment indications and methods for UC and CD, and explains the practical aspects of laparoscopic surgery, which has made remarkable progress in recent years, for such cases.

Colitis, Ulcerative↗

PubMed2006

[Cytokines in the pathogenesis of inflammatory bowel diseases].

Inflammatory bowel disease (IBD) is produced by an exaggerated response to bacterial flora within the intestinal mucous, in which both environmental and genetic factors are involved. T lymphocytes are involved during the genesis and maintenance of IBD, and their cytokine profile in Crohn's disease (mostly Th1 cytokines) is different from that in ulcerative colitis (mainly Th2 cytokines). After the inflammatory response has been established, the balance between proinflammatory and regulatory cytokines determines the degree of mucosal damage and the form of presentation. A deeper knowledge of the immunological mechanisms involved in IBD has opened new research lines aimed to the development of new therapies such as the neutralization of proinflammatory cytokines with antibodies and the administration of antiinflammatory cytokines, which are currently at different stages of research.

Animals↗

PubMed2004

Proteomics and chronic inflammatory bowel diseases.

Inflammatory bowel diseases (IBD) are relatively frequent in developed countries. Physiopathological events involved in the etiology of IBDs include activation of immune, mesenchymal and epithelial cells. This review gives an overview of the currently applied proteomics technologies. It describes metabolic changes and goes into the approaches using this methodology to understand the molecular mechanisms implicated in the development of the disease.

Electrophoresis, Gel, Two-Dimensional↗

PubMed1989

Medical management of inflammatory bowel disease.

Inflammatory bowel disease is a serious ailment that afflicts nearly one million people in the U.S. alone. The medical management of this disorder currently includes salicylates, corticosteroids, immunosuppressive therapy, and symptomatic treatment with antidiarrheal agents, although several promising new drugs have been developed. The epidemiology, etiology, pathogenesis, and medical management of the disease are discussed in this article.

Humans↗

PubMed1997

Autoimmune reactivity in inflammatory bowel disease.

Inflammatory bowel disease remains a poorly understood chronic inflammatory condition of the bowel. No etiologic agents, or agreed upon pathogenesis is currently known. Recent findings that perinuclear antineutrophil cytoplasmic antibodies (P-ANCA) are present in the vast majority of patients with this disease have proven to be of use in epidemiologic studies. Its clinical use is currently being explored by several investigators.

Antibodies, Antineutrophil Cytoplasmic↗

PubMed1998

Connective tissue growth factor: a novel regulator of mucosal repair and fibrosis in inflammatory bowel disease?

Inflammatory bowel disease (IBD) is a multifactorial disorder which is characterized by massive damage of the epithelium and the underlying mesenchyme of the intestine. Due to the potent effect of connective tissue growth factor (CTGF) on fibroblast proliferation and connective tissue deposition we speculated about a possible role of this mitogen in IBD. Here we demonstrate a strikingly increased expression of CTGF mRNA in surgical specimens of patients suffering from two forms of IBD, Crohn's disease and ulcerative colitis. In most specimens, the levels of CTGF mRNA correlated with the degree of inflammation as assessed by histological analysis of adjacent tissue samples and by expression analysis of the pro-inflammatory cytokine interleukin-1 beta. However, areas of little inflammation which were characterized by severe fibrosis also revealed high levels of CTGF mRNA. Expression of transforming growth factor beta-1 (TGF-beta 1), the only known inducer of CTGF so far, as well as of the CTGF target genes collagen I alpha 1, fibronectin and integrin alpha 5 revealed a strong correlation with the expression of CTGF. These data suggest a prominent role of CTGF in the repair of mucosal injury in IBD and in the aberrant deposition of extracellular matrix leading to fibrosis and stenosis, one major complication in IBD, especially in Crohn's disease.

Animals↗

PubMed2005

[What is inflammatory bowel disease?].

Inflammatory bowel diseases are chronic conditions of unknown origin that result from continuous or intermittent inflammation of a part of the intestinal wall. The main classic types of IBD are ulcerative colitis, Crohn's disease and indeterminate colitis that cannot be classified accurately as ulcerative colitis or Crohn's disease with pure colonic involvement. The two main subtypes of microscopic colitis, namely lymphocytic and collagenous colitis, fulfill the criteria that define IBD and should be considered as true IBD.

Colon↗

PubMed1997

Therapeutic effects of interleukin-4 gene transfer in experimental inflammatory bowel disease.

Inflammatory bowel disease (IBD) is characterized by altered immunoregulation and augmented intestinal synthesis of nitric oxide. The purpose of this study was to determine the effects of exogenous IL-4, introduced by a recombinant human type 5 adenovirus (Ad5) vector, on the tissue injury associated with an experimental model of colonic immune activation and inflammation. Colitis was induced in rats by the intrarectal administration of trinitrobenzene sulfonic acid (TNB) dissolved in 50% ethanol, and control rats received saline via the same route. 1 h later, all rats were randomized into two groups. The first group was injected intraperitoneally (ip) with 3.0 x 10(6) plaque forming units (PFUs) of Ad5 transfected with murine interleukin-4 (Ad5IL-4) and the second group was injected ip with the same amount of Ad5 expressing the Escherichia coli Lac Z gene (Ad5LacZ). One-half of the colitic and control rats were injected again with 3.0 x 10(6) PFUs of Ad5IL-4 or Ad5LacZ on day 3 of the 6-d study. When introduced once or twice via the peritoneal route into control rats, Ad5LacZ was localized to the serosal lining of the peritoneal cavity, the diaphragm and the liver on day 6. One or two injections of Ad5IL-4 into rats also produced measurable levels of circulating IL-4. TNB-colitis in both Ad5LacZ-treated groups was associated with pronounced elevations in serum IFN-gamma, and mucosal ulceration of the distal colon. Myeloperoxidase and inducible nitric oxide synthase II (NOS II) synthetic activity were also increased by 30- and fivefold, respectively, above control levels in the distal colon. However, two injections of Ad5IL-4 into colitic rats caused the overexpression of IL-4, and significantly inhibited tissue damage, serum and colon IFN-gamma levels and myeloperoxidase activity in the distal colon. In addition, NOS II gene expression and NOS II nitric oxide synthesis was significantly inhibited. No therapeutic effect was observed in rats injected once with Ad5IL-4. Thus, IL-4, introduced by Ad5, is therapeutic during acute inflammation in the rat colon. The therapeutic effect of IL-4 was associated with an inhibition of inducible nitric oxide expression and a reduction in nitric oxide synthesis.

Adenoviruses, Human↗

PubMedDate not supplied

Inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a term used to describe ulcerative colitis and Crohn's disease. Both are chronic, lifelong conditions characterised by periods of exacerbation and remission. The management of IBD is complex for the health care team. Following an exploration of the physical, psychological and sociological impact of the condition, the medications used to control the symptoms are described, together with consideration of the surgical options used in the management of IBD. Finally, the role of the nurse in meeting holistically the needs of patients with IBD is highlighted.

Humans↗

PubMed1999

Effect of DA-6034, a derivative of flavonoid, on experimental animal models of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a multifactorial disorder with unknown etiology and pathogenesis. DA-6034, 7-carboxymethyloxy-3', 4', 5-trimethoxy flavone, is a synthetic flavonoid known to possess anti-inflammatory activity. This study was performed to evaluate the oral therapeutic effect of DA-6034 in three experimental animal models of IBD: two chemical-induced IBD models of rats and the human leukocyte antigen (HLA)-B27 transgenic rat model known to develop spontaneous colitis without the use of exogenous agents. Acute chemical colitis was induced by intracolonic instillation of 1.2 ml of 4% acetic acid solution. Prednisolone (1 mg/kg), sulfasalazine (100 mg/kg) and DA-6034 (0.3 to approximately 3 mg/kg) were orally administered twice daily for 6 days in these rats. In addition, chronic chemical colitis was induced by intracolonic administration of trinitrobenzene sulfonic acid (TNBS) 30 mg in 50% ethanol and agents were orally administered for 6 or 20 days. In chemical-induced IBD models, all of these agents reduced the severity of colitis and specially, DA-6034 (3 mg/kg) showed more potent effect than other drugs in macroscopic lesion score. In HLA-B27 transgenic rats, DA-6034 (3 mg/kg) and prednisolone (0.5 mg/kg) were treated orally twice daily for 6 weeks. The HLA-B27 transgenic rats showed only mild colitis, compared with the chemical-induced colitis models. DA-6034 ameliorated the loose stool and decreased microscopic damage, which is the important indicator of this model. In conclusion, oral therapy of DA-6034 attenuated the macroscopic and histologic damages of the colon in all three experimental models of IBD, which suggest that DA-6034 could be a promising drug in the treatment of IBD.

Acetic Acid↗

PubMed1996

Future aspects on inflammatory bowel disease.

Inflammatory bowel diseases (IBD) are probably multifactorial diseases caused by an interplay of the external and internal environment. External environmental factors revealed in the literature so far can be grouped into four major groups or hypotheses: (a) the sheltered child, (b) infectious agents, (c) dietary factors, and (d) vascular factors. Internal environmental factors mainly concern genetics which have been studied in families or twins. At present, HLA class II antigens are most in focus but also genetic markers such as pANCA. However, the internal environment can be changed by external factors changing the balance of the faecal or mucosa related flora, such as infectious agents or antibiotic treatment. This in turn may upset the building up and degradation of colonic mucin, making the mucosa more vulnerable. The increasing knowledge of external and internal environmental factors might affect our way of treatment in the future. So also may our increasing knowledge of immunology which will probably lead to targeted treatment directed against individual components within the inflammatory cascade.

Environmental Exposure↗

PubMed2005

5-aminosalicylic acid is an attractive candidate agent for chemoprevention of colon cancer in patients with inflammatory bowel disease.

Inflammatory bowel disease (IBD) is classically subdivided into ulcerative colitis (UC) and Crohn's disease (CD). Patients with IBD have increased risk for colorectal cancer. Because the pathogenesis of colorectal carcinoma has not been entirely defined yet and there is no ideal treatment for colon cancer, cancer prevention has become increasingly important in patients with IBD. The two adopted methods to prevent the development of colon cancer in clinical practice include the prophylactic colectomy and colonoscopic surveillance. But patients and physicians seldom accept colectomy as a routine preventive method and most patients do not undergo appropriate colonoscopic surveillance. Chemoprevention refers to the use of natural or synthetic chemical agents to reverse, suppress, or to delay the process of carcinogenesis. Chemoprevention is a particularly useful method in the management of patients at high risk for the development of specific cancers based on inborn genetic susceptibility, the presence of cancer-associated disease, or other known risk factors. Prevention of colorectal cancer by administration of chemopreventive agents is one of the most promising options for IBD patients who are at increased risks of the disease. The chemopreventive efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) against intestinal tumors has been well established. But with reports that NSAIDs aggravated the symptoms of colitis, their sustained use for the purpose of cancer chemoprevention has been relatively contraindicated in IBD patients. Another hopeful candidate chemoprevention drug for IBD patients is 5-aminosalicylic acid (5-ASA), which is well tolerated by most patients and has limited systemic adverse effects, and no gastrointestinal toxicity. 5-ASA lacks the well-known side effects of long-term NSAIDs use. Retrospective correlative studies have suggested that the long-term use of 5-ASA in IBD patients may significantly reduce the risk of development of colorectal cancer. According to the literature, this agent might well satisfy clinical expectations with respect to a safe and effective chemopreventive agent.

Colonic Neoplasms↗

PubMed1996

Health-related quality of life in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is characterised by a chronic, but frequently remitting, clinical course involving significant morbidity. As medical and surgical advances have occurred, focus has shifted from merely reducing mortality to efforts on decreasing morbidity and improving health status. With this paradigm shift has come the need for qualitative and quantitative assessment of outcomes important to the individual patient. Existing disease activity measures fall short in this area. Health-related quality of life encompasses the areas of physical function, somatic sensation, psychological state and social interactions that are affected by one's health status. Instruments have recently been developed for both generic and disease-specific health states, such as IBD. These psychometric measures have proven to be useful tools for patient assessment. Both medical and surgical trials have incorporated these measures as salient outcomes. An additional outcome that has come under closer scrutiny is the cost of medical interventions. The literature on the cost of IBD is sparse but is likely to increase logarithmically in the future. Quality of life and cost issues are becoming central to the study of not just IBD but all of medicine.

Aminosalicylic Acids↗

PubMed2005

Important cutaneous manifestations of inflammatory bowel disease.

Inflammatory bowel disease (IBD) has many extraintestinal manifestations. Cutaneous manifestations are usually related to the activity of the bowel disease but may have an independent course. Anyone presenting with IBD should be examined for cutaneous manifestations. Pyoderma gangrenosum is a severe painful ulcerating disease that requires moist wound management and, in the absence of secondary infection, systemic corticosteroids, cyclosporine, or both. Infliximab may also be used. Erythema nodosum is a common cause of tender red nodules of the shins. Management includes leg elevation, NSAIDs, and potassium iodide. Oral manifestations of IBD include aphthous stomatitis, mucosal nodularity (cobblestoning), and pyostomatitis vegetans. Treatment should be directed both at the cutaneous lesions and at the underlying systemic condition.

Erythema Nodosum↗

PubMed2006

Recent trends in the epidemiology of inflammatory bowel diseases: up or down?

Inflammatory bowel disease (IBD) is traditionally considered to be common in the Western world, and its incidence has sharply increased since the early 1950s. In contrast, until the last decade, low prevalence and incidence rates have been reported from other parts of the world including Eastern Europe, South America, Asia and the Pacific region. Recent trends indicate a change in the epidemiology of IBD with previously low incidence areas now reporting a progressive rise in the incidence, while in West European and North American countries the figures have stabilized or slightly increased, with decreasing incidence rates for ulcerative colitis. Some of these changes may represent differences in diagnostic practices and increasing awareness of the disease. The quality of studies is also variable. Additional epidemiologic studies are needed to better define the burden of illness, explore the mechanism of association with environmental factors, and identify new risk factors.

Age Distribution↗

PubMed2006

Therapeutic approaches targeting intestinal microflora in inflammatory bowel disease.

Inflammatory bowel diseases, ulcerative colitis, and Crohn's disease, are chronic intestinal disorders of unknown etiology in which in genetically susceptible individuals, the mucosal immune system shows an aberrant response towards commensal bacteria. The gastrointestinal tract has developed ingenious mechanisms to coexist with its autologous microflora, but rapidly responds to invading pathogens and then returns to homeostasis with its commensal bacteria after the pathogenic infection is cleared. In case of disruption of this tightly-regulated homeostasis, chronic intestinal inflammation may be induced. Previous studies showed that some commensal bacteria are detrimental while others have either no influence or have a protective action. In addition, each host has a genetically determined response to detrimental and protective bacterial species. These suggest that therapeutic manipulation of imbalance of microflora can influence health and disease. This review focuses on new insights into the role of commensal bacteria in gut health and disease, and presents recent findings in innate and adaptive immune interactions. Therapeutic approaches to modulate balance of intestinal microflora and their potential mechanisms of action are also discussed.

Animals↗