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PubMed2003

Trichuris suis seems to be safe and possibly effective in the treatment of inflammatory bowel disease.

OBJECTIVES: Inflammatory bowel disease (IBD), especially Crohn's disease (CD), probably results from failure to downregulate a chronic Th1 intestinal inflammatory process. Induction of a Th2 immune response by intestinal helminths diminishes Th1 responsiveness. This study evaluates the safety and effectiveness of helminthic ova in the treatment of active IBD. METHODS: We studied four patients with active CD and three with ulcerative colitis (UC). In an initial treatment and observation period, a single dose of 2500 live Trichuris suis eggs was given orally, and patients were followed every 2 wk for 12 wk. Baseline medications were continued at the same dose throughout the study. Safety was monitored by following the patients' clinical status and laboratory studies at regular intervals. Patients also were monitored regularly using the Crohn's Disease Activity Index, Simple Clinical Colitis Activity Index (SCCAI), and the Inflammatory Bowel Disease Quality of Life Index (IBDQ). To assess safety and efficacy with repetitive doses, two patients with CD and two with UC were given 2500 ova at 3-wk intervals as maintenance treatment using the same evaluation parameters. RESULTS: During the treatment and observation period, all patients improved clinically without any adverse clinical events or laboratory abnormalities. Three of the four patients with CD entered remission according to the Crohn's Disease Activity Index; the fourth patient experienced a clinical response (reduction of 151) but did not achieve remission. Patients with UC experienced a reduction of the Clinical Colitis Activity Index to 57% of baseline. According to the IBD Quality of Life Index, six of seven patients (86%) achieved remission. The benefit derived from the initial dose was temporary. In the maintenance period, multiple doses again caused no adverse effects and sustained clinical improvement in all patients treated every 3 wk for >28 wk. CONCLUSIONS: This open trial demonstrates that it is safe to administer eggs from the porcine whipworm, Trichuris suis, to patients with CD and UC. It also demonstrates improvement in the common clinical indices used to describe disease activity. The benefit was temporary in some patients with a single dose, but it could be prolonged with maintenance therapy every 3 wk. The study suggests that it is possible to downregulate aberrant intestinal inflammation in humans with helminths.

Administration, Oral↗

PubMed2006

Vicious circles in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease can present with a bewildering array of disease manifestations whose overall impact on patient health is difficult to disentangle. The multitude of disease complications and therapeutic side effects result in conflicting ideas on how to best manage a patient. The aim of the study is to test the usefulness of influence diagrams in resolving conflicts centered on managing complex disease processes. METHODS: The influences of a disease process and the ensuing medical interventions on the health of a patient with inflammatory bowel disease are modeled by an influence diagram. Patient health is the focal point of multiple influences affecting its overall strength. Any downstream influence represents the focal point of other preceding upstream influences. The mathematics underlying the influence diagram is similar to that of a decision tree. Its formalism allows one to consider additive and inhibitory influences and include in the same analysis qualitatively different types of parameters, such as diagnoses, complications, side effects, and therapeutic outcomes. RESULTS: Three exemplary cases are presented to illustrate the potential use of influence diagrams. In all three case scenarios, Crohn's disease resulted in disease manifestations that seemingly interfered with its own therapy. The presence of negative feedback loops rendered the management of each case particularly challenging. The analyses by influence diagrams revealed subtle interactions among the multiple influences and their joint contributions to the patient's overall health that would have been difficult to appreciate by verbal reasoning alone. CONCLUSION: Influence diagrams represent a decision tool that is particularly suited to improve decision-making in inflammatory bowel disease. They highlight key factors of a complex disease process and help to assess their quantitative interactions.

Adult↗

PubMed2001

[MRI in chronic inflammatory bowel disease].

Chronic inflammatory bowel disease is diagnosed and monitored by the combination of colonoscopy and small bowel enteroklysis. Magnetic resonance imaging has become the gold standard for the imaging of perirectal and pelvic fistulas. With the advent of ultrafast MRI small and large bowel imaging has become highly attractive and is being advocated more and more in the diagnostic work up of inflammatory bowel disease. Imaging protocols include fast T1-weighted gradient echo and T2-weighted TSE sequences and oral or rectal bowel distension. Furthermore, dedicated imaging protocols are based on breath-hold imaging under pharmacological bowel paralysis and gastrointestinal MR contrast agents (Hydro-MRI). High diagnostic accuracy can be achieved in Crohn's disease with special reference to the pattern of disease, depth of inflammation, mesenteric reaction, sinus tract depiction and formation of abscess. In ulcerative colitis, the mucosa-related inflammation causes significantly less bowel wall thickening compared to Crohn's disease. Therefore with MRI, the extent of inflammatory changes is always underestimated compared to colonoscopy. According to our experience in more than 200 patients as well as the results in other centers, Hydro-MRI possesses the potential to replace enteroklysis in the diagnosis of chronic inflammatory bowel disease and most of the follow-up colonoscopies in Crohn's disease. Further technical improvements in 3D imaging will allow interactive postprocessing of the MR data.

Adult↗

PubMed1995

Circulating soluble interleukin-2 receptor alpha and beta chain in inflammatory bowel disease.

OBJECTIVES: Inflammatory bowel disease is characterized by T cell activation. Activated T cells shed interleukin-2 receptors (IL-2R) in a soluble form. A positive correlation between sIL-2R alpha (CD25) and disease activity in inflammatory bowel disease has been shown previously, whereas IL-2R beta (CD122) has never before been investigated in this respect. Serum from 27 patients with ulcerative colitis (UC), 31 with Crohn's disease (CD), and 29 healthy volunteers was obtained. METHODS: Disease activity was scored according to a semiquantitative score for UC and by Crohn's disease activity index for CD. sIL-2R alpha and -beta chains were assessed by a sandwich ELISA technique using monoclonal antibodies specific for CD25 and CD122, respectively. RESULTS: The median concentration of sIL-2R alpha was 4424 pg/ml in healthy controls, 6460 in UC (p < 0.004), and 6371 in CD (p < 0.01). The corresponding value of sIL-2R beta in healthy volunteers was 605 pg/ml; in active UC, significantly lower levels were found at 233 pg/ml (p < 0.01), whereas in inactive UC, no such difference was observed at 725 pg/ml (p > 0.05). In CD, the levels were 839 pg/ml in inactive and 920 pg/ml in active disease stages (p > 0.05 vs controls). A positive and significant correlation existed between sIL-2R levels of alpha and beta chains in CD (r = 0.64; p < 0.01) but not in UC (r = -0.32; p > 0.05) or in healthy volunteers (r = 0.16; p > 0.05). CONCLUSION: Future longitudinal studies will be necessary to learn whether this newly assessed sIL-2R beta (CD122), which may interfere with IL-15R, could be used to predict disease exacerbation and to monitor anti-inflammatory therapy in UC.

Adult↗

PubMed1993

Immune activation genes in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease is associated with enhanced activation of T cells, but the genes responsible for this state are not well characterized. METHODS: T-cell activation genes were studied in peripheral blood and intestinal mucosal mononuclear cells of control, Crohn's disease, and ulcerative colitis patients. RESULTS: In all groups the expression of interleukin-2 (IL-2), IL-2 receptor alpha (IL-2R alpha), and IL-2R beta messenger RNA (mRNA) was significantly higher in intestinal than circulating cells, and it correlated well with protein levels. Both IL-2R alpha and IL-2R beta mRNA were abundant in mucosal cells, suggesting that a substantial number of them displays high affinity IL-2R. This would explain why intestinal cells proliferate more, express more IL-2 transcripts, and secrete more IL-2 than peripheral cells. Inflammatory bowel disease cells produced similar or higher IL-2R alpha and IL-2R beta mRNA than controls but generated significantly lower IL-2 mRNA. Thus, the reported defect of IL-2 activity in Crohn's disease and ulcerative colitis is probably related to decreased IL-2 transcription. Crohn's disease intestinal cells had the highest expression of IL-2R gene products. This provides a mechanism for their increased response to IL-2 and supports claims that elevated soluble IL-2R alpha serum levels reflect gut T-cell hyperactivity in this disease. CONCLUSIONS: These findings underscore the importance of T cells in mucosal immunity and indicate that abnormal T-cell activation is intimately associated to the pathogenesis of inflammatory bowel disease.

Adolescent↗

PubMed2004

Celiac disease and inflammatory bowel disease in pregnancy.

An adverse influence on reproductive life and obstetric complications are known to occur in women with celiac disease (clinical and subclinical disease) or inflammatory bowel diseases. Treatment can improve the pregnancy outcome; therefore, it is advisable that a clinical evaluation is performed by a joint team of obstetricians, internists and surgeons. The preconception clinical evaluation of the affected women is useful to focus on the different clinical aspects of the disease and to indicate specific therapeutic strategies. In this study a review of the literature regard to celiac disease and inflammatory bowel disease in pregnancy is presented.

Celiac Disease↗

PubMed2002

[Immunologic methods in diagnosis of inflammatory bowel disease].

Chronic inflammatory bowel disease is included into autoimmune diseases, which is proved by presence of inflammatory lesions, circulating autoantibodies and the deposits of immune complexes in tissues. Coeliac disease (classic and atypical form), Crohn's Disease and ulcerative colitis are considered as chronic autoimmune bowel diseases. The auto-antibodies can be detected with indirect immunofluorescence, ELISA and immunoblotting methods. In coeliac disease the autoantibodies against endomysium (tissue transglutaminase) and antibodies against gliadin are found in patient's sera. The auto-antibody detecting is helpful in establishing diagnosis, controlling gluten-free diet effectiveness and during gluten challenge. In Crohn's disease and ulcerative colitis immunological laboratory tests are helpful to confirm the clinical diagnosis. The following auto-antibodies are tested: against cytoplasm of exocrinal pancreatic cells, and products of these cells, against the neutrophile cytoplasm and against goblet cells. The antibodies against Saccharomyces cerevisiae are also investigated. The clinical relevance of above autoantibodies is not clear, but it is suggested that their presence correlates with exacerbations and severe clinical outcome. In the present study the pictures of autoantibodies from fluorescent microscope were shown.

Autoantibodies↗

PubMed2003

The immunological and genetic basis of inflammatory bowel disease.

The inflammatory bowel diseases (IBDs), Crohn's disease and ulcerative colitis, are chronic inflammatory disorders of the gastrointestinal tract. Enormous progress has been made recently in understanding the pathogenesis of these diseases. Through the study of patients and mouse models, it has emerged that Crohn's disease is driven by the production of interleukin-12 (IL-12) and interferon-gamma (IFN-gamma), whereas ulcerative colitis is probably driven by the production of IL-13. A second area of progress is in the identification of specific genetic abnormalities that are responsible for disease. The most important finding is the identification of mutations in the gene that encodes NOD2 (nucleotide-binding oligomerization domain 2) protein in a subgroup of patients with Crohn's disease. Here, we discuss these recent findings and the implications for therapy.

Animals↗

PubMed1998

Review article: bone and joint diseases in inflammatory bowel disease.

The intestinal and articular systems are closely linked in inflammatory bowel disease. Clinical and immunological studies support an important aetio-pathogenetic link between intestinal and articular inflammation. There is increasing evidence for a negative link between bone mass density and intestinal inflammation. This paper will focus on the prevalence, aetio-pathogenesis and treatment of arthritis (peripheral, sacroiliitis and spondylitis) and osteoporosis in inflammatory bowel disease.

Animals↗

PubMed2000

Clinical and radiological characteristics of lung disease in inflammatory bowel disease.

The pulmonary associations of inflammatory bowel disease (IBD) are poorly characterized. The clinical, physiological and high-resolution computed tomographic thorax characteristics of the lung disease in patients with IBD presenting with respiratory symptoms are described. Detailed clinical information was obtained and standard pulmonary physiological tests and thorax high-resolution computed tomography performed on 14 patients with ulcerative colitis (UC) and three with Crohn's disease (CD), 10 male, aged 38-83 yrs. Respiratory symptoms had been present for 2-50 yrs and extraintestinal manifestations were present in three (17.6%). Normal pulmonary physiology (six patients) was associated with the high resolution computed tomographic changes of bronchiectasis, mosaic perfusion and air trapping suggestive of obliterative bronchiolitis and a pattern of centrilobular nodules and branching linear opacities ("tree in bud" appearance) suggestive of either cellular bronchiolitis or bronchiolectasis with mucoid secretions. Bronchiectasis was found in 13 patients (11 UC, 2 CD), 11 had air trapping and five had a "tree in bud" appearance on computed tomography. One patient had a predominantly peripheral reticular pattern at the lung bases similar to that found in cryptogenic fibrosing alveolitis and one patient had a mixed reticular and ground-glass pattern in the midzones with a patchy distribution in the central and peripheral portions of the lungs with air trapping. Eleven patients (three with alveolitis) exhibited a clinical and/or physiological response to steroids. Pulmonary abnormalities in ulcerative colitis and Crohn's disease can present years after the onset of the bowel disease and can affect any part of the lungs. Early recognition is important as they can be strikingly steroid-responsive.

Adult↗

PubMed1996

Picotamide inhibition of excess in vitro thromboxane B2 release by colorectal mucosa in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease is associated with increased mucosal release of eicosanoids. Among these, thromboxane A2 has been proposed as a possible inflammatory mediator; its suppression may be a useful therapeutic option. METHODS: Using a tissue incubation technique, we compared release of immunoreactive thromboxane B2 by colonic biopsies from patients with ulcerative colitis, Crohn's disease and controls, and assessed the inhibitory effect of picotamide, a thromboxane synthesis inhibitor-receptor antagonist, which has been widely used in Italy for management of ischaemic heart and cerebrovascular disease. RESULTS: Increased amounts of thromboxane B2 were released from biopsies from patients with active ulcerative colitis (median 238 pg/20 min/mg wet weight (interquartile range 147-325), n = 12) and active Crohn's disease (252 (174-450), 6) compared with those from patients with quiescent ulcerative colitis (95 (61-140), 12) or Crohn's disease (105 (57-201), 13), or controls (136 (64-206), 8). Incubation with picotamide at concentrations between 100 microM and 1 mM reduced thromboxane B2 release (IC50 890 microM). CONCLUSION: Since increased thromboxane A2 production may have pathogenetic importance, thromboxane synthesis inhibitor-receptor antagonists such as picotamide merit therapeutic trial in the management of inflammatory bowel disease.

Adult↗

PubMed2002

[Clinical features and diagnosis of inflammatory bowel disease].

The inflammatory bowel disease is common term for heterogenous group of the chronic recidivant idiopathic diseases with bowel inflammation as a common sign. Although within common term, traditionally we distinguish two diseases, Chrohns disease (CD) and ulcerative colitis (UC), in certain clinical situations those terms are not sufficient to describe all variants of inflammatory bowel diseases. Today increasingly, we have more and more knowledge about clinical, immunological, genetical heterogenicity in Crohns disease and ulcerative colitis. New evidences advocate theory that IBD represents folding subgroups of inflammatory bowel disorders in particular continuity with CD and UC as extremes of one spectrum.

Colitis, Ulcerative↗

PubMed1980

Association of coeliac disease and inflammatory bowel disease.

The association of coeliac disease and inflammatory bowel disease is rare, as only three individual cases have been reported. Four additional cases of the association are described. A review of the prevalence figures for the two disorders suggests that this is more than a chance association.

Adolescent↗

PubMedDate not supplied

[The prevalence of radiographic sacroiliitis in patients affected by inflammatory bowel disease with inflammatory low back pain].

Inflammatory bowel diseases (IBD), as Crohn's disease (CD) or ulcerative colitis (UC), are frequently complicated by joint complaints with prevalence that varies between 10 and 28%. The IBD related arthropathy may be expressed as peripheral arthritis or axial one frequently indistinguishable from the classical ankylosing spondylitis (AS). According to ESSG criteria for spondyloarthropathy, the presence of synovitis or the inflammatory back pain (IBP) in IBD patients is diagnostic for spondyloarthropathy, but for diagnosis of ankylosing spondylitis also radiological criteria must be fulfilled. There are few studies regarding the radiological prevalence of sacroiliitis in patients with IBD. We examined, by plain film radiograms of pelvis, 100 sacroiliac joints (SJ) of 50 IBD patients with IBP. The New York (1984) SJ radiological score with gradation from 0 to 4 was applied. Total sacroiliac score (SJS) was summarized between left and right side (from 0 to 8). Fourteen patients fulfilled New York modified criteria for AS and 8 patients had unilateral 2nd grade sacroiliitis. Only 4 of 14 AS patients (28%) were HLA B27 positive. Thirty patients had localized IBP, 10 extended to buttock and 4 extended to sacrum. Sixteen patients had sciatica-like extension of back pain. A difference in SJS between left and right side was observed only in CD patients (1.3 +/- 0.8 and 0.8 +/- 0.9 respectively; p < 0.05), but not in UC (1.5 +/- 1.2 vs 1.5 +/- 1.3; p = ns) nor in total IBD patients (1.4 +/- 1.0 vs 1.2 +/- 1.2; p = ns). Total SJS was higher in UC respect CD, but not significantly (2.9 +/- 2.3 vs 2.1 +/- 1.5; p = ns). Our data confirm the importance of these symptoms in patients with IBD, who need to be carefully investigated also for these aspects.

Adult↗

PubMed2000

Disease outcome in inflammatory bowel disease: mortality, morbidity and therapeutic management of a 796-person inception cohort in the European Collaborative Study on Inflammatory Bowel Disease (EC-IBD).

BACKGROUND: The course of inflammatory bowel diseases (IBD) has mainly been studied using different methods in single patient cohorts. The aim of the present study was to assess clinical aspects of disease outcome in a population-based cohort of IBD patients over a 4-year period in multiple centres across Europe. METHODS: A total of 796 patients with IBD diagnosed in 10 centres between October 1991 and October 1993, registered at the EC IBD study centre (98% of the original cohort), participated in the study. Investigators filled out a standard follow-up form containing questions on the method of follow-up, vital status of the patient, change in diagnosis, extraintestinal manifestations, medical and surgical treatment, and physician's global assessment of disease activity. RESULTS: Complete relief of the complaints was reported in 255 (48%) patients with ulcerative colitis (UC), 9 (50%) with indeterminate colitis (IC), but only in 87 (35%) of patients with Crohn disease (CD). Improvement was reported in 195 (37%) patients with UC, 113 (45%) with CD and 6 (33%) with IC. During the 4-year follow-up period, 23 patients died (14 UC, 8 CD. and 1 IC). The mean age at death was 69.3 years (s, 14.9 years). The deaths of three patients were recorded as directly due to IBD. CONCLUSIONS: With the present approach to therapeutic management the short-term outcome of patients with IBD seems to be favourable in 10 medical centres in the north and south of Europe. However, more detailed studies including both objective and subjective measures are necessary.

Adult↗

PubMed2002

Role of reactive metabolites of oxygen and nitrogen in inflammatory bowel disease.

The inflammatory bowel diseases (IBD; Crohn's disease, ulcerative colitis) are a collection of chronic idiopathic inflammatory disorders of the intestine and/or colon. Although the pathophysiology of IBD is not known with certainty, a growing body of experimental and clinical data suggests that chronic gut inflammation may result from a dysregulated immune response to normal bacterial antigens. This uncontrolled immune system activation results in the sustained overproduction of reactive metabolites of oxygen and nitrogen. It is thought that some of the intestinal and/or colonic injury and dysfunction observed in IBD is due to elaboration of these reactive species. This review summarizes the current state-of-knowledge of the role of reactive oxygen species and nitric oxide in the pathophysiology of IBD.

Animals↗

PubMed2003

[Indications for surgical treatment in idiopathic inflammatory bowel disease].

Idiopathic inflammatory bowel disease requires complex treatment and patients are often considered to undergo the surgery in the course of therapy. Though the conservative treatment of the Crohn's disease and ulcerative colitis has no major differences, the strategy of surgical treatment and the extent of the operation are in these two diseases markedly different. In an aforethought patient in the clinically and metabolically good shape, the postoperative morbidity and mortality is much lower. It is therefore desirable to do the most of surgeries as elective, though such goal is not always achievable. Beside the appropriate time for the operation, the surgery should be done in the most proper extent, therefore with the maximal care and considering the type and activity of the disease also with the sufficient curative effect. As the surgical therapy of idiopathic inflammatory bowel diseases requires profound experience in order to choose the correct type of operation, the close collaboration between the gastroenterologist and surgeon is necessary and should be performed preferably at specialized departments.

Colitis, Ulcerative↗

PubMed2003

Quality of life in Chinese patients with inflammatory bowel disease: validation of the Chinese translation of the Inflammatory Bowel Disease Questionnaire.

BACKGROUND: Health-related quality of life is an important outcome measure in inflammatory bowel disease. The Inflammatory Bowel Disease Questionnaire is a quality of life questionnaire that has not been validated previously in Chinese patients with inflammatory bowel disease. AIM: To develop and validate a Chinese translation of the Inflammatory Bowel Disease Questionnaire, specifically determining its construct validity, discriminant ability, reliability and sensitivity to change. METHODS: We developed a Chinese version of the Inflammatory Bowel Disease Questionnaire. Chinese patients with Crohn's disease and ulcerative colitis completed the Chinese Inflammatory Bowel Disease Questionnaire and visual analogue scales measuring systemic, social, bowel and emotional well-being. Patients also completed a validated Chinese SF-36 generic quality of life questionnaire, the Crohn's disease activity index or the clinical activity index for ulcerative colitis. RESULTS: One hundred and thirty-five patients (59 with Crohn's disease and 76 with ulcerative colitis) were enrolled, 99 of whom also completed the Chinese Inflammatory Bowel Disease Questionnaire for a second time. The Chinese Inflammatory Bowel Disease Questionnaire correlated well with the SF-36 for all four domains (Spearman: r = 0.55-0.80), the Crohn's disease activity index (r = -0.62-0.72) and the clinical activity index for ulcerative colitis (r = -0.44-0.68), as well as with the visual analogue scales. The Chinese Inflammatory Bowel Disease Questionnaire accurately distinguished between active and inactive disease. Test-re-test reliability showed excellent intra-class correlation (0.76-0.92; all P < 0.001). The Chinese Inflammatory Bowel Disease Questionnaire was also sensitive to changes in disease activity (P < 0.05). CONCLUSION: The Chinese Inflammatory Bowel Disease Questionnaire is a valid and reliable test that correlates well with the patients' subjective well-being and clinical disease activity.

Adolescent↗