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Increased concentrations of eosinophilic cationic protein in whole-gut lavage fluid from children with inflammatory bowel disease.

BACKGROUND: Eosinophils may be involved in the pathogenesis of inflammation in inflammatory bowel disease. The purpose of this study was to verify whether concentrations of eosinophilic cationic protein in gut lavage fluid from children with inflammatory bowel disease correlate with clinical and laboratory indexes of disease activity. METHODS: Twenty-three children with Crohn's disease, 14 with ulcerative colitis, and 22 age-matched control subjects entered the study. Radioimmunoassay and sandwich enzyme-linked immunosorbent assay techniques were used to measure eosinophilic cationic protein, total immunoglobulin G and interleukin-1beta, respectively. RESULTS: Gut lavage eosinophilic cationic protein levels were significantly (p < 0.005) higher in patients with Crohn's disease and ulcerative colitis than in control subjects. Intestinal eosinophilic cationic protein levels decreased in three of four children with Crohn's disease who were fed an elemental diet. There was a significant (p < 0.001) correlation between eosinophilic cationic protein concentrations and immunoglobulin G and interleukin-1beta levels in gut lavage fluid. CONCLUSIONS: Elevated intestinal eosinophilic cationic protein levels in inflammatory bowel disease suggest that eosinophils are involved in the gastrointestinal inflammation in this disease. Intestinal eosinophilic cationic protein concentration is another marker with which to discriminate between active and inactive inflammatory bowel disease.

Adolescent↗

Recent advances in the diagnosis and treatment of pediatric inflammatory bowel disease.

The diagnosis and management of inflammatory bowel disease (IBD) in children and adolescents is a challenge to patients, their families, and to the healthcare team. This review highlights recent advances in the epidemiology, diagnosis, and management of pediatric IBD. Among the most prominent advances are the new diagnostic serologic assays that can help screen for IBD in the absence of physical signs of disease and help discriminate between ulcerative and Crohn's colitis. Other tests have been identified as potential noninvasive markers of disease activity, including color Doppler abdominal ultrasound and sugar permeability tests. Recent advances in pharmacogenetics afford clinicians the ability to optimize and individualize therapy using azathioprine or 6-mercaptopurine. Finally, bone health has come forth as a major issue in the complete management of pediatric IBD.

Adolescent↗

[Imaging methods in diagnosis of chronic inflammatory bowel diseases].

In diagnostic imaging of chronic inflammatory bowel diseases, endoscopy and radiologic techniques are used complementarily. For primary evaluation, endoscopy has greater impact, and radiologic techniques are restricted to the assessment of the small bowel. In acute and chronic complications, cross-section methods are superior because extraenteric lesions can be detected precisely. By means of fast sequences and development of gastrointestinal contrast media, magnetic resonance imaging is of increasing value because multiplanar sections can be performed and irradiation risk can be avoided.

Diagnosis, Differential↗

[Inflammatory bowel diseases]

OBJECTIVE: To present a review about inflammatory bowel diseases in childhood so that pediatricians become familiar with two diseases (ulcerative colitis and Crohn s disease) that are increasing in incidence. METHODS: Articles of specific gastroenterological journals were analyzed. Information was also obtained from the author s extensive professional experience in the area. RESULTS: The two diseases are described. Etiopathogenesis is obscure. Clinical presentation, diagnosis, and treatment are discussed, with details and practical aspects to enable the pediatrician to promptly understand the subject. CONCLUSIONS: The inflammatory bowel disease is a condition of high morbidity, and the pediatrician who assists the case must have a very good technical knowledge about the disease, and must be very comprehensive and emotionally serene, in order to afford the young patient a better quality of life throughout the complicated evolution of this disease.

Journal Article↗

Epidemiology of inflammatory bowel disease in Italy.

The incidence of inflammatory bowel diseases is similar throughout Italy. Two prospective multicentre studies in the same period have shown an incidence very similar to Northern Europe. The incidence of ulcerative colitis ranged from 3.4 to 10.5. The incidence of Crohn's disease ranged from 1.9 to 6.6. The time trends seem to indicate an increase in both diseases. The need to set up General Registries of disease is underlined. The clinical behaviour and the diagnostic approach are homogeneous throughout the country. Compared to Northern Europe, surgery was less common in ulcerative colitis. Among the risk factors, familial occurrence has been shown to have the same prevalence as in Northern Europe suggesting a common genetic background. Studies on other risk factors are warranted considering the lack of data. Data on mortality show that there is a decrease in deaths in ulcerative colitis and a slight increase in mortality for Crohn's disease in the first few years after diagnosis. A retrospective study on costs has shown a greater economic burden from ulcerative colitis, however, new multicentre prospective studies are necessary.

Costs and Cost Analysis↗

Clinical relevance of oxygen radicals in inflammatory bowel disease--facts and fashion.

Oxygen radicals particularly superoxide and hydroxyl radicals are very reactive species believed to be involved in cell and tissue damage in a variety of diseases including inflammatory bowel disease (IBD). Today there are four major arguments for such a role in IBD: Infiltration of the inflamed intestinal mucosa with myeloperoxidase containing activated neutrophils able to produce superoxide, hydroxyl and hypochlorite, increased chemoluminescence response of peripheral and mucosal phagocytic cells to various stimuli, decreased inflammation following specific scavenger treatment in animal models of colitis and defined radical scavenger and inhibitory properties of drugs, especially aminosalicylates used in the therapy of IBD. In the absence of a specific therapy, radical scavenging and/or inhibition may be an adjunctive modality in IBD.

Aminosalicylic Acids↗

Evaluation of Helicobacter species in inflammatory bowel disease.

BACKGROUND: Bacteria have been implicated in the pathogenesis of inflammatory bowel disease. Helicobacter species have been shown to cause colitis in animal models and have been identified in human diarrhoeal illness and Crohn's disease. AIM: To determine whether Helicobacter species are present in human inflammatory bowel disease tissue. METHODS: Thirty patients undergoing colonoscopy for clinical reasons were studied. Nine had Crohn's disease, 11 had ulcerative colitis and 10 had histologically normal colons. Tissue was snap-frozen at -70 degrees C. DNA was extracted and examined by five different polymerase chain reaction (PCR) assays that were either genus or species specific for Helicobacter. RESULTS: Analyses of colonic biopsies by two Helicobacter genus-specific PCR assays, two H. pylori-specific assays and a PCR assay designed to amplify fragments of 'H. heilmannii'-like organisms demonstrated that product was not generated by any test. Internal control PCR demonstrated that PCR results for the five assays were not negative due to the presence of residual substances inhibitory to PCR. CONCLUSIONS: Helicobacter species were not identified in this study, using multiple PCRs to eliminate the problems of non-specific cross-reaction. This suggests that Helicobacter species do not play a role in the pathogenesis of inflammatory bowel disease.

Adult↗

Extraintestinal manifestations and complications in inflammatory bowel diseases.

Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel diseases (IBD) that often involve organs other than those of the gastrointestinal tract. These nonintestinal affections are termed extraintestinal symptoms. Differentiating the true extraintestinal manifestations of inflammatory bowel diseases from secondary extraintestinal complications, caused by malnutrition, chronic inflammation or side effects of therapy, may be difficult. This review concentrates on frequency, clinical presentation and therapeutic implications of extraintestinal symptoms in inflammatory bowel diseases. If possible, extraintestinal manifestations are differentiated from extraintestinal complications. Special attention is given to the more recently described sites of involvement; i.e. thromboembolic events, osteoporosis, pulmonary involvement and affection of the central nervous system.

Biliary Tract Diseases↗

Review article: Osteoporosis and inflammatory bowel disease.

Studies using dual-energy X-ray absorptiometry have suggested a high prevalence of osteoporosis in inflammatory bowel disease. However, population-based data on fracture incidence suggest only a small increased risk of fracture amongst patients with inflammatory bowel disease compared with the general population. Therefore, it would be helpful to identify patients with inflammatory bowel disease at particularly high risk for fracture so that these risks might be modified or interventions might be undertaken. The data on calcium intake as a predictor of bone mineral density are conflicting. Although there are data suggesting that a one-time survey to determine current calcium intake will not help to predict bone mineral density in inflammatory bowel disease, persistently reduced calcium intake does appear to lead to lower bone mineral density. In the general population, body mass is strongly correlated with bone mineral density, which also appears to be true in Crohn's disease. Hence, subjects with inflammatory bowel disease and considerable weight loss, or who are obviously malnourished, could be considered for bone mineral density testing, and the finding of a low bone mineral density would suggest the need for more aggressive nutritional support. Although vitamin D is undoubtedly important in bone health, vitamin D intake and serum vitamin D levels do not correlate well with bone mineral density. Sex hormone deficiency can also adversely affect bone health, although a well-developed strategy for sex hormone measurements in patients with inflammatory bowel disease remains to be established. Ultimately, the determination of genetic mutations that accurately predict fracture susceptibility may be the best hope for developing a simplified strategy for managing bone health in inflammatory bowel disease. The therapy of osteoporosis in inflammatory bowel disease has been adapted from other osteoporosis settings, such as post-menopausal or corticosteroid-induced osteoporosis. To date, there remains no therapy proven to be efficacious in inflammatory bowel disease-related osteoporosis; however, calcium and vitamin D supplementation and bisphosphonates have their roles.

Adrenal Cortex Hormones↗

Evaluation of polypoid lesions in inflammatory bowel disease.

This article discusses patients with inflammatory bowel disease (IBD), a group which is at increased risk for colorectal carcinoma based on extent and duration of their disease. Patients with chronic IBD (at least 8-10 years duration) should be screened with colonoscopy every 1 to 2 years with multiple jumbo biopsies every 10 cm through the entire colon. Patients with sporadic adenomas can be followed after complete polypectomy, whereas patients with adenoma-like dysplasia-associated lesion or mass (DALMs) need increased surveillance. Patients with flat dysplasia or non adenoma-like DALMs are at high risk for progression and should undergo colectomy. The patients who have indeterminate lesions can be differentiated based on the endoscopic, histologic, and molecular features of the lesion. Long-term follow-up is necessary to determine the natural history of these lesions.

Adenocarcinoma↗

Prospective survey of childhood inflammatory bowel disease in the British Isles.

The incidence of inflammatory bowel disease in children in western countries may be rising. Since there is no prospective national data on the incidence of inflammatory bowel disease in the UK and Republic of Ireland (ROI), we undertook a prospective survey to determine this incidence. The incidence during 1998 and 1999 was 5.2/100,000 per year in children aged younger than 16 years. Those from an Asian background were over-represented and more likely to have ulcerative colitis.

Adolescent↗

The important "impostors" in the differential diagnosis of inflammatory bowel disease.

When evaluating patients suspected to have inflammatory bowel disease, we generally focus on the important differential features which distinguish ulcerative colitis from Crohn's disease. A distinction between them is possible in 80-90% of cases when accepted clinical, radiographic, and pathologic criteria are applied. The remaining idiopathic cases are usually classified as colitis, indeterminate type. In this presentation, major attention will also be directed to a variety of other disorders which may masquerade as idiopathic inflammatory bowel disease. The pathologic features to be described which serve to identify these "impostors" will emphasize appearances in biopsy material.

Anti-Bacterial Agents↗

Review article: steroid resistance in inflammatory bowel disease - mechanisms and therapeutic strategies.

BACKGROUND: Steroid resistance in inflammatory bowel disease presents a difficult clinical challenge. The advent of biological therapies coupled with an increasing understanding of the pathogenesis of inflammatory bowel disease has provided new therapeutic options. METHODS: We review the available literature of the mechanisms behind steroid resistance. In addition, we outline some of the options available for treating those patients who fail to respond adequately to glucocorticoids. RESULTS: Approximately 30% of patients prescribed glucocorticoids will not achieve clinical remission. Many such patients are offered immunosuppressive or, recently, biological agents. However, these agents are ineffective in a large proportion of patients. Immunosuppressive agents only bring 40-60% of patients into remission, and biological agents typically induce remission in just 40% of patients. In this review, the possible explanations for glucocorticoid resistance are discussed. Recent evidence suggests that in many patients it is mediated by interleukin-2. Basiliximab, a biological agent that interrupts interleukin-2 signalling, has shown significant benefit in early clinical studies. CONCLUSIONS: Patients who fail to respond to steroid therapy should have alternative agents introduced in a timely fashion. Steroid refractory inflammatory bowel disease remains a difficult condition to treat, but new therapies and managements are emerging.

Biological Therapy↗

Etiopathogenesis of inflammatory bowel diseases.

Theories explaining the etiopathogenesis of inflammatory bowel disease (IBD) have been proposed ever since Crohn's disease (CD) and ulcerative colitis (UC) were recognized as the two major forms of the disease. Although the exact cause(s) and mechanisms of tissue damage in CD and UC have yet to be completely understood, enough progress has occurred to accept the following hypothesis as valid: IBD is an inappropriate immune response that occurs in genetically susceptible individuals as the result of a complex interaction among environmental factors, microbial factors, and the intestinal immune system. Among an almost endless list of environmental factors, smoking has been identified as a risk factor for CD and a protective factor for UC. Among microbial factors, no convincing evidence indicates that classical infectious agents cause IBD, while mounting evidence points to an abnormal immune response against the normal enteric flora as being of central importance. Gut inflammation is mediated by cells of the innate as well as adaptive immune systems, with the additional contribution of non-immune cells, such as epithelial, mesenchymal and endothelial cells, and platelets.

Environment↗

Inflammatory bowel disease: management issues during pregnancy.

INTRODUCTION: Inflammatory bowel disease often affects women during their reproductive years, causing management concerns for obstetricians caring for these patients during pregnancy. TREATMENT: Apart from methotrexate, most drugs used regularly to treat ulcerative colitis and Crohn's disease can safely be used by pregnant women. No causal relationship has been established between exposure to sulfasalazine or other 5-aminosalicylic acid drugs and the development of congenital malformations and these drugs may be used with relative safety during pregnancy and lactation. Current evidence indicates that maternal use of azathioprine and mercaptopurine is not associated with an increased risk of congenital malformations, though impaired foetal immunity, intrauterine growth retardation and prematurity are occasionally observed. Cyclosporin is not teratogenic, but may be associated with growth retardation and prematurity. CONCLUSIONS: Pregnancy should be avoided in women treated with methotrexate because of its known abortifacient effects and risk of causing typical malformations. There is no actual evidence of adverse effect in pregnant women receiving Infliximab but the amount of clinical information is small. The treatment with metronidazole or ciprofloxacin for short durations appear to be safe, but there is no data about the effects of increased length of treatment as required in Crohn's disease remains unknown. Control of disease activity before conception and during pregnancy is critical to optimise both maternal and foetal health. A multidisciplined approach involving both obstetrician and gastroenterologist and education about pregnancy are essential components of the treatment of any young women with IBD.

Abnormalities, Drug-Induced↗

Measuring quality of life in children with inflammatory bowel disease: the impact-II (NL).

Inflammatory bowel disease (IBD) is a chronic debilitating disorder. Measures of quality of life are only available for adult patient populations. We developed a new disease-specific health-related quality of life instrument in Dutch for pediatric patients with IBD, called Impact-II (NL). We translated and strongly modified the original (Canadian) Impact questionnaire. It comprises 35 items in six domains. Eighty-three children (66%) completed the questionnaire, 39 children were assessed twice. Disease symptoms were recorded and disease course severity assessed through chart review. Summated disease activity scores and disease course severity scores were dichotomized into two categories. Reliability coefficients were good for five out of six domains (Cronbach's alpha ranged from 0.57 to 0.86) and measures of test-retest stability in clinically stable patients were good for all domains (intra-class correlation coefficients ranged from 0.67 to 0.91). The instrument showed good discriminant validity between symptom groups and disease course severity on all domains. Convergent validity with a validated generic instrument [TNO-AZL Children's Quality of life questionnaire (Tacqol)] showed satisfactory coefficients. In conclusion, the developed questionnaire shows good psychometric properties. Test-retest stability and responsiveness to change should be further assessed in larger patient samples. Cross-cultural translation and validation procedures into other languages are being conducted to enable international use of Impact-II.

Adolescent↗

Antibodies to human recombinant lipocortin-I in inflammatory bowel disease.

1. Corticosteroid drugs are widely employed for the treatment of active inflammatory bowel disease. Not all patients receiving corticosteroid treatment, however, respond satisfactorily, their disease either remaining active in spite of continued treatment, or relapsing upon corticosteroid withdrawal. Raised levels of autoantibodies to lipocortin-I, a corticosteroid-inducible protein with anti-inflammatory activity in vitro, in patients receiving chronic oral corticosteroid therapy have been associated with poor clinical response in rheumatoid arthritis. 2. To determine whether a similar mechanism is responsible for the variable clinical response to corticosteroids in inflammatory bowel disease, we have measured circulating lipocortin-I antibody levels in sera from affected patients and related them to disease activity, treatment and subsequent outcome. 3. IgM, but not IgG, lipocortin-I antibody levels were elevated in patients with ulcerative colitis and Crohn's disease compared with healthy control subjects. In patients with Crohn's disease not taking corticosteroids, IgM lipocortin-I antibody levels were directly related to disease activity scored clinically. 4. IgM lipocortin-I antibody levels were higher in patients receiving sulphasalazine or no treatment and in patients receiving corticosteroids who responded to treatment within 2 months (steroid responders) than in those patients undergoing long-term corticosteroid therapy because of continued disease activity or repeated relapse on corticosteroid withdrawal (steroid non-responders). 5. The high levels of IgM lipocortin-I antibodies in patients with inflammatory bowel disease not taking corticosteroids provides further evidence of disturbed immunity in inflammatory bowel disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗