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[Possible role of mucosal lymphocyte homing in the pathogenesis of extraintestinal manifestations in inflammatory bowel diseases].

Patients with inflammatory bowel disease are likely to develop several extraintestinal complications including skin, eye, joint or liver disorders. Some of them tend to correlate with underlying bowel inflammation or may run a chronic independent course from the bowel disease. Tissue infiltration with lymphocytes seems to be the most prominent feature of extraintestinal manifestations. Recent reports have suggested that these lymphocytes are originally activated in the inflamed bowel and then aberrantly recruited to sites outside the gut. Furthermore the hypothesized existence of an enterohepatic circulation of lymphocytes could also contribute to the pathogenesis of liver complications.

Cell Adhesion↗

Antiphospholipid antibodies in inflammatory bowel diseases.

Patients with inflammatory bowel diseases are susceptible to thrombosis in the active phase of the disease. Tests and some factors of coagulability have shown the existence of hypercoagulability of the blood in the active phase of these diseases. In the last few years some authors have found increased levels of antiphospholipid antibodies in the blood of patients with severe forms of Crohn's disease and ulcerative colitis. In a prospective study anticardiolipin antibodies have been measured in the blood of 12 patients, eight with ulcerative colitis and four with Crohn's disease. Six patients with ulcerative colitis and two with Crohn's disease were in the active phase of the disease, and the others in the remission. None of the patients had any clinical signs of thrombosis. Anticardiolipin antibodies were slightly increased in only one patient with severe ulcerative colitis complicated with erythema nodosum and swelling of the ankles. In nine patients anticardiolipin antibodies were in the normal range, but in two they were not found. Results of our study do not allow any definite conclusion regarding the possible role of antiphospholipid antibodies in the development of thrombosis in inflammatory bowel diseases: the number of the patients is relatively low and in half of the cases the disease was moderately active. Further studies are therefore necessary.

Adult↗

A scoring index for disease activity in canine inflammatory bowel disease.

The clinical course of inflammatory bowel disease (IBD) in dogs is characterized by spontaneous exacerbations and remissions, which makes assessment of disease burden difficult. The objectives of this study were to develop a scoring system for evaluation of canine IBD activity and to validate this scoring method by correlating it to objective laboratory and histologic indices of intestinal inflammation. Fifty-eight dogs with IBD were evaluated prospectively and compared to 9 disease-free control dogs. Clinical disease activity was quantified by a simple scoring system, the canine IBD activity index (CIBDAI), and compared to serum concentrations of C-reactive protein (CRP), haptoglobin (HAP), alpha-acid glycoprotein (AGP), and serum amyloid A (SAA), as well as histology scores derived from endoscopic biopsy specimens. Forty-six dogs were available for a reevaluation of the CIBDAI, CRP HAP, and AGP, and 34 dogs had repeat analysis of SAA performed after medical therapy. Serum concentrations of CRP were significantly (P < .02) increased in dogs with CIBDAI scores > or = 5 (mild disease activity or greater) compared to controls. Among IBD dogs, the CIBDAI showed good correlation (r = 0.82, P < .0001) to both histology and HAP scores, but CRP also was a strong co-correlate of disease activity. The IBD dogs showed significantly (P < .0001) decreased CIBDAI and CRP values but significantly (P < .0001) increased HAP concentrations after medical therapy compared to pretreatment values. We conclude that the CIBDAI is a reliable measure of inflammatory activity in canine IBD and that CRP is suitable for laboratory evaluation of the effect of therapy in these patients.

Aging↗

Bone density in young males with recently diagnosed inflammatory bowel disease.

OBJECTIVES: Patients with inflammatory bowel disease are at increased risk of developing osteopenia and osteoporosis. Our study was designed to determine the degree of decreased bone density in steroid naïve young male patients with inflammatory bowel disease and to unmask possible risk factors. METHODS: Before the initiation of any treatment in young male patients aged 26 +/- 4.8 years with inflammatory bowel disease, ultrasound bone density measurement at the right calcaneous was performed using a Lunar Achilles plus device. Stiffness Index and T-score were measured. We also performed an ultrasound bone density measurement at right calcaneous in healthy age- and sex-matched controls. RESULTS: Nine out of 32 patients with inflammatory bowel disease had osteopenia or osteoporosis (approximately 28%). Of controls, two individuals had osteopenia (approximately 7%). There was a positive correlation between T-score and body mass index, but not between T-score and age in patients with inflammatory bowel disease. There was a statistically significant difference in T-score between patients with disease duration>6 months and those with disease duration<6 months (P=0.032), but not between the patients with Crohn's disease compared with the patients with ulcerative colitis. CONCLUSION: Steroid naïve young male patients with inflammatory bowel disease have lower bone density values than healthy controls. According to our findings, duration of disease above 6 months and low body mass index are major risk factors for low bone density in these patients. Bone density measurement should be performed in all patients with inflammatory bowel disease in an early stage of the disease.

Adult↗

Inflammatory bowel disease in children.

Inflammatory bowel disease remains a serious chronic illness in children. Recent developments in the care of these patients involves both basic science research into the pathophysiology of ulcerative colitis and Crohn's disease and the development of refinements in the surgical techniques and medical therapies available as treatment options. In Crohn's disease, a new steroid analogue (budesonide) shows some promise as a possible medical treatment that would limit the devastating side effects of steroids in children. In addition, the bowel-sparing technique of strictureplasty has now been reported in children with good results. In ulcerative colitis, the surgical technique of endorectal pull-through continues to evolve with reports of the efficacy of specific pouch designs and surgical techniques. An understanding of pouchitis, the most common complication of endorectal pull-through, has focused on documenting specific alterations in the microbiology and physiology of the pouch, as well as investigating a possible link between autoantibodies and susceptibility to this complication.

Administration, Topical↗

Assessment of disease activity in inflammatory bowel disease; relevance for clinical trials.

In patients with inflammatory bowel disease, assessment of disease activity is important in order to monitor and adjust therapy. In individual patients, disease evaluation is largely based on subjective symptoms. However, for disease evaluation in clinical trials, an objective and reproducible disease activity index is needed. At present, a number of activity indices are available for Crohn's disease and for ulcerative colitis. These indices may be distinguished in more subjective clinical indices, more objective endoscopic and histological indices, and in indices with combinations of both subjective and objective parameters. In the design of a new clinical trial, an appropriate disease activity index should be selected which is based on the patient selection criteria and the aims of the study.

Clinical Trials as Topic↗

Inflammatory bowel disease in mother or father and neonatal outcome.

UNLABELLED: Even a minor decrease in birthweight predisposes to adult disease. Inflammatory bowel disease (IBD) in the mother is a risk factor for low birthweight and preterm infants. This study investigated the effect of IBD in the mother or father, adjusting for confounders, on the newborn infant, with the focus on birthweight and pregnancy duration. A total of 10399 single-birth mother-infant pairs was prospectively enrolled within the ABIS project (All Babies In Southeast Sweden). Outcome measures included birth week, preterm birth (<37 wk), birthweight, low birthweight (<2500 g), birth length, caesarean section and neonatal hospital care. Ulcerative colitis (UC) in the mother was associated with lower birthweight in the infant (adjusted difference: -330 g, adjusted 95% confidence interval: -509 to -150 g, p < 0.001), and with even lower birthweight when the mother was treated with Mesalazine or steroids. No decrease in birthweight was seen in infants whose mother suffered from Crohn's disease (CD) (adjusted difference: -65 g, adjusted 95% confidence interval: -354 to 224 g, p > 0.05). Maternal UC or CD did not affect the pregnancy duration. The neonatal outcome of infants whose father suffered from UC and CD did not differ from the control group. CONCLUSION: UC in the mother affects the birthweight of the infant, which may predispose to future disease in the infant. Most women and men with UC and CD can, however, expect a healthy child with neither preterm birth nor low birthweight.

Birth Weight↗

Unexplained bronchopulmonary disease with inflammatory bowel disease.

Six patients developed severe, unexplained, chronic bronchopulmonary disease from 3 to 13 years after the onset of nonspecific inflammatory disease of the colon. All had chronic bronchitis, bronchiectasis was diagnosed in four, and an obstructive type of pulmonary dysfunction was noted in five. Four of the six, including the two with only chronic bronchitis, had no history of smoking. There was an initial correlation between the pulmonary symptoms and the intestinal disease, except in two patients who developed overt pulmonary disease following total proctocolectomy. The frequent occurence of extraintestinal lesions has suggested that ulcerative colitis and regional enteritis are systemic disorders. Chronic unexplained bronchopulmonary disease may be another infrequent complication in such patients.

Bronchi↗

Increased carotid intima-media thickness in patients with inflammatory bowel disease.

BACKGROUND: Patients with inflammatory bowel disease have an increased risk of thrombotic complications; moreover, mesenteric microvascular thrombosis has been hypothesized as a contributing factor in the pathogenesis of inflammatory bowel disease. AIM: To assess the extent of subclinical atherosclerosis in inflammatory bowel disease by measuring the intima-media thickness of the common carotid artery. METHODS: Fifty-two patients were enrolled in the study. Patients aged >45 years, with a history of cardiovascular disease and known risk factors for atherosclerosis were excluded from the study. Twenty healthy subjects were studied as controls. Carotid ultrasonography was performed in all patients and controls. intima-media thickness was measured proximal to the carotid bifurcation over both right and left common carotid arteries. The clinical characteristics and the laboratory parameters relevant to disease activity were recorded for all inflammatory bowel disease patients. In particular, plasma homocysteine, a well-known risk factor for thrombosis, was assessed. RESULTS: Common carotid artery intima-media thickness was significantly higher in inflammatory bowel disease patients (0.63 +/- 0.15 mm) compared with controls (0.53 +/- 0.08 mm). Multiple regression analysis revealed a significant association of carotid intima-media thickness with homocysteine levels and age. CONCLUSIONS: Inflammatory bowel disease patients have an increased risk of early atherosclerosis than healthy controls as showed by greater values of carotid intima-media thickness. Homocysteine levels and age resulted independently associated with the increased arterial wall thickness.

Adult↗

Biomarkers in inflammatory bowel disease.

PURPOSE OF REVIEW: Inflammatory bowel disease is characterized by chronic intestinal inflammation in the absence of a recognized pathogen. In its classic description, there are two principal forms of inflammatory bowel disease: Crohn disease and ulcerative colitis. The clinical heterogeneity of these disorders alludes to the possibility of diverse pathogenetic mechanisms underlying inflammatory bowel diseases. The purpose of this review is to summarize the latest information on biomarkers of Crohn disease and ulcerative colitis. RECENT FINDINGS: The authors have focused on serologic markers for which emerging data support their use as predictors of disease evolution. Serologic markers such as perinuclear antineutrophil cytoplasmic antibody, anti-Saccharomyces cerevisiae antibody, anti-OmpC, and anti-I2 may be useful in distinguishing inflammatory bowel diseases from functional disorders and ulcerative colitis from Crohn disease and predicting complications of disease. Genetic markers such as CARD15/NOD2 may be useful in the future when combined with other markers to predict disease course. Biochemical markers of inflammation such as C-reactive protein are useful to stratify patients likely to respond to biologic therapies and to follow response to treatment. In the future, functional genomics and proteomics will be used to rapidly screen patients for subclinical characteristics that can predict disease course and response to therapy. SUMMARY: A variety of biomarkers can be used to stratify patients with inflammatory bowel disease into more homogeneous subgroups with respect to response to therapy and disease progression.

Journal Article↗

New developments in the treatment of inflammatory bowel disease.

Therapy of inflammatory bowel disease (IBD) is rapidly changing with the advent of new discoveries in disease pathogenesis. The need for targeted therapies against the uncontrolled immuno-inflammatory reaction in IBD together with a prerequisite for minimal side effects is driving improvement in old medicines and is leading to the development of new drugs. This review introduces emerging changes in IBD treatment, such as improvements in conventional IBD medications or their use. Balsalazide, budesonide and changes in the use of 5-aminosalicylate (5-ASA) products and purine analogues, such as azathioprine, are discussed. Additionally, studies examining the role of drugs newly introduced into IBD therapy, such as mycophenolate mofetil (MMF), thalidomide and heparin, are stated. Emerging biological therapies, such as therapies against TNF, therapies to enhance anti-inflammatory cytokines, therapeutic manoeuvres to disrupt immune cell trafficking, anti-oxidant therapies, as well as non-conventional treatments, such as diet therapies, prebiotics and probiotics, and helminth therapies are discussed.

Anti-Bacterial Agents↗

Feline inflammatory bowel disease: a review.

Inflammatory bowel disease (IBD), while a popular diagnosis, may not occur as commonly as it is diagnosed. It is a diagnosis of exclusion, meaning that it is important to eliminate diseases that mimick it. Dietary intolerance or allergy in particular, can have the same clinical and histologic appearance as IBD. Likewise, well-differentiated alimentary lymphosarcoma can also be confused with it. Intestinal biopsies are useful, but must be taken carefully and then evaluated by someone with interest and expertise in alimentary tract pathology. Therefore, it behoves the clinician to carefully consider the diagnosis instead of starting multiple drug therapy in a cavalier fashion. Well constructed dietary therapy can often be beneficial for both dietary problems and IBD.

Animals↗

[Serum bone marker measurements in bone metabolism disorders associated with inflammatory bowel diseases].

Patients with inflammatory bowel disease (IBD) have decreased bone mineral density (BMD), which is usually much more remarkable in patients with Crohn's disease (CD) than those with ulcerative colitis (UC). The aim of the present study was to investigate the usefulness of serum beta-Crosslaps (bCL) and osteocalcin (OC) determinations to assess bone metabolism in patients with IBD. Forty-nine patients with IBD (23 UC, 26 CD) and 46 healthy controls were studied. Serum bCL and OC were measured by Elecsys immunoassay. Compared to controls (0.275 +/- 0.14 ng/ml) the mean bCL concentration was significantly higher in the CD (mean = 0.489 +/- 0.25 ng/ml; p < 0.001) and UC groups (mean = 0.439 +/- 0.3 ng/ml; p < 0.01). The mean OC concentration was significantly higher in the CD group (28.52 +/- 14.75 ng/ml) than in controls (21.42 +/- 7.43 ng/ml) but OC level was not significantly increased in the UC group (24.89 +/- 15.08 ng/ml). There was no significant difference in bCL or OC concentrations between the CD and UC groups. These results indicate that the accelerated bone resorption is not associated with increased bone formation in patients with IBD. These two marker of the bone metabolism could be a good laboratory parameter of bone pathology in patients with IBD, especially in CD.

Adult↗

Pathological features of inflammatory bowel disease in childhood.

Inflammatory bowel disease (IBD) in childhood is realistically interpreted to mean ulcerative colitis (UC) and Crohn's disease of the colon. Their gross and microscopic features are discussed along with the differential diagnosis from other childhood conditions associated with bloody diarrhea.

Child↗

Posterior segment manifestations of inflammatory bowel disease.

Thirteen patients with inflammatory bowel disease and posterior segment disease were subject to a retrospective review. Eight patients had Crohn's disease and five had ulcerative colitis. In six patients, the inflammatory bowel disease was active when ocular inflammation occurred. Patients had one or more posterior segment findings that included serous retinal detachment (8), choroidal infiltrates (6), retrobulbar neuritis (1), papillitis (1), retinal pigment epithelium disturbance (1), and choroidal folds (1). Posterior segment disease responded to systemic and periocular corticosteroids in 9 of 13 cases. Four patients whose disease relapsed after corticosteroid therapy was suspended responded to bowel resection. Ophthalmologists should be aware of the wide spectrum of posterior segment abnormalities associated with inflammatory bowel disease that may require and respond to anti-inflammatory agents.

Adolescent↗

[Inflammatory bowel disease and pregnancy].

Inflammatory bowel disease (ulcerative colitis and Crohn's disease) is a chronic illness, often affecting people of reproductive age. Treatment involves drugs which have potential side effects and because of this pregnancy causes considerable concern. The course of the disease is not much affected by pregnancy. The relapse rate is only slightly increased when the disease is active at the time of conception. Relapses during pregnancy should be treated in the usual manner. Surgical intervention should be carried out on the same indications as in those who are not pregnant. Frequency of complications is not increased during pregnancy, at delivery or post partum. Sectio may be necessary in perianal disease. With few exceptions, drug treatment should be continued throughout pregnancy. No adverse effects are seen with normal doses of sulfasalazine, 5-amino-salicylic acid and steroids. Planned pregnancies should be started in periods of quiescent disease.

Animals↗

Experimental models of inflammatory bowel disease.

Etiology of inflammatory bowel disease (IBD) is still unknown. A lot of experimental models of these diseases have been developed during the last years. They can be classified as spontaneous and induced models. Spontaneous models are infectious, genetic or of unknown etiology. Induced models are infectious, immune-mediated, chemical or genetic. All these models share some characteristics with IBD. In general, they are characterized by a chronic inflammation of the gut, and often, this inflammation appears secondary to mucosal abnormalities leading to an abnormal immune and inflammatory response toward luminal material. The most interesting models are thus those that share not only clinical and pathological characteristics with IBD, but also early mucosal abnormalities. From that point of view, the nonsteroidal anti-inflammatory drug (NSAID) enteropathy is probably one of the most interesting model for Crohn's disease (CD). In effect, this model shares an early modification with CD, that is increased intestinal permeability. In animals NSAID enteropathy, the increased intestinal permeability appears early after NSAID administration and is followed by inflammatory lesions. These lesions seem to be secondary to the increased permeability and depend on intraluminal materials, such as alimentary antigens or bacterial fragments. A possible link between the increased permeability and the inflammatory lesions could be an abnormal immune and inflammatory response toward the intraluminal materials. If the increased intestinal permeability in CD was confirmed, the same mechanisms could be implicated in its pathophysiology.

Animals↗

Infections in the immunopathogenesis of chronic inflammatory bowel disease.

In chronic inflammatory bowel disease, self-destructive, exaggerated inflammation seems to occur in the absence of a well defined pathogen. However, epidemiological data strongly suggests that development of disease does not depend on endogenous factors alone. In this review, we summarize how a possible role for microbial factors can be reconciled with the current understanding of etiology and pathogenesis of IBD. The data presented does not support that IBD is an infectious disease nor that it is a self-antigen-specific autoimmune disease, however, recent findings increasingly suggest that tissue damage might be caused by a non-specific autoaggressive inflammation which is driven by common, ubiquitous microbial agents derived from the bacterial flora in the intestinal lumen.

Animals↗