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PubMed2002

[Neurologic complications in inflammatory bowel diseases].

Some inflammatory diseases of the gastrointestinal system are associated with neurological symptoms which, in rare cases, may precede the onset of the gastrointestinal manifestation of the disease. Celiac sprue is characterized by an intolerance to the wheat protein gluten. The typical neurological manifestation of celiac sprue is cerebellar ataxia. The ataxia as well as the gastrointestinal symptoms can be treated with a strictly gluten-free diet. The neurological symptoms of Whipple's disease, a disorder caused by gram-positive bacilli, are variable. Typical symptoms of cerebral Whipple's disease include dementia, ophthalmoplegia, movement disorders, and signs of hypothalamic dysfunction. Nowadays, the diagnosis of cerebral Whipple's disease is made by PCR detection of the bacilli in the CSF. Crohn's disease and ulcerative colitis are associated with neurological symptoms to a similar proportion. Various forms of polyneuropathies have been observed. The CNS manifestations of inflammatory bowel diseases include thromboembolic stroke, cerebral venous thrombosis, and cerebral vasculitis.

Brain Diseases↗

PubMed2003

[Biologic therapy of inflammatory bowel disease].

Biological therapies in inflammatory bowel disease reflect the exponential advancement in understanding the human intestinal immune system and particularly the biology of intestinal inflammation during the past decade. The better understanding of the mechanisms of inflammatory bowel disease has evolved from desriptive clinical data and genetically engineered animal models. It led to great interest in the evaluation of a variety of new therapeutic agents with novel actions. This review will discuss the mechanisms of biologicals (antibodies against pro-inflammatory cytokines, T cell antibodies, anti-inflammtory cytokines, adhesion molecule blockers, growth factors, hormones, colony stimulating factors, fusion proteins, anti-sense oligonucleotides, trefoil peptides, immunostimulatory [ISS] DNA) used in the treatment of inflammatory bowel disease and summarizes the available data on established biologic therapies as well as investigational agents and briefly touch on probiotics. Based on the data discussed, it seems that biologicals will play an important role in managing inflammatory bowel disease in the near future.

Animals↗

PubMedDate not supplied

Early atherosclerosis in patients with inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) have an increased risk of thrombotic complications. Arterial and venous system may be involved. Moreover, mesenteric microvascular thrombosis has been hypothesised as a contributing factor in the pathogenesis of IBD. Early atherosclerosis is a clinical feature common to several inflammatory and immunological diseases in which atherothrombotic complication represents one of the most important cause of mortality and morbidity. We investigate the prevalence and the entity of the early stages of vascular disease in a population of IBD patients without the classical cardiovascular risk factors, by measuring the intima-media thickness (IMT) of the common carotid artery. We found that IBD patients have an increased risk of early atherosclerosis than healthy controls as showed by greater values of carotid IMT and that homocysteine levels and age were independently associated with the increased arterial wall thickness.

Age Factors↗

PubMed2006

Bacteria in the pathogenesis of inflammatory bowel disease.

PURPOSE OF REVIEW: Inflammatory bowel disease is thought to result from an abnormal response to the gut microbiota. This review discusses advances in knowledge of the changes in gut microbiota and host response in inflammatory bowel disease. RECENT FINDINGS: Approximately 15% of Crohn's disease cases in western populations result from mutations in NOD2/CARD15. This disease leads to defective intestinal defensin production and defective monocyte interleukin-8 response to bacterial peptidoglycan. A similar defective interleukin-8 response and consequent delayed neutrophil recruitment have also been shown in patients with Crohn's disease who do not have the NOD2 mutation. A consequence seems to be the accumulation in tissue of macrophages containing various bacteria, perhaps particularly Escherichia coli. In keeping with this patients with Crohn's disease have circulating antibodies against bacterial flagellar proteins of enterobacteria and clostridia. In ulcerative colitis, there is less evidence for invasion by or immune response to bacteria but changes in gut microbiota include a relative deficiency of bifidobacteria. There is considerable interest in probiotic or prebiotic therapies although so far little evidence for their efficacy. SUMMARY: Molecular techniques are giving us better insight into the gut microbiota in inflammatory bowel disease that should translate into improved therapies.

Animals↗

PubMed1987

Leucocyte elastase in chronic inflammatory bowel diseases: a marker of inflammatory activity?

Leucocyte elastase is a neutral proteinase which plays an important role in the pathogenesis of inflammatory disorders. Infiltration of bowel mucosa by neutrophil and eosinophilic granulocytes is a characteristic feature of chronic inflammatory bowel diseases. We studied plasma elastase in 44 patients suffering from Crohn's disease or ulcerative colitis. Plasma levels were significantly higher in these patients compared to 7 patients with non-inflammatory bowel diseases or 53 healthy controls. Elevated plasma levels were more often found in patients with active inflammation than in those with inactive disease. Elastase did neither correlate with leucocyte counts, serum albumin, ESR, alpha 1-proteinase inhibitor and orosomucoid nor with clinical indices or the faecal excretion of 111In-labelled granulocytes. In serial studies of 15 patients, elastase did not always run parallel to the disease activity. We conclude that plasma elastase does not reliably indicate the inflammatory activity in chronic inflammatory bowel diseases.

Adult↗

PubMedDate not supplied

Surgical treatment of inflammatory bowel diseases in northwestern Italy: a multicentric study by the G.S.M.I.I. (Inflammatory Bowel Disease Study Group).

BACKGROUND AND AIMS: Improved medical therapy and bowel sparing and sphincter saving techniques have changed surgery for UC and CD. Collaboration between gastroenterologists and surgeons is necessary to uniform the indications for surgical treatment reducing emergency operations. GISMII multicentric study aimed to show indications, timing and impact of surgery, through retrospective analysis of cases observed between 1992 to 1996. METHODS: Data were obtained by 16 departments of General Surgery. RESULTS: 102 UC and 376 CD patients were analyzed. In UC patients surgery was performed for failure of medical therapy in 54%, complications in 28.4%, cancer or dysplasia in 10% of cases, 83.3% elective procedures. 30.4% ileo-anal pouch, 30.4% total procto-colectomies with definitive ileostomies, 32.4% total colectomies with ileo-rectal anastomosis, 6.8% segmental resections, were performed. In CD patients surgery was performed in 21% for medical therapy failure, in 79% for complications. 53.4% of patients were submitted to 1 operation, 84% elective procedures. Reoperations were performed in 46.6% of patients, 70.3% elective procedures. In the first operation bowel resection was performed in 79.1%, stricturoplasty in 14.3%; in the subsequent operations bowel resection 62.8%, stricturoplasty 21.7%, increasing number of temporary or definitive ileo-stomies. CONCLUSIONS: Collaboration between gastroenterologists and surgeons is necessary to obtain optimal results, reducing the incidence of emergency surgery, and complications. The short period observed between diagnosis and operation (21.4 months) is due to the increasing tendency of gastroenterologists to anticipate a surgical procedure when young patients with a chronic disease need a prolonged medical therapy.

Adolescent↗

PubMed1999

Fecal eosinophil granule-derived proteins reflect disease activity in inflammatory bowel disease.

OBJECTIVES: The aims of this study were: 1) to examine whether the fecal levels of eosinophil granule-derived proteins reflect disease activity in inflammatory bowel disease (IBD); and 2) to examine the extracellular release of these proteins from eosinophils and their stability in feces by an in vitro study. METHODS: We investigated 42 patients with ulcerative colitis (UC), 37 patients with Crohn's disease (CD), and 29 control subjects. The stool samples were collected at 4 degrees C over 48 h and were homogenized. The fecal levels of eosinophil cationic protein (ECP) and eosinophil protein X (EPX) were measured by radioimmunoassay. Fecal Hb (Hb), alpha1-antitrypsin (AT), and lactoferrin (Lf) were also measured by ELISA. RESULTS: Fecal ECP and EPX concentrations were significantly increased in both active UC and active CD compared to inactive UC and inactive CD, respectively. Fecal EPX concentration correlated with the fecal Hb, AT, and Lf concentrations more closely than fecal ECP concentration. Even in the inactive stage, CD patients who relapsed within the following 3 months showed higher fecal ECP and EPX concentrations compared to the patients who did not. EPX was released extracellularly more efficiently than ECP (18.6% vs 6.3%, after incubation for 15 min at 25 degrees C). EPX was more stable in the feces than ECP. CONCLUSIONS: The measurement of eosinophil granule-derived proteins in feces is useful for evaluating disease activity and predicting relapse in patients with IBD. EPX may be more suitable than ECP as a fecal eosinophil marker.

Adult↗

PubMed1987

Nonsteroidal anti-inflammatory drugs activate quiescent inflammatory bowel disease.

Four patients with quiescent inflammatory bowel disease had prompt exacerbations when given nonsteroidal anti-inflammatory drugs. Nonsteroidal anti-inflammatory drugs can have noxious effects on the distal intestine as well as on the proximal gut. Eight previous cases of exacerbation of ulcerative colitis have been reported, as have instances of de-novo colitis and ileitis in persons treated with nonsteroidal anti-inflammatory drugs who did not have preexisting inflammatory bowel disease. Nonsteroidal anti-inflammatory drug ingestion should be considered in the differential diagnosis of inflammatory bowel disease. These drugs should be administered to patients with inflammatory bowel disease only after consideration of their possible harmful effects.

Adult↗

PubMed1996

Fecal lactoferrin as a marker for disease activity in inflammatory bowel disease: comparison with other neutrophil-derived proteins.

OBJECTIVES: 1) To investigate which neutrophil-derived proteins in feces most accurately reflect disease activity in inflammatory bowel disease. 2) To examine the extracellular release of these proteins by activated neutrophils and their stability in feces by in vitro study. METHODS: We studied 41 patients (91 samples) with ulcerative colitis (UC), 34 patients (105 samples) with Crohn's disease (CD), and 25 control subjects. Fecal levels of lactoferrin (Lf), polymorphonuclear neutrophil elastase (PMN-E), myeloperoxidase (MPO), and lysozyme (Lys) were measured by ELISA. We also measured fecal hemoglobin (Hb) and alpha 1-antitrypsin (alpha 1-AT), useful markers of disease activity in UC and CD, respectively. For the in vitro study, blood samples were stimulated with phorbol myristate acetate or latex beads. For the assessment of stability, homogenized stool samples were stored at 4 degrees C, 25 degrees C, and 37 degrees C for various periods. RESULTS: 1) Fecal Lf, PMN-E, MPO, and Lys concentrations were significantly increased in the active phase of the disease compared to the inactive phase in both UC and CD. 2) Fecal Lf, PMN-E, MPO, and Lys concentrations correlated significantly with fecal Hb concentration in UC, whereas fecal Lf, PMN-E, and MPO concentrations correlated significantly with alpha 1-AT concentration in CD. In UC, fecal Lf, PMN-E, MPO, and Lys concentrations were high in 15, 9, 14, and 14 samples, respectively, of 25 samples with normal Hb concentration. In CD, fecal Lf, PMN-E, and MPO concentrations were high in 19, 10, and 16 samples, respectively, of 30 samples with normal alpha 1-AT concentration. 3) The extracellular release of Lf was the most efficient and this molecule was the most stable in feces. CONCLUSIONS: Both our clinical and our in vitro studies suggested that Lf is the most suitable of these proteins to use as neutrophil-derived fecal marker of inflammation for clinical application.

Adult↗

PubMed2006

Bone mineral density in Iranian patients with inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) are at increased risk of developing osteopenia and osteoporosis. The aim of the study was to investigate the prevalence of decreased bone density and related risk factors in Iranian IBD patients. A total of 126 ulcerative colitis (UC) and 39 Crohn's disease (CD) patients were enrolled. Dual-energy x-ray absorptiometry technique was used to measure bone density, and blood samples were obtained to measure biochemical markers. To find predictive variables for bone mineral density (BMD), stepwise regression analysis was carried out. A total of 53 IBD patients (32.1%) had diminished bone mineral density at either lumbar spine (L1-L4) or femoral neck. Of these, 9 (5.4%) had osteoporosis; however, 44 (26.7%) were osteopenic. Femoral neck bone density was significantly decreased among CD patients (p<0.04). There was no significant difference in BMD between men and women. We have found significant differences in BMD T scores at lumbar L1-L4, L2-L4, and femoral neck in corticosteroid ever-users (p<0.002, p<0.001, p<0.003, respectively). There was no significant difference in biochemical markers between UC and CD patients, except that more CD patients were hypocalcemic (p<0.001). Stepwise regression analysis has revealed lumbar spine T score was predicted by age (p<0.0001), corticosteroid use (p<0.002), and body mass index (BMI) (p<0.005); however, femoral neck was predicted by age (p<0.0001), BMI (p<0.0001), smoking (p<0.009), and corticosteroid use (p<0.028). Low bone density in Iranian UC and CD patients is in accordance with Western societies. Treatment with corticosteroid has increased this possibility in both groups. Corticosteroid use, age, smoking, and BMI are predictive factors for low bone density.

Absorptiometry, Photon↗

PubMed2006

Colorectal cancer prognosis among patients with inflammatory bowel disease.

BACKGROUND & AIMS: Inflammatory bowel disease (IBD) is associated with an increased risk for colorectal cancer (CRC). However, the genetic, endoscopic, and histologic features of IBD-associated CRC differ from cancers that arise sporadically. The objectives of this study were to describe the clinicopathologic features of IBD-associated CRC and to compare survival rates between patients with IBD-associated CRC and patients with sporadic CRC. METHODS: There were 290 patients with IBD-associated CRC (241 with chronic ulcerative colitis [CUC] and 49 with Crohn's disease) and an equal number of age- and sex-matched sporadic CRC patients who were evaluated at the Mayo Clinic between 1976 and 1996. Medical records were reviewed retrospectively for demographic features, endoscopic and histologic characteristics, and vital status at the time of the last follow-up evaluation. The actuarial survival of each group was calculated by the Kaplan-Meier method. The influence of clinical features on survival was assessed using Cox proportional hazards regression modeling. RESULTS: The median age at diagnosis of IBD-related CRC was 48 years. Fifty-five percent of IBD-related tumors were distal to the splenic flexure compared with 78% of sporadic tumors. During a median follow-up period of 5 years, 163 IBD-associated CRC patients died (56%), compared with 164 sporadic CRC patients (57%). The 5-year survival rates were 54% in the IBD-CRC subgroup vs 53% in the sporadic CRC subgroup (P = .94, log-rank). CONCLUSIONS: CUC-related CRC is diagnosed at a relatively young age, and IBD-related tumors tend to be distributed more evenly across the colorectum than sporadic tumors. The survival rates for IBD-associated and sporadic CRC were similar.

Adolescent↗

PubMed1983

Medical and surgical treatment of inflammatory bowel disease in pregnancy.

Inflammatory bowel disease is a relatively common spectrum of disorders of the gastrointestinal tract in women of the reproductive age group. Although Crohn's disease may decrease fertility, female reproductive ability is normal in UC. In general, IBD is not a contraindication to pregnancy or vaginal delivery and is not an indication for therapeutic abortion. Pregnancy will have a variable effect on IBD, and the patient's experience in previous pregnancies is not prognostic of future pregnancies. Whenever possible, pregnancies should be planned when IBD is quiescent and the patient is on a minimal drug regimen. The treatment of IBD is essentially the same regardless of pregnancy. Aggressive medical management with supportive therapy, corticosteroids, and sulfasalazine is effective in the treatment for this disorder. Sulfasalazine is effective in preventing recurrence of UC. Surgical treatment may be necessary in pregnancy. An enlarged uterus may make recognition of acute complications difficult, and fear of radiation may decrease the number of diagnostic x-ray studies performed. A proctocolectomy and ileostomy is curative for UC, but no procedure will cure Crohn's disease. In pregnancy, a limited surgical procedure may be necessary. There is a high incidence of fetal loss if surgery is required in IBD. This fetal loss is probably caused by the fulminant nature of the disease rather than surgery itself. If surgery is indicated, however, it should be performed for maternal indications despite the risk to the fetus. As can be seen, management of IBD in pregnancy is not to be taken lightly and requires extensive collaboration between obstetrician, gastroenterologist, surgeon, and other support personnel.

Adrenocorticotropic Hormone↗

PubMed1982

Inflammatory bowel disease and pregnancy.

Inflammatory bowel disease (IBD) commonly affects women of childbearing age, leading to concerns about the effects of the disease on fertility and pregnancy, the effect of pregnancy on the disease, and the diagnosis and treatment of IBD in the pregnancy women. The literature regarding these issues is reviewed, and a representative case report is discussed. Ulcerative colitis has no effect on fertility. Crohn's disease appears to be associated with an increased risk of infertility. "Subfertility," a temporary inability to conceive associated with chronic disease activity, is perhaps a more suitable description. There have been no studies regarding infertility and males with IBD, although sulfasalazine has recently been reported to cause reversible infertility in men. Ulcerative colitis is not associated with a higher spontaneous abortion rate than the general population, although it is not clear whether certain subgroups of patients have a higher rate of abortion. A similar conclusion has been reached for Crohn's disease, although reported abortion rates of 10-25% are somewhat higher than the general population. Approximately 30-50% of pregnant women with ulcerative colitis have exacerbations during their pregnancy or postpartum, a figure that is applicable to Crohn's disease as well, and which is no different than a control population of nonpregnant women with IBD. Patients with active ulcerative colitis at conception have a higher incidence of disease exacerbation than those with quiescent disease. Postpartum recurrences are more frequent in Crohn's disease, occurring in up to 40% of patients, but respond to standard medical therapy. Women who have had an ileostomy for ulcerative colitis consistently and successfully carry pregnancy to term. There is no data regarding women who have had an ileostomy for Crohn's disease. The approach to the women with abdominal pain during pregnancy is reviewed, including the use of radiographic procedures. No amount of radiation exposure can be considered safe, but the judicious use of standard radiographic tests when considered necessary for the health of the mother appear to be associated with little risk for the fetus. The medial treatment of IBD during pregnancy is the same as that for the nonpregnant patient. Despite animal data to the contrary, the bulk of human data suggests that steroids, when used to treat a variety of conditions including IBD, pose little risk to the human fetus. Similarly, despite the theoretical risk of kernicterus, sulfasalazine appears to be a safe drug even when used during the third trimester of pregnancy.U

Abortion, Spontaneous↗

PubMed1998

Factor V Leiden mutation is not increased in patients with inflammatory bowel disease.

Individuals with inflammatory bowel disease (IBD) are known to have an increased incidence of thromboembolic disease. Activated protein C resistance (APCR) has been identified as one of several inherited disorders of coagulation that predispose individuals to thromboembolic problems. This resistance results from a single point mutation in the factor V gene, called factor V Leiden. It has been suggested that many patients with IBD have APCR, as tested by a clotting assay. We have evaluated a series of 49 patients with IBD, none of whom had a history of thromboembolic disease. We assayed for the factor V Leiden mutation by polymerase chain reaction and found only one heterozygote. Seventeen of the 49 patients were negative for APCR by the clotting assay. Factor V Leiden mutation is not more common in patients with IBD than in the general population. We were unable to confirm a prior report indicating that patients with IBD have a higher prevalence of resistance to activated protein C.

Activated Protein C Resistance↗

PubMed2002

Clinical aspects and pathophysiology of inflammatory bowel disease.

The chronic inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis, are recognized as important causes of gastrointestinal disease in children and adults. In this review we delineate the clinical manifestations and diagnostic features of IBD. In addition, we summarize important recent advances in our understanding of the immune mediators of intestinal inflammation. This information has led to new therapeutic approaches in IBD. Further, we discuss the considerable data that point to the significance of genetic factors in the development of IBD and the genetic loci which have been implicated through genome-wide searches. The commensal bacterial flora also appears to be a critical element, particularly in regards to Crohn's disease, although the precise role of the bacteria in the disease manifestations remains unclear. Current investigations promise to yield fresh insights in these areas.

Adult↗

PubMed1977

Basal and stimulated serum growth hormone concentrations in inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) manifest growth failure which may antecede abdominal symptoms by some years. Eight of ten children with documented IBD had records of decreasing growth velocities. Investigation of growth hormone reserves showed excessive rather than impaired responses. Mean basal GH level was 6.2 +/- 0.75 (SEM) ng/ml. During sleep, the mean GH level rose to 26.0 +/- 4.7 ng/ml and following propranolol-glucagon stimulation, to 46.0 +/- 4.5 ng/ml. All values were significantly higher than levels obtained in a control population of 25 children investigated for short stature who were not GH deficient. The mean peak GH response following insulin in the IBD group (10.8 +/- 3.8 ng/ml), however, did not differ from the mean peak response in the control group (13.5 +/- 3.3 ng/ml). Growth failure in patients with IBD is not the result of GH deficiency and is not an irreversible phenomenon. On the contrary, judicious use of glucocorticoids aimed at the control of the disease usually produces compensatory growth acceleration ("catch-up growth").

Adolescent↗

PubMed1987

Extracolonic manifestations of inflammatory bowel disease.

Patients with inflammatory bowel disease may develop various extracolonic manifestations. Oral and eye complaints are common. Recognition is important because these may be clues to subclinical chronic ulcerative colitis or Crohn's disease. Treatment of the bowel inflammation may improve the extracolonic manifestations, such as peripheral arthritis or erythema nodosum.

Arthritis↗

PubMed1995

Enhanced superoxide anion release of normal neutrophil granulocytes primed with sera of patients with inactive inflammatory bowel disease.

During active inflammatory bowel disease (IBD) the respiratory burst of neutrophil granulocytes has been shown to be impaired using isolated circulating neutrophil granulocytes of patients with active disease. Using normal neutrophil granulocytes of healthy volunteers the present study examines the potential priming effect of sera of patients with active and quiescent IBD. The superoxide anion (O2-)-release of normal neutrophil granulocytes in response to N-formyl-methionyl-leucyl-phenylalanine (FMLP) has been investigated after incubation with sera of patients with active and inactive Crohn's disease and ulcerative colitis. O2(-)-release was measured using the superoxide dismutase inhibitable reduction of ferricytochrome c. The O2(-)-release of normal neutrophil granulocytes primed with sera of patients with inactive Crohn's disease (607.1 +/- 218.2 nmol/60 min, n = 10, p = 0.001) or cultured with sera of patients with quiescent ulcerative colitis (497.4 +/- 94.9 nmol/60 min, n = 3, p = 0.005) was significantly enhanced when compared with sera of normal controls (319.8 +/- 86.5 nmol/60 min, n = 10). There was no significant difference between priming with sera of patients with quiescent or active Crohn's disease (481.0 +/- 113.0 nmol/60 min, n = 5). Normal neutrophil granulocytes primed with sera of patients with active ulcerative colitis produce significantly larger amounts of O2- (809.5 +/- 256.9 nmol/60 min, n = 4, p = 0.001) when compared with sera of normal controls. The study shows that sera of patients with quiescent IBD as well as sera of patients with active disease have the potential to prime normal neutrophil granulocytes for an enhanced O2(-)-release in response to FMLP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗