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See detailTraitement de la maladie de Crohn de l'adulte par anticorps anti-tumor necrosis factor-alpha (TNF alpha)
Belaiche, Jacques ULg; Louis, Edouard ULg

in Revue Médicale de Liège (2000), 55(9), 827-32

Crohn's disease (CD) is a chronic inflammatory disease of the bowel characterized by segmental transmural inflammation and granulomatous changes. TNF alpha is a member of a large family of proteins and ... [more ▼]

Crohn's disease (CD) is a chronic inflammatory disease of the bowel characterized by segmental transmural inflammation and granulomatous changes. TNF alpha is a member of a large family of proteins and receptors that are involved in immune regulation. It is a proinflammatory and immunoregulatory cytokine synthesized by monocytes, macrophages, and T cells. TNF alpha plays an early central role in the cytokine cascade of the inflammatory process. Recently, chimeric monoclonal antibodies that inhibits TNF alpha have been used in the treatment of Crohn's disease. Infliximab has been the most largely used antibody. It is commercialized in the USA and has recently obtained an European marketing approvement. Infliximab is indicated for the treatment of moderately to severely active CD in patients having an inadequate response to conventional therapy. Clinical trials have demonstrated efficacy when the agent is initiated as a 5 mg/kg single intravenous infusion. In patients with fistulizing CD, administration of 2 subsequent 5 mg/kg doses 2 and 6 weeks after the initial dose appears to be efficacious. Limited clinical data also suggest that infliximab retreatment regimen restores response and maintains remission rates. Infliximab appears to be well tolerated. To date, very little is known about the potential for long-term toxicity with infliximab therapy. [less ▲]

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See detailFrequently Relapsing Crohn's Disease Is Characterized by Persistent Elevation in Interleukin-6 and Soluble Interleukin-2 Receptor Serum Levels During Remission
Van Kemseke, Catherine ULg; Belaiche, Jacques ULg; Louis, Edouard ULg

in International Journal of Colorectal Disease (2000), 15(4), 206-10

We examined immune and inflammatory activation during remission in patients with Crohn's disease who presented with various clinical profiles (prolonged remission vs. relapsing disease). Thirty-six ... [more ▼]

We examined immune and inflammatory activation during remission in patients with Crohn's disease who presented with various clinical profiles (prolonged remission vs. relapsing disease). Thirty-six patients with at least 3 years' follow-up starting from a remission period were studied retrospectively. Relapses were defined by a retrospective calculation of the Crohn's disease activity index or by the clinical judgement of the physicians in charge of the patients. Disease course over the study period was assessed by the mean number of annual relapses. Analysis used measurements during remission of the following: erythrocytes sedimentation rate, relative lymphocytosis, acid alpha1-glycoprotein, interleukin-6 (IL-6), and soluble interleukin-2 receptor (sIL-2R) serum levels. During the study period 21 patients experienced at least one relapse and 15 did not. Mean serum levels of sIL-2R and mean relative lymphocytosis in remission significantly discriminated between relapsing and nonrelapsing patients. Only the mean sIL-2R serum level was selected by multivariate analysis, with a cutoff value of 82 pM/1 (sensitivity of 76% and specificity of 80%). The only features correlated with mean number of annual relapses in the relapsing patients were mean serum levels of sIL-2R (r=0.58, P=0.015) and IL-6 in remission (r=0.45, P=0.039). Multivariate analysis demonstrated statistical significance only for the mean serum level of IL-6 (P=0.014). In Crohn's disease the persistent elevation in sIL-2R serum levels during remission corresponds to chronic active disease, while high serum levels of IL-6 in these patients is associated with a high frequency of relapse. [less ▲]

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See detailReflux gastro-oesophagien de l'adulte: diagnostic et traitement
Louis, Edouard ULg; Belaiche, Jacques ULg

in Revue Médicale de Liège (2000), 55(5), 341-4

Gastro-oesophageal reflux is a frequent problem affecting up to one third of the Belgian adult population. It is most often a benign non evolutive disease. It is however frequently chronic, with a ... [more ▼]

Gastro-oesophageal reflux is a frequent problem affecting up to one third of the Belgian adult population. It is most often a benign non evolutive disease. It is however frequently chronic, with a significant negative impact on quality of life. The diagnostic and therapeutic management must be adapted to each individual case. In the majority of cases, the purpose of therapy is the control of symptoms and, in a small number of cases with severe oesophagitis the aim is a complete and persistent healing of lesions. A Franco-Belgian consensus meeting on diagnostic and therapeutic management of gastro-oesophageal reflux disease in adults was recently held. Guidelines have been proposed. The aim of the present paper is to highlight the main principles of these guidelines and to comment on their adjustment to current belgian medical practice. [less ▲]

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See detailIncreased production of matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-1 by inflamed mucosa in inflammatory bowel disease
Louis, Edouard ULg; Ribbens, Clio ULg; Barreto Dos Santos, Amelia ULg et al

in Clinical & Experimental Immunology (2000), 120(2), 241-246

Inflammatory bowel diseases (IBD) are characterized by a sustained inflammatory cascade that gives rise to the release of mediators capable of degrading and modifying bowel wall structure. Our aims were ... [more ▼]

Inflammatory bowel diseases (IBD) are characterized by a sustained inflammatory cascade that gives rise to the release of mediators capable of degrading and modifying bowel wall structure. Our aims were (i) to measure the production of matrix metalloproteinase-3 (MMP-3), and its tissue inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), by inflamed and uninflamed colonic mucosa in IBD, and (ii) to correlate their production with that of proinflammatory cytokines and the anti-inflammatory cytokine, IL-10. Thirty-eight patients with IBD, including 25 with Crohn's disease and 13 with ulcerative colitis, were included. Ten controls were also studied. Biopsies were taken from inflamed and uninflamed regions and inflammation was graded both macroscopically and histologically. Organ cultures were performed for 18 h. Tumour necrosis factor-alpha (TNF-alpha), IL-6, IL-1beta, IL-10, MMP-3 and TIMP-1 concentrations were measured using specific immunoassays. The production of both MMP-3 and the TIMP-1 were either undetectable or below the sensitivity of our immunoassay in the vast majority of uninflamed samples either from controls or from those with Crohn's disease or ulcerative colitis. In inflamed mucosa, the production of these mediators increased significantly both in Crohn's disease (P < 0.01 and 0.001, respectively) and ulcerative colitis (P < 0.001 and 0.001, respectively). Mediator production in both cases was significantly correlated with the production of proinflammatory cytokines and IL-10, as well as with the degree of macroscopic and microscopic inflammation. Inflamed mucosa of both Crohn's disease and ulcerative colitis show increased production of both MMP-3 and its tissue inhibitor, which correlates very well with production of IL-1beta, IL-6, TNF-alpha and IL-10. [less ▲]

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See detailClinical biliary complications after adult liver transplantation: a prospective study
Detry, Olivier ULg; Maweja, Sylvie ULg; Delwaide, Jean ULg et al

in Acta Gastro-Enterologica Belgica (2000, March), 63(1), 56

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See detailTumour Necrosis Factor (Tnf) Gene Polymorphism in Crohn's Disease (Cd): Influence on Disease Behaviour?
Louis, Edouard ULg; Peeters, Marc; Franchimont, D. et al

in Clinical & Experimental Immunology (2000), 119(1), 64-8

Crohn's disease (CD) is a multifactorial disease with genetic heterogeneity. TNF-alpha plays a key role in the development of the mucosal lesions. The aim of our work was to study a single base pair ... [more ▼]

Crohn's disease (CD) is a multifactorial disease with genetic heterogeneity. TNF-alpha plays a key role in the development of the mucosal lesions. The aim of our work was to study a single base pair polymorphism located in the promoter region of TNF gene, in a large population of CD patients with well defined phenotypes. One hundred and ninety-three patients with CD and 98 ethnically matched controls were studied. The -308 single base pair polymorphism of TNF gene was studied using an allele-specific polymerase chain reaction. Genotype and allelic frequencies were compared between patients and controls and between subgroups of patients defined by sex, age at diagnosis, familial history, location of disease, type of disease, extra-intestinal manifestations, and response to steroid treatment. In 29 patients a measure of TNF-alpha production by colonic biopsies was performed. The frequency of the allele TNF2 as well as the proportion of carriers of the allele TNF2 were slightly but not significantly lower in CD than in controls (11.9% versus 14.8% and 21.5% versus 27.6%, respectively). A more prominent difference in frequencies of allele TNF2 and in proportions of TNF2 carriers was found when comparing subgroups of patients. The frequency of allele TNF2 was significantly higher in steroid-dependent than in non-steroid-dependent disease (28.1% versus 10.3%; Delta = 17.8%, 95% confidence interval (CI) = 6.3-29.5%, P = 0.0027) and tended to be higher in colonic than in small bowel disease and in fistulizing than in stricturing disease. Furthermore, TNF2 carriers tended to be more frequent in patients with steroid-dependent than non-steroid-dependent disease (43.8% versus 19.3%; Delta = 24.5%, 95% CI = 3.6-45.4%, P = 0.022), in patients with fistulizing than stricturing disease (26.5% versus 9.6%; Delta = 16.9%, 95% CI = 1. 1-32.6%, P = 0.036), and in patients with colonic than small bowel disease (26.5% versus 11.1%; Delta = 15.4%, 95% CI = -0.8-31.6%, P = 0.063). Finally, patients carrying at least one copy of allele 2 were found to produce slightly more TNF-alpha at the colonic level. The -308 TNF gene polymorphism may have a slight influence on the behaviour of CD. The carriage of allele 2 may favour steroid-dependent disease and to a lesser extent fistulizing and colonic disease, possibly secondary to a more intense TNF-alpha-driven inflammatory reaction at the mucosal level. [less ▲]

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See detailAutoimmune pancreatitis mimicking cancer of the pancreas
Detry, Olivier ULg; Servais, Anne; Pestieau, S. R. et al

in Acta Gastro-Enterologica Belgica (2000, January), 63(1), 57

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See detailTraitement médical des colites aiguës inflammatoires sévères
Belaiche, Jacques ULg; Louis, Edouard ULg

in Hépato-Gastro (2000), 7

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See detailInitial Medical Management of Severe Acute Ulcerative Colitis
Belaiche, Jacques ULg; Louis, Edouard ULg

in Acta Gastro-Enterologica Belgica (2000), 63(3, Jul-Sep), 275-8

Severe colitis is life-threatening complication of ulcerative colitis. Early recognition of the severity of the colitis, intensive medical therapy and prompt surgery when necessary have all contributed to ... [more ▼]

Severe colitis is life-threatening complication of ulcerative colitis. Early recognition of the severity of the colitis, intensive medical therapy and prompt surgery when necessary have all contributed to improved outcome. Initial medical treatment should be instituted as soon as the diagnosis is made with an intravenous corticosteroid associated with supportive treatment. If the patient fails to response to this intensive treatment after 5-7 days, cyclosporin should be initiated. If cyclosporin is not used then colectomy should be performed immediately. Moreover, significant deterioration at any point during medical therapy is an indication for colectomy. The gravity of the patient's condition require close interaction between physician an surgeon. [less ▲]

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See detailGenetics of Crohn's Disease Behaviour
Louis, Edouard ULg; Belaiche, Jacques ULg

in Acta Gastro-Enterologica Belgica (2000), 63(4, Oct-Dec), 377-9

Crohn's disease is probably an heterogeneous entity. This heterogeneity may be linked to either genetics or environment. In particular the behaviour of the disease, i.e. the tendency to develop ... [more ▼]

Crohn's disease is probably an heterogeneous entity. This heterogeneity may be linked to either genetics or environment. In particular the behaviour of the disease, i.e. the tendency to develop stricturing and/or penetrating lesions, may be linked to the genetic background. While epidemiological and clinical data suggest the relevance of these behavioural classifications, the progresses in the characterization of the immuno-inflammatory reaction in the bowel wall shed a new light on possible candidate genes for these genetic predispositions to various Crohn's disease behaviours. Association studies an linkage analysis focusing on growth factors, metalloproteinases and their tissue inhibitors as well as cytokines may bring new interesting data in this field. [less ▲]

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See detailEvidence-Based Medicine: traitement de l'hépatite chronique C. GLEVHE. Groupe Liégeois d'Etude des Virus Hépatotropes.
Delwaide, Jean ULg; Gerard, Christiane ULg; Belaiche, Jacques ULg et al

in Revue Médicale de Liège (2000), 55(5), 337-340

The Hepatitis C virus (HCV) infects nearly 170 million people in the world. The major characteristic of virus C is its tendency to chronicity in more than 85% of cases. Generally asymptomatic, HCV ... [more ▼]

The Hepatitis C virus (HCV) infects nearly 170 million people in the world. The major characteristic of virus C is its tendency to chronicity in more than 85% of cases. Generally asymptomatic, HCV infection may also evolve with time to cirrhosis and hepatocellular carcinoma. During the last few years, HCV-related end-stage cirrhosis has become the first cause of liver transplantation. In 10 years only, very significant progress has been made in the knowledge of the virus, not only in the field of diagnosis but also in therapy. Several consensus conferences taking last discoveries into account have been organized in order to promote recommendations useful for the management of hepatitis C patients. The aim of this short overview is to summarize practical recommendations that emerged recently from consensus meetings. [less ▲]

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See detailAcute pancreatitis attributed to the use of interferon alfa-2b
Eland, I. A.; Rasch, M. C.; Sturkenboom, M. J. et al

in Gastroenterology (2000), 119(1), 230-233

Two patients experienced episodes of acute pancreatitis shortly after starting treatment with interferon alfa-2b (IFN-alpha) for a chronic hepatitis C infection. The first patient was a 40-year-old man ... [more ▼]

Two patients experienced episodes of acute pancreatitis shortly after starting treatment with interferon alfa-2b (IFN-alpha) for a chronic hepatitis C infection. The first patient was a 40-year-old man who developed acute pancreatitis after 15 weeks of treatment with 3 MU IFN-alpha subcutaneously (SC) 3 times weekly and 1200 mg ribavirin. After disappearance of symptoms and normalization of laboratory values, oral intake of solid foods and IFN-alpha therapy were restarted. Within hours, a relapse of acute pancreatitis occurred. A rechallenge with IFN-alpha 4 days later was followed by a prompt increase in serum lipase level, and IFN-alpha therapy was discontinued. The second patient was a 38-year-old man who developed acute pancreatitis 2 hours after SC administration of 5 MU IFN-alpha. Ultrasound endoscopy showed sludge in the gallbladder. The patient was rechallenged 5 weeks later with 3 MU IFN-alpha SC. Although serum amylase and lipase levels increased after readministration of IFN-alpha, treatment was continued. The patient was readmitted 2 weeks later with severe abdominal pain, and IFN-alpha administration was discontinued. Considering the temporal relationship between the start of IFN-alpha treatment and development of acute pancreatitis, the absence of other clear etiologic factors for acute pancreatitis, disappearance of symptoms after discontinuation of IFN-alpha, and positive reactions to rechallenge, IFN-alpha is the most probable cause for development of acute pancreatitis in these patients. [less ▲]

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See detailReflux gastro-oesophagien et asthme
Lamproye, Anne ULg; Louis, Edouard ULg; Louis, Renaud ULg et al

in Revue Médicale de Liège (1999), 54(10), 805-8

Gastro-oesophageal reflux (GER) is more frequent in asthmatic patients than in the community at large. A causative association between the two diseases is suspected. Twenty-four hour ambulatory ... [more ▼]

Gastro-oesophageal reflux (GER) is more frequent in asthmatic patients than in the community at large. A causative association between the two diseases is suspected. Twenty-four hour ambulatory intraoesophageal pH monitoring represents the golden standard for the diagnosis of GER. The medical and/or surgical treatment of reflux in asthmatic patients with GER can improve pulmonary symptoms and to a lesser extent pulmonary function. The selection of the patients who will benefit from a GER treatment is difficult. Some symptoms like intrinsic asthma, nocturnal crises, could predict a good response to GER treatment. [less ▲]

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See detailAcute Lower Gastrointestinal Bleeding in Crohn's Disease: Characteristics of a Unique Series of 34 Patients. Belgian Ibd Research Group
Belaiche, Jacques ULg; Louis, Edouard ULg; D'Haens, Geert et al

in American Journal of Gastroenterology (1999), 94(8), 2177-81

OBJECTIVE: Acute lower gastrointestinal bleeding is a rare complication of Crohn's disease, which represents a diagnostic and therapeutic challenge. The aim of this study was to define epidemiological ... [more ▼]

OBJECTIVE: Acute lower gastrointestinal bleeding is a rare complication of Crohn's disease, which represents a diagnostic and therapeutic challenge. The aim of this study was to define epidemiological characteristics and therapeutic options of hemorrhagic forms of Crohn's disease. METHODS: Thirty-four cases of hemorrhagic forms of Crohn's disease were studied retrospectively. Acute lower gastrointestinal hemorrhage was defined as acute rectal bleeding originating in diseased bowel and requiring a transfusion of at least 2 units of red blood cells within 24 h. Upper gastrointestinal tract hemorrhage or anal lesions and postoperative bleeding were excluded. RESULTS: Mean age at time of hemorrhage was 34.2 +/- 14 yr. Mean duration of disease before the hemorrhage was 5.6 +/- 6 yr. The hemorrhage occurred during a flare up of the disease in 35% of cases. The hemorrhage revealed Crohn's disease in 23.5% of cases. The hemorrhage was more frequent in colonic disease (85%) than in isolated small bowel disease (15%) (p < 0.0001). The origin of bleeding was identified in 65% of cases, by colonoscopy (60%), by angiography (3 patients), or at surgery (1 patient). The bleeding lesion was an ulcer in 95% of cases, most often in the left colon. The treatment was surgical in 20.5% (colectomy in 36%), endoscopical (7 patients, including 5 successes), or medical. Hemorrhage recurred in 12 patients (35%) within a mean time of 3 yr (4 days-8 yr), requiring surgery in 3 cases. No death was observed. CONCLUSIONS: This study performed in a series characterized by a nonsurgical recruitment, the largest to date, shows that hemorrhagic forms of Crohn's disease may reveal disease in 23.5%, occurs in quiescent Crohn's disease in two-thirds of cases. Given the potential efficacy of endoscopical or medical treatment, as well as the absence of mortality, a conservative approach may be suggested as first-line therapy in the majority of patients. [less ▲]

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See detailTumor Necrosis Factor Alpha Decreases, and Interleukin-10 Increases, the Sensitivity of Human Monocytes to Dexamethasone: Potential Regulation of the Glucocorticoid Receptor
Franchimont, Denis; Martens, Henri ULg; Hagelstein, Marie-Thérèse ULg et al

in Journal of Clinical Endocrinology and Metabolism (1999), 84(8), 2834-9

Resistance to glucocorticoid therapy has been observed in patients with autoimmune/inflammatory diseases and may be related to the inflammatory process itself. The aim of this study was to examine the ... [more ▼]

Resistance to glucocorticoid therapy has been observed in patients with autoimmune/inflammatory diseases and may be related to the inflammatory process itself. The aim of this study was to examine the ability of tumor necrosis factor alpha (TNFalpha, a proinflammatory cytokine) and interleukin (IL)-10 (an anti-inflammatory cytokine) to differentially regulate the sensitivity of human monocytes/macrophages to glucocorticoids. To accomplish this, we first analyzed the pattern of TNFalpha and IL-10 inhibition by dexamethasone in LPS-stimulated whole-blood cell cultures. Second, we studied the modulation of the sensitivity of these cells to dexamethasone by preincubation with TNFalpha or IL-10 and measurement of LPS-stimulated IL-6 secretion. In addition, we evaluated the effect of dexamethasone on phorbolmyristate-acetate-stimulated IL-1 receptor antagonist secretion by the human monocytic cell line U937. Finally, we investigated whether the modulation of corticosensitivity in TNFalpha- and IL-10-pretreated U937 cells was related to a change of the glucocorticoid receptor concentration and affinity. Dexamethasone had different effects on LPS-induced TNFalpha and IL-10 secretion; whereas it suppressed TNFalpha in a dose-dependent fashion, its effect on IL-10 secretion was biphasic, producing stimulation at lower, and inhibition at higher doses. The concentration of LPS employed influenced the effect of dexamethasone on IL-10 secretion (P < 0.001). Pretreatment with TNFalpha diminished, and with IL-10 improved, the ability of dexamethasone to suppress IL-6 secretion in whole-blood cell cultures (P < 0.01 for both) and to enhance IL-1 receptor antagonist secretion by U937 cells (P < 0.05 for both). TNFalpha decreased (P < 0.001), while IL-10 increased (P < 0.001), the concentration of dexamethasone binding sites in these cells, with no discernible effect on their binding affinity. We conclude that glucocorticoids differentially modulate TNFalpha and IL-10 secretion by human monocytes in a LPS dose-dependent fashion and that the sensitivity of these cells to glucocorticoids is altered by TNFalpha or IL-10 pretreatment; TNFalpha blocks their effects, whereas IL-10 acts synergistically with glucocorticoids. This is accompanied by opposite glucocorticoid receptor changes, respectively opposing and favoring glucocorticoid actions. This study suggests that the pattern of pro-/antiinflammatory cytokine secretion may alter the response of patients to glucocorticoid therapy. [less ▲]

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See detailUse of the Enteroscope for Colo-Ileoscopy: Low Yield in Unexplained Lower Gastrointestinal Bleeding
Belaiche, Jacques ULg; Van Kemseke, Catherine ULg; Louis, Edouard ULg

in Endoscopy (1999), 31(4), 298-301

BACKGROUND AND STUDY AIMS: The small intestine is a potential origin of bleeding in patients with unexplained gastrointestinal tract hemorrhage or iron-deficiency anemia. Most reports on the investigation ... [more ▼]

BACKGROUND AND STUDY AIMS: The small intestine is a potential origin of bleeding in patients with unexplained gastrointestinal tract hemorrhage or iron-deficiency anemia. Most reports on the investigation of these patients describe the use of upper tract enteroscopy. The diagnostic yield of combined upper and lower enteroscopy has not been widely assessed and remains to be clarified. The aim of this study was to assess the benefit of lower gastrointestinal tract enteroscopy in occult digestive bleeding. PATIENTS AND METHODS: Between 1 December 1995 and 15 January 1998, 54 patients with gastrointestinal bleeding of unknown origin were prospectively studied using upper and lower video push enteroscopy (44 for chronic iron-deficiency anemia and 10 for unexplained gastrointestinal tract hemorrhage with no potential site having been identified by other investigations). Examinations were done using a Olympus video enteroscope (SIF-100) under general anesthesia in a one-day clinic. An upper tract examination was done first, directly followed by the lower tract investigation. RESULTS: The upper tract enteroscopy was successful in 53 patients (98%) and retrograde ileoscopy in 21 patients (39%). In 18 (38%) cases the technical failure resulted from the impossibility of intubating the ileocecal valve. A potential source of upper gastrointestinal bleeding was detected in 35% of patients with chronic iron-deficiency anemia and in 20% of those with unexplained gastrointestinal tract hemorrhage. The most common lesion in the small bowel was angiodysplasia (25%). The lower tract video push enteroscopy disclosed 11 lesions in patients with chronic anemia. However the lesions, including two ileocecal valve cancers, were mainly located in the colon and had been missed by previous colonoscopy. No case of ileal lesion was detected in this group of patients. In patients with unexplained gastrointestinal tract hemorrhage, three lesions were detected but only one of these was in the ileum. Associated colonic and jejunal lesions were observed in three patients (5.5%). Overall, the diagnostic yield of lower video push enteroscopy was less than 2%. CONCLUSION: This prospective study has shown that using an enteroscope as a colonoscope in the management of patients with gastrointestinal bleeding of unknown origin is of little help. It might actually be more appropriate to perform a second colonoscopy. This however remains controversial and a prospective study is needed to answer that question. [less ▲]

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See detailBronchial Eosinophilic Infiltration in Crohn's Disease in the Absence of Pulmonary Disease
Louis, Edouard ULg; Louis, Renaud ULg; Shute, J. et al

in Clinical & Experimental Allergy : Journal of the British Society for Allergy & Clinical Immunology (1999), 29(5), 660-6

BACKGROUND: Immunological and functional bronchopulmonary abnormalities may be present in up to two-thirds of patients with Crohn's disease. Having recently described a mild increase in methacholine ... [more ▼]

BACKGROUND: Immunological and functional bronchopulmonary abnormalities may be present in up to two-thirds of patients with Crohn's disease. Having recently described a mild increase in methacholine airways responsiveness in these patients, we investigated whether this physiological abnormality is associated with bronchial inflammation since it has previously been described in asthma. METHODS: Eighteen patients with Crohn's disease and 15 healthy controls matched for age, atopy and smoking habit, were studied. All the subjects underwent a bronchial methacholine challenge (1, 4 and 16 mg/mL) and a sputum induction by inhalation of hypertonic saline (NaCl 4.5%). The sputum samples were analysed for their cellular composition as well as for the levels of several mediators and proteins in the fluid phase, including eosinophil cationic protein (ECP), myeloperoxydase, albumin, alpha2-macroglobulin, interleukin-8 (IL-8), IgA and IL-8/immunoglobulin A complexes. RESULTS: When compared to control subjects, patients with Crohn's disease had significantly higher sputum eosinophil counts (14.5% [0-79.9%] vs 0.2% [0-2.3%]; P < 0. 001) and ECP levels (26.2 microg/L [4-124.2 microg/L] vs 9.8 microg/L [0-94.2 microg/L]; P < 0.05). However, patients with Crohn's disease had no sign of increased plasma exudation as reflected by sputum levels of albumin and alpha2-macroglobulin similar to those seen in control subjects. Furthermore the sputum levels of IL-8, IgA and IL-8/IgA complexes were not significantly different between the two groups. The magnitude of the fall in forced expiratory volume in 1 s after methacholine inhalation was significantly increased in Crohn's disease patients although it did not correlate with the extent of sputum eosinophilia or with the sputum ECP levels. CONCLUSIONS: Crohn's disease patients without any clinical respiratory involvement have airway eosinophilia without local increased plasma exudation. However, bronchial eosinophilia in Crohn's disease per se is not sufficient to induce clinically significant airway hyperresponsiveness, suggesting that other factors than bronchial eosinophilic infiltration are required for the clinical expression of an airway instability. [less ▲]

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See detailSurveillance d'une maladie de Crohn en rémission de l'adulte
Belaiche, Jacques ULg; Louis, Edouard ULg

in Hépato-Gastro (1999), 6

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See detailMaladie de Crohn. Récidives post-opératoires. Conduite à tenir.
Belaiche, Jacques ULg; Louis, Edouard ULg

in Acta Endoscopica (1999), 29

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See detailTreatment of Inflammatory Bowel Disease with Azathioprine: How to Use It in 1999
Louis, Edouard ULg; Belaiche, Jacques ULg

in Acta Gastro-Enterologica Belgica (1999), 62(4, Oct-Dec), 437-9

Azathioprine and 6-mercaptopurine are effective drugs in the management of steroid dependent and chronic active inflammatory bowel diseases. They are also well tolerated on the long term. However, their ... [more ▼]

Azathioprine and 6-mercaptopurine are effective drugs in the management of steroid dependent and chronic active inflammatory bowel diseases. They are also well tolerated on the long term. However, their use is still hampered by some drawbacks including delay before efficacy, 20-35% of non responders, relapse at withdrawal of the drugs, possible bone marrow toxicity and other side effects. During the last few years, these drawbacks have been challenged by important studies showing that a better knowledge of the metabolism of these drugs may help to improve their use. [less ▲]

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