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See detailPharma-clinics le medicament du mois. Le rabeprazole (Pariet)
Louis, Edouard ULg

in Revue Médicale de Liège (2002), 57(1), 53-6

Proton pomp inhibitors (PPI) have revolutionized the treatment of gastro-oesophageal reflux disease and gastro-duodenal ulcers. Rabeprazole (Pariet) is the last PPI arrived on the Belgian market ... [more ▼]

Proton pomp inhibitors (PPI) have revolutionized the treatment of gastro-oesophageal reflux disease and gastro-duodenal ulcers. Rabeprazole (Pariet) is the last PPI arrived on the Belgian market. Controlled studies have shown an efficacy similar to emeprazole in the treatment of oeso-gastro-duodenal acid diseases. Rabeprazole has a favourable profile with rapid action and good safety. [less ▲]

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See detailThe role of aminosalicylates in the treatment of ulcerative colitis.
Van Assche, Gert; Baert, Filip; De Reuck, Marc et al

in Acta Gastro-Enterologica Belgica (2002), 65(4), 196-9

Aminosalicylates (5-ASA, sulfasalazine and mesalazine) play a central role in the treatment of ulcerative colitis (UC). For acute treatment of mild to moderate flares and in maintenance treatment, their ... [more ▼]

Aminosalicylates (5-ASA, sulfasalazine and mesalazine) play a central role in the treatment of ulcerative colitis (UC). For acute treatment of mild to moderate flares and in maintenance treatment, their efficacy has been established. Since ulcerative colitis is limited to the distal colon in two thirds of the patients, topical therapy also plays an important role. In mild/moderate active disease 5-ASA 4 g/d is as effective as oral corticosteroids. Ulcerative proctitis is treated with 2 x 500 mg or 1 x 1 g suppositories and proctosigmoiditis with 1 to 4 g enemas. Oral 5-ASA is also safe in maintenance treatment and is generally well tolerated. The risk of colorectal tumours is increased in patients with longstanding ulcerative colitis and epidemiological evidence indicates that chronic 5-ASA treatment reduces this risk. However, at present there is insufficient evidence to maintain patients on life-long 5-ASA maintenance treatment for this indication. [less ▲]

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See detailBudesonide in Collagenous colitis: A Double-Blind Placebo-Controlled Trial With Histologic Follow-Up
Baert, Filip; Schmit, Alain; D'Haens, Geert et al

in Gastroenterology (2002), 122

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See detailPregnancy and inflammatory bowel disease
Louis, Edouard ULg; Belaiche, Jacques ULg

in Acta Gastro-Enterologica Belgica (2002), 65(4, Oct-Dec), 230-232

Overall, around 25% of women with inflammatory bowel disease will conceive during their disease. Most of the women with inflammatory bowel disease will have a normal pregnancy and healthy children ... [more ▼]

Overall, around 25% of women with inflammatory bowel disease will conceive during their disease. Most of the women with inflammatory bowel disease will have a normal pregnancy and healthy children. However, specific problems may arise related to these pregnancies. This paper reviews what is known on fertility, risk of disease transmission, effect of the disease on the pregnancy and the reverse, delivery, medical follow up and treatment as well as breastfeeding in the setting of inflammatory bowel disease. [less ▲]

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See detailObservational survey of NSAID-related upper gastro-intestinal adverse events in Belgium
Belaiche, Jacques ULg; Burette, A.; De Vos, M. et al

in Acta Gastro-Enterologica Belgica (2002), 65(2, Apr-Jun), 65-73

Objectives : To evaluate the impact of NSAID use on current routine upper GI endoscopy (UGIE) and to compare the lesions found in NSAID users and non-users. Methods : Participating gastroenterologists ... [more ▼]

Objectives : To evaluate the impact of NSAID use on current routine upper GI endoscopy (UGIE) and to compare the lesions found in NSAID users and non-users. Methods : Participating gastroenterologists; consecutively documented outpatients with and without suspicion of bleeding, referred for upper gastrointestinal endoscopy. Patient characteristics, presence of risk factors, NSAID use and endoscopic findings were reported on standard data collection forms. Main results : A total of 2685 non-bleeding and 159 bleeding patients were enrolled within a time period of 2 months. NSAID therapy was present in 20% of the non-bleeding patients and at least 9% of referrals for endoscopy were directly related to suspected NSAID adverse events. Nearly half of acute bleeding patients (42%) were NSAID users, including aspirin for cardioprevention. Warning digestive symptoms prior to acute bleeding were frequently absent (56%). Oesophagitis was the main endoscopic diagnosis (51% of patients). Gastroduodenal (GD) ulcer was significantly more frequent in NSAID users, whereas oesophagitis and bleeding oesophageal varices were more frequent among non-users. Analysis of odds ratio's demonstrated NSAID use to significantly increase the risk for gastric ulcer in the whole patient group (OR = 2.73; 95% confidence interval (CI) : 1.983.77; p < 0.001) and, in addition, for duodenal ulcer in the elderly (>65y) subgroup (OR = 2.91; 95 % CI : 1.52-5.59; p < 0.05). Conclusions : This survey confirms the high incidence of GD ulcers in NSAID users and the risk for serious gastrointestinal complications, often occurring without warning symptoms. It underlines the impact of NSAID use on the routine endoscopy load, the necessity of careful selection of patients for NSAID prescriptions and the need for gastropreventive measures, particularly in elderly patients and patients associating multiple risk factors. [less ▲]

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See detailBehaviour of Crohn's Disease According to the Vienna Classification: Changing Pattern over the Course of the Disease
Louis, Edouard ULg; Mathieu, Anne ULg; Oger, A. F. et al

in Gut (2001), 49(6), 777-82

BACKGROUND: Crohn's disease is a heterogeneous disorder with both a genetic and environmental aetiology. Clinical classifications of the disease, such as the newly proposed Vienna classification, may help ... [more ▼]

BACKGROUND: Crohn's disease is a heterogeneous disorder with both a genetic and environmental aetiology. Clinical classifications of the disease, such as the newly proposed Vienna classification, may help to define subgroups of patients suitable for studying the influence of specific genetic or environmental factors. AIM: To assess the stability over the course of the disease of its location and behaviour, as determined according to the Vienna classification. PATIENTS AND METHODS: The notes of 297 Crohn's disease patients regularly followed up at our institution were carefully reviewed retrospectively. The behaviour and location of the disease according to the Vienna classification were determined at diagnosis and after 1, 3, 5, 10, 15, 20, and 25 years of follow up. The proportions of the different behaviours and locations of the disease were calculated at these time points. A statistical analysis of the evolution of these characteristics over 10 years was performed on a subgroup of 125 patients with at least 10 years of follow up. The influence of age at diagnosis on location and behaviour of the disease was assessed as well as the influence of location on the behaviour of the disease. RESULTS: The location of the disease remained relatively stable over the course of the disease. Although the proportion of patients who had a change in disease location became statistically significant after five years (p=0.01), over 10 years only 15.9% of patients had a change in location (p<0.001). We observed a more rapid and prominent change in disease behaviour, which was already statistically significant after one year (p=0.04). Over 10 years, 45.9% of patients had a change in disease behaviour (p<0.0001). The most prominent change was from non-stricturing non-penetrating disease to either stricturing (27.1%; p<0.0001) or penetrating (29.4%; p<0.0001) disease. Age at diagnosis had no influence on either location or behaviour of disease. Ileal Crohn's disease was more often stricturing, and colonic or ileocolonic Crohn's disease was more often penetrating: this was already the case at diagnosis and became more prominent after 10 years (p<0.05). CONCLUSIONS: Location of Crohn's disease, as defined by the Vienna classification, is a relatively stable phenotype which seems suitable for phenotype-genotype analyses. Behaviour of Crohn's disease according to the Vienna classification varies dramatically over the course of the disease and cannot be used in phenotype-genotype analyses. The potential influence of genes on the behaviour of Crohn's disease should be studied in subgroups of patients defined by their disease behaviour after a fixed duration of disease. [less ▲]

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See detailIncreased Response of Blood Eosinophils to Various Chemotactic Agents in Quiescent Crohn Disease
Denis, M. A.; Louis, Renaud ULg; Malaise, Michel ULg et al

in Scandinavian Journal of Gastroenterology (2001), 36(2), 190-5

BACKGROUND: The number of eosinophils is increased in the mucosae of the digestive and the respiratory tracts in Crohn disease, even clinically quiescent. The mechanisms underlying this panmucosal ... [more ▼]

BACKGROUND: The number of eosinophils is increased in the mucosae of the digestive and the respiratory tracts in Crohn disease, even clinically quiescent. The mechanisms underlying this panmucosal eosinophilia are unknown. METHODS: The response of blood eosinophils to various chemotactic agents was assessed in 15 patients with clinically quiescent Crohn disease. The results were compared with 15 healthy controls. After purification, eosinophils were placed in Boyden microchambers and the chemotactic effect of PAF (10(-7) M), RANTES (50 ng/ml), IL-5 (0-20 ng/ml), IL-8 (0-50 ng/ml), Eotaxin (0-50 ng/ml) was evaluated. The number of eosinophils in induced sputum of these Crohn disease patients and controls was also assessed and the correlation between chemotaxis and eosinophil count in induced sputum was studied. RESULTS: PAF and RANTES induced a chemotactic effect both in Crohn disease patients and controls. The chemotactic index was significantly higher in Crohn than controls for PAF (2.09+/-0.24 versus 1.37+/-0.14; P < 0.05) but not RANTES. With IL-5, IL-8 and Eotaxin, there was no detectable chemotactic effect in controls while in Crohn, we observed a significant dose-dependent chemotactic effect. Furthermore, with Eotaxin 50 ng/ml, the chemotactic index was significantly higher in Crohn disease patients than controls (2.42+/-0.18 versus 1.56+/-0.28; P < 0.05). A significant increase in sputum eosinophil count and a significant decrease in sputum macrophage count in Crohn disease were observed. However, there was no correlation between eosinophil chemotaxis and sputum eosinophil count in individual patients. CONCLUSION: There is an increased response of blood eosinophils to various chemotactic agents, mainly PAF and Eotaxin, in clinically quiescent Crohn disease. This may participate in the mucosal infiltration by eosinophils in this disease. [less ▲]

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See detailTherapeutic Drug Monitoring of Azathioprine and 6-Mercaptopurine Metabolites in Crohn Disease
Belaiche, Jacques ULg; Desager, J. P.; Horsmans, Y. et al

in Scandinavian Journal of Gastroenterology (2001), 36(1), 71-6

BACKGROUND: 6-Mercaptopurine (6-MP) and its prodrug azathioprine (AZA) have proven efficacy in the treatment of Crohn disease (CD). The immunosuppressive properties of AZA/6-MP are mediated by the ... [more ▼]

BACKGROUND: 6-Mercaptopurine (6-MP) and its prodrug azathioprine (AZA) have proven efficacy in the treatment of Crohn disease (CD). The immunosuppressive properties of AZA/6-MP are mediated by the intracellular metabolism of 6-MP into its active metabolites, 6-thioguanine nucleotides (6TGN) and 6methylmercaptopurine (6-MMP). Preliminary studies have suggested that the red blood cell concentration of 6TGN (RBC 6TGN) is a potential guide to therapy. The aims of the study were to evaluate the RBC 6TGN concentrations in adult patients with CD under long-term AZA/6-MP therapy and to correlate it with response to treatment and haematological parameters. METHODS: Twenty-eight CD patients treated for at least 3 months with AZA/6-MP were prospectively studied. Patients were separated into three main groups: group 1 (n = 19), corresponding to quiescent CD receiving AZA (dose: 2.05 +/- 0.4 mg/kg/day for a mean of 28.6 +/- 25 months) or 6-MP (dose: 1.4 +/- 01 mg/kg/day for a mean of 7.5 +/- 3.5 months) alone; group 2 (n = 6), corresponding to quiescent CD treated by AZA (dose: 2.14 +/- 0.5 mg/kg/day for a mean of 29.5 +/- 22 months) with oral steroids; and group 3 (n = 3), corresponding to active CD on AZA (dose: 1.94 +/- 0.6 mg/kg/day for a mean of 31.3 +/- 35 months) as the only treatment. An assessment was also made by merging groups 1 and 2 forming a larger group of patients (n = 25) defined by clinical remission and groups 2 and 3 forming a larger group of patients (n = 9), non-complete responders with AZA/6-MP alone. Crohn disease index activity (CDAI), blood samples for full blood count and differential white cell count and measurement of RBC 6TGN and 6-MMP concentrations were evaluated at inclusion and at 6 months (n = 17). RBC 6TGN were measured using high performance liquid chromatography (HPLC) on heparinized blood. RESULTS: The baseline characteristics of the three groups of patients were similar. There was no significant difference among the three groups of patients regarding the dose and the duration of immunosuppressive treatment. There was no significant difference between groups according to various parameters tested. Particularly, the median RBC 6TGN concentration at inclusion was similar in the three groups of patients (166 (105-688), 183 (90-261) and 160 (52-194) pmol/8 x 10(8) RBC, respectively). The majority of patients had no detectable level of 6-MMP metabolite, except for 3 patients. There was also no difference between merging groups. Furthermore, there was no significant correlation between RBC 6TGN concentrations and the various biological parameters tested except for the mean erythrocyte volume. At 6 months, all patients of group 1 remained in remission and median RBC 6TGN concentration remained stable. No side effects were observed. CONCLUSIONS: There is, contrary to preliminary studies, a broad overlap in RBC 6TGN levels as well as for haematological parameters in patients in remission or not and responders or not to AZA/6-MP therapy. This suggests, beside a variability in the metabolism of these drugs, the existence of complex mechanisms of action. Nevertheless, beside the use of RBC 6TGN determination to confirm compliance to therapy, this dosage could be useful in non-responding patients, allowing, in absence of leukopenia, to increase the dose of AZA/6-MP safely. [less ▲]

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See detailIleo-caecal actinomycosis: Report of a case simulating complicated inflammatory bowel disease
Postal, Alain; Detry, Olivier ULg; Louis, Edouard ULg et al

in Acta Gastro-Enterologica Belgica (2001), 64(4, Oct-Dec), 318-320

Abdominal actinomycosis is a rare infectious disease caused by Actinomyces israelii, a gram-positive anaerobic saprophyte germ that is a normal inhabitant of the upper intestinal tract in humans ... [more ▼]

Abdominal actinomycosis is a rare infectious disease caused by Actinomyces israelii, a gram-positive anaerobic saprophyte germ that is a normal inhabitant of the upper intestinal tract in humans. Actinomyces israelii rarely cause abdominal infections or actinomycosis. Abdominal actinomysosis is characterised by fistulae and abscesses and may mimic cancer or inflammatory bowel disease. Abdominal actinomycosis is difficult to diagnose preoperatively, and often require surgical removal of the diseased tissue, allowing pathologists for giving the definitive diagnosis, revealed by characteristic "sulfur granules". The authors report herein the case of a 47-year-old man who presented with diarrhoea and abdominal pain. Abdominal computed tomography evoked complicated inflammatory bowel disease and surgical procedure was decided. Laparoscopic exploration did not provide further significant information, and laparotomy with diseased bowel resection was performed. Pathology demonstrated "sulfur granules" and allowed the diagnosis of abdominal actinomycosis. This case demonstrated that abdominal actinomycosis should be included in the differential diagnosis when computed tomography shows an infiltrative and inflammatory mass. [less ▲]

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See detailThe Immuno-Inflammatory Reaction in Crohn's Disease and Ulcerative Colitis: Characterisation, Genetics and Clinical Application. Focus on Tnf Alpha
Louis, Edouard ULg

in Acta Gastro-Enterologica Belgica (2001), 64(1), 1-5

Inflammatory bowel diseases are multifactorial polygenic diseases. The author has worked on the characterisation of the mucosal immuno-inflammatory reaction, on genetic predisposition and on potential ... [more ▼]

Inflammatory bowel diseases are multifactorial polygenic diseases. The author has worked on the characterisation of the mucosal immuno-inflammatory reaction, on genetic predisposition and on potential clinical application of blood immuno-inflammatory markers in these diseases. This paper summarizes some aspects of this work, focusing on TNF. Following points are developed: production of TNF by inflamed mucosa, genetic control of TNF production, TNF gene polymorphim in inflammatory bowel disease, and evaluation of serum TNF as a marker of disease activity or evolutivity. [less ▲]

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See detailCytokine Production from Peripheral Whole Blood in Atopic and Nonatopic Asthmatics: Relationship with Blood and Sputum Eosinophilia and Serum Ige Levels
Bettiol, J.; Bartsch, Pierre ULg; Louis, Renaud ULg et al

in Allergy (2000), 55(12), 1134-41

BACKGROUND: The cytokine network is thought to be essential in orchestrating airway inflammation in asthma. Although evidence has accumulated to suggest that atopic asthma is a Th2 disease, much less is ... [more ▼]

BACKGROUND: The cytokine network is thought to be essential in orchestrating airway inflammation in asthma. Although evidence has accumulated to suggest that atopic asthma is a Th2 disease, much less is known about nonatopic asthma. METHODS: We have compared the production of IL-4, IL-6, IFN-gamma, and TNF-alpha from peripheral blood leukocytes between atopic (n=21) and nonatopic (n=22) asthmatics and healthy nonatopic subjects (n=20). Peripheral blood was incubated for 24 h either without stimulus or with LPS or PHA. Cytokines were measured by the immunotrapping technique (Dynamic Immunoassay). RESULTS: When compared to healthy nonatopic subjects, both atopic and nonatopic asthmatics showed increased blood and sputum eosinophilia associated with raised total serum IgE levels. Similarly, both asthma groups displayed spontaneous, endotoxin-induced overproduction of IL-6. Enhanced spontaneous, endotoxin-induced release of IL-4 combined with reduced spontaneous IFN-gamma production was seen only in atopic asthma. In this group of patients, the production of IL-4 was related to the extent of blood and sputum eosinophilia. In nonatopic asthmatics, serum levels of IgE were inversely related to the production of IFN-gamma. CONCLUSIONS: Both atopic and intrinsic asthma display raised blood and airway eosinophilia, raised total serum IgE, and overproduction of IL-6 from peripheral blood. Atopic asthma is also characterized by impaired spontaneous release of IFN-gamma and increased production of IL-4 that correlates with the magnitude of eosinophilic inflammation. [less ▲]

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See detailLack of Association between Adult Asthma and the Tumour Necrosis Factor Alpha-308 Polymorphism Gene
Louis, Renaud ULg; Leyder, E.; Malaise, Michel ULg et al

in European Respiratory Journal (2000), 16(4), 604-8

Tumour necrosis factor (TNF)alpha is a cytokine endowed with potent inflammatory properties that may contribute to airway inflammation in asthma. It has previously been shown that the single base pair ... [more ▼]

Tumour necrosis factor (TNF)alpha is a cytokine endowed with potent inflammatory properties that may contribute to airway inflammation in asthma. It has previously been shown that the single base pair polymorphism-308 (G to A substitution) in the promoter of TNFalpha gene results in enhanced cytokine secretion. Whether this polymorphism is associated with the presence of phenotypic expression of asthma is questioned. In this study the relative frequency of TNF1 and TNF2 alleles in a population of adult healthy subjects (n=98) and adult Caucasian asthmatics (n=95) was compared taking into account their disease severity, atopic status and their smoking habit. For the whole group of asthma the genotype frequency for 1/1, 1/2, 2/2 were 67%, 33% and 0%, respectively, and not significantly different from those found in the control group that reached 70%, 28% and 2% respectively (p>0.05). The allele frequencies in asthma were 86% and 14% for TNF1 and TNF2 respectively while the corresponding figures were 85% and 15% in the control group (p>0.05). Furthermore, subdividing asthmatics into severe forced expiratory volume in one second <60% pred), atopic or smoking patients did not show any significant association with this TNFalpha polymorphism. To conclude the polymorphism -308 in the promoter of the TNFalpha gene does not confer a susceptibility to develop asthma nor to grade its severity. [less ▲]

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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 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 detailThe medical management of severe acute and chronic ulcerative colitis--current recommendations from the Belgian Working Group.
Melange, M.; D'Haens, G.; Devos, Martine ULg et al

in Acta Gastro-Enterologica Belgica (2000), 63(3), 273-4

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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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