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Biomedical subjects

F Baert

Publications and source records attributed to F Baert.

At least 19 recordsLinked to original sources

Once daily MMX mesalazine for the treatment of mild-to-moderate ulcerative colitis: a phase II, dose-ranging study.

BACKGROUND: SPD476 (MMX mesalazine), is a novel, once daily, high-strength mesalazine formulation (1.2 g/tablet) that utilizes Multi Matrix System (MMX) technology to delay and extend delivery of the active drug throughout the colon. AIM: To assess the safety and efficacy of MMX mesalazine in patients with mild-to-moderately active ulcerative colitis, in a pilot, phase II, randomized, multicentre, double-blind, parallel-group, dose-ranging study (SPD476-202). METHODS: Thirty-eight patients with mild-to-moderately active ulcerative colitis were randomized to MMX mesalazine 1.2, 2.4 or 4.8 g/day given once daily for 8 weeks. Remission ulcerative colitis-disease activity index (UC-DAI) < or =1, a score of 0 for rectal bleeding and stool frequency, and > or =1 -point reduction in sigmoidoscopy score from baseline was the primary end point. RESULTS: Week 8 remission rates were 0%, 31% and 18% of patients receiving MMX mesalazine 1.2, 2.4 and 4.8 g/day respectively. No statistically significant difference in remission was observed between treatment groups. MMX mesalazine 2.4 and 4.8 g/day groups demonstrated greater improvement in overall UC-DAI and component scores from baseline, compared with the 1.2 g/day group. CONCLUSION: MMX mesalazine given as 2.4 or 4.8 g/day once daily is well tolerated and effective for the treatment of mild-to-moderately active ulcerative colitis.

Adolescent↗

Intracellular acidification delays hormonal G2/M transition and inhibits G2/M transition triggered by thiophosphorylated MAPK in Xenopus oocytes.

Xenopus oocyte maturation is analogous to G2/M transition and characterized by germinal vesicle breakdown (GVBD), spindle formation, activation of MPF and Mos-Xp42(Mpk1) pathways. It is accompanied prior to GVBD by a transient increase in intracellular pH. We determined that a well known acidifying compound, NH(4)Cl, delayed progesterone-induced GVBD in a dose-dependent manner. GVBD(50) was delayed up to 2.3-fold by 10 mM NH(4)Cl. Cyclin B2 phosphorylation, Cdk1 Tyr15 dephosphorylation as well as p39(Mos) accumulation, Xp42(Mpk1) and p90(Rsk) phosphorylation induced by progesterone were also delayed by incubation of oocyte in NH(4)Cl. The delay induced by NH(4)Cl was prevented by injection of MOPS buffer pH 7.7. In contrast to acidifying medium, alkalyzing treatment such as Tris buffer pH 9 injections, accelerated GVBD, MPF and Xp42(Mpk1) activation, indicating that pHi changes control early steps of G2/M dynamics. When injected in an immature recipient oocyte, egg cytoplasm triggers GVBD through MPF auto-amplification, independently of protein synthesis. In these conditions, GVBD and Xp42(Mpk1) activation were delayed by high concentration of NH(4)Cl, which never prevented or delayed MPF activation. Strickingly, NH(4)Cl strongly inhibited thiophosphorylated active MAPK-induced GVBD and MPF activation. Nevertheless, Tris pH 9 did not have any effects on egg cytoplasm- or active MAPK-induced GVBD. Taken together, our results suggest that dynamic of early events driving Xp42(Mpk1) and MPF activation induced by progesterone may be negatively or positively regulated by pH(i) changes. However Xp42(Mpk1) pathway was inhibited by acidification alone. Finally, MPF auto-amplification loop was not sensitive to pH(i) changes.

Acid-Base Equilibrium↗

European evidence based consensus on the diagnosis and management of Crohn's disease: special situations.

This third section of the European Crohn's and Colitis Organisation (ECCO) Consensus on the management of Crohn's disease concerns postoperative recurrence, fistulating disease, paediatrics, pregnancy, psychosomatics, extraintestinal manifestations, and alternative therapy. The first section on definitions and diagnosis reports on the aims and methods of the consensus, as well as sections on diagnosis, pathology, and classification of Crohn's disease. The second section on current management addresses treatment of active disease, maintenance of medically induced remission, and surgery of Crohn's disease.

Anti-Bacterial Agents↗

CT colonography with fecal tagging after incomplete colonoscopy.

The objective of this study was to evaluate dietary fecal tagging (FT) as a cleansing method prior to CT colonography (CTC) in patients with incomplete conventional colonoscopy (CC). After written informed consent was obtained, 24 patients had standard colonoscopic preparation (ScCl), and 25 patients had FT as cleansing method. Segmental distention, fluid levels, fecal residues, tagged appearance of fluid levels, and residual stool were evaluated. Mann-Whitney U test was used to test for significant differences between FT and ScCl groups. Compared with ScCl, FT improved distention (p=0.001), reduced the amount of fluid (p=0.043), but suffered from residual stool (p=0.046). A clear correlation was found between distention and fluid. No differences were found in stool size between FT and ScCl. FT showed a good labeling of fecal residues, and acceptable labeling of fluid levels. Compared with ScCl, FT reduces fluid, favors distention, but suffers from fecal residues. The tagged nature of these residues, however, allows differentiation from polyps.

Adult↗

[Choking phobia in childhood: a differential diagnosis with anorexia nervosa].

INTRODUCTION: Choking phobia has been rarely described in the literature and its prevalence has not yet been determined. Because of its clinical picture (female predominance, avoidance or refusal of certain foodstuffs, secondary weight loss, associated obsessive-compulsive symptoms), it is often misdiagnosed as anorexia nervosa. CASE REPORT: The authors describe the case of an 11-year-old girl, hospitalised for anorexia, who actually had choking phobia. Following a long history of anxiety disorders (including separation anxiety, social phobia, obsessive-compulsive disorder), the choking phobia had been triggered by a traumatic choking episode occurred in her grandfather. The disorder was successfully treated by cognitive-behavioural techniques associated with an antidepressant therapy. CONCLUSION: This typical case questions the relationships between choking phobia and the other anxiety disorders of childhood and adolescence. According to data from the literature, the authors conclude that choking phobia may be regarded as a non developmental specific phobia, whose occurrence is facilitated by the presence of pre-existing anxiety disorders. The disorder is usually improved by cognitive-behavioural treatment.

Airway Obstruction↗

Crohn's disease and intestinal endometriosis: an intriguing co-existence.

OBJECTIVES: We present a series of eight female patients who came to surgery for complicated Crohn's disease of the terminal ileum (n = 7) or colon (n = 1). Indications for surgery were medically intractable disease in three, steroid dependence in four and ileal perforation in one. RESULTS: Histological examination using routine haematoxylin-eosin stained sections revealed the presence of intestinal endometriosis of the ileum (n = 6), colon (n = 1) or ileum and rectum (n = 1) in addition to the typical features of Crohn's disease. In particular, chronic transmural inflammation was observed in locations other than the endometriotic deposits, which were confined to the serosa in three, the muscularis propria in two, both the serosa and the muscularis propria in one and the serosa, muscularis propria and submucosa in two. In none of these patients had the diagnosis of intestinal endometriosis been suspected pre-operatively based on clinical (gynaecological) or radiological tests. CONCLUSION: Intestinal endometriosis and Crohn's disease can occur simultaneously. The diagnosis is often only made after surgical resection of the diseased segment. In Crohn's disease, endometriosis of the terminal ileum seems more common.

Adolescent↗

Endoscopic and histological healing with infliximab anti-tumor necrosis factor antibodies in Crohn's disease: A European multicenter trial.

BACKGROUND & AIMS: Tumor necrosis factor (TNF) is a pivotal cytokine in intestinal inflammation. Controlled trials using a chimeric anti-TNF antibody (infliximab) have shown its efficacy in refractory Crohn's disease. METHODS: Endoscopic and histological response to infliximab was investigated in a multicenter, randomized, double-blind, and placebo-controlled trial including 30 patients with active Crohn's disease undergoing ileocolonoscopy before and 4 weeks after intravenous administration of 5, 10, or 20 mg/kg of infliximab or placebo as a single infusion. Lesions were scored by means of the validated Crohn's Disease Endoscopic Index of Severity (CDEIS). Endoscopic biopsy specimens were taken during both procedures from 9 of 30 patients and scored by a single gastrointestinal pathologist. RESULTS: CDEIS scores decreased significantly in most infliximab-treated patients without an apparent dose response. No endoscopic improvement was observed in the placebo group. The changes in CDEIS correlated highly with those of the Crohn's Disease Activity Index. At a histological level, disappearance of the inflammatory infiltrate was observed in infliximab-treated patients but not in placebo-treated ones; however, architectural changes persisted in most patients. Strictures developed in several patients. CONCLUSIONS: Clinical improvement after infliximab therapy in active Crohn's disease is accompanied by significant healing of endoscopic lesions and disappearance of the mucosal inflammatory infiltrate.

Adult↗

New strategies in the management of inflammatory bowel disease.

The incidence and prevalence of IBD increase in our Western populations. Standard therapy with glucocorticosteroids and 5-ASA formulations allow control in only about half of the patients with substantial toxicity for the former drug. Since it became apparent that both UC and Crohn's disease are disorders mediated through abnormalities in the mucosal immune system immunosuppression and immunomodulation have become current practice in the treatment of refractory IBD. In UC cyclosporin is the main immunosuppressive agent. In Crohn's disease azathioprine is the mainstay of therapy for refractory disease. Recently anti-TNF strategies have been developed which hold great promise for the treatment of Crohn's disease.

Adjuvants, Immunologic↗

Methotrexate in refractory Crohn's disease.

BACKGROUND: Recent trials suggested that methotrexate may be effective in refractory Crohn's disease (CD). We analyzed the data of 20 patients treated with methotrexate because of corticodependent or refractory CD. METHODS: Between January 1995 and June 1997, 20 azathioprine-resistant or -intolerant patients with active CD requiring continuous glucocorticosteroid treatment were treated with parenteral methotrexate. Clinical response was assessed by the Harvey-Bradshaw clinical activity index. Concomitant steroid use and steroid withdrawal rates were recorded. Patients were assessed at 12 weeks, 6 months, 9 months, and 12 months after the start of methotrexate therapy. RESULTS: At 12 weeks, a clinical response was obtained in 14/20 patients (70%). These response rates decreased to 10/20 patients at 6 months, 8/17 patients at 9 months, and 4/14 evaluable patients at 12 months. In initial responders (n = 14), maintenance of remission was observed in 9/14, 6/11, and 3/9 patients at 6, 9, and 12 months, respectively. Methotrexate allowed corticosteroid tapering in 85% of patients and discontinuation in 60% of patients at 6 months. Side effects were rather frequent but usually mild and prompted discontinuation in two patients. CONCLUSIONS: In this retrospective study, parenteral methotrexate appeared to be effective in inducing a clinical response in 70% of azathioprine-resistant or -intolerant CD patients and often permitted corticosteroid tapering, with an acceptable short-term toxicity. The potential of methotrexate to maintain long-term remission in refractory patients, however, appears less convincing.

Adolescent↗

Acute lower gastrointestinal bleeding in Crohn's disease: characteristics of a unique series of 34 patients. Belgian IBD Research Group.

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.

Acute Disease↗

Lymphocytic colitis: a distinct clinical entity? A clinicopathological confrontation of lymphocytic and collagenous colitis.

BACKGROUND AND AIMS: It is not known whether lymphocytic colitis and collagenous colitis represent different clinical entities or constitute part of a spectrum of disease. METHODS: Detailed clinical features and histological findings were compared in a large series of patients with confirmed lymphocytic and collagenous colitis. RESULTS: Histological diagnosis was confirmed in 96 patients with collagenous colitis and 80 with lymphocytic colitis. Twenty eight per cent of patients with collagenous colitis and 26% of patients with lymphocytic colitis had overlapping but less pronounced histological features. Both groups were equal in terms of age, use of aspirin and non-steroidal anti-inflammatory drugs, associated autoimmune conditions, arthritis, diarrhoea, and abdominal pain. The male:female ratio was 27:73 for collagenous colitis and 45:55 for lymphocytic colitis (p=0.013). Twenty five per cent of patients with collagenous colitis compared with 14% of patients with lymphocytic colitis were active smokers; only 8.3% of patients with collagenous colitis had stopped smoking compared with 23% of patients with lymphocytic colitis (p=0.013). Drug induced disease was suspected for ticlopidine (two collagenous colitis, four lymphocytic colitis) and flutamide (four lymphocytic colitis). Mean duration of symptoms before diagnosis was two months for lymphocytic colitis and four months for collagenous colitis. Overall prognosis was generally mild; 84% of patients with lymphocytic colitis and 74% of patients with collagenous colitis reported resolution or significant improvement (p=0.033). CONCLUSIONS: Collagenous and lymphocytic colitis are similar but not identical. Patients with lymphocytic colitis present somewhat earlier and are less likely to be active smokers. Symptoms are milder and more likely to disappear in lymphocytic colitis. Ticlopidine and flutamide should be added to the list of drugs inducing colitis.

Adult↗

Early lesions of recurrent Crohn's disease caused by infusion of intestinal contents in excluded ileum.

BACKGROUND & AIMS: Postoperative recurrence of Crohn's disease may be triggered by agents in the fecal stream. The aim of this study was to examine intestinal mucosal inflammation induced by contact with intestinal fluids in surgically excluded ileum. METHODS: The effects of infusion of intestinal luminal contents into excluded ileum in 3 patients with Crohn's disease who had undergone a curative ileocolonic resection with ileocolonic anastomosis and temporary protective proximal loop ileostomy were studied by histopathology and electron microscopy. RESULTS: Contact with intestinal fluids for 8 days induced focal infiltration of mononuclear cells, eosinophils, and polymorphonuclear cells in the lamina propria, small vessels, and epithelium in the excluded neoterminal ileum that was previously normal. Epithelial HLA-DR expression increased, and mononuclear cells expressed the KP-1 antigen associated with activation. Marked up-regulation of RFD-7, RFD-9, intercellular adhesion molecule 1, and lymphocyte function-associated antigen 1 was observed after infusion, reflecting epithelioid transformation and transendothelial lymphocyte recruitment. At the ultrastructural level, dilatation of the endoplasmic reticulum and Golgi apparatus occurred in epithelial cells, where also basally located transport vesicles were identified. CONCLUSIONS: Intestinal contents trigger postoperative recurrence of Crohn's disease in the terminal ileum proximal to the ileocolonic anastomosis in the first days after surgery.

Adult↗

Clustering of increased small intestinal permeability in families with Crohn's disease.

BACKGROUND & AIMS: Small intestinal permeability is increased in a proportion of patients with Crohn's disease (CD) and a subset of their healthy relatives. A primary permeability defect was postulated in the pathogenesis of the disease. The aim of this study was to identify a possible genetic pattern in the distribution of CD and/or abnormal permeability. METHODS: Differential urinary excretion of lactulose and mannitol (L/ M) in complete CD families was determined. Controls included healthy families and families with ulcerative colitis. Pedigrees were used to compare the distribution of CD and/or increased permeability. RESULTS: The L/M was significantly increased in patients with CD. Seventeen of 67 first-degree relatives (25%) had a ratio greater than the upper limit (P95 = 0.0170). Permeability results of CD families showed a highly significant familial aggregation. The lack of a genetic pattern in relation with CD and occurrence of disturbed permeability especially within generation, points toward a shared environmental factor. Five of 14 healthy spouses (36%) of patients with CD had also an increased permeability, and prevalence of increased permeability was not higher in families with known familial occurrence (P = 0.85). CONCLUSIONS: This large family study confirms an increased permeability in a subset of healthy relatives of patients with CD. However, the absence of a typical family pattern and the high prevalence in spouses is in favor of a common nongenetic factor or a subclinical disease manifestation.

Adolescent↗

Immunomodulator therapy of inflammatory bowel disease.

While 5-ASA and corticosteroids are still the mainstay of treatment, more potent immunosuppressive agents should be considered in refractory and steroid dependant patients not amenable to surgery. The activity and side effect profile of 6-MP/azathioprine, methotrexate and cyclosporine are now well established. Other agents such as mycophenolaat-mophetil, FK 506 and combination therapies may provide additional benefits in the future. Advances in the field of mucosal immunology have prompted interest in more specific immunologic approaches. Recombinant genetic engineering techniques enable us to test cytokines, anti cytokines, anti adhesion molecules etc. some of which with very promising clinical results. More data on long term safety and specific indications should be awaited before broader use of these agents can be advocated. An updated review is given from the current immunological based treatment modalities for both Crohn's disease and ulcerative colitis.

Antimetabolites, Antineoplastic↗

Patchy cecal inflammation associated with distal ulcerative colitis: a prospective endoscopic study.

OBJECTIVES: It is generally believed that the mucosal inflammation in ulcerative colitis is characterized by a diffuse, continuous involvement starting from the rectum without "skip areas." It was the aim of this study to examine 20 patients with established "left-sided ulcerative colitis" prospectively by ileocolonoscopy with biopsies to determine the extent and the continuity of the mucosal inflammation and the incidence of skip lesions in ulcerative colitis. METHODS: Twenty patients with left-sided ulcerative colitis underwent a complete ileocolonoscopy with biopsies of the terminal ileum and all colonic segments. The patients remained in clinical follow-up for at least 8 yr after the initial examination. RESULTS: The upper margin of inflammation was sharply demarcated in 6 patients and gradual in 14. Segmental inflammation, separated from the distal inflamed segment by apparently uninvolved mucosa, was found in 15 patients (75%) and always included the area around the appendiceal orifice. The correlation between endoscopic abnormalities and histological changes was excellent. CONCLUSION: In so-called "left-sided" ulcerative colitis distal involvement may be accompanied by more proximal areas of inflammation, particularly in the periappendiceal area of the cecum.

Adolescent↗