Biomedical subjects

Karel Geboes

Publications and source records attributed to Karel Geboes.

57 records · Page 4Linked to original sources

PubMed2002

Metastatic Crohn's disease of the forehead.

BACKGROUND: Metastatic Crohn's disease (CD) involves the presence of cutaneous granuloma distant from the intestinal lesions related to the disease, usually observed in colonic CD. CASE HISTORY: A 35-year-old female with a permanent ileostomy following proctocolectomy for CD presented in 1999 with a 2-month history of an unusual skin lesion of the forehead. A diagnosis of CD of the ileum, colon, and rectum had been made in 1994. In 1997, a proctocolectomy with ileostomy was performed due to fistulizing severe refractory disease. Microscopic aspects of the intestinal lesions showed deep and fissuring ulcers. After surgery, she went into remission, and a small bowel follow-up in 1999 showed no recurrence, when she presented with the skin lesion of the forehead. MICROSCOPIC DATA: Histological analysis of endoscopical and surgical intestinal specimens showed chronic granulomatous inflammation of the ileum, colon, and rectum, confirming the diagnosis of CD. The forehead skin biopsy was examined by three independent histopathologists. The lesion was composed of numerous small granulomas (Ziehl-Nielsen negative), with no foreign bodies, mainly composed of CD68-positive and periodic acid Schiff-negative monocytes. Despite the low number of lymphocytes, the macroscopical and microscopical aspect of the forehead lesion, together with the clinical history, led to a diagnosis of rare metastatic CD of the forehead. CONCLUSIONS: This case report describes the development of an unusual granulomatous skin lesion of the forehead in a patient with established CD showing no postoperative recurrence.

Adult↗

PubMed2002

Anti-tumor necrosis factor treatment restores the gut barrier in Crohn's disease.

OBJECTIVES: A primary defect of the tight junctions and, hence, increased intestinal epithelial permeability has been proposed as a basic pathogenic event in Crohn's disease. Challenge of the mucosal immune system by the commensal gut flora would then result in chronic inflammation. Alternatively, increased permeability could be the result of inflammation. Our aim was to study intestinal permeability in refractory Crohn's disease before and after treatment with monoclonal chimeric antibodies directed against tumor necrosis factor (TNF) to investigate whether the abnormal permeability persists after control of inflammation. METHODS: Twenty-three patients with active Crohn's disease were evaluated before and 4 wk after a single infusion of 5 mg/kg infliximab. Intestinal permeability was studied by measurement of urinary excretion of 51Cr-EDTA after oral intake. RESULTS: The increased permeation of 51Cr-EDTA through the small intestine (1.63% interquartile range [IQR] 1.06-2.07) and the overall permeation (3.27% IQR 2.40-4.38) before therapy decreased significantly after infliximab infusion to values (1.04% IQR 0.74-1.54 and 2.42% IQR 2.03-2.80, respectively) in the range of those found in normal volunteers (1.12% IQR 0.85-1.58 and 2.28% IQR 1.88-2.86, respectively). CONCLUSION: Inhibiting the proinflammatory cytokine tumor necrosis factor dramatically reduces gut inflammation and largely restores the gut barrier in Crohn's disease. Our data confirm the central role of TNF in gut barrier modulation in inflammatory conditions in vivo.

Adult↗

PubMedDate not supplied

In vitro analysis of interferon gamma (IFN-gamma) and interleukin-12 (IL-12) production and their effects in ileal Crohn's disease.

Crohn's disease is an inflammatory disease of the gut in which tumour necrosis factor (TNF) and T helper 1 (Th1) cytokines (interleukin (IL)-12, interferon (IFN)-gamma) are thought to play a major role. After the successes obtained with neutralisation of TNF, interest is now growing for therapy aiming at neutralisation of Th1-associated cytokines. Since cytokines are linked in a delicate network, in vitro cultures of ileal lamina propria mononuclear cells (LPMC) were set up for evaluation of a) IFN-gamma and IL-12 production, b) effects of rhIFN-gamma and rhIL-12 and c) effects of anti-IFN-gamma and anti-IL-12 on pro-inflammatory cytokines and IL-10 production. LPMC were isolated from surgical specimens of a total of 27 Crohn's disease and 17 caecum carcinoma (control) patients. Cells were stimulated with CD40L (which triggers myeloid CD40-expressing cells) or anti-CD3 +CD80 (which triggers T cells). LPMC from involved ileal, Crohn's disease produced, in both non-stimulated and stimulated conditions, more IFN-gamma and IL-12p70 than LPMC from non-involved tissue or from control patients. rhIFN-gamma significantly enhanced TNF production in both controls and in ileal Crohn's disease patients, while rhIL-12 enhanced IFN-gamma but not TNF production. LPMC from involved tissue were more sensitive to IL-12 than control LPMC. LP-T cell-dependent activation of monocytes was then studied by co-culture of anti-CD3/CD80-stimulated LPMC with fresh monocytes, which resulted in high IL-12, IFN-gamma, TNF and IL-10 production. The data show that neutralisation of either IL-12 or IFN-gamma with mAb in these cultures also affects secretion of the reciprocal cytokine and (in the case of anti-IL-12) also that of the anti-inflammatory cytokine IL-10. However, no effect of anti-IL-12 or anti-IFN-gamma on production of TNF, a cytokine with an important pathogenic role in Crohn's disease, could be found. Therapies aiming at neutralisation of IFN-gamma or IL-12 are therefore unlikely to replace anti-TNF, but they might provide an additive or synergistic effect.

Case-Control Studies↗