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Biomedical subjects

K Geboes

Publications and source records attributed to K Geboes.

At least 37 records · Page 2Linked to original sources
PubMed2005

Chemo-radiotherapy versus radiotherapy alone in the pre-operative treatment of resectable rectal cancer.

AIM: To determine the differences in downstaging, local control (LC), disease free survival (DFS) and overall survival (OS) between combined pre-operative chemoradiation and pre-operative radiotherapy alone in the treatment of resectable rectal cancer. METHODS: One hundred and ten patients who underwent pre-operative radiotherapy or chemo-radiotherapy were reviewed. Fifty-seven patients were treated with radiotherapy (30 Gy/3 Gy) alone and 53 patients with chemo-radiotherapy (bolus 5FU+45 Gy/1.8 Gy). The median interval between the end of neo-adjuvant treatment and surgery was 28 and 46 days for the patients treated with radiotherapy alone and chemo-radiotherapy. RESULTS: The groups were homogeneously distributed for all characteristics except for cN-stage with more clinically node positive patients in the combined modality treatment group (47 vs 73%). A significant downstaging for tumour and/or lymph node status was observed in both groups. More ypT0-x-is were observed after chemoradiation than after radiotherapy alone (26 vs 7%; p=0.02). The local control rate at 3 years was 94% for both groups. DFS after radiation and chemoradiation was comparable with a 3-year DFS of 83 and 88%, respectively. CONCLUSION: Both pre-operative schemes have similar outcomes concerning DFS, OS and LC. Tumour downstaging is associated with improved survival.

Adenocarcinoma↗
PubMed2005

Adalimumab induces apoptosis of human monocytes: a comparative study with infliximab and etanercept.

BACKGROUND: Adalimumab, a fully human monoclonal antibody to tumour necrosis factor, was recently introduced for therapy of Crohn's disease. AIM: Since induction of apoptosis of inflammatory cells is thought to be an important mechanism of action of the antitumour necrosis factor monoclonal antibody infliximab, we studied the induction of apoptosis of activated peripheral blood monocytes by adalimumab. METHOD: Apoptosis was analysed at the levels of the cell membrane, mitochondria and DNA by flow cytometry. RESULTS: We found that both adalimumab and infliximab induced apoptosis in cultured monocytes, while etanercept did not. Apoptosis induction was caspase-dependent and detectable already after 2 h. The production of interleukin-10 and interleukin-12 by monocytes was down-regulated significantly by adalimumab and infliximab but not by etanercept, while levels of soluble tumour necrosis factor in monocyte cultures were down-regulated by all three reagents. CONCLUSIONS: These data show that both adalimumab and infliximab affect monocyte cytokine production and induce apoptosis of activated monocytes. Our findings will have to be further correlated to therapeutic efficacy of these antitumour necrosis factor reagents.

Adalimumab↗
PubMed2005

In vivo evaluation of a colonic delivery system using isotope techniques.

AIM: To evaluate, using isotope techniques, the in vivo effectiveness of a pH-dependent colonic delivery system. METHODS: In order to dispose of differently labelled substrates for measurement of orocaecal transit time, inulin-14C-carboxylic acid was evaluated as an alternative substrate to inulin and lactose-13C-ureide. Secondly, the time of release of 13C- and 15N-urea from the colonic delivery system was compared with the orocaecal transit time, measured using inulin and inulin-14C-carboxylic acid. This study was repeated after a 2-week lactulose intake period. RESULTS: The orocaecal transit time determined using inulin-14C-carboxylic acid (398 min) was not significantly different from the orocaecal transit time determined using inulin (420 min) or lactose-13C-ureide (396 min). Before lactulose intake, the 13CO2 excretion time was 358 min and the orocaecal transit times determined with the inulin-14C-carboxylic acid and inulin breath test were 376 and 375 min respectively. After lactulose, the 13CO2 excretion time was 383 min and orocaecal transit times were 354 min for inulin-14C-carboxylic acid and 392 min for inulin. A highly significant correlation was found. Good agreement was found between the urinary 15N excretion and the appearance of 13CO2 in breath. CONCLUSION: Isotope techniques provide an excellent non-invasive tool for the in vivo evaluation of a colonic delivery system.

Adult↗
PubMed2005

Effect of repeated cycles of acute esophagitis and healing on esophageal peristalsis, tone, and length.

Severe esophagitis is associated with motor abnormalities in the esophageal body and lower esophageal sphincter. Reflux disease involves repeated episodes of mucosal inflammation and spontaneous or treatment-induced healing. The aims of this study were 1) to further assess changes induced by acute esophagitis on esophageal peristalsis, tone, and shortening and 2) to assess the effect of repeated sequences of acute esophagitis-healing on these motor parameters. Experiments were performed on adult cats. Esophageal manometry and barostat were performed before, 24 h after, and every 7 days after intraesophageal acid perfusion (0.1 N HCl, 80 min). Esophageal length was measured during manometry, and compliance of the esophageal body was assessed with barostat. The identical protocol was performed 8 and 16 wk after the first acid perfusion. The degree of esophageal mucosal damage was evaluated by endoscopy, histopathology, and myeloperoxidase activity. Acid perfusion induced severe esophagitis. At 24 h, distal peristaltic contractions disappeared, lower esophageal sphincter pressure was reduced by 60%, the esophagus length was 1-2 cm shorter, and esophageal compliance was reduced by 30%. Most parameters recovered in 4 wk. Subsequent repeated acute injuries induced similar endoscopic esophagitis but a different pattern of inflammatory infiltration and fibrosis in the mucosa and muscle layers, resulting in milder motor disturbances. Acute experimental esophagitis provokes severe but reversible hypomotility. Spaced repeated acute injuries provoke milder motor effects, suggesting an adaptive response.

Acute Disease↗
PubMed2005

Actinomycosis, a rare and unsuspected cause of anal fistulous abscess: report of three cases and review of the literature.

Primary perianal actinomycosis is rare. Sporadic cases, with lesions varying in extent have been reported. The infection is caused by the bacterium Actinomyces, which often is a saprophyte. Male gender and diabetes are risk factors, but the exact pathogenic mechanism remains speculative. The diagnosis is a challenge and often delayed, with a protracted history of masses and sinuses extending into the gluteal and genital region. The treatment, a combination of surgery and antibiotics, is poorly standardized. We report three cases and compare their characteristics to those of published cases, found by a computerized literature search (1968-2002). The lesions, a simple fistula-in-ano or a mass, were diagnosed in an early stage in all three patients. The infection always spread into the scrotum. There were no risk factors other than gender, except in one patient. The diagnosis was suspected by the observation of draining sulfur granules and promptly confirmed by histology in the three cases. All patients healed with antibiotics in addition to simple surgical procedures. Treatment consisted of amoxicillin for two weeks in two cases and more extended antimicrobial treatment in the third. These findings are contrasting with the classic picture of perianal actinomycosis. It is concluded that perianal actinomycosis can occur in the absence of risk factors and that early diagnosis requires a high degree of suspicion. An infection with Actinomyces should be suspected in the presence of lesions containing watery purulent material with sulfur granules. The indication for extended antibiotherapy combined with sphincter damaging surgery may need to be revised in the presence of early detection.

Abscess↗
PubMed2005

Crohn's-like changes in the colon due to mycophenolate?

OBJECTIVE: Mycophenolate mofetil (MMF) is used for prevention of allograft rejection in kidney transplant patients. A subset of patients suffers from chronic diarrhoea of unknown origin. The aim of the study was to investigate the effect of MMF on the colonic mucosa. MATERIALS AND METHODS: Colonic mucosal biopsies from 24 kidney transplant patients receiving MMF and presenting with chronic diarrhoea were analysed using routine stainings and immunohistochemistry for Ki67 and E-cadherin. Results were compared with a control group of 19 kidney transplant patients not receiving MMF. In all patients routine clinical and laboratory investigations were performed in order to explain the diarrhoea. RESULTS: In 11 patients, the diarrhoea seemed to be of infectious origin. Furthermore, 19/24 of MMF-patients showed characteristic histological alterations of the mucosa that were Crohn's disease-like: discontinuous crypt architectural distortion, increased epithelial mucin secretion, mildly active inflammation and focal presence of dilated and inflamed crypts. Ki67 staining was abnormal in 6/24 MMF patients but also in 4/19 control patients. E-Cadherin staining was normal in most MMF and control patients. CONCLUSIONS: Diarrhoea following MMF treatment is frequently infectious in origin and associated with morphological changes with a Crohn's-like pattern in the colonic mucosa in a subset of patients. MMF does not induce major alteration in the proliferative compartment of colonic epithelium. The diarrhoea is not associated with altered E-cadherin expression in the colonic epithelium.

Adolescent↗
PubMed2005

Epithelioid granulomas, pattern recognition receptors, and phenotypes of Crohn's disease.

INTRODUCTION: Crohn's disease is a chronic inflammatory disorder of the gut. It is assumed that a defective interaction between the bacterial flora of the gut and the innate immune system plays a key role in the pathogenesis of the disease. This may lead to specific histological lesions. The epithelioid granuloma is particularly interesting in this regard as it is also observed in several bacterial infections of the gut. AIMS AND METHODS: We hypothesised that genetic or environmental factors with a known influence on inflammation or immunity would lead to an increased prevalence of granulomas. Therefore, surgical specimens from 161 patients were evaluated for the presence of granulomas. Patients were genotyped for the three single nucleotide polymorphisms in caspase recruitment domain 15 (CARD15)/NOD2 associated with CD and for Asp299Gly in Toll-like receptor 4 (TLR4). RESULTS: The overall prevalence of granulomas was 68.9%. We did not find a significant correlation between granulomas and TLR4 or CARD15 variants. The frequency of granulomas increased with more distal disease (63% small bowel, 72% right colon, 88% left colon, 90% rectum; p=0.01). Granulomas were more frequent in younger patients (odds ratio 0.95 (95% confidence interval 0.92-0.98) p=0.007). CONCLUSION: In this study of 161 well documented CD patients, we found no significant association between CARD15 and TLR4 variants and granulomas. This finding seems to refute our initial hypothesis. However, it may be that additional factors are needed for granuloma development. Granulomas may develop only when specific bacterial components are present. Therefore, future research on granuloma pathogenesis should be orientated towards detection and identification of bacterial components in these lesions.

Adult↗
PubMed2004

Identical cytokeratin expression pattern CK7+/CK20- in esophageal and cardiac cancer: etiopathological and clinical implications.

Surgical treatment and prognosis is different in esophageal, cardiac and distal gastric adenocarcinomas. Determination of the origin, in particular of adenocarcinomas situated at the gastroesophageal junction, may be difficult. It has been suggested that esophageal adenocarcinomas are characterized by a specific cytokeratin pattern, namely the CK7+/CK20- pattern. According to the same authors, this cytokeratin pattern is absent in gastric adenocarcinomas. The aim of our study is to evaluate if this cytokeratin pattern CK7+/CK20- is absent in cardiac and distal gastric adenocarcinomas. Therefore, we evaluated the combined immunohistochemical expression of CK7 and CK20 on paraffin-embedded material of 214 resection specimens for adenocarcinoma, comprising 66 esophageal, 73 cardiac and 75 distal gastric adenocarcinomas (UICC-classification). The adenocarcinomas were subtyped into intestinal- and diffuse-type according to the Lauren classification. The immunohistochemical staining was considered as positive if 50% or more of the tumor cells were stained. Statistical analysis has been performed applying the chi2-test. The tumors situated at the gastroesophageal junction, esophageal as well as cardiac adenocarcinomas, showed predominantly a CK7+/CK20- expression pattern (67 vs 68%), whereas this cytokeratin pattern is rather uncommon in distal gastric adenocarcinomas (31%, P<4 x 10(-5)). Independent of their localization, intestinal- as well as diffuse-type adenocarcinomas have a similar cytokeratin pattern. Our data show that the combined expression of CK7 and CK20 is different for the adenocarcinomas situated on both sides of the gastroesophageal junction compared to the distal gastric adenocarcinomas. However, in contrast to data in the literature, the combined expression of CK7 and CK20 has a low specificity in the distinction between esophageal and cardiac adenocarcinomas. This may suggest a similar origin (cell lineage) and thus may have an impact on therapeutic strategies.

Adenocarcinoma↗
PubMed2004

Inducible nitric oxide synthase and vascular endothelial growth factor are colocalized in the retinas of human subjects with diabetes.

PURPOSE: Nitric oxide (NO) mediates vascular endothelial growth factor (VEGF)-induced angiogenesis and vascular hyperpermeability. This study was undertaken to study the cellular distribution of inducible nitric oxide synthase (iNOS) and VEGF in the retinas from human subjects with diabetes mellitus. In addition, glial reactivity and peroxynitrite generation were detected by immunolocalization of glial fibrillary acidic protein (GFAP) and nitrotyrosine, respectively. METHODS: Eight post-mortem eyes from four consecutive subjects with diabetes mellitus and eight eyes from four subjects without diabetes and without known ocular disease were prospectively collected and examined. We used immunohistochemical techniques and antibodies directed against iNOS, VEGF, GFAP, and nitrotyrosine. RESULTS: In retinas from all subjects without diabetes, weak GFAP immunoreactivity was confined to nerve fibre and ganglion cell layers. There was no immunoreactivity for iNOS, nitrotyrosine, and VEGF. All diabetic retinas showed GFAP induction in Müller cells and GFAP upregulation in nerve fibre and ganglion cell layers. All diabetic retinas showed cytoplasmic immunoreactivity for iNOS, and VEGF in ganglion cells, cells in the inner nuclear layer, and glial cells. In serial sections, ganglion cells and cells in the inner nuclear layer expressing VEGF were localized in the same area of iNOS-expressing ganglion cells and cells in the inner nuclear layer. Six retinas from three subjects with diabetes showed immunoreactivity for nitrotyrosine in vascular endothelial cells in inner retinal layer. CONCLUSIONS: iNOS and VEGF are colocalized in diabetic retinas. Increased GFAP immunoreactivity is a pathological event in the retina during diabetes.

Adult↗
PubMed2004

The in vivo use of the stable isotope-labelled biomarkers lactose-[15N]ureide and [2H4]tyrosine to assess the effects of pro- and prebiotics on the intestinal flora of healthy human volunteers.

Amongst the various claimed beneficial effects of pro- and prebiotics for the human host, it has been hypothesised that functional foods are able to suppress the generation and accumulation of toxic fermentation metabolites (NH3, p-cresol). Direct evidence supporting this hypothesis is lacking mainly because of the unavailability of reliable biomarkers. Preliminary data indicate that lactose-[15N]ureide and [2H4]tyrosine may be potential biomarker candidates. The aim of the present study was to evaluate the effect of pro- and prebiotics on the colonic fate of these biomarkers in a randomised, placebo-controlled, cross-over study with nineteen healthy volunteers. At the start of the study and at the end of each 2-week study period, during which they were administered either a probiotic (n 10; 6.5 x 10(9) Lactobacillus casei Shirota cells twice daily) or a prebiotic (n 9; lactulose 10 g twice daily), the volunteers consumed a test meal containing the two biomarkers. Urine was collected during 48 h. Results were expressed as percentage of the administered dose. As compared with the placebo, the decrease in the percentage dose of p-[2H4]cresol in the 24-48 h urine fraction was significantly higher after probiotic intake (P=0.042). Similar changes were observed for the 15N tracer (P=0.016). After prebiotic intake, a significantly higher decrease in the percentage dose of p-[2H4]cresol (P=0.005) and 15N tracer (P=0.029) was found in the 0-24 h urine collection. The present results demonstrate that suppression of the generation and accumulation of potentially toxic fermentation metabolites by pro- and prebiotics can reliably be monitored in vivo by the use of stable isotope-labelled biomarkers.

Adult↗
PubMed2004

Involvement of interleukin 18 in Crohn's disease: evidence from in vitro analysis of human gut inflammatory cells and from experimental colitis models.

An imbalance of immunoregulatory factors and/or cells contributes to uncontrolled mucosal T cell activation and inflammation in Crohn's disease (CD). Bioactive interleukin (IL)-18 has been shown to be produced by macrophages in CD lesions. We report here that T cells freshly isolated from inflamed tissue of CD patients (and not T cells from control intestinal tissue) were responsive to IL-18. In the presence of IL-18, these T cells produced more interferon (IFN)-gamma and less IL-10. To analyse further the role of IL-18 in this disease, an acute and a chronic model of murine colitis were used. IL-18 mRNA was significantly enhanced in trinitrobenzene sulphonic acid (TNBS) induced colitis, and treatment with IL-18 binding protein (IL-18BPa), which neutralizes IL-18 bioactivity, significantly reduced the severity of colitis. However, IL-18BPa did not affect the course of chronic colitis in CD45RBhighCD4+ T cell reconstituted SCID mice. Production of IFN-gamma in lamina propria mononuclear cell cultures from IL-18BPa-treated SCID mice was decreased, but at the same time fewer lamina propria CD4+ T cells harvested from IL-18BPa-treated mice compared to non-treated mice were in apoptosis. We conclude that IL-18 clearly has a modulatory role in the inflammatory cascade of CD and experimental colitis by affecting IFN-gamma and IL-10 production, and apoptosis. In view of the divergent effects of IL-18 neutralization in the two different murine colitis models, it is unlikely that IL-18 is at the top of this cascade.

Adult↗
PubMed2003

Cyclooxygenase-2 in human and experimental ischemic proliferative retinopathy.

BACKGROUND: Intravitreal neovascular diseases, as in ischemic retinopathies, are a major cause of blindness. Because inflammatory mechanisms influence vitreal neovascularization and cyclooxygenase (COX)-2 promotes tumor angiogenesis, we investigated the role of COX-2 in ischemic proliferative retinopathy. METHODS AND RESULTS: We describe here that COX-2 is induced in retinal astrocytes in human diabetic retinopathy, in the murine and rat model of ischemic proliferative retinopathy in vivo, and in hypoxic astrocytes in vitro. Specific COX-2 but not COX-1 inhibitors prevented intravitreal neovascularization, whereas prostaglandin E2, mainly via its prostaglandin E receptor 3 (EP3), exacerbated neovascularization. COX-2 inhibition induced an upregulation of thrombospondin-1 and its CD36 receptor, consistent with the observed antiangiogenic effects of COX-2 inhibition; EP3 stimulation reversed effects of COX-2 inhibitors on thrombospondin-1 and CD36. CONCLUSIONS: These findings point to an important role for COX-2 in ischemic proliferative retinopathy, as in diabetes.

Adult↗
PubMed2003

Topical cidofovir (HPMPC) is an effective adjuvant to surgical treatment of anogenital condylomata acuminata.

PURPOSE: Human papilloma virus infections of the anogenital region are very common and cause condylomata acuminata; cervical, penile, vulvar, or perianal intraepithelial neoplasia; and more rarely, invasive cancer. The currently available therapies often result in painful, extensive, slow-healing ulcerations and frequent early relapses. This study was aimed at determining the efficacy of topical application of the antiviral agent cidofovir at 1 percent. METHODS: Twenty patients treated with coagulations were compared with 27 patients treated with cidofovir. Lesions refractory to cidofovir were cleared up with additional coagulations. The number of patients previously treated for condylomata did not differ between the two groups. Significantly more patients treated with cidofovir, however, had an impaired immune status (37 percent) compared with the patients treated with coagulations (5 percent). RESULTS: Cidofovir alone cured the lesions in 32 percent of the patients and induced partial regression in 60 percent. However, in smokers, complete resolution of the condylomata occurred only in 16.6 percent compared with 66 percent of nonsmokers (P = 0.03). The number of coagulation sessions was much lower (P < 0.0005) in the cidofovir treated group (1 +/- 0.8 vs. 2.9 +/- 2). Furthermore, the relapse rate was significantly lower in the cidofovir group (3.7 vs. 55). All recurrences in the electrocoagulation group occurred within four months of confirmed lesion clearance. Topical applications of cidofovir 1 percent were well tolerated. Thirty-three percent of the patients reported only mild pain caused by erosive dermatitis. In contrast, coagulations caused painful ulcerations that necessitated the use of analgesics in all patients treated this way. CONCLUSIONS: Topical applications of cidofovir, an antiviral compound with activity against human papilloma virus, is effective in the majority of patients with perianal condylomata and is a valuable adjuvant to surgical treatment of these lesions.

Administration, Topical↗
PubMed2003

Immuno-histochemical evaluation of conjunctival remodelling in vernal keratoconjunctivitis.

PURPOSE: To study the expression of the extracellular matrix (ECM) proteins, tenascin, laminin, and fibronectin in the conjunctiva of patients with active vernal keratoconjunctivitis (VKC). METHODS: Conjunctival biopsy specimens were obtained from nine patients with active VKC and 6 normal control subjects. The presence and distribution of tenascin, laminin, and fibronectin were assessed microscopically with immunohistochemical techniques and a panel of monoclonal and polyclonal antibodies directed against tenascin, laminin, and fibronectin. RESULTS: In normal conjunctiva, weak immunoreactivity for tenascin was localized to the walls of blood vessels in the upper substantia propria. Weak immunoreactivity for laminin was located at the epithelial-stromal junction and in the walls of blood vessels. Staining for fibronectin was absent. In VKC specimens, intense immunoreactivity for tenascin was noted in the substantia propria associated with the inflammatory infiltrate and in the perivascular stroma. Intense immunoreactivity for laminin around all stromal vessels and fibrillar immunoreactivity among basal epithelial cells were noted. There was no immunoreactivity for fibronectin. CONCLUSION: Our data indicate increased deposition of tenascin and laminin in the conjunctiva from patients with active VKC. Our findings suggest that tenascin and laminin might play distinct roles in chronic inflammation seen in VKC.

Adolescent↗