369 results on '"Kleibeuker JH"'
Search Results
2. Rectaal bloedverliesaambeien anamnese darmkanker diagnostiek laboratoriumonderzoek lichamelijk onderzoek maagdarmklachten
- Author
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Reenders, K, Reedijk, L, and Kleibeuker, JH
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- 2002
- Full Text
- View/download PDF
3. Diffuse and intestinal type gastric carcinomas differ in their expression of apoptosis related proteins
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van der Woude, CJ, Kleibeuker, JH, Tiebosch, ATGM, Homan, M, Beuving, A, Jansen, PLM, and Moshage, H
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Cell proliferation -- Physiological aspects -- Research -- Health aspects ,Clinical pathology -- Research -- Physiological aspects -- Health aspects ,Immunohistochemistry -- Research -- Physiological aspects -- Health aspects ,Stomach cancer -- Health aspects -- Diagnosis -- Research ,Nitric oxide -- Physiological aspects -- Health aspects -- Research ,Proteins -- Physiological aspects -- Health aspects -- Research ,Apoptosis -- Health aspects -- Causes of -- Research -- Physiological aspects ,Health - Abstract
Background: Gastric carcinomas can be divided into intestinal and diffuse types, with the last type having a worse prognosis. Aims: To investigate whether specific patterns in the expression of apoptosis [...]
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- 2003
4. Non-steroidal anti-inflammatory drugs and molecular carcinogenesis of colorectal carcinomas
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Huls, G, Koornstra, JJ, and Kleibeuker, JH
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- 2003
- Full Text
- View/download PDF
5. [Treatment of servere ulcerative colitis]
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Weersma, RK, van Dullemen, HM, Kleibeuker, JH, Ploeg, RJ, and Dijkstra, G
- Abstract
10-15% of patients with ulcerative colitis experience a severe episode of colonic inflammation that does not respond to mesalazine and oral corticosteroids. These patients require hospitalisation and treatment with intravenous corticosteroids. However, 25% of these patients do not respond to treatment. In these cases, intravenous cyclosporin is effective. Infliximab, an antibody against tumour necrosis factor alpha, is also beneficial. With these new treatment options, the colectomy rate in the acute phase has declined to about 35%. Other new therapies are under investigation in phase 2 and 3 trials. Surgery remains an important treatment option. Patients, gastroenterologists and surgeons should be involved in the clinical decision-making process.
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- 2016
6. Hyperplastic Polyps in Hereditary Nonpolyposis Colorectal Cancer
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Rijcken, FEM, Van der Sluis, T, Hollema, H, Kleibeuker, JH, Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Targeted Gynaecologic Oncology (TARGON)
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Adult ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,Heterozygote ,CARCINOMA ,DNA MICROSATELLITE INSTABILITY ,Base Pair Mismatch ,Colonic Polyps ,Risk Assessment ,Statistics, Nonparametric ,Age Distribution ,ADENOMAS ,Humans ,Genetic Predisposition to Disease ,Genetic Testing ,Sex Distribution ,neoplasms ,Aged ,Probability ,REPAIR PROTEIN EXPRESSION ,Hepatology ,MUTATIONS ,Incidence ,Biopsy, Needle ,Gastroenterology ,nutritional and metabolic diseases ,ENDOMETRIAL ,Colonoscopy ,IMMUNOHISTOCHEMICAL PATTERN ,Middle Aged ,TUMORS ,Colorectal Neoplasms, Hereditary Nonpolyposis ,Immunohistochemistry ,digestive system diseases ,GENETIC ALTERATIONS ,Female ,Precancerous Conditions ,GENOMIC INSTABILITY ,Follow-Up Studies - Abstract
OBJECTIVES: Hereditary nonpolyposis colorectal cancer (HNPCC) is a genetic syndrome caused by germline mutations in DNA mismatch repair (MMR) genes, in particular hMLH1, hMSH2, and hMSH6. Dysfunction of MMR genes leads to loss of MMR protein expression and to microsatellite instability (MSI). MSI is also detected in 10-20% of sporadic colorectal cancers. Hyperplastic polyps (HP) may serve as precursor for these MSI+ sporadic colorectal cancers. The aim of this study was to examine whether hyperplastic polyps are also possible premalignant lesions in HNPCC. METHODS: All HPs resected from (suspected) mismatch repair gene mutation carriers were retrieved from a screening program database. Clinical information on patient age at colonoscopy and location of the HP was collected. MLH1, MSH2, and MLH6 protein expression was evaluated using immunohistochemistry. RESULTS: A total of 90 HPs were resected from 21 men and 19 women. The mean patient age at resection was 45.7 yr (44.7 yr in men and 46.6 yr in women). In all patients, 19 (21%) HPs were resected from the proximal colon, 23 (26%) from the distal colon, and 48 (53%) from the rectum. None of the HPs demonstrated loss of MMR protein expression. CONCLUSIONS: Mismatch repair dysfunction in HPs of HNPCC patients is apparently very rare. It seems unlikely that HPs in HNPCC patients are precursors for (MSI+) cancers in these patients.
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- 2003
7. Association between JC virus and the development of colorectal neoplasia after liver transplantation
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Blom M, Selgrad M, de Jong S, Fini L, Dijkstra G, Verdonk RC, Williams S, Meyer R, Goel A, Kleibeuker JH, Haagsma EB, Boland CR, Koornstra J.J., RICCIARDIELLO, LUIGI, Blom M, Selgrad M, de Jong S, Fini L, Dijkstra G, Verdonk RC, Williams S, Meyer R, Goel A, Kleibeuker JH, Haagsma EB, Ricciardiello L, Boland CR, and Koornstra JJ.
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COLORECTAL CANCER ,jc viru ,LIVER TRANSPLANTATION - Published
- 2008
8. Microscopic colitis: prevalence and distribution throughout the colon in patients with chronic diarrhoea
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Thijs, WJ, van Baarlen, J, Kleibeuker, JH, Kolkman, JJ, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
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SMALL-INTESTINE ,microscopic colitis ,CELIAC-DISEASE ,DIAGNOSIS ,digestive system diseases ,COLLAGENOUS-COLITIS ,diarrhoea ,colonoscopy ,distribution ,LYMPHOCYTIC COLITIS ,BIOPSY ,SPRUE ,SENSITIVE ENTEROPATHY ,GLUTEN SENSITIVITY - Abstract
Background: Microscopic colitis presents with chronic diarrhoea with or without abdominal pain. Microscopic colitis is an important cause of chronic diarrhoea. It can be distributed throughout the colon, as well as limited to the right colon. Microscopic colitis is associated with coeliac disease. We studied the prevalence and distribution of microscopic colitis in patients with diarrhoea and normal colonoscopy and we studied the association with coeliac disease. Methods: Colonoscopy was performed. Biopsies were taken from every segment of the colon. Lymphocytic colitis was defined as the presence of more than 20 lymphocytes per 100 epithelial cells and collagenous colitis was defined as thickening of the basal membrane of more than 10 mu m. Upper endoscopy was performed if upper intestinal symptoms were present., If this was the case, small bowel biopsies were taken. Results: Microscopic colitis was found in 13 Out Of 103 patients. The distribution was diffuse throughout the colon in ten and restricted to the right colon in three patients. In seven patients, upper endoscopy was performed. Marsh I/II lesions were found in six out of seven patients. Conclusion: Microscopic colitis was limited to the right colon in 23% of patients. Biopsies of macroscopically normal colonic mucosa in patients with diarrhoea is mandatory.
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- 2005
9. The HLA class III subregion is responsible for an increased breast cancer risk (vol 12, pg 2311, 2003)
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de Jong, MM, Nolte, IM, de Vries, EGE, Schaapveld, M, Kleibeuker, JH, Oosterom, E, Oosterwijk, JC, van der Hout, AH, van der Steege, G, Bruinenberg, M, Boezen, HM, te Meerman, GJ, van der Graaf, WTA, University of Groningen, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Life Course Epidemiology (LCE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Targeted Gynaecologic Oncology (TARGON), and Groningen Research Institute for Asthma and COPD (GRIAC)
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- 2003
10. Inflammatory bowel disease after liver transplantation: the effect of different immunosuppressive regimens
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Haagsma, EB, Van den Berg, AP, Kleibeuker, JH, Slooff, MJH, Dijkstra, G, Faculteit Medische Wetenschappen/UMCG, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Institute for Organ Transplantation (GIOT), and Translational Immunology Groningen (TRIGR)
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RECIPIENTS ,MICE ,surgical procedures, operative ,ULCERATIVE-COLITIS ,FEATURES ,AUTOIMMUNITY ,TACROLIMUS ,PRIMARY SCLEROSING CHOLANGITIS - Abstract
Background: Seemingly conflicting results have been reported on the prevalence and severity of inflammatory bowel disease after liver transplantation. Regimens with different combinations of drugs can be used for immunosuppression after transplantation. Aim: To study retrospectively the prevalence of inflammatory bowel disease after liver transplantation, and the possible relationship with maintenance immunosuppressive regimens. Methods: All 78 patients with end-stage primary sclerosing cholangitis (48 patients) or autoimmune cirrhosis (30 patients), transplanted between 1979 and July 2001, and with a follow-up of at least 1 year, were eligible for this study. In addition to patient and transplant characteristics, data on inflammatory bowel disease and immunosuppression before and after transplantation were collected. The Kaplan-Meier method was used for survival analysis. Possible risk factors for inflammatory bowel disease after transplantation were analysed by Cox univariate and multivariate regression. Results: The median follow-up after transplantation was 7.2 years (range, 1.1-22.3 years). Nine of 25 patients with pre-transplant inflammatory bowel disease experienced flare-ups after transplantation. Six of 53 patients without pre-transplant inflammatory bowel disease developed de novo inflammatory bowel disease after transplantation. The cumulative risks (standard errors in parentheses) for inflammatory bowel disease were 6% (3%), 12% (4%) and 20% (5%) at 1, 3 and 5 years after transplantation, respectively. The inflammatory bowel disease-free survival was significantly higher in patients not receiving tacrolimus vs. those receiving tacrolimus, in patients receiving azathioprine vs. those not receiving azathioprine and in patients taking the regimen prednisolone-azathioprine-ciclosporin A vs. those taking tacrolimus-prednisolone. Pre-transplant inflammatory bowel disease and the use of tacrolimus were found to be independent predictors for inflammatory bowel disease after transplantation. Conclusions: The prevalence of inflammatory bowel disease after liver transplantation is affected by the immunosuppression used. Azathioprine seems to have a protective effect and tacrolimus a promoting effect.
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- 2003
11. Expression of TRAIL (TNF-related apoptosis-inducing ligand) and its receptors in normal colonic mucosa, adenomas, and carcinomas
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Koornstra, JJ, Kleibeuker, JH, van Geelen, CMM, Rijcken, FEM, Hollema, H, de Vries, EGE, de Jong, S, Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Targeted Gynaecologic Oncology (TARGON)
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DECOY RECEPTORS ,BRAIN-TUMORS ,ANTITUMOR-ACTIVITY ,apoptosis ,DEATH FACTOR ,NECROSIS-FACTOR-ALPHA ,TRAIL ,colorectal cancer ,COLORECTAL-CANCER ,MEMBER ,CELLS ,adenoma ,IN-VIVO ,GENE-EXPRESSION - Abstract
Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis intumour cell lines. Four membrane-bound receptors for TRAIL have been identified, two apoptosis-mediating receptors, DR4 and DR5, and two apoptosis-inhibiting receptors, DcR1 and DcR2. The aim of this study was to examine the role of TRAIL and its receptors in colorectal cancer development. The immunohistochemical expression and localization of TRAIL and its receptors were investigated in normal mucosa (n = 10), adenomas (n = 19), and carcinomas (n = 21). Correlations between the expression of TRAIL and its receptors and the degree of apoptosis (assessed by M30 expression) and histopathological characteristics were explored. TRAIL and its receptors were expressed in normal mucosal epithelium. Expression of the receptors was seen in adenomas and carcinomas. TRAIL expression was lost in a subset of colorectal tumours, more frequently in carcinomas than in adenomas (p
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- 2003
12. Calcium: a protective agent against colorectal cancer?
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Kleibeuker, JH, De Vries, EGE, Van Der Meer, R, Scheppach, W, Scheurlen, M, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
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FECAL WATER ,EPITHELIAL-CELL PROLIFERATION ,BILE-ACIDS ,ADENOMATOUS POLYPS ,CONTROLLED CLINICAL-TRIAL ,SUPPLEMENTAL DIETARY CALCIUM ,COLON-CANCER ,RECTAL MUCOSAL PROLIFERATION ,RANDOMIZED CONTROLLED TRIAL ,VITAMIN-D - Published
- 2003
13. Low-penetrance genes and their involvement in colorectal cancer susceptibility
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de Jong, MM, Nolte, IM, te Meerman, Gerard J., van der Graaf, WTA, de Vries, EGE, Sijmons, RH, Hofstra, RMW, Kleibeuker, JH, Life Course Epidemiology (LCE), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
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GLUTATHIONE-S-TRANSFERASE ,FRAGMENT LENGTH POLYMORPHISM ,SECRETORY PHOSPHOLIPASE A(2) ,FAMILIAL ADENOMATOUS POLYPOSIS ,ALPHA PROMOTER POLYMORPHISM ,METHYLENETETRAHYDROFOLATE REDUCTASE POLYMORPHISM ,HETEROCYCLIC AMINE CARCINOGENS ,ARYLAMINE-N-ACETYLTRANSFERASE ,NONPOLYPOSIS COLON-CANCER ,TUMOR-NECROSIS-FACTOR - Abstract
This report focuses on low-penetrance genes that are associated with colorectal adenoma and/or cancer or that are in strong linkage disequilibrium with colorectal adenoma and/or cancer causing variants. A pooled analysis was performed for 30 polymorphisms in 20 different genes that have been reported in more than one colorectal adenoma or cancer study. An association with colorectal cancer was found for seven polymorphisms in seven genes reported in more than one study; no associations were found with colorectal adenoma. Four of the polymorphisms exhibited an increased colorectal cancer risk [GSTT1, NAT2 (phenotype), HRAS1, and ALDH2]. Two others [MTHFR, Tp53 (intron 3)] exhibited a decreased risk. For the tumor necrosis factor (TNF)a polymorphism of the TNF-alpha gene, one allele was associated with an increased risk (a2 allele) and two other TNFa alleles with decreased risks (a5 and a13 allele). No association with colorectal adenoma and/or cancer was detected for 23 other polymorphisms in 15 genes. However, of all 30 polymorphisms, only three pooled analyses had sufficiently large samples to confirm (MTHFR) or to exclude (GSTM1 and NAT2 genotype) the association with a P
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- 2002
14. Changes in bile acid composition and effect on cytolytic activity of fecal water by ursodeoxycholic acid administration: A placebo-controlled cross-over intervention trial in healthy volunteers
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van Gorkom, BAP, van der Meer, R, Boersma-van Ekm, W, Termont, DSML, de Vries, EGE, Kleibeuker, JH, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
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PRIMARY BILIARY-CIRRHOSIS ,DIETARY CALCIUM ,biomarkers ,SALTS ,CANCER ,colon carcinogenesis ,UDCA ,EPITHELIAL-CELL PROLIFERATION ,fecal water ,COLON ,chemoprevention ,RAT ,CYTOTOXICITY ,FATTY-ACIDS ,CHENODEOXYCHOLIC ACID - Abstract
Background: Ursodeoxycholic acid (UDCA) has been shown to affect membrane-damaging effects of bile acids in vitro and fecal bile acid composition in rats. This study evaluates the effect of UDCA on fecal bile acid composition and on cytolytic activity of fecal water in man to clarify the potential chemopreventive role of UDCA for colorectal cancer. Methods: In this placebo-controlled crossover intervention trial, the effect of 900 mg/day UDCA orally in 15 healthy volunteers was studied. At the end of each 4-week period, 72 h feces were collected. Total and individual bile acids in feces were determined by gas chromatography and soluble bile acids were analyzed by high-performance liquid chromatography. Cytolytic activity of fecal water was measured using an erythrocyte lysis assay. Results: In feces, the percentages of primary bile acids-cholic acid (CA) and chenodeoxycholic acid (CDCA)-and of secondary bile acid-deoxycholic acid (DCA)-decreased after supplementation with UDCA, whereas those of UDCA and LCA increased from 2.7 +/- 0.4% to 23.7 +/- 2.6%, P
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- 2002
15. Cytotoxicity of rhein, the active metabolite of sennoside laxatives, is reduced by multidrug resistance-associated protein 1
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van Gorkom, BAP, Timmer-Bosscha, H, de Jong, S, Kleibeuker, JH, de Vries, EGE, Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Targeted Gynaecologic Oncology (TARGON)
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EXPRESSION ,ANTHRAQUINONE GLYCOSIDES ,colon ,MRP ,apoptosis ,DRUG EFFLUX ,LINE ,anthranoids ,TRANSPORT ,COLONIC EPITHELIAL-CELLS ,multidrug resistance ,HUMAN TUMOR-CELLS ,MELANOSIS-COLI ,carcinogeresis ,INDUCED APOPTOSIS - Abstract
Anthranoid laxatives, belonging to the anthraquinones as do anthracyclines, possibly Increase colorectal cancer risk. Anthracyclines Interfere with topoisomerase II, Intercalate DNA and are substrates for P-glycoprotein and multidrug resistance-associated protein I. P-glycoprotein and multidrug resistance-associated protein I protect colonic epithelial cells against xenobiotics. The aim of this study was to analyse the interference of anthranoids with these natural defence mechanisms and the direct cytotoxicity of anthranoids in cancer cell lines expressing these mechanisms In varying combinations, A cytotoxicity profile of men, aloe emodin and danthron was established in related cell lines exhibiting different levels of topoisomerases, multidrug resistance-associated protein I and P-glycoprotein. Interaction of rhein with multidrug resistance-associated protein I was studied by carboxy fluorescein efflux and direct cytotoxicity by apoptosis induction. Rhein was less cytotoxic in the multidrug resistance-associated protein I overexpressing GLC4/ADR cell line compared to GLC4. Multidrug resistance-associated protein I inhibition with MK571 increased rhein cytotoxicity. Carboxy fluorescein efflux was blocked by rhein. No P-glycoprotein dependent rhein efflux was observed, nor was topoisomerase II responsible for reduced toxicity. Rhein induced apoptosis but did not intercalate DNA. Aloe emodin and danthron were no substrates for MDR mechanisms. Rhein is a substrate for multidrug resistance-associated protein I and induces apoptosis. It could therefore render the colonic epithelium sensitive to cytotoxic agents, apart from being toxic in itself, (C) 2002 Cancer Research UK.
- Published
- 2002
16. The accuracy of the Helicobacter pylori stool antigen test in diagnosing H-pylori in treated patients - Reply
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Arents, NL, van Zwet, AA, Thijs, JC, de Jong, A, Pool, MO, Kleibeuker, JH, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
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PCR ,ENZYME-IMMUNOASSAY ,SPECIMENS - Published
- 2002
17. MLH1 and MSH2 protein expression as a pre-screening marker in hereditary and non-hereditary endometrial hyperplasia and cancer
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Berends, MJW, Hollema, H, Wu, Y, van der Sluis, T, Mensink, RGJ, ten Hoor, KA, Sijmons, RH, de Vries, EGE, Pras, E, Mourits, MJE, Hofstra, RMW, Buys, CHCM, Kleibeuker, JH, van der Zee, AGJ, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Targeted Gynaecologic Oncology (TARGON)
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congenital, hereditary, and neonatal diseases and abnormalities ,CARCINOMA ,MISMATCH REPAIR GENES ,MICROSATELLITE INSTABILITY ,MUTATIONS ,HMSH2 ,MLH1 ,nutritional and metabolic diseases ,NONPOLYPOSIS COLORECTAL-CANCER ,FREQUENT ,TUMORS ,digestive system diseases ,MSH2 ,endometrial cancer ,ALTERED EXPRESSION ,HMLH1 PROMOTER HYPERMETHYLATION ,protein expression ,endometrial hyperplasia - Abstract
The predictive value of MLH1 or MSH2 protein expression for the presence of truncating germline mutations was examined in benign and (pre)malignant endometrial samples from 3 patient groups: (1) 10 endometrial cancer patients from hereditary non-polyposis colorectal cancer (HNPCC) families with (n = 6) or without (n = 4) a known germline mutation; (11) 15 women from HNPCC families with (n = 7) or without (n = 8) a known germline mutation, who underwent endometrial sampling for non-malignant reasons; (III) 38 endometrial cancer patients 2001 Wiley-Liss. Inc.
- Published
- 2001
18. Red meat and colon cancer: dietary haem, but not fat, has cytotoxic and hyperproliferative effects on rat colonic epithelium
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Sesink, ALA, Termont, DSML, Kleibeuker, JH, Van der Meer, R, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
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DEOXYCHOLATE ,RISK ,EXCRETION ,BILE-ACID CONCENTRATIONS ,digestive, oral, and skin physiology ,PHOSPHATE ,BRAN ,CONSUMPTION ,CALCIUM ,COLORECTAL-CANCER ,CELL-PROLIFERATION - Abstract
High intake of red meat is associated with an increased risk of colon cancer. It has been suggested that fat from red meat is responsible, because high fat intake increases the concentration of cytotoxic lipids in the colon. Experimental studies have not unequivocally supported such a role fbr fat, however. Recently, we showed that dietary haem, which is abundant in red meat, increased colonic cytotoxicity and epithelial proliferation. In this study, we wanted to clarify whether dietary fat affects colon cancer risk by itself or by modulating the detrimental effects of haem on the colonic epithelium. Rats were fed control or haem-supplemented diets with 10%, 25% or 40% of the energy derived from fat for 14 days. Faeces were collected for biochemical analyses. Colonic cytotoxicity was determined from the degree of lysis of erythrocytes by faecal water: Colonic epithelial proliferation was measured in vivo using [H-3]thymidine incorporation. Increasing the fat content of the control diets stimulated faecal disposal of both fatty acids and bile acids. It also increased the concentration of fatty acids, but not that of bile acids, in faecal water in control rats. The cytolytic activity of faecal water and colonic epithelial proliferation were unaffected. Dietary haem increased faecal cation content and cytolytic activity of faecal water at all fat levels, suggesting that the colonic mucosa was exposed to high amounts of luminal irritants. This effect was smaller in rats on the low-fat diet. Dietary haem also increased colonic epithelial proliferation at all fat levels. The haem-induced effects were independent of fatty acids or bile acids in the faecal water. In western societies, 30-40% of ingested energy is supplied by dietary fat, so our results suggest that the association between consumption of red meat and risk of colon cancer is mainly due to its haem content, and is largely independent of dietary fat content.
- Published
- 2000
19. One year growth hormone replacement therapy does not alter colonic epithelial cell proliferation in growth hormone deficient adults
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Beentjes, JAM, van Gorkom, BAP, Sluiter, WJ, de Vries, Emma, Kleibeuker, JH, Dullaart, RPF, Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Lifestyle Medicine (LM)
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EXPRESSION ,POLYPS ,TUMOR RECURRENCE ,FACTOR-I RECEPTORS ,COLORECTAL MUCOSA ,GASTROINTESTINAL-TRACT ,CHILDREN ,MELANOCYTIC NEVI ,HYPOPITUITARISM ,CANCER - Abstract
OBJECTIVE Increased colonic epithelial cell proliferation has been found in various conditions associated with increased risk of colorectal cancer including acromegaly. In a placebo-controlled study we determined the effect of growth hormone (GH) replacement therapy in GH deficient adults on the colonic epithelial proliferation rate. PATIENTS AND DESIGN Sixteen GH deficient adults were randomised to low dose GH therapy (1 U (0.5 mg) subcutaneously per day, n = 5), high dose GH therapy (2 U daily, n = 5) or placebo (n = 6) during 6 months. Thereafter, all patients were treated with 2 U of GH daily during a 6-months open extension period. MEASUREMENTS Plasma Insulin-like growth hormone I (IGF-I) and IGF binding protein 3 (IGF BP3) concentrations were measured using commercial RIA kits. The colonic epithelial proliferation rate, expressed as overall crypt labelling index (LI) using 5-bromo-2'-deoxyuridine (BrdU) immunostaining, was determined at baseline, after 6 months treatment and at the end of the 6 months open extension period. RESULTS IGF-I rose from 8.9 +/- 6.7 to 34.6 +/- 20.0 nmol/l after 6 months in 8 GH treated patients (P 0.40 from baseline; P > 0.80 from change with placebo). In the extension study, overall crypt LI was also unchanged in those patients who received GH after placebo (n = 5, P > 0.40) and in those who continued GH replacement (n = 9, P > 0.60; P > 0.80 from change in initially placebo treated patients). Separate evaluation of the LI at the basal, mid and luminal portions of the colonic crypts also did not reveal any effect of GH treatment on BrdU labelling. CONCLUSIONS Six to 12 months of GH replacement therapy, aimed to increase plasma IGF-I into the (high) physiological range, does not adversely affect colonic epithelial cell proliferation as a biomarker for the risk of development of colorectal cancer.
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- 2000
20. Red meat and colon cancer: The cytotoxic and hyperproliferative effects of dietary heme
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Sesink, ALA, Termont, DSML, Kleibeuker, JH, Van der Meer, R, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
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FAT ,IRON ,FECAL EXCRETION ,EPITHELIUM ,FIBER ,RAT COLON ,LIPID-PEROXIDATION ,CALCIUM ,COLORECTAL-CANCER ,MILK-PRODUCTS - Abstract
The intake of a Western diet with a high amount of red meat is associated with a high risk for colon cancer. We hypothesize that heme, the iron carrier of red meat, is involved in diet-induced colonic epithelial damage, resulting in increased epithelial proliferation. Rats were fed purified control diets, or purified diets supplemented with 1.3 mu mol/g of hemin (ferriheme), protoporphyrin LY, ferric citrate, or bilirubin (rt = 8/group) for 14 days. Feces were collected for biochemical analyses. Fecal cytotoxicity was determined from the degree of lysis of erythrocytes by fecal water. Colonic epithelial proliferation was measured in vivo using [H-3]thymidine incorporation into colonic mucosa. The colonic epithelial proliferation in heme-fed rats was significantly increased compared to control rats [55.2 +/- 5.8 versus 32.6 +/- 6.3 dpm/mu g DNA (mean +/- SE); P
- Published
- 1999
21. Reliability of biopsy-based diagnostic tests for Helicobacter pylori after treatment aimed at its eradication
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van der Wouden, ET, Thijs, JC, van Zwet, AA, Oey, HB, and Kleibeuker, JH
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TRIPLE THERAPY ,NONINVASIVE TESTS ,Helicobacter pylori ,diagnosis ,polymerase chain reaction ,ACCURACY ,BREATH TEST ,POLYMERASE CHAIN-REACTION ,CAMPYLOBACTER-PYLORI ,post-treatment ,culture ,RAPID UREASE TEST ,histology ,INFECTION ,GASTRIC BIOPSIES ,DUODENAL-ULCER ,urease test - Abstract
Objective Recurrence of Heliobacter pylori after apparently successful treatment mostly represents resurgence of the infection, rather than a new one. Therefore, the reliability of biopsy-based tests after treatment was investigated. Methods Four weeks or more after treatment, antral biopsy samples were taken for culture, histology, urease test and polymerase chain reaction (PCR), and a corpus specimen for culture. Treatment failure was defined as greater than or equal to 2 tests positive. If one test was positive, a C-13-urea breath test was performed and considered conclusive. Results One hundred and ninety-seven patients were evaluated. Endoscopy was performed 53 days (27-92 days) after treatment Twenty-one patients with missing test results and 19 patients on acid-suppressive drugs were excluded. in 140 of 156 patients (89.7%), H. pylori was eradicated. Sensitivity and specificity of culture of antrum were, respectively, 100% and 100%; culture of corpus, 100% and 100%; rapid urease test, 87% and 99%; haematoxylin/eosin stain, 94% and 95%; Giemsa stain, 81% and 99%; and PCR, 88% and 100%. Conclusion Although all biopsy-based tests are reliable after treatment, culture is the biopsy-based test of first choice as it is the most accurate and gives additional information on antibiotic resistance. (C) 1999 Lippincott Williams & Wilkins.
- Published
- 1999
22. Association of hereditary nonpolyposis colorectal cancer-related tumors displaying low microsatellite instability with MSH6 germline mutations
- Author
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Wu, Y, Berends, MJW, Mensink, RGJ, Kempinga, C, Sijmons, RH, van der Zee, AGJ, Hollema, H, Kleibeuker, JH, Buys, CHCM, Hofstra, RMW, Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Targeted Gynaecologic Oncology (TARGON)
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EXPRESSION ,congenital, hereditary, and neonatal diseases and abnormalities ,CARCINOMA ,MISMATCH REPAIR GENE ,2-DIMENSIONAL DNA ELECTROPHORESIS ,CELLS ,GTBP ,nutritional and metabolic diseases ,HNPCC ,neoplasms ,digestive system diseases ,II RECEPTOR GENE - Abstract
Hereditary nonpolyposis colorectal cancer (HNPCC) (Amsterdam criteria) is often caused by mutations in mismatch repair (MMR) genes, and tumors of patients with HNPCC show microsatellite instability (MSI-high phenotype), Germline mutations of MMR genes have rarely been found in families that have HNPCC or suspected HNPCC and that do not show microsatellite instability (MSI-low phenotype). Therefore, an MSI-high phenotype is often used as an inclusion criterion for mutation testing of MMR genes. Correction of base-base mismatches is the major function of MSH6. Since mismatches present with an MSI-low phenotype, we assumed that the phenotype in patients with HNPCC-related tumors might be associated with MSH6 germline mutations. We divided 36 patients with suspected HNPCC into an MSI-low group (n = 18) and an MSI-high group (n = 18), on the basis of the results of MSI testing. Additionally, three unrelated patients from Amsterdam families with MSI-low tumors were investigated. All patients were screened for MSH2, MLH1, and MSH6 mutations. Four presumably causative MSH6 mutations were detected in the patients (22%) who had suspected HNPCC and MSI-low tumors. Furthermore, we detected one frameshift mutation in one of the three patients with HNPCC and MSI-low tumors. In the MSI-high group, one MSH6 missense mutation was found, but the same patient also had an MLH1 mutation, which may explain the MSI-high phenotype. These results suggest that MSHG may be involved in a substantial proportion of patients with HNPCC or suspected HNPCC and MSI-low tumors. Our data emphasize that an MSI-low phenotype cannot be considered an exclusion criterion for mutation testing of MMR genes in general.
- Published
- 1999
23. The influence of Helicobacter pylori on oesophageal acid exposure in GERD during acid suppressive therapy
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Peters, FTM, Kuipers, EJ, Ganesh, S, Sluiter, WJ, Klinkenberg-Knol, EC, Lamers, CBHW, Kleibeuker, JH, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
- Subjects
SPECTRUM ,REFLUX ESOPHAGITIS ,RANITIDINE ,STRAINS ,BARRETTS-ESOPHAGUS ,INFECTION ,OMEPRAZOLE ,DUODENAL-ULCER ,bacterial infections and mycoses ,GASTROESOPHAGEAL REFLUX ,GASTRITIS - Abstract
Background: Helicobacter pylori exaggerates the effect of acid suppressive drugs on intragastric pH. It is unknown whether this is relevant for the treatment of GERD. Aim: To compare oesophageal acid exposure and symptoms in H. pylori-negative and H. pylori-positive GERD patients during low and profound acid suppression. Methods: Barrett's oesophagus patients with gastro-oesophageal acid reflux were studied by 24-h oesophageal pH-metry at baseline and during randomized treatment with omeprazole 40 mg b.d. or ranitidine 150 mg b.d. a pylori status was determined by a serum IgG ELISA. Symptoms were scored on a four-graded scale. Results: Of 58 patients, 26 (14 H. pylori-negative, 12 H. pylori-positive) were randomized to omeprazole, 32 (16 H. pylori-negative, 16 H. pylori-positive) to ranitidine. At baseline, oesophageal acid exposure and symptoms did not differ between H. pylori-negative and H. pylori-positive: mean time proportion pH
- Published
- 1999
24. The influence of metronidazole resistance on the efficacy of ranitidine bismuth citrate triple therapy regimens for Helicobacter pylori infection
- Author
-
Van der Wouden, EJ, Thijs, JC, Van Zwet, AA, Kooy, A, Kleibeuker, JH, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
- Subjects
ERADICATION ,CLARITHROMYCIN ,SUSCEPTIBILITY - Abstract
Aim: To assess the influence of metronidazole resistance on the efficacy of ranitidine bismuth citrate-based triple therapy regimens in two consecutive studies. Methods: In the first study, patients with a culture-proven Helicobacter pylori infection were treated with ranitidine bismuth citrate 400 mg, metronidazole 500 mg, and clarithromycin 500 mg, all twice dairy for 1 week (RMC). In the second study, amoxycillin 1000 mg was substituted for clarithromycin (RMA). Susceptibility testing for metronidazole was performed with the E-test. Follow-up endoscopy was performed after greater than or equal to 4 weeks. Antral biopsy samples were taken for histology and urease test, and culture and corpus samples for histology and culture. Results: 112 patients, 53 males, age 55 +/- 14 years (39 duodenal ulcer, 7 gastric ulcer and 66 gastritis) were treated with RMC, and 89 patients, 52 males, age 58 +/- 15 years (23 duodenal ulcer, 7 gastric ulcer and 59 gastritis) were treated with RMA. For RMC, intention-to-treat eradication results were 98% (59/60, 95% CI: 91-100%) and 95% (20/21, 95% CI: 76-100%) for metronidazoIe susceptible and resistant strains, respectively (P = 0.45). For RMA these figures were 87% (53/61, 95% CT: 76-94%) for metronidazole susceptible strains and 22% (2/9, 95% CI: 3-60%) for resistant strains (P = 0.0001). Conclusion: Both regimens are effective in metronidazole susceptible strains. However, in contrast to the amoxycillin-containing regimen, that containing clarithromycin is also effective in resistant strains.
- Published
- 1999
25. The importance of family history in young patients with endometrial cancer
- Author
-
Berends, MJW, Kleibeuker, JH, de Vries, EGE, Mourits, MJE, Hollema, H, Pras, E, van der Zee, AGJ, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Targeted Gynaecologic Oncology (TARGON)
- Subjects
RISK ,CARCINOMA ,endometrial cancer ,genetic factors ,HNPCC ,WOMEN ,NONPOLYPOSIS COLORECTAL-CANCER ,BREAST - Abstract
Endometrial cancer occurs primarily in postmenopausal women older than 60 years of age. Especially in young patients with endometrial cancer, a positive family history with respect to cancer and/or development of synchronous or metachronous tumors can be indicative of hereditary factors. One generic disorder, playing an important role in the development of endometrial cancer in young women, is hereditary non-polyposis colorectal cancer (HNPCC). The mean age to develop endometrial cancer because of a mutation in one of thr HNPCC-genes is below 50 years. Mutation carriers have a life-rime risk of about 50% for endometrial cancer. Especially young patients with endometrial cancer should always be asked for the family history and after primary treatment the family history should regularly he updated during follow-up. (C) 1999 Elsevier Science Ireland Ltd, All rights reserved.
- Published
- 1999
26. Epithelial cell proliferative activity of Barrett's esophagus: methodology and correlation with traditional cancer risk markers
- Author
-
Peters, FTM, Ganesh, S, Kuipers, EJ, De Jager-Krikken, A, Karrenbeld, A, Harms, Geert, Sluiter, WJ, Koudstaal, J, Klinkenberg-Knol, EC, Lamers, CBHW, Kleibeuker, JH, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
- Subjects
EXPRESSION ,CARCINOMA ,proliferation ,ERADICATION ,GASTRIC-MUCOSA ,5-bromodeoxyuridine labeling ,NUCLEAR ANTIGEN ,ADENOCARCINOMA ,THERAPY ,digestive system diseases ,Barrett's esophagus ,dysplasia ,HELICOBACTER-PYLORI ,BOWEL - Abstract
Barrett's esophagus (BE) is a premalignant condition, due to chronic gastroesophageal reflux. Effective antireflux therapy may diminish cancer risk. To evaluate this option an intermediate marker is needed. We developed a methodology for measurement of epithelial cell proliferative activity of Barrett's mucosa as an intermediate marker and correlated the activity with traditional cancer risk markers and other parameters. Fifty-six patients (21-74 years of age) with Barrett's esophagus and established acid gastroesophageal reflux were included. Biopsies were taken from Barrett's mucosa at 3-cm intervals. Reflux was measured by 24-hr pH-metry. Proliferative activity was determined using in vitro labeling with 5-bromodeoxyuridine and immunohistochemistry and was expressed as labeling index (LI). The length of BE correlated with erect acid reflux (P = 0.002). LI in specialized columnar metaplasia was higher than in gastric metaplasia, especially in crypt epithelium (P
- Published
- 1998
27. Milk products and intestinal health
- Author
-
Van der Meer, R, Bovee-Oudenhoven, IMJ, Sesink, ALA, Kleibeuker, JH, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
- Subjects
bile acids ,RISK ,BILE-ACIDS ,calcium ,CALCIUM-PHOSPHATE ,DIETARY CALCIUM ,salmonella ,COLON-CANCER ,COLORECTAL MUCOSA ,food and beverages ,infection ,colon cancer ,BACTERIAL TRANSLOCATION ,cytotoxicity ,FATTY-ACIDS - Abstract
Milk products may improve intestinal health by means of the cytoprotective effects of their high calcium phosphate (CaPi) content. We hypothesized that this cytoprotection may increase host defenses against bacterial infections as well as decrease colon cancer risk. This paper summarizes our studies of these proposed protective effects. In rats, lactic acid in yoghurt and CaPi in milk products inhibited the gastrointestinal survival and colonisation of salmonellae. CaPi also inhibited translocation of salmonellae to extraintestinal organs, probably because it stimulates protective bacteria, like lactobacilli, and strengthens the mucosal barrier in the small intestine. In the large intestine, cytotoxic surfactants, like secondary bile acids and fatty acids can damage colonic epithelial cells and thus induce a compensatory hyperproliferation of crypt cells, which increases colon cancer risk. In rats this carcinogenic sequence is inhibited by milk CaPi. Also in humans, milk CaPi precipitates colonic cytotoxic surfactants and thus inhibits colonic cytotoxicity. These results suggest that milk products may decrease colon cancer risk. (C) 1998 Elsevier Science Ltd. All rights reserved.
- Published
- 1998
28. Mechanisms of the intestinal effects of dietary fats and milk products on colon carcinogenesis
- Author
-
VanderMeer, R, Lapre, JA, Govers, MJAP, Kleibeuker, JH, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
- Subjects
bile acids ,dietary calcium ,CYTOLYTIC ACTIVITY ,FECAL WATER ,RISK ,BILE-ACIDS ,CALCIUM-PHOSPHATE ,PROLIFERATION ,MEN ,digestive system diseases ,COLORECTAL-CANCER ,SUPPLEMENTATION ,colon cancer ,cytotoxicity ,hyperproliferation ,animal fat - Abstract
Dietary fat may promote colon cancer by increasing fatty acids (FA) and secondary bile acids (BA) in the colonic lumen. These cytotoxic surfactants can damage colonic epithelial cells and thus induce a compensatory hyperproliferation of crypt Cells. Our studies show that the hyperproliferative effect of type and amount of dietary fat is not simply due to changes in colonic FA and BA. This indicates that an additional, at present unknown, cytotoxic factor is involved. The hyperproliferative effect of dietary fat is inversely related to the amount of calcium in the diet. In rat and man, dietary calcium precipitates colonic cytotoxic surfactants and thus inhibits luminal cytotoxicity. These inhibitory effects on metabolic risk factors suggest a preventive effect of dietary calcium on colon carcinogenesis. (C) 1997 Elsevier Science Ireland Ltd.
- Published
- 1997
29. Increased epithelial cell proliferation in the colon of patients with acromegaly
- Author
-
Cats, A, Dullaart, RPF, Kleibeuker, JH, Kuipers, F, Sluiter, WJ, Hardonk, MJ, deVries, EGE, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Center for Liver, Digestive and Metabolic Diseases (CLDM), and Lifestyle Medicine (LM)
- Subjects
POLYPS ,EXPRESSION ,CHOLIC-ACID ,BILE-ACIDS ,PATTERN ,HUMAN GROWTH-HORMONE ,COLORECTAL MUCOSA ,SOMATOSTATIN ,CANCER-PATIENTS ,TUMORS - Abstract
To gain insight into the possible physiological mechanisms responsible for the increased incidence of colonic neoplasms in patients with acromegaly, a prospective cohort study was carried out in 30 patients with acromegaly. Seven patients had a newly diagnosed acromegaly and 23 were studied during follow-up. Serum growth hormone and insulin-like growth factor-1 (IGF-1) were determined on two separate occasions, During diagnostic endoscopy, mucosal biopsies were obtained for immunohistochemical determination of sigmoidal epithelial cell proliferation, expressed as labeling index (LI), Duodenal and fecal bile acid analyses were performed using gas-liquid chromatography. Results were compared with normal ranges of the laboratory. An increased overall LI was found in 54% of the patients, Increased LI of the luminal, middle, and basal crypt compartments was found in 11, 64, and 28%, respectively. Similarly, comparisons of the mean +/- SEM of the overall LI and the LI of the middle and basal compartments between acromegalic patients and a control group showed overall LI 10.0 +/- 0.8% versus 5.7 +/- 0.6% (P
- Published
- 1996
30. RE - EXCESSIVELY HIGH CELL-PROLIFERATION IN SIGMOID COLON AFTER AN ORAL PURGE WITH ANTHRAQUINONE GLYCOSIDES - REPLY
- Author
-
KLEIBEUKER, JH, CATS, A, DEVRIES, EGE, University of Groningen, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
- Published
- 1995
31. EVALUATION OF CLINICAL AND HOME PERFORMANCE OF THE C-13-UREA BREATH TEST FOR THE DETECTION OF HELICOBACTER-PYLORI
- Author
-
THIJS, WJ, THIJS, JC, KLEIBEUKER, JH, ELZINGA, H, STELLAARD, F, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
- Subjects
HELICOBACTER PYLORI ,C-13-UREA BREATH TEST - Abstract
Objective: This study analyses the C-13-urea breath test with the aim of determining the optimal time interval between dosing and breath sampling and examines the feasibility of having patients perform the test without supervision at home. Design: Prospective study comparing the C-13-urea breath test with four antral biopsy-based tests in a random population undergoing upper gastrointestinal endoscopy. Setting: One university hospital and one general hospital. Patients: One hundred and four patients were included; 61 were Helicobacter pylori-positive and 43 H. pylori-negative according to biopsy-based tests. Interventions: The C-13-urea breath test was performed at home by collecting a baseline and two post-dosing samples; the next day it was performed clinically by collecting a baseline and six post-dosing samples. A 100 mg dose of C-13-urea and a test meal were used. Outcome measures: The breath samples collected were analysed. Excess delta (CO2)-C-13/(CO2)-C-12 values above five per million were considered positive. Results: The specificity of the clinical test was 100% whereas that of the home-based test was 95.1%. The sensitivity of the clinical test depended on the time interval between dosing and collection of the evaluated sample. Sensitivity was 100% if the sample was taken 50 min or more after dosing. The home-based test had a sensitivity of 94.8%. Conclusion: To obtain maximum sensitivity (100%) using the single-sample technique the sample has to be collected at least 50 min after dosing. It is feasible to have the test performed at home. Patient selection and thorough instruction are necessary.
- Published
- 1995
32. EXCESSIVELY HIGH CELL-PROLIFERATION IN SIGMOID COLON AFTER AN ORAL PURGE WITH ANTHRAQUINONE GLYCOSIDES
- Author
-
KLEIBEUKER, JH, CATS, A, ZWART, N, MULDER, NH, HARDONK, MJ, DEVRIES, EGE, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
- Subjects
RISK ,MUCOSA ,INDUCTION ,LARGE-BOWEL ,HYDROXYANTHRAQUINONES ,CANCER ,RATS - Published
- 1995
33. CHRONIC MESENTERIC ISCHEMIA - DIAGNOSTIC CHALLENGES AND TREATMENT OPTIONS
- Author
-
HOOGENBERG, K, VANESSEN, LH, VANDENDUNGEN, JJAM, LIMBURG, AJ, BOEVE, WJ, KLEIBEUKER, JH, Faculteit Medische Wetenschappen/UMCG, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
- Subjects
MALABSORPTION ,ANGINA ,CHRONIC INTESTINAL ISCHEMIA ,REVASCULARIZATION ,CHRONIC MESENTERIC ,ANGIOGRAPHY ,DIETARY TREATMENT ,DISEASE ,ISCHEMIA ,COLLATERAL VESSELS ,GASTRIC ULCER - Abstract
Objectives. A description of the clinical presentation, diagnostic procedure and mode of therapy in three patients suffering from chronic mesenteric ischaemia. Design and interventions. In all cases, the diagnosis was made on the basis of abdominal complaints in combination with angiographic findings. The primary treatment objective was restoration of blood flow via a revascularization procedure, for the patient in whom this could not be accomplished an enteral feeding programme was undertaken. Results. One patient had a panmalabsorption syndrome which was treated with an aortomesenteric bypass operation, the second one presented with multiple gastric ulcerations which only improved after a percutaneous transluminal angioplasty. In the third patient, neither surgery or angioplasty were feasible and a tentative enteral feeding programme was given, after which the ability to consume a normal oral diet without abdominal distress was regained. Conclusions. These three cases illustrate the diverse clinical pictures by which chronic mesenteric ischaemia may present itself. This diagnosis should be kept in mind when other more common causes of a patient's abdominal complaints cannot be found, hence giving consideration to abdominal angiography as the next diagnostic procedure. With respect to therapy, restoring blood now through surgery or angioplasty is the primary form of treatment. However, if neither of these therapeutic options is feasible, it is suggested that such patients may benefit from a nutritional training programme.
- Published
- 1995
34. HEREDITARY NONPOLYPOSIS COLORECTAL-CANCER - RESULTS OF LONG-TERM SURVEILLANCE IN 50 FAMILIES
- Author
-
VASEN, HFA, TAAL, BG, NAGENGAST, FM, GRIFFIOEN, G, MENKO, FH, KLEIBEUKER, JH, OFFERHAUS, GJA, KHAN, PM, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
- Subjects
KINDREDS ,PATHOLOGY ,HOMOLOG ,TUMOR SPECTRUM ,NETHERLANDS ,HEREDITARY NONPOLYPOSIS COLORECTAL CANCER ,LYNCH SYNDROME ,SURVEILLANCE ,ADENOMAS ,digestive system diseases - Abstract
A surveillance programme comprising either colonoscopy or sigmoidoscopy plus barium enema every 2-3 years was instituted in 50 hereditary nonpolyposis colorectal cancer (HNPCC) families. The families included 238 patients with colorectal cancer (CRC) (mean age at diagnosis: 43.7 years; range: 16-86 years). These patients had 597 first-degree relatives of whom 493 could be traced and 388 (79%) accepted the invitation for screening. The control group were relatives (index patients) with symptomatic CRC. The average follow-up duration was 5 years (1-20 years). Screening led to the detection of adenomas in 33 patients and CRC in 11 patients. Pathological examination revealed 1 Dukes' A, 7 Dukes' B and 3 Dukes' C cancers. In contrast, among the control group 47% had advanced CRC (Dukes' C or distant metastases). The 5-year survival of the screen-detected cases was 87% versus 63% in the control group. Of the 11 CRC cases in the screening group, 4 were detected within 1-4 years after a negative colonic examination. A large proportion of the polyps found in the screening and control groups showed a villous growth pattern and/or a high degree of dysplasia. We conclude that periodic examination of HNPCC families allows the detection of cancer at an earlier stage than in patients not under surveillance. Because of the possibly more aggressive nature of polyps associated with HNPCC, we recommend a screening interval of 1-2 years.
- Published
- 1995
35. CALCIUM AND VITAMIN-D - POSSIBLE PROTECTIVE AGENTS AGAINST COLORECTAL-CANCER
- Author
-
KLEIBEUKER, JH, VANDERMEER, R, DEVRIES, EGE, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
- Subjects
FECAL WATER ,CYTOLYTIC ACTIVITY ,COLORECTAL CANCER ,BILE-ACIDS ,CARCINOGENESIS ,COLON CANCER ,CALCIUM ,EPITHELIAL-CELL PROLIFERATION ,ADENOMATOUS POLYPS ,CELL PROLIFERATION ,COLON ,SUPPLEMENTAL DIETARY CALCIUM ,PHOSPHATE ,CYTOTOXICITY ,FATTY-ACIDS ,BILE ACIDS ,VITAMIN-D ,FATTY ACIDS - Abstract
Nutritional factors are important determinants of colorectal cancer risk. Diets high in fat and/or low in fibre are especially recognised to increase risk. Dietary calcium and vitamin D have been suggested to be protective against colorectal cancer. With respect to calcium, its possible effect is thought to be mediated at least in part through intraluminal precipitation of hydrophobic, cytotoxic substances, in particular fatty and bile acids, which can promote colorectal cancer development. Data from studies in vitro and in animals support a protective effect of calcium, but studies in humans, both epidemiological and interventional, have given inconclusive results. With respect to vitamin D, data from only a small number of studies are available. Results suggest a protective effect by inhibition of cell proliferation, mediated through specific receptors. It is concluded that there are currently insufficient reasons to supplement subjects at increased colon cancer risk with calcium or vitamin D, especially when dietary intake of these substances is in agreement with general guidelines.
- Published
- 1995
36. CLINICAL HETEROGENEITY OF FAMILIAL COLORECTAL-CANCER AND ITS INFLUENCE ON SCREENING PROTOCOLS
- Author
-
VASEN, HFA, TAAL, BG, GRIFFIOEN, G, NAGENGAST, FM, CATS, A, MENKO, FH, OSKAM, W, KLEIBEUKER, JH, OFFERHAUS, GJA, KHAN, PM, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
- Subjects
KINDREDS ,CARCINOMA ,MYOTONIC-DYSTROPHY ,NETHERLANDS - Abstract
The age at onset of non-polyposis colorectal cancer (CRC) was investigated in 49 families with at least three relatives affected in two successive generations. Forty one of these families satisfy the accepted minimum criteria for hereditary non-polyposis CRC. The remaining eight families were distinguished by a late age of disease onset and, hence, could not be included in the group. The condition in these latter families has been designated provisionally, as late onset familial CRC. The hereditary non-polyposis CRC families include 194 patients, 110 men and 84 women (mean age at diagnosis: 44 years; range: 16-74 years). Ninety two per cent of the patients were diagnosed by age 60. Colorectal cancer was diagnosed at progressively earlier ages in successive generations (p
- Published
- 1994
37. PERIOPERATIVE MEASURES DURING LIVER-TRANSPLANTATION FOR ERYTHROPOIETIC PROTOPORPHYRIA
- Author
-
MEERMAN, L, SLOOFF, MJH, VANHATTUM, J, KLEIBEUKER, JH, HAAGSMA, EB, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
- Subjects
CIRRHOSIS - Published
- 1994
38. ANAEROBES AND THEIR FERMENTATION PRODUCTS IN FECES OF PATIENTS WITH FAMILIAL ADENOMATOUS POLYPOSIS BEFORE AND AFTER SUBTOTAL COLECTOMY AND ILEORECTAL ANASTOMOSIS
- Author
-
MEIJERSEVERS, GJ, CATS, A, VERSCHUEREN, RCJ, VANSANTEN, E, KLEIBEUKER, JH, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
- Subjects
FECES ,FLORA ,CULTURAL COUNTS ,SHORT-CHAIN FATTY ACIDS ,SUBTOTAL COLECTOMY ,FECAL FLORA ,digestive system ,digestive system diseases ,ANAEROBES ,CHAIN FATTY-ACIDS ,FAMILIAL ADENOMATOUS POLYPOSIS ,COLON ,RECTAL POLYPS ,ILEORECTAL ANASTOMOSIS ,HEALTHY-HUMAN VOLUNTEERS ,FECAL BACTERIOLOGY - Abstract
In view of the importance of short-chain fatty acids (SCFA) for the colonic epithelial function and their possible relation with the reported spontaneous regression of rectal polyps after subtotal colectomy with ileorectal anastomosis, we compared the SCFA concentrations in faeces of five familial adenomatous polyposis (FAP) patients before, and in 10 FAP patients after operation to each other and to those of 10 healthy controls. Anaerobe cultural counts and concentrations of organic acids were also investigated in the same faecal samples from FAP patients and controls. The preoperative cultural counts were not significantly different from those of the controls. After colectomy, the Bacteroides (P
- Published
- 1993
39. EPITHELIAL-CELL PROLIFERATION IN THE SIGMOID COLON OF PATIENTS WITH ADENOMATOUS POLYPS INCREASES DURING ORAL CALCIUM SUPPLEMENTATION
- Author
-
KLEIBEUKER, JH, WELBERG, JWM, MULDER, NH, VANDERMEER, R, CATS, A, LIMBURG, AJ, KREUMER, WMT, HARDONK, MJ, DEVRIES, EGE, Faculteit Medische Wetenschappen/UMCG, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
- Subjects
HIGH-RISK ,MUCOSA ,DIETARY CALCIUM ,FAT ,PH ,PHOSPHATE ,COLORECTAL-CANCER - Abstract
To study the effect of oral supplemental calcium on colonic epithelial proliferation, 17 adenomatous polyp patients received 1.5 g Ca2+ as calcium carbonate daily during 12 weeks, while on a calcium constant diet, based on the patients' habitual diet. Seven subsequently continued calcium supplementation for 9 months without dietary restrictions. Epithelial proliferation rate in colonic biopsies, expressed as labelling index (%), was determined with 5-bromodeoxyuridine and immunohistochemistry. Biopsies were taken from the midsigmoid at time of polyp excision and at the end of the intervention period. Median labelling index increased from 6.1% before to 8.7% after 12 weeks calcium (n = 17, P
- Published
- 1993
40. MECHANISM OF THE PROTECTIVE EFFECT OF SUPPLEMENTAL DIETARY CALCIUM ON CYTOLYTIC ACTIVITY OF FECAL WATER
- Author
-
LAPRE, JA, DEVRIES, HT, TERMONT, DSML, KLEIBEUKER, JH, DEVRIES, EGE, VANDERMEER, R, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
- Subjects
EPITHELIAL-CELL PROLIFERATION ,BILE-ACIDS ,HIGH-RISK ,FAT ,PHOSPHATE ,COLON CANCER - Abstract
Dietary calcium supplementation inhibits hyperproliferation of rectal epithelium, possibly by precipitating luminal surfactants and thus preventing their cell-damaging effects. Therefore, we studied the effects of supplemental dietary calcium (35.5 mmol/day) on composition and cytolytic activity of fecal water and on the release of the epithelial marker alkaline phosphatase in 12 healthy volunteers. Fecal water was isolated by low-speed centrifugation. Cytolytic activity was determined as lysis of human erythrocytes by fecal water. Intestinal alkaline phosphatase activity in fecal water was measured with the use of the uncompetitive inhibitor L-phenylalanine. Supplemental calcium increased soluble calcium and decreased soluble P(i). The logarithm of the concentration product of calcium and phosphate was linearly dependent on pH. These observations indicate formation of insoluble calcium phosphate. Supplemental calcium did not alter the total bile acid concentration in fecal water but significantly decreased the ratio of more hydrophobic to more hydrophilic bile acids from 3.3 to 2.3. Calcium also significantly decreased the concentration of fatty acids (from 2.9 to 2.1 mm). Consistent with these decreases in hydrophobic surfactants, calcium decreased the cytolytic activity of fecal water from 47 +/- 9 to 27 +/- 8% (n = 12, P
- Published
- 1993
41. RECENT DEVELOPMENTS IN DIAGNOSIS AND TREATMENT OF METASTATIC CARCINOID-TUMORS
- Author
-
DEVRIES, EGE, KEMA, IP, SLOOFF, MJH, VERSCHUEREN, RCJ, KLEIBEUKER, JH, MULDER, NH, SLEIJFER, DT, WILLEMSE, PHB, Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Lifestyle Medicine (LM)
- Subjects
ALPHA-2B INTERFERON ,ENDOCRINE PANCREATIC TUMORS ,SYMPTOMS ,ISLET-CELL CARCINOMA ,CARCINOID TUMOR ,HEPATIC-ARTERY EMBOLIZATION ,HUMAN-LEUKOCYTE INTERFERON ,SEROTONIN ,STREPTOZOCIN ,SOMATOSTATIN ANALOG ,THERAPY - Abstract
In carcinoid patients a tumour of enterochromaffin cell origin is present, which dependent on the site of origin can result in increased serotonin production. Metastasized carcinoids are often diagnosed by measuring 5-hydroxyindoleacetic acid excretion in the urine. This excretion, however, can be influenced by food intake. On the other hand, serotonin measured in blood platelets is unaffected by food intake and, in addition, is found to be more sensitive. Therapy of metastasized carcinoids is directed at tumour reduction or only reduction of symptoms. Tumour reduction can be achieved surgically or by embolization. Combination chemotherapy has a maximum response percentage of about 33%. Over the last few years, both octreotide and interferon alpha have been used in these patients. They rarely result in a reduction of the tumour size (10-20%). Symptom reduction is achievable in most patients with these agents, however. Recently, increasing knowledge obtained concerning the various serotonin receptors and their antagonists is now being used in the treatment of patients with a metastasized carcinoid. In the future it is expected that the different modalities will be combined increasingly.
- Published
- 1993
42. THE REDUCED CANINE PANCREAS TO STUDY THE EFFECTS OF INTRAOPERATIVE RADIOTHERAPY
- Author
-
HEIJMANS, HJ, MEHTA, D, KLEIBEUKER, JH, SLUITER, WJ, HOEKSTRA, HJ, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
- Subjects
PANCREAS, CANINE ,INTRAOPERATIVE RADIOTHERAPY ,RETROPERITONEAL STRUCTURES ,DOGS ,RADIOTHERAPY, INTRAOPERATIVE ,RADIATION ,TOLERANCE ,THERAPY ,IRRADIATION - Abstract
A canine model is described to study the tolerance of the pancreas to intra-operative radiotherapy (IORT). The canine pancreas is a horseshoe-shaped organ. To create a homogeneous delivery of IORT to the whole pancreas surgical manipulation is necessary which may induce pancreatitis. A resection of the left and right lobes of the pancreas facilitates the delivery of IORT, reduces the risk of pancreatitis and will demonstrate, eventually, minimal functional changes in the exocrine and endocrine pancreas at an earlier stage. Sixteen beagles were used. Investigations before and after the reduction procedure were intravenous glucose tolerance tests, serum insulin levels, faecal fat excretion, blood chemistry tests and body weight. Eight weeks after the pancreas reduction 1 5 dogs underwent an IORT procedure in which 25, 30 or 35 Gy IORT was delivered to the pancreatic remnant. We conclude that the pancreas reduction technique used to study the effects of IORT to the canine pancreas is feasible without mortality or morbidity. Endocrine and exocrine pancreatic function remained normal with a minimal follow-up of 3 months.
- Published
- 1993
43. ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES (ANCA) IN AUTOIMMUNE LIVER-DISEASE
- Author
-
MULDER, AHL, HORST, G, HAAGSMA, EB, KLEIBEUKER, JH, KALLENBERG, CGM, Gross, WL, Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Translational Immunology Groningen (TRIGR)
- Published
- 1993
44. REGULATION OF GASTRIC-ACID SECRETION BY GASTRIN IN DUODENAL-ULCER PATIENTS AND HEALTHY-SUBJECTS
- Author
-
EYSSELEIN, VE, KOVACS, TOG, KLEIBEUKER, JH, MAXWELL, [No Value], REEDY, T, WALSH, JH, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
- Subjects
SERUM GASTRIN ,PH ,PYLORI ,MEALS - Published
- 1992
45. ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES IN PRIMARY SCLEROSING CHOLANGITIS, ULCERATIVE-COLITIS, AND AUTOIMMUNE-DISEASES
- Author
-
TERVAERT, JWC, MULDER, AHL, HORST, G, HAAGSMA, EB, KLEIBEUKER, JH, KALLENBERG, CGM, Faculteit Medische Wetenschappen/UMCG, Guided Treatment in Optimal Selected Cancer Patients (GUTS), and Translational Immunology Groningen (TRIGR)
- Published
- 1992
46. EFFECTS OF CISAPRIDE ON THE ESOPHAGEAL MOTOR FUNCTION OF PATIENTS WITH PROGRESSIVE SYSTEMIC-SCLEROSIS OR MIXED CONNECTIVE-TISSUE DISEASE
- Author
-
LIMBURG, AJ, SMIT, AJ, KLEIBEUKER, JH, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Groningen Kidney Center (GKC), and Vascular Ageing Programme (VAP)
- Subjects
ESOPHAGEAL MOTILITY ,SCLERODERMA ,PROGRESSIVE SYSTEMIC SCLEROSIS ,PATHOGENESIS ,CISAPRIDE ,LOWER ESOPHAGEAL SPHINCTER ,GASTROINTESTINAL MANIFESTATIONS ,DYSFUNCTION ,MIXED CONNECTIVE TISSUE DISEASE - Abstract
In a double-blind crossover study lower esophageal sphincter pressure and distal esophageal motility were studied in 10 patients with progressive systemic sclerosis or mixed connective tissue disease, following a single intravenous dose of cisapride or placebo. The measurements were carried out under basal conditions and 30 min after intravenous administration of 10 mg cisapride or placebo. No effects on lower esophageal sphincter pressure or distal esophageal motility were observed.
- Published
- 1991
47. Anastomotic biliary strictures after liver transplantation: prevalence, presentation, management and outcome
- Author
-
Verdonk, RC, primary, Buis, CI, additional, Porte, RJ, additional, van der Jagt, EJ, additional, Limburg, AJ, additional, van den Berg, AP, additional, Slooff, MJH, additional, Kleibeuker, JH, additional, and Haagsma, EB, additional
- Published
- 2006
- Full Text
- View/download PDF
48. TRAIL induces apoptosis in human colorectal adenomas and human colorectal adenoma cell lines
- Author
-
Jalving, M, primary, Koornstra, J.J, additional, de Jong, S, additional, Zwart, N, additional, Boersma-van Ek, W, additional, Wesseling, J, additional, de Vries, EGE, additional, and Kleibeuker, JH, additional
- Published
- 2006
- Full Text
- View/download PDF
49. The role of TRAIL-mediated apoptosis in the development of colorectal cancer and possibilities for treatment and prevention (Final report Maag Lever Darm Stichting project WS 01-31)
- Author
-
Koornstra, JJ, primary, Jalving, M, additional, Rijcken, FEM, additional, de Jong, S, additional, Hollema, H, additional, de Vries, EGE, additional, and Kleibeuker, JH, additional
- Published
- 2006
- Full Text
- View/download PDF
50. Proton pump inhibitor use is associated with the development of sporadic fundic gland polyps
- Author
-
Jalving, M, primary, Koornstra, JJ, additional, de Jong, S, additional, Wesseling, J, additional, and Kleibeuker, JH, additional
- Published
- 2006
- Full Text
- View/download PDF
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