Ulcerative Colitis: Klump B

Fölsch UR, Hoffmann J, Höhne W, Janke KH, Klump B, Rogler G, Schreiber S. · Klinik für Allgemeine Innere Medizin, I. Medizinische Klinik, Universitätsklinikum Kiel, Schittenhelmstrasse 12, 24105 Kiel. · Internist (Berl). · Pubmed #12524923 No free full text.

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Janke KH, Steder-Neukamm U, Bauer M, Raible A, Meisner C, Hoffmann JC, Gregor M, Klump B, Häuser W. · Universitätsklinikum Tübingen, Abteilung Innere Medizin I, Kompetenznetz CED -- Core Facility Tübingen. · Gesundheitswesen. · Pubmed #16217720 No free full text.

Abstract: BACKGROUND: Health-related quality of life (HRQOL) is an important outcome-parameter in health research and care. The aim of the working group Quality of Life in the Competence Network Inflammatory Bowel Disease (IBD; in the original German: "Kompetenznetz chronisch entzündliche Darmerkrankungen") is to generate instruments for assessment of HRQOL and its implementation as standards in clinical trials, health care and research in IBD. METHODS: The Inflammatory Bowel Disease Questionnaire (IBDQ) is an international validated disease specific instrument for HRQOL-assessment. A German version of the IBDQ was elaborated and tested in 415 outpatients with Crohn's disease (CD, n = 306) and ulcerative colitis (UC, n = 109). The aim of the study was to compare the results of HRQOL-assessment (IBDQ-D) with international investigations, to correlate HRQOL results with disease activity and to preform a pretest of psychometric properties. RESULTS: International data suggest that the IBDQ-D is a suitable instrument for HRQOL-assessment in CD and UC. For both disease a statistically significant negative correlation with disease activity was found. Tested psychometric properties do not suggest that a revision of the IBDQ-D is required. The IBDQ-D offers the HRQOL-assessment as an primary or secondary outcome in clinical trials in IBD in Germany.

Spoettl T, Hausmann M, Klebl F, Dirmeier A, Klump B, Hoffmann J, Herfarth H, Timmer A, Rogler G. · Department of Internal Medicine I, University of Regensburg, Germany. · Inflamm Bowel Dis. · Pubmed #17260368 links to  free full text

Abstract: BACKGROUND: Tumor necrosis factor alpha (TNFalpha) is a proinflammatory cytokine and an important mediator in the pathophysiology of inflammatory bowel disease (IBD). The effects of TNFalpha are mediated by 2 specific receptors, a 55-kDa protein (TNF-RI) and a 75-kDa receptor (TNF-RII), which are usually bound to the cell surface. Soluble TNF receptors I and II (sTNF-RI + II) are released by proteolytic cleavage of the extracellular domains of these receptors. Soluble TNF-Rs act as TNF antagonists and can inhibit TNFalpha-mediated proinflammatory effects. METHODS: Levels of sTNF-RI + II were measured using commercially available enzyme-linked immunosorbent assays (ELISAs). Serum levels of sTNF-RI + II of 76 healthy volunteers were compared to serum levels of 373 clinically well-characterized patients with Crohn's disease (CD) and 118 patients with ulcerative colitis (UC) with different disease activity from the German IBD competence network serum bank. CD patient subgroups were defined according to the Vienna Classification. RESULTS: The serum levels of sTNF-RI were significantly increased in all groups (active, chronic active, and remission) of CD and UC patients compared to healthy controls. sTNF-RII levels were significantly higher in active CD patients compared to UC patients with no overlap of the 95% confidence interval. Significantly higher values of sTNF-RII compared to controls were also observed in CD patients and UC patients in remission. There was no statistically significant difference in sTNF-RI or sTNF-RII levels when patient subgroups were analyzed according to disease behavior or disease localization. CONCLUSION: sTNF-RI is upregulated in the serum of IBD patients compared to healthy controls and could be used as a marker for disease activity. sTNF-RII levels are significantly more elevated in serum of active CD patients as compared to UC and could be used as an additional parameter to discriminate both diseases.

Janke KH, Klump B, Steder-Neukamm U, Hoffmann J, Häuser W. · Medizinische Klinik und Poliklinik, Abteilung Innere Medizin I, Universitätsklinikum Tübingen. · Psychother Psychosom Med Psychol. · Pubmed #16715461 No free full text.

Abstract: The Inflammatory Bowel Disease Questionnaire (IBDQ) is the standard disease-specific instrument for assessment of health-related quality of life (HRQOL) in patients with inflammatory bowel diseases (IBD). A German translation has not been validated. 415 outpatient IBD-patients (Crohn's Disease n = 306, Ulcerative Colitis n = 109) completed the German version of the IBDQ (Competence network IBD, IBDQ-D), the Hospital Anxiety and Depression Scale German Version (HADS-D) and the Questions on Life Satisfaction FLZ. Face validity was assessed by a physicians' and patients' panel. Disease activity was measured by the German Inflammatory Bowel Disease Activity Index (GIBDI). With 97.3 % completed items the acceptance was high. The Cronbach's alpha for the subscales ranged from 0.88 to 0.89. The correlation coefficients with comparable subscales of other instruments ranged between 0.09 and 0.70. Patients in remission and different disease activities differed significantly (p < 0.001) in all IBDQ-D-subscales.

Janke KH, Klump B, Gregor M, Meisner C, Haeuser W. · Department of Internal Medicine I, University Hospital Tübingen, Competence Network IBD-Core Facility, Tübingen, Germany. · Inflamm Bowel Dis. · Pubmed #15735434 No free full text.

Abstract: In patients with Crohn's disease (CD) and ulcerative colitis (UC), medical, sociodemographic, and psychologic "risk and protective" factors for general and health-related life satisfaction (GLS and HRLS, respectively)--defined as preference-based judgments of general and health-related quality of life--have not been studied to date. METHODS: A total of 429 of 868 (49%) outpatients (CD, n = 317; UC, n = 112) attending 3 tertiary care centers and members of the German Crohn's Disease/Ulcerative Colitis Foundation completed the sociodemographic and medical questionnaires of the German "Competence Network Inflammatory Bowel Diseases," the Hospital Anxiety and Depression Scale, and the "Questions on Life Satisfaction(Modules)". Disease activity was assessed by the German Inflammatory Bowel Disease Activity Index. "Questions on Life Satisfaction(Modules)" data were compared with a representative sample of the German general population. RESULTS: GLS and HRLS were reduced compared with the general German population (P < 0.005). Logistic regression showed that mental disorder was a risk factor of reduced GLS in CD [odds-ratio (OR), 2.7; P < 0.01] and UC (OR, 6.3; P < 0.02). Membership in a self-help organization offered no protection against reduced GLS in CD (OR, 0.5; P < 0.02). In CD, psychiatric (OR, 10.4; P < 0.01) and medical comorbidity (OR, 2.0; P < 0.02) and disease activity (OR, 4.0; P < 0.01) were risk factors of reduced HRLS, whereas in UC, only disease activity (OR, 6.6; P < 0.01) predicted reduced HRLS. CONCLUSIONS: To improve GLS and HRLS in inflammatory bowel disease, both the treatment of bowel disease and medical and psychiatric comorbidity are necessary. Strengthening of social support is an additional way to promote GLS.

Janke KH, Raible A, Bauer M, Clemens P, Meisner C, Häuser W, Steder-Neukamm U, Henrich G, Herschbach P, Gregor M, Klump B. · Competence Network IBD--Core Facility Tübingen, Department of Internal Medicine I, University Hospital Tübingen, Otfried-Müller-Strasse 10, 72076 Tübingen, Germany. · Int J Colorectal Dis. · Pubmed #14586630 No free full text.

Abstract: BACKGROUND AND AIMS: When assessing quality of care the outcome in terms of quality of life (QOL) is of major significance. This study examined QOL in IBD outpatients and the contribution of individual expectations and various other factors including disease activity. PATIENTS AND METHODS: The study included 306 outpatients with Crohn's disease and 109 with ulcerative colitis (UC). General and health-related QOL was quantified using the instrument Questions on Life Satisfaction(Modules). Disease activity was assessed by a questionnaire. Data were compared with a normal population sample. RESULTS: Life satisfaction scores on general items and on health-related items were significantly lower than in a control sample (60.5+/-37.3 and 74.4+/-41.5, respectively) among both CD patients (54.3+/-33.2, 59.1+/-38.8) and UC patients (45.4+/-34.0, 52.1+/-40.7). Scores were significantly related to severity of disease activity. IBD patients attributed particular importance to health-related issues. CONCLUSION: Both health-related and general life satisfaction is compromised in IBD outpatients, and health-related topics have major impact. Not surprisingly, inflammatory activity compromises QOL, which underlines the importance of anti-inflammatory strategies. The importance attributed to health-related features is higher in IBD patients than in the normal population.

Holzmann K, Weis-Klemm M, Klump B, Hsieh CJ, Borchard F, Gregor M, Porschen R. · Medizinische Klinik und Poliklinik, Abt. Innere Medizin I, Universitätsklinikum Tübingen, Germany. · Scand J Gastroenterol. · Pubmed #11761024 No free full text.

Abstract: BACKGROUND: We evaluate the usefulness of screening for p53 and Ki-ras mutations in comparison with histological and flow cytometric findings. METHODS: We analyzed 1486 biopsy samples from 769 locations of 83 patients with long-standing ulcerative colitis enrolled in a surveillance program by means of histology, flow cytometry and SSCP analysis. As a control we used 66 biopsy samples of 16 patients with irritable bowel disease. RESULTS: With respect to all biopsy samples analyzed, DNA aneuploidy was found in 32.5% (27/83) of patients, dysplasia in 22.9% (15/83), p53 in 21.7% (18/83) and Ki-ras mutations in 18.1% (15/83) of patients. None of these markers was found in our control group. In 7 out of 10 patients who displayed dysplastic findings during endoscopic surveillance p53 and / or Ki-ras mutations were present in at least one colonoscopy. Statistically significant associations were observed between dysplasia and DNA aneuploidy (P < 0.001), between dysplasia and p53 mutations (P = 0.05) and between dysplasia and p53 and/or Ki-ras mutations (P = 0.002). No significant associations were found between dysplasia and Ki-ras mutations alone. The results for the SSCP analysis showed a much broader variation than those for the flow cytometric analysis. CONCLUSIONS: These results show that screening for p53 and Ki-ras mutations can be a useful adjunct in surveillance of patients with long-standing ulcerative colitis.

Holzmann K, Klump B, Borchard F, Gregor M, Porschen R. · Department of Internal Medicine I, Eberhard-Karls-University Tübingen, Tübingen, Germany. · Dis Colon Rectum. · Pubmed #11598473 No free full text.

Abstract: PURPOSE: To examine the prevalence of DNA aneuploidy as a function of the extent of ulcerative colitis and to study the correlation of aneuploidy with clinical characteristics. Furthermore, the occurrence of aneuploidy and dysplasia during colonoscopic surveillance was studied in a subset of these patients. METHODS: By analyzing 5404 biopsy samples of 368 patients with ulcerative colitis, we have evaluated the importance of DNA ploidy measured by flow cytometry. We have also investigated the influence of extent (219 patients with extensive or total colitis vs. 149 patients with localized colitis) and duration of colitis on the development of dysplasia (patients with biopsy specimens that showed inflammation alone were compared with those with biopsy specimens that were equivocal or positive for dysplasia) and aneuploidy. Included was a subgroup of patients with ulcerative colitis and primary sclerosing cholangitis (n = 16). RESULTS: Aneuploidy was found in 8.7 percent (32/368) of all patients. The prevalence of aneuploidy increased by the extent of ulcerative colitis (2 percent localized, 6.8 percent extensive colitis, 14.9 percent total colitis). The frequency of aneuploidy was higher in patients with disease duration longer than 10 years (P = 0.007). Patients with ulcerative colitis and primary sclerosing cholangitis were more likely to develop aneuploidy (9/16, 56.3 percent vs. 14/120, 11.7 percent; P < 0.001) and dysplasia (4/16, 25 percent vs. 10/120, 8.3 percent; P = 0.06) than patients without primary sclerosing cholangitis. CONCLUSION: Because DNA aneuploidy represents an early alteration during neoplastic transformation in ulcerative colitis, flow cytometry is a valuable tool in the surveillance of those patients. Primary sclerosing cholangitis represents an additional risk factor for the development of DNA aneuploidy and dysplasia.

Holzmann K, Klump B, Weis-Klemm M, Hsieh CJ, Borchard F, Gregor M, Porschen R. · Department of Gastroenterology, University of Tuebingen, Germany. · Anticancer Res. · Pubmed #11268482 No free full text.

Abstract: Telomerase activity is frequently associated with neoplasia. It is a ribonucleoprotein capable of replacing telomeric DNA sequences that are lost at each cell division. Neoplastic progression in chronic ulcerative colitis is characterized by the development of epithelial dysplasia which is accompanied by genetic alterations. Therefore we tested telomerase activity in 128 biopsy samples of four colectomy specimens with long-standing ulcerative pancolitis by using the Telomerase PCR ELISA System. In three patients with multiple dysplastic or carcinomatous lesions, telomerase activity was detected in 22 samples with a regional association to dysplastic or carcinomatous areas. 15 of the samples with telomerase activity (68%) were found in dysplastic/carcinomatous samples or in the direct vicinity of dysplastic areas, 4 (18%), 2 positions (about 4 cm) and the remaining three (14%) not more than 3 positions away from such areas. In the fourth patient, resected because of clinical deterioration despite medical treatment and who had no dysplastic lesions, no telomerase activity was detected. These results show that telomerase activity might be used as a complementary marker to histology for the identification of patients with ulcerative colitis who are at an increased risk for neoplastic progression.