Ulcerative Colitis: Kruis W

Kruis W, Anonymous00189. · No affiliation provided · Z Gastroenterol. · Pubmed #11215365 No free full text.

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Böhm SK, Kruis W. · Evangelisches Krankenhaus Kalk, Abteilung für Innere Medzin, Universität Zu Köln, Buchforststrasse 2, Köln, Germany. · Ann N Y Acad Sci. · Pubmed #17057214 No free full text.

Abstract: There is currently a growing appreciation for the role of the enteric flora in health and disease. In the past years overwhelming evidence has accumulated for the role of commensal gut bacteria in the inflammatory bowel diseases Crohn's disease and ulcerative colitis. Both entities are mainly located in areas with high bacterial concentrations. Reduction of the enteric bacterial concentration by antibiotics, lavage, or surgical bypass results in a mitigation of symptoms, while experimental colitis models depend on the presence of the bacterial flora and the NOD2/CARD15-mutation results in inefficient clearance of invasive bacteria. Those findings helped to bring the concept of probiotic therapy to the forefront, a therapy that had been known for millennia, but had been disregarded by the scientific world. Probiotics are meanwhile established in the maintenance therapy of ulcerative colitis and chronic recurrent or refractory pouchitis. Promising data exist for the primary prevention of pouchitis. Probiotic research at the intersection of gastroenterology, immunology and microbiology is highly dynamic in both the basic and the clinical field. Further understanding of the complex molecular mechanisms leading to the effectiveness of probiotics will also spur the development of more successful probiotic formulations.

Böhm S, Kruis W. · Evangelisches Krankenhaus Kalk, Köln. · MMW Fortschr Med. · Pubmed #16995360 No free full text.

Abstract: Current data show that probiotics are more effective in preventing the recrudescence of an inflammatory process than in suppressing active disease.This is reflected in the solid evidence for the effect of E. coli Nissle 1917 (Mutaflor) in the maintenance of remission of ulcerative colitis, and of VSL#3 in preventing the recurrence of pouchitis. These indications have since been incorporated in valid guidelines. Initial clinical studies have also provided promising results regarding the efficacy of VSL#3 in preventing pouchitis immediately following proctocolectomy.

Hoffmann JC, Zeitz M, Bischoff SC, Brambs HJ, Bruch HP, Buhr HJ, Dignass A, Fischer I, Fleig W, Fölsch UR, Herrlinger K, Höhne W, Jantschek G, Kaltz B, Keller KM, Knebel U, Kroesen AJ, Kruis W, Matthes H, Moser G, Mundt S, Pox C, Reinshagen M, Reissmann A, Riemann J, Rogler G, Schmiegel W, Schölmerich J, Schreiber S, Schwandner O, Selbmann HK, Stange EF, Utzig M, Wittekind C. · Medizinische Klinik I mit Schwerpunkt Gastroenterologie/Infektiologie/Rheumatologie, Charité, Universitätsmedizin Berlin. · Z Gastroenterol. · Pubmed #15455267 No free full text.

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Kruis W. · Evangelisches Krankenhaus Kalk, Teaching Hospital for the University of Cologne, Germany. · Aliment Pharmacol Ther. · Pubmed #15352898 links to  free full text

Abstract: Treatment with antibiotics in inflammatory bowel disease has a long tradition and is widely used. The indications for antibiotic therapy are wide ranging, from specific situations such as abscesses or fistulae, to patients with severe disease (as an unspecific 'protective' measure), and to address the hypothesis that the enteric flora as a whole, or specific microorganisms such as mycobacteria, are involved in the pathogenesis of inflammatory bowel disease. The best-studied single antibiotic compound is metronidazole. However, overall, the scientific basis for the use of antibiotics is limited, which may reflect a lack of interest from sponsors within the pharmaceutical industry. Despite this weak evidence base, antibiotics are a globally established therapeutic tool in inflammatory bowel disease. Growing evidence from human and animal studies points towards a pivotal pathogenetic role of intestinal bacteria in inflammatory bowel disease. In view of these experimental findings, clinical trials have been undertaken to elucidate the therapeutic effects of probiotics in inflammatory bowel disease. Probiotics are viable nonpathogenic microorganisms which confer health benefits to the host by improving the microbial balance of the indigenous microflora. So far, of the many candidates, one specific strain (Escherichia coli Nissle 1917) and a mixture of eight different bacteria have demonstrated convincing therapeutic efficacy in controlled studies. Maintenance therapy in ulcerative colitis and prevention therapy, as well as the treatment of pouchitis, have emerged as areas in which probiotic therapy offers a valid therapeutic alternative to current treatments. Further investigations may detect additional clinically effective probiotics and other clinical indications.

Hoffmann RM, Kruis W. · Innere Abteilung, Evangelisches Krankenhaus Kalk, Buchforststrasse 2, 51103 Köln. · Internist (Berl). · Pubmed #12524920 No free full text.

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Stange EF, Riemann J, von Herbay A, Lochs H, Fleig WE, Schölmerich J, Kruis W, Porschen R, Bruch HP, Zeitz M, Schreiber S, Moser G, Matthes H, Selbmann HK, Goebell H, Caspary WF. · Abteilung Innere Medizin 1 Robert-Bosch-Krankenhaus Auerbachstrasse 110 70376 Stuttgart. · Z Gastroenterol. · Pubmed #11215358 No free full text.

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Duchmann R, Lochs H, Kruis W. · Innere Medizin II, Universität des Saarlandes, Homburg/Saar. · MMW Fortschr Med. · Pubmed #10949626 No free full text.

Abstract: Crohn's disease (CD) and ulcerative colitis (UC) are clinical entities characterized by spontaneous relapses and are thought to be caused in large part by a dysregulated immune response to inflammatory stimuli. Specific infectious agents or antigens inducing or perpetuating inflammation, however, are not known. Recent results in contrast support the hypothesis, that the normal intestinal flora plays a central role in the pathogenesis of both diseases. Studies performed with E. coli Nissle 1917 demonstrated that this bacterium can positively affect the course of disease in UC and CD patients. The clinical efficacy of probiotics can yield valuable information about disease pathogenesis and, as a modification of current standard therapy, opens new and interesting therapeutic alternatives.

Pohl C, Hombach A, Kruis W. · Innere Abteilung, Evangelisches Krankenhaus Köln Kalk, Germany. · Hepatogastroenterology. · Pubmed #10690586 No free full text.

Abstract: Colorectal cancer represents the major cause for excess morbidity and mortality by malignant disease in ulcerative colitis as well as in Crohn's disease. The risk for ulcerative colitis associated colorectal cancer is increased at least 2-fold compared to the normal population and colorectal cancer is observed in 5.5-13.5% of all patients with ulcerative colitis and 0.4-0.8% of patients with Crohn's disease. Established risk factors include long duration of the disease, large extent of the disease, low activity of the disease, young age at onset, presence of complicating primary sclerosing cholangitis or stenotic disease and possibly lack of adequate surveillance, inadequate pharmacological therapy, folate deficiency and non-smoking. Crohn's disease is associated with an increased risk of colorectal carcinoma in patients with long-standing disease, strictures and fistulae under the condition that the colon is involved, tumors of the small intestine may occur occasionally. Extracolonic malignancies are rare, with the exception of biliary tract cancer. Ulcerative colitis associated colorectal cancer typically can occur in the entire colon, is often multifocal and of undifferentiated histology. Stage distribution and prognosis of ulcerative colitis associated colorectal cancer appears to be similar to that of sporadic colorectal cancer with an overall survival of about 40% (15-65%) after 5 years with tumor stage at diagnosis being the most important predictive parameter for survival. Tumor markers helpful for the diagnosis of sporadic colorectal cancer fail to differentiate between inflammatory response and malignant transformation. In contrast the histologic evidence of dysplasia was shown to be a strong indicator of underlying carcinoma or developing malignant transformation. The presence of a surface projection termed dysplasia associated lesion or mass is highly indicative of underlying or associated cancer. While the routinely performed search for dysplasia is hampered by high interobserver variation the demonstration of DNA-aneuploidy or genetic changes which may confirm the ongoing malignant transformation has not yet become clinical routine. The genetic alterations found in ulcerative colitis associated colorectal cancer involve many of the same targets found in sporadic colorectal tumors and include multiple sites of allelic deletion, microsatellite instabilities, and mutations of APC, p53, Ki-ras as well as MSH2 and other genes. The progression of dysplasia to carcinoma is generally accompanied by an accumulation of these mutations and the similarities in the biology of colorectal cancer associated with ulcerative colitis and sporadic colorectal cancer appear to outweigh their difference. In regard to the management of dysplasia and cancer, the role of surveillance programs for the early detection of ulcerative colitis associated colorectal cancer at a curable stage is still under debate. Although these programs failed at tumor prevention and lethal carcinomas are still found inadvertently in patients under surveillance, the majority of surveillance programs could reduce mortality by detecting more cancers at a still curable stage. Current recommendations for surveillance include, therefore, biennial colonoscopy with extensive biopsies after 8-10 years of total colitis or after 15-20 years of left-sided colitis. In the presence of cancer or unequivocal high-grade dysplasia and/or dysplasia associated lesion or mass proctocolectomy is considered adequate. The evidence of low-grade dysplasia should be confirmed before proctocolectomy is considered.

Kruis W, Pohl C. · Innere Abteilung des Evangelischen Krankenhauses Köln-Kalk. · Med Klin (Munich). · Pubmed #10194945 No free full text.

Abstract: Sulfasalazine (SASP), since 60 years standard in the treatment of ulcerative colitis, is a double molecule where 5-aminosalicylic acid (5-ASA) and sulfapyridine (SP) are linked together by an azobond. Bacterial splitting of SASP within the colon allows delivery of 5-ASA for its topical action (prodrug system). To target 5-ASA without the less tolerable SP down to the lower intestine new prodrugs have been developed and, in addition, mesalazine is offered which contains 5-ASA prepared as a delayed release preparation. A clinical comparison (metaanalysis) tended towards superiority of the new prodrugs and mesalazine over SASP for inducing remission, while SASP was more effective in maintaining remission. Only few studies exist comparing the efficacy of the new drugs and mesalazine. To date a slight superiority of the new prodrugs is implied. With the exception of SASP safety profiles do not significantly differ between the different drugs containing 5-ASA.

Kruis W, Kiudelis G, Rácz I, Gorelov IA, Pokrotnieks J, Horynski M, Batovsky M, Kykal J, Boehm S, Greinwald R, Mueller R, Anonymous00095. · Evangelisches Krankenhaus Kalk, University of Cologne, Cologne, Germany. · Gut. · Pubmed #18832520 links to  free full text

Abstract: OBJECTIVES: To determine the therapeutic equivalence and safety of once daily (OD) versus three times daily (TID) dosing of a total daily dose of 3 g Salofalk (mesalazine) granules in patients with active ulcerative colitis. DESIGN: A randomised, double-blind, double-dummy, parallel group, multicentre, international, phase III non-inferiority study. SETTING: 54 centres in 13 countries. PATIENTS: 380 patients with confirmed diagnosis of established or first attack of ulcerative colitis (clinical activity index (CAI)>4 and endoscopic index > or =4 at baseline) were randomised and treated. INTERVENTIONS: 8-week treatment with either 3 g OD or 1 g TID mesalazine granules. MAIN OUTCOME MEASURES: Clinical remission (CAI< or =4) at study end. RESULTS: 380 patients were evaluable for efficacy and safety by intention-to-treat (ITT); 345 for per protocol (PP) analysis. In the ITT population, 79.1% in the OD group (n = 191) and 75.7% in the TID group (n = 189) achieved clinical remission (p<0.0001 for non-inferiority). Significantly more patients with proctosigmoiditis achieved clinical remission in the OD group (86%; n = 97) versus the TID group (73%; n = 100; p = 0.0298). About 70% of patients in both treatment groups achieved endoscopic remission, and 35% in the OD group and 41% in the TID group achieved histological remission. About 80% of all patients preferred OD dosing. Similar numbers of adverse events occurred in 55 patients (28.8%) in the OD group and in 61 patients (32.3%) in the TID group, indicating that the two dosing regimens were equally safe and well tolerated. CONCLUSIONS: OD 3 g mesalazine granules are as effective and safe as a TID 1 g schedule. With respect to the best possible adherence of patients to the treatment, OD dosing of mesalazine should be the preferred application mode in active ulcerative colitis.

Oxelmark L, Hillerås P, Dignass A, Mössner J, Schreiber S, Kruis W, Löfberg R. · Department of Medicine, Karolinska University Hospital, Solna, Sweden. · Scand J Gastroenterol. · Pubmed #17354122 No free full text.

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Kruis W, Dignass A, Steinhagen-Thiessen E, Morgenstern J, Mössner J, Schreiber S, Vecchi M, Malesci A, Reinshagen M, Löfberg R. · Evangelisches Krankenhaus Kalk, Innere Abteilung, Universität zu Köln, Germany. · World J Gastroenterol. · Pubmed #16437606 links to  free full text

Abstract: AIM: To study the efficacy, safety, and feasibility of a granulocyte adsorptive type apheresis system for the treatment of patients with chronically active ulcerative colitis despite standard therapy. METHODS: An open label multicenter study was carried out in 39 patients with active ulcerative colitis (CAI 6-8) despite continuous use of steroids (a minimum total dose of 400 mg prednisone within the last 4 wk). Patients received a total of five aphereses using a granulocyte adsorptive technique (Adacolumn (reg), Otsuka Pharmaceutical Europe, UK). Assessments at wk 6 and during follow-up until 4 mo comprised clinical (CAI) and endoscopic (EI) activity index, histology, quality of life (IBDQ), and laboratory tests. RESULTS: Thirty-five out of thirty-nine patients were qualified for intent-to-treat analysis. After the apheresis treatment at wk 6, 13/35 (37.1%) patients achieved clinical remission and 10/35 (28.6%) patients had endoscopic remission (CAI<4, EI<4). Quality of life (IBDQ) increased significantly (24 points, P<0.01) at wk 6. Apheresis could be performed in all but one patient. Aphereses were well tolerated, only one patient experienced anemia. CONCLUSION: In patients with steroid refractory ulcerative colitis, five aphereses with a granulocyte/monocyte depleting filter show potential short-term efficacy. Tolerability and technical feasibility of the procedure are excellent.

Musch E, Andus T, Kruis W, Raedler A, Spehlmann M, Schreiber S, Krakamp B, Malek M, Malchow H, Zavada F, Engelberg Feurle G. · Department of Internal Medicine, Marienhospital Bottrop, Bottrop, Germany. · Clin Gastroenterol Hepatol. · Pubmed #15952100 No free full text.

Abstract: BACKGROUND & AIMS: We performed a randomized, double-blind, placebo-controlled, multicenter trial to investigate the efficacy and safety of recombinant interferon-beta-1a (rIFN-beta-1a) in outpatients with active steroid-refractory ulcerative colitis. METHODS: Ninety-one randomized patients subcutaneously received 3 MIU rIFN-beta-1a (group A, n = 32), 1 MIU rIFN-beta-1a (group B, n = 30), or placebo (group C, n = 29) 3 times a week over a period of 8 weeks in addition to standard therapy. An intention-to-treat analysis was performed to evaluate the efficacy and safety of treatment. Results: In all 3 groups, the median prestudy clinical activity index (CAI) was 10. In 18 of 32 patients (56%) in group A, in 11 of 30 patients (36%) in group B, and in 10 of 29 patients (34%) in group C, a reduction of the CAI of 6 points or greater (response) was achieved (differences were not statistically significant). Complete response (reduction of CAI to < or =4) was achieved in 56%, 30%, and 38% of patients in groups A, B, and C, respectively. Compared with baseline, the median endoscopic index had been reduced by 5, 3, and 4 points in groups A, B, and C, respectively. Steroid reduction was 12 mg in group A, 6 mg in group B, and 10 mg in group C. Identical side effects occurred in all 3 groups. Seven serious adverse events were reported (1 in group A and 6 in group C). All were unrelated to therapy as judged by the investigating physicians. CONCLUSIONS: rIFN-beta-1a was safe but not significant, at the dosage and/or duration of treatment used, in steroid-refractory ulcerative colitis. Further studies are indicated.

Kruis W, Fric P, Pokrotnieks J, Lukás M, Fixa B, Kascák M, Kamm MA, Weismueller J, Beglinger C, Stolte M, Wolff C, Schulze J. · Evangelisches Krankenhaus Kalk, University of Cologne, Germany. · Gut. · Pubmed #15479682 links to  free full text

Abstract: BACKGROUND AND AIMS: Evidence exists for the pathogenic role of the enteric flora in inflammatory bowel disease. Probiotics contain living microorganisms which exert health effects on the host. We compared the efficacy in maintaining remission of the probiotic preparation Escherichia coli Nissle 1917 and established therapy with mesalazine in patients with ulcerative colitis. PATIENTS AND METHODS: In total, 327 patients were recruited and assigned to a double blind, double dummy trial to receive either the probiotic drug 200 mg once daily (n = 162) or mesalazine 500 mg three times daily (n = 165). The study lasted for 12 months and patients were assessed by clinical and endoscopic activity indices (Rachmilewitz) as well as by histology. The primary aim of the study was to confirm equivalent efficacy of the two drugs in the prevention of relapses. RESULTS: The per protocol analysis revealed relapses in 40/110 (36.4%) patients in the E coli Nissle 1917 group and 38/112 (33.9%) in the mesalazine group (significant equivalence p = 0.003). Subgroup analyses showed no differences between the treatment groups in terms of duration and localisation of disease or pretrial treatment. Safety profile and tolerability were very good for both groups and were not different. CONCLUSIONS: The probiotic drug E coli Nissle 1917 shows efficacy and safety in maintaining remission equivalent to the gold standard mesalazine in patients with ulcerative colitis. The effectiveness of probiotic treatment further underlines the pathogenetic significance of the enteric flora.

Kruis W, Bar-Meir S, Feher J, Mickisch O, Mlitz H, Faszczyk M, Chowers Y, Lengyele G, Kovacs A, Lakatos L, Stolte M, Vieth M, Greinwald R. · Evangelisches Krankenhaus Kalk, University of Cologne, Cologne, Germany. · Clin Gastroenterol Hepatol. · Pubmed #15017515 No free full text.

Abstract: BACKGROUND AND AIMS: 5-Aminosalicylate is the gold standard for inducing remission in patients with mildly to moderately active ulcerative colitis. The optimal dose is as yet not defined. Despite some recent developments, the ideal formulation for 5-aminosalicylic acid is still awaited. A new pellet preparation was designed combining slow and delayed release properties. Aims of the study were to find the optimal dose and to test efficacy and safety of a new 5-aminosalicylic acid formulation. METHODS: Three hundred twenty-one patients were included in a double-blind multicenter trial. Inclusion criteria were active ulcerative colitis (Clinical Activity Index [CAI] and Endoscopic Index [EI] according to Rachmilewitz, CAI 6-12; EI >/=4). Three different doses of 5-aminosalicylic acid (0.5 g 3 times a day, 1.0 g 3 times a day, and 1.5 g 3 times a day) were studied for 8 weeks. RESULTS: Clinical remission rate (CAI </=4) was highest in the 1.0 g 3 times a day group (66 %), 50% in the 0.5 g 3 times a day group, and 55% in the 1.5 g 3 times a day group. Hierarchical testing showed no significance, indicating a lack of dose response across the 3 mesalamine doses. In addition, times to first clinical response were similar: 26.5 days (1.0 g 3 times a day), 27.5 days (0.5 g 3 times a day), and 21.5 days (1.5 g 3 times a day). Endoscopic improvement was better with 1.0 g mesalamine 3 times a day than with 0.5 g 3 times a day, but overall endoscopic and histologic improvement was not different between treatment groups. Baseline activity, duration, and localization of ulcerative colitis did have some influence on the therapeutic activity, but there was no significant interaction with the dose of the study drug. Safety, with special focus on kidney function, was excellent in all 3 groups. CONCLUSIONS: There is no significant dose response between mesalamine 1.5 g/day, 3.0 g/day, and 4.5 g/day. The optimal dose to induce remission of ulcerative colitis is 0.5 g 5-aminosalicylic acid 3 times a day. Patients failing with this dose may benefit from an increase of the dose up to 1.0 g 3 times a day, but should also be considered for alternative treatment. A newly developed pellet formulation of 5-aminosalicylic acid has promising efficacy and excellent safety.

Kruis W, Schreiber S, Theuer D, Brandes JW, Schütz E, Howaldt S, Krakamp B, Hämling J, Mönnikes H, Koop I, Stolte M, Pallant D, Ewald U. · Evangelisches Krankenhaus Kalk, Teaching Hospital of the University of Cologne, Germany. · Gut. · Pubmed #11709512 links to  free full text

Abstract: BACKGROUND: Balsalazide is a new 5-aminosalicylic acid (5-ASA) containing prodrug. Its efficacy in comparison with standard mesalazine therapy and the optimum dose for maintaining remission of ulcerative colitis are still unclear. AIMS: To compare the relapse preventing effect and safety profile of two doses of balsalazide and a standard dose of Eudragit coated mesalazine. METHODS: A total of 133 patients with ulcerative colitis in remission were recruited to participate in a double blind, multicentre, randomised trial: 49 patients received balsalazide 1.5 g twice daily, 40 received balsalazide 3.0 g twice daily, and 44 received mesalazine 0.5 g three times daily. Efficacy assessments were clinical activity index (CAI) and endoscopic score according to Rachmilewitz, and a histological score. In addition, laboratory tests were performed and urinary excretion of 5-ASA and its metabolite N-Ac-5-ASA was analysed. The study lasted for 26 weeks. RESULTS: Balsalazide 3.0 g twice daily resulted in a significantly higher clinical remission rate (77.5%) than balsalazide 1.5 g twice daily (43.8%) and mesalazine 0.5 g three times daily (56.8%) (p=0.006). The respective times to relapse were 161 days, 131 days (p=0.003), and 144 days (NS). Accordingly, pairwise contrasts of the final endoscopic score demonstrated a significant difference (p=0.005) between the two balsalazide treatment groups while differences between either of these two groups and mesalazine were not statistically significant. Patients treated with balsalazide excreted less 5-ASA and N-Ac-5-ASA than patients receiving mesalazine but these differences were not statistically significant. Discontinuation of the trial because of adverse effects occurred in nine patients: three in the balsalazide 1.5 g twice daily group, two in the balsalazide 3.0 g twice daily group, and four in the mesalazine 0.5 g three times daily group. No clinically important new drug safety related findings were identified in this study. CONCLUSIONS: High dose balsalazide (3.0 g twice daily) was superior in maintaining remission in patients with ulcerative colitis compared with a low dose (1.5 g twice daily) or a standard dose of mesalazine (0.5 g three times daily). All three treatments were safe and well tolerated.

Bantel H, Berg C, Vieth M, Stolte M, Kruis W, Schulze-Osthoff K. · Department of Internal Medicine B, Medical Clinics, University of Münster, Germany. · Am J Gastroenterol. · Pubmed #11151876 No free full text.

Abstract: OBJECTIVES: The salicylate mesalazine is commonly used for the treatment of inflammatory bowel diseases, yet its precise mechanism of action is unknown. Because transcription factor NF-kappaB plays an important role in inflammatory bowel diseases, we investigated the effects of mesalazine therapy on NF-kappaB activation in patients with ulcerative colitis. METHODS: A total of 20 patients with moderately active ulcerative colitis received mesalazine for 8 wk. Biopsies were taken before and after drug administration and analyzed for NF-kappaB activation using an antibody specific for active NF-kappaB. RESULTS: In biopsies of active ulcerative colitis but not in noninflamed mucosa, activation of NF-kappaB was detected predominantly in macrophages. Mesalazine therapy resulted, in a strong abrogation of NF-kappaB activation in situ. CONCLUSIONS: Our results suggest that the therapeutic properties of mesalazine rely at least in part on the inhibition of NF-kappaB activation, resulting in the suppression of proinflammatory gene expression in the inflamed mucosa.

Allgayer H, Roisch U, Zehnter E, Ziegenhagen DJ, Dienes HP, Kruis W. · Department of Gastroenterology and Metabolism, Rehaklinik Ob der Tauber, Bad Mergentheim, Academic Teaching Hospital, University of Heidelberg, Heidelberg, Germany. · Dig Dis Sci. · Pubmed #17171446 No free full text.

Abstract: The role of colonic mucosal ornithine decarboxylase (ODC) in inflammatory bowel disease (IBD) remains controversial. This study assessed mucosal ODC activity in IBD patients segment by segment with regard to patient characteristics, disease activity/duration, medication, degree of mucosal inflammation, and presence/absence of epithelial regeneration and guanosine triphosphate (GTP) stimulation. Mucosal ODC activity was determined in biopsy specimens from the terminal ileum, cecum/ascending, transverse, and descending colon, and the sigmoid/rectum of 35 patients with IBD (18 with Crohn's disease, 17 with ulcerative colitis) and 29 controls, using the amount of 14CO2 liberated from (carboxyl-14C)ornithine hydrochloride. GTP-stimulatable activity was expressed as the ratio of ODC activity in the presence and absence of GTP (70 micromol/L). Mucosal inflammation was assessed endoscopically/microscopically with previously described criteria. Presence/absence of mucosal regeneration also was determined by predefined criteria. Mucosal ODC-activity did not significantly differ in IBD patients and controls. There was a 4.4-fold activity gradient from the ileum to the rectum. Mucosal ODC activity was significantly higher in areas with epithelial regeneration compared to those without regeneration, and was stimulated by GTP by a factor of 1.42 in Crohn's disease and 1.19 in ulcerative colitis patients compared to controls (p < 0.004). On the other hand, there was no significant association/relationship of mucosal ODC activity with disease activity/duration and the endoscopic/histologic degree of mucosal inflammation. The observation of unchanged mucosal ODC activity in patients with IBD and the absence of a significant relationship with clinical and endoscopic/histologic disease characteristics speaks against a major role of ODC in IBD as a major disease marker. The role of the ileorectal gradient, the enhanced activity in areas with epithelial regeneration, and the GTP-stimulatable form, however, need further investigation with regard to a possible involvement in carcinogenesis in IBD.

Buschhausen L, Kruis W, Aymaz S, Weber M, Krakamp B. · Medizinische Klinik I, Kliniken der Stadt Köln gGmbH, Köln-Merheim. · Med Klin (Munich). · Pubmed #17039321 No free full text.

Abstract: BACKGROUND AND PURPOSE: Patients with ulcerative colitis have a higher rate of tubular nephropathies. Data concerning the cause of these lesions is rare and inconsistent, the occurrence may be part of the disease itself or a side effect of 5-aminosalicylates (5-ASA). This study investigated proteinuria and eosinophiluria in patients with moderate ulcerative colitis under treatment with 5-ASA. PATIENTS AND METHODS: Urine specimens (microelectrophoresis and eosinophiluria) of 34 patients with acute onset of moderate ulcerative colitis who were treated only with 5-ASA as active drug were analyzed. RESULTS: Data of 27 patients could be evaluated. Twelve patients had tubular proteinuria previous to treatment. By the end of the study, urine specimens normalized in six, in further six the proteinuria remained unaltered, two patients developed proteinuria under treatment. In 14 patients, proteinuria was not detectable at any time. Eosinophiluria was found in none of the specimens. CONCLUSION: Under treatment with 5-ASA no toxic or allergic nephropathy developed. One initially pathologic urine specimen normalized under treatment coming along with remission of the intestinal symptoms and histological findings. This indicates an association between the activity of the ulcerative colitis and might be caused by renal excretion of pro-inflammatory cytokines.

Holtmann MH, Krummenauer F, Claas C, Kremeyer K, Lorenz D, Rainer O, Vogel I, Böcker U, Böhm S, Büning C, Duchmann R, Gerken G, Herfarth H, Lügering N, Kruis W, Reinshagen M, Schmidt J, Stallmach A, Stein J, Sturm A, Galle PR, Hommes DW, D'Haens G, Rutgeerts P, Neurath MF. · First Department of Medicine, Johannes Gutenberg University, Mainz, Germany. · Dig Dis Sci. · Pubmed #16927148 No free full text.

Abstract: In Crohn's disease the optimal duration of azathioprine treatment is still controversial and for ulcerative colitis only limited data are available to support its efficacy. Charts of 1176 patients with IBD from 16 European centers were analyzed. Flare incidences and steroid dosages were assessed for the time before and during treatment and after discontinuation. Within the first 4 years, azathioprine suppressed flare incidence and steroid consumption in both diseases (P < 0.001). While in CD discontinuation after 3-4 years did not lead to reactivation, this was the case in UC. However, continuation beyond 4 years further improved clinical activity in CD and steroid requirement in both diseases (P < 0.001). Discontinuation of azathioprine may thus be considered after 3-4 years in CD patients in complete remission without steroid requirement. In all other CD patients and for UC patients in general, continuation seems beneficial. These results support a novel differential algorithm for long-term azathioprine therapy in IBD.

Kruis W, Schreiber S. · Abt. Innere Medizin, Evangelisches Krankenhaus Köln-Kalk. · Z Gastroenterol. · Pubmed #15455275 No free full text.

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Kruis W. · Evangelisches Krankenhaus Kalk, Innere Abteilung. · Dtsch Med Wochenschr. · Pubmed #15368174 No free full text.

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Kruis W. · Innere Abteilung, Evangelisches Krankenhaus Kalk, Köln, Germany. · Int J Colorectal Dis. · Pubmed #10954189 No free full text.

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Allgayer H, Kruis W. · No affiliation provided · Clin Gastroenterol Hepatol. · Pubmed #16616360 No free full text.

This publication has no abstract.