Crohn Disease: Lochs H

Lochs H, Dejong C, Hammarqvist F, Hebuterne X, Leon-Sanz M, Schütz T, van Gemert W, van Gossum A, Valentini L, Anonymous00249, Lübke H, Bischoff S, Engelmann N, Thul P, Anonymous00250. · Department of Gastroenterology, Charité-Universitätsmedizin, CCM, Berlin, Germany. · Clin Nutr. · Pubmed #16698129 No free full text.

Abstract: Undernutrition as well as specific nutrient deficiencies have been described in patients with Crohn's disease (CD), ulcerative colitis (UC) and short bowel syndrome (SBS). The present guideline gives evidence-based recommendations for the indication, application and type of formula of enteral nutrition (EN) (oral nutritional supplements (ONS) or tube feeding (TF)) in these patients. It was developed in an interdisciplinary consensus-based process in accordance with officially accepted standards and is based on all relevant publications since 1985. ONS and/or TF in addition to normal food is indicated in undernourished patients with CD or CU to improve nutritional status. In active CD EN is the first line therapy in children and should be used as sole therapy in adults mainly when treatment with corticosteroids is not feasible. No significant differences have been shown in the effects of free amino acid, peptide-based and whole protein formulae for TF. In remission ONS is recommended only in steroid dependent patients in CD. In patients with SBS TF should be introduced in the adaptation phase and should be changed with progressing adaptation to ONS in addition to normal food.

Lochs H. · No affiliation provided · Inflamm Bowel Dis. · Pubmed #17985374 links to  free full text

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Büning C, Lochs H. · Department of Gastroenterology, Hepatology & Endocrinology, Charité Campus Mitte, Universitätsmedizin Berlin, Schumannstrasse 20/21, Berlin 10117, Germany. · World J Gastroenterol. · Pubmed #16937460 links to  free full text

Abstract: Crohn's disease (CD) is a multifactorial disorder of unknown cause. Outstanding progress regarding the pathophysiology of CD has led to the development of innovative therapeutic concepts. Numerous controlled trials have been performed in CD over the last years. However, many drugs have not been approved by regulatory authorities due to lack of efficacy or severe side effects. Therefore, well-known drugs, including 5-ASA, systemic or topical corticosteroids, and immunosuppressants such as azathioprine, are still the mainstay of CD therapy. Importantly, biologicals such as infliximab have shown to be efficacious in problematic settings such as fistulizing or steroid-dependent CD. This review is intended to give practical guidelines to clinicians for the conventional treatment of CD. We concentrated on the results of randomized, placebo-controlled trials and meta-analyses, when available, that provide the highest degree of evidence. We provide evidence-based treatment algorithms whenever possible. However, many clinical situations have not been answered by controlled clinical trials and it is important to fill these gaps through expert opinions. We hope that this review offers a useful tool for clinicians in the challenging treatment of CD.

Lochs H. · Medizinische Klinik mit Schwerpunkt Gastroenterologie, Hepatologie und Endokrinologie, Charité Universitätsmedizin Berlin, Schumannstr 20/21, D 10117 Berlin, Germany. · Gut. · Pubmed #16474102 links to  free full text

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Sandborn WJ, Feagan BG, Hanauer SB, Lochs H, Löfberg R, Modigliani R, Present DH, Rutgeerts P, Schölmerich J, Stange EF, Sutherland LR. · The Clinical Trials Task Force of the International Organization of Inflammatory Bowel Disease. · Gastroenterology. · Pubmed #11832465 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.

Teml A, Kratzer V, Schneider B, Lochs H, Norman GL, Gangl A, Vogelsang H, Reinisch W. · Universitätsklinik für Innere Medizin IV, Abteilung für Gastroenterologie und Hepatologie, and Institut für Medizinische Statistik, Universtität Wien, Vienna, Austria. · Am J Gastroenterol. · Pubmed #14572572 No free full text.

Abstract: OBJECTIVES: An increased prevalence of elevated serum anti-Saccharomyces cerevisiae antibody (ASCA) levels in patients with Crohn's disease (CD) has been described. The aim of the present work was to investigate serum ASCA levels during the courses of prednisolone and mesalamine therapy in CD patients. METHODS: Serum samples of 25 patients with active CD were studied for ASCA levels before as well as 2 and 9 wk after initiation of a prednisolone tapering regimen. The influence of mesalamine (4 g o.d.) on serum ASCA levels compared to that of placebo was tested over 1 yr in 38 patients (20 mesalamine and 18 placebo) participating in a postoperative prophylaxis study. Serum IgG and IgA ASCA levels were measured by ELISA. Sera of 91 CD and 40 ulcerative colitis (UC) patients as well as 334 healthy donors were tested for ASCA to recalculate new cut-off values. RESULTS: For IgG ASCA cut-off values were determined to be 17.0 U and 25.0 U, and for IgA ASCA 9.3 U and 14.0 U. At baseline visit, 73.0% (46/63) of patients displayed serum ASCA positivity. During prednisolone therapy, a decrease in serum IgG and IgA ASCA levels from baseline to wk 2 (p < 0.0001 and p < 0.001, respectively) as well as to wk 9 (p < 0.001 and p = 0.01, respectively) was observed. A trend toward an association of ASCA positivity and steroid responsiveness was calculated (p = 0.07). During mesalamine treatment, no differences in changes of ASCA levels were observed compared to placebo at any time point. CONCLUSIONS: ASCA are stable markers during steroid and mesalamine treatment, highlighting their reliability for use in diagnosis of CD.

Andus T, Gross V, Caesar I, Schulz HJ, Lochs H, Strohm WD, Gierend M, Weber A, Ewe K, Schölmerich J, Anonymous00232. · Klinikum Stuttgart, Krankenhaus Bad Cannstatt, Stuttgart, Germany. · Dig Dis Sci. · Pubmed #12643618 No free full text.

Abstract: Glucocorticosteroids (GCS) are established in the treatment of active Crohn's ileitis and ileocolitis. Recently, the topical steroid budesonide was found to be effective in untreated patients with Crohn's disease (CD) causing less side effects than conventional GCS. No clinical data have been reported about the effects of switching from conventional GCS to budesonide in terms of side effects and disease activity. The primary aim of this study was to evaluate the development of side effects after switching from conventional GCS treatment to Eudragit L-coated budesonide (pH-modified release formulation) in patients taking 5-30 mg prednisolone equivalent per day for at least two weeks. In all, 178 patients with active CD (N = 88) or CD in remission during GCS treatment (N = 90) were included. Conventional GCS treatment was tapered down during a maximum of three weeks, with simultaneous intake of 3 x 3 mg budesonide. Thereafter, patients received 3 x 3 mg budesonide alone for six weeks. GCS-related side effects, disease activity and adverse events were documented at study entry and after 0, 2, 4, and 6 weeks of budesonide treatment. The percentage of patients with GCS-related side effects decreased from 65.2% (intention-to-treat-population) at entry to 43.3% (P < 0.0001) at the end of the trial. The total number of GCS-related side effects decreased significantly from 269 to 90. Of the patients who entered the study with active disease under conventional GCS therapy, 38.6% were in remission at the end of the study. Of the patients who entered the study with CD in remission, 78% stayed in remission after switching from conventinal GCS to budesonide. In conclusion, switching from conventional GCS treatment to budesonide leads to a significant reduction of GCS related side effects in patients with CD without causing rapid deterioration of the disease.

Bauditz J, Wedel S, Lochs H. · Charité University Hospital, 4th Department of Medicine, Berlin, Germany. · Gut. · Pubmed #11788559 links to  free full text

Abstract: BACKGROUND: Thalidomide improves clinical symptoms in patients with therapy refractory Crohn's disease, as shown in two recent studies. The mechanism of this effect however is still unknown. Suppression of tumour necrosis factor alpha (TNF-alpha) by thalidomide has been suggested as a possible mechanism. However, effects on other cytokines have not been adequately investigated. AIM: The aim of our study was to investigate the effects of thalidomide on cytokine production in patients with inflammatory bowel disease (IBD). METHODS: Ten patients with therapy refractory IBD (nine Crohn's disease, one ulcerative colitis) received thalidomide 300 mg daily in a 12 week open label study. Production of TNF-alpha, interleukin (IL)-1 beta, IL-6, and IL-12 was investigated in short term cultures of stimulated colonic lamina propria mononuclear cells (LPMC) and peripheral blood monocytes (PBMC) before and after 12 weeks of treatment. LPMC were also cultured with graded doses of thalidomide. RESULTS: Three patients discontinued treatment because of sedative side effects. In the other patients, disease activity decreased significantly, with four patients achieving remission. Production of TNF-alpha and IL-12 decreased during treatment with thalidomide: LPMC (TNF-alpha: 42.3 (8.3) pg/ml v 16.4 (6.3); IL-12: 9.7 (3.3) v 5.0 (2.5); p<0.04) and PBMC (TNF-alpha: 62.8 (14.6) v 22.5 (9.2); p<0.02). Production of IL-1 beta and IL-6 did not change significantly. Culturing of LPMC with thalidomide showed a dose dependent decrease in TNF-alpha and IL-12 production. CONCLUSION: The clinical effects of thalidomide in Crohn's disease may be mediated by reduction of both TNF-alpha and IL-12.

Schreiber S, Nikolaus S, Malchow H, Kruis W, Lochs H, Raedler A, Hahn EG, Krummenerl T, Steinmann G, Anonymous00274. · First Medical Department, University Hospital Kiel, Germany. · Gastroenterology. · Pubmed #11313303 No free full text.

Abstract: BACKGROUND & AIMS: ISIS-2302, an antisense oligonucleotide directed against intercellular adhesion molecule 1, was effective in steroid refractory Crohn's disease in a pilot trial. The aim of this study was to investigate safety and efficacy of ISIS-2302 in chronic active Crohn's disease (CACD). METHODS: A dose-interval, multicenter, placebo-controlled trial was conducted in 75 patients with steroid-refractory CACD (Crohn's Disease Activity Index [CDAI], 200-400). The primary endpoint was steroid-free remission (CDAI <150) at week 14. RESULTS: Only 2 of 60 (3.3%) ISIS-2302-treated and no placebo patients reached the primary endpoint. Steroid-free remission at week 26 (secondary endpoint) was reached in 8 of 60 (13.3%) active treatment and 1 of 15 (6.7%) placebo patients. A greater proportion of ISIS-2302-treated than placebo patients achieved a steroid dose <10 mg/day at weeks 14 and 26 (48.3% vs. 33.3% and 55.0% vs. 40.0%, respectively, and a glucocorticoid dose of 0 mg [prednisone equivalent] at week 26 [23.3% vs. 6.7%, respectively]). Treatment with ISIS-2302 was safe. The most common side effects were injection site reactions in the active treatment group (23% in ISIS-2302-treated patients vs. none in placebo patients). No statistically significant differences in the frequency of side effects were detected between dose groups. CONCLUSIONS: The trial did not prove clinical efficacy of ISIS-2302 based on the primary endpoint. Positive trends were observed in some of the secondary endpoints.

Lochs H, Mayer M, Fleig WE, Mortensen PB, Bauer P, Genser D, Petritsch W, Raithel M, Hoffmann R, Gross V, Plauth M, Staun M, Nesje LB. · IV Medizinische Klinik, Universitätsklinikum Charité, Humboldt Universität, Berlin, Germany. · Gastroenterology. · Pubmed #10648454 No free full text.

Abstract: BACKGROUND & AIMS: This study investigated if long-term treatment with high-dose mesalamine reduces the risk of clinical relapse of Crohn's disease after surgical resection. METHODS: In a prospective, randomized, double-blind, multicenter study, 4 g of mesalamine (Pentasa; Ferring A/S, Vanlose, Denmark) daily was compared with placebo in 318 patients. Treatment was started within 10 days after resective surgery and continued for 18 months. Primary outcome parameter was clinical relapse as defined by an increase in Crohn's Disease Activity Index, reoperation, septic complication, or newly developed fistula. Risk factors for recurrence were prospectively defined to be analyzed in a stepwise proportional hazards model. RESULTS: Cumulative relapse rates (+/-SE) after 18 months were 24.5% +/- 3.6% and 31.4% +/- 3.7% in the mesalamine (n = 152) and placebo (n = 166) groups, respectively (P = 0.10, log-rank test, 1-sided). Retrospective analysis showed a significantly reduced relapse rate with mesalamine only in a subgroup of patients with isolated small bowel disease (n = 124; 21.8% +/- 5.6% vs. 39.7% +/- 6.1%; P = 0.02, log-rank test). Probability of relapse was predominantly influenced by the duration of disease (P = 0.0006) and steroid intake before surgery (additional risk, P = 0.0003). CONCLUSIONS: Eighteen months of mesalamine, 4 g daily, did not significantly affect the postoperative course of Crohn's disease. Some relapse-preventing effect was found in patients with isolated small bowel disease.

Lochs H, Adler G, Beglinger C, Duchmann R, Emmrich J, Ewe K, Gangl A, Gasché C, Hahn E, Hoffmann P, Kaskas B, Malchow H, Pohl C, Raedler A, Renner E, Schölmerich J, Schreiber S, Stange E, Tilg H, Vogelsang H, Weigert N, Zeitz M. · Medizinische Klinik mit Schwerpunkt Gastroenterologie, Hepatologie und Endokrinologie, Charité, Medizinische Fakultät der Humboldt-Universität zu Berlin. · Z Gastroenterol. · Pubmed #10427657 No free full text.

Abstract: The chimeric anti-TNF antibody Remicade (Infliximab) has recently been approved for human use by the FDA and is now available on the market. Since there is considerable interest in this kind of treatment among patients with Crohn's disease, an international working group has summarized the presently available information about efficacy, side effects and possible problems of this treatment. Studies show that Remicade is effective in the treatment of active Crohn's disease, maintaining remission and fistulae. The working group does not see Infliximab as a first-line treatment for Crohn's disease. It may be used in active phase recurrent disease, chronic active disease and fistulae if standard treatment was not successful. For the surveillance special attention has to be given to the unknown malignancy rate of Infliximab. Infusion should be performed in an institution, routinely performing intravenous infusions and a two-hour surveillance of the patients should be guaranteed to recognize anaphylactic reactions or acute side effects. There is presently no information indication that the combination with immunosuppressants might increase risks or side effects of this treatment. Due to the limited information available the working group would prefer to use Remicade in studies only and recommends central collection and documentation of all data on efficacy and side effects for the next year.

Schneeweiss B, Lochs H, Zauner C, Fischer M, Wyatt J, Maier-Dobersberger T, Schneider B. · Intensive Care Unit, University of Vienna, Austria. · J Nutr. · Pubmed #10203559 links to  free full text

Abstract: The aim of the study was to evaluate the possible contribution of changes in energy metabolism and substrate oxidation rates to malnutrition in Crohn's disease and to assess the effect of enteral nutrition on these parameters. Energy metabolism was evaluated by indirect calorimetry in 32 patients with active Crohn's disease and 19 age- and sex-matched healthy individuals. Measurements were done in the postabsorptive state. Seven out of 32 patients received enteral nutrition via a nasogastric tube. In these patients, resting energy metabolism was determined at d 0 (postabsorptive), 7, 14 (during full enteral nutrition) and 15 (postabsorptive). Resting energy expenditure was not significantly different between patients and controls, whereas the respiratory quotient (RQ) was lower in patients (0.78 +/- 0.05 vs. 0.86 +/- 0.05; P < 0.05). During enteral nutrition in 7 patients with Crohn's disease, the RQ increased on d 7 compared with d 0 and remained high even after cessation of enteral nutrition (d 0, 0.78 +/- 0.03; d 7, 0.91 +/- 0.04; d 15, 0. 84 +/- 0.05; P < 0.05; d 7 and 15 vs. d 0). No effects of enteral nutrition on resting energy expenditure were found. Active Crohn's disease is associated with changes in substrate metabolism that resemble a starvation pattern. These changes appear not to be specific to Crohn's disease but to malnutrition and are readily reversed by enteral nutrition. Enteral nutrition did not affect resting energy expenditure. Wasting is a consequence of malnutrition but not of hypermetabolism in Crohn's disease.

Haas V, Büning C, Buhner S, von Heymann C, Valentini L, Lochs H. · Charité University Clinic, Berlin, Germany. · Eur J Clin Invest. · Pubmed #19200167 No free full text.

Abstract: BACKGROUND: Gastroduodenal and small intestinal permeability are increased in patients with Crohn's disease (CD) and intensive care patients. The relevance of colonic permeability has not yet been adequately investigated. The aim of this study was to investigate the clinical value of sucralose excretion as indicator for colonic permeability in these patient groups. DESIGN: After oral administration of four sugars and subsequent analysis of urinary excretion, gastroduodenal and intestinal permeability were calculated from saccharose excretion and lactulose/mannitol (L/M) ratio over 5 h, and sucralose excretion from 5 to 26 h in 100 healthy controls, 29 CD and 35 patients after coronary surgery (CABG). RESULTS: In controls, sucralose excretion was highly variable (0.67+/-0.92%) and not related to small intestinal permeability. In CD and CABG, L/M ratio was increased (0.054+/-0.060; 0.323+/-0.253 vs. 0.018+/-0.001 in controls). Sucralose excretion was increased in 77% of CABG but only in 7% of CD. There was an association between gastroduodenal and intestinal permeability in CD and CABG (r=0.72, and r=0.51), but sucralose excretion was not related to either one of these two parameters. Other than a weak association between sucralose and length of stay in intensive care in CABG patients (P=0.099), sucralose excretion was not related to clinical outcome. CONCLUSIONS: The proposed cut-off for normal sucralose excretion is 2.11%, but its high variability and lack of association to gastrointestinal permeability or clinical outcome leave it open, if it can provide information beyond established permeability tests.

Valentini L, Wirth EK, Schweizer U, Hengstermann S, Schaper L, Koernicke T, Dietz E, Norman K, Buning C, Winklhofer-Roob BM, Lochs H, Ockenga J. · Department of Gastroenterology, Hepatology and Endocrinology, Campus Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany. · Nutrition. · Pubmed #18849144 No free full text.

Abstract: OBJECTIVE: Adipokines are fat-derived hormones and cytokines with immune-modulating and metabolic properties. Most of them are associated with insulin resistance. The aim of the present investigation was to evaluate circulating levels of adipokines and glucose homeostasis in patients with inflammatory bowel disease (IBD) and to evaluate possible associations with the course and characteristics of the disease. METHODS: Serum leptin, resistin, visfatin, retinol-binding protein-4, adiponectin, glucose, insulin, and inflammatory parameters were analyzed in 93 patients with inactive IBD (49 with Crohn's disease [CD], 44 with ulcerative colitis [UC]), 35 patients with active IBD (18 with CD, 17 with UC), and 37 age- and body mass index-matched healthy controls. Ninety-two patients were followed for 6 mo. RESULTS: Leptin was similar in patients with IBD and controls, whereas resistin and visfatin were increased in patients with active disease but not in those in remission. In active and inactive disease, adiponectin was decreased (P < 0.001) and retinol-binding protein-4 was increased (P < 0.001) compared with controls. About 60% of patients with IBD showed increased levels of insulin, whereas serum glucose remained normal, resulting in increased homeostasis model assessment values in most patients. Hyperinsulinemia was associated with the decrease in adiponectin (r = -0.572, P < 0.001) and proved to be an independent protective factor for 6-mo maintenance of remission (P = 0.016). CONCLUSION: IBD led to largely similar alterations in circulating adipokines and hyperinsulinemia in patients with CD and those with UC. The unexpected protective effect of hyperinsulinemia on relapse rate denotes the role of the metabolic-inflammatory response as a modulator in IBD.

Valentini L, Schaper L, Buning C, Hengstermann S, Koernicke T, Tillinger W, Guglielmi FW, Norman K, Buhner S, Ockenga J, Pirlich M, Lochs H. · Department of Gastroenterology, Hepatology and Endocrinology, CCM, Charité-Universitätsmedizin Berlin, Berlin, Germany. · Nutrition. · Pubmed #18499398 No free full text.

Abstract: OBJECTIVE: This prospective, controlled, and multicentric study evaluated nutritional status, body composition, muscle strength, and quality of life in patients with inflammatory bowel disease in clinical remission. In addition, possible effects of gender, malnutrition, inflammation, and previous prednisolone therapy were investigated. METHODS: Nutritional status (subjective global assessment [SGA], body mass index, albumin, trace elements), body composition (bioelectrical impedance analysis, anthropometry), handgrip strength, and quality of life were assessed in 94 patients with Crohn's disease (CD; 61 female and 33 male, Crohn's Disease Activity Index 71 +/- 47), 50 patients with ulcerative colitis (UC; 33 female and 17 male, Ulcerative Colitis Activity Index 3.1 +/- 1.5), and 61 healthy control subjects (41 female and 20 male) from centers in Berlin, Vienna, and Bari. For further analysis of body composition, 47 well-nourished patients with inflammatory bowel disease were pair-matched by body mass index, sex, and age to healthy controls. Data are presented as median (25th-75th percentile). RESULTS: Most patients with inflammatory bowel disease (74%) were well nourished according to the SGA, body mass index, and serum albumin. However, body composition analysis demonstrated a decrease in body cell mass (BCM) in patients with CD (23.1 kg, 20.8-28.7, P = 0.021) and UC (22.6 kg, 21.0-28.0, P = 0.041) compared with controls (25.0 kg, 22.0-32.5). Handgrip strength correlated with BCM (r = 0.703, P = 0.001) and was decreased in patients with CD (32.8 kg, 26.0-41.1, P = 0.005) and UC (31.0 kg, 27.3-37.8, P = 0.001) compared with controls (36.0 kg, 31.0-52.0). The alterations were seen even in patients classified as well nourished. BCM was lower in patients with moderately increased serum C-reactive protein levels compared with patients with normal levels. CONCLUSION: In CD and UC, selected micronutrient deficits and loss of BCM and muscle strength are frequent in remission and cannot be detected by standard malnutrition screening.

Büning C, Schmidt HH, Molnár T, Drenth JP, Fiedler T, Gentz E, Todorov T, Baumgart DC, Sturm A, Nagy F, Lonovics J, de Jong DJ, Landt O, Kage A, Nickel R, Büttner J, Lochs H, Witt H. · Department of Gastroenterology, Hepatology & Endocrinology, Charité, Campus Mitte, Universitätsmedizin Berlin, Germany. · Inflamm Bowel Dis. · Pubmed #18092344 links to  free full text

Abstract: BACKGROUND: A recent study reported that the c.30T>A (p.Cys10Ter; rs2043211) variant, in the CARD8 (TUCAN) gene, is associated with Crohn's disease (CD). The aim of this study was to analyze the frequency of p.C10X in 3 independent European (IBD) cohorts from Germany, Hungary, and the Netherlands. METHODS: We included a European IBD cohort of 921 patients and compared the p.C10X genotype frequency to 832 healthy controls. The 3 study populations analyzed were: (1) Germany [CD, n = 317; ulcerative colitis (UC), n = 180], (2) Hungary (CD, n = 149; UC, n = 119), and (3) the Netherlands (CD, n = 156). Subtyping analysis was performed in respect to NOD2 variants (p.Arg702Trp, p.Gly908Arg, c.3020insC) and to clinical characteristics. Ethnically matched controls were included (German, n = 413; Hungarian, n = 202; Dutch, n = 217). RESULTS: We observed no significant difference in p.C10X genotype frequency in either patients with CD or patients with UC compared with controls in all 3 cohorts. Conversely to the initial association study, we found a trend toward lower frequencies of the suggestive risk wild type in CD from the Netherlands compared with controls (P = 0.14). We found neither evidence for genetic interactions between p.C10X and NOD2 nor the C10X variant to be associated with a CD or UC phenotype. CONCLUSIONS: Analyzing 3 independent European IBD cohorts, we found no evidence that the C10X variant in CARD8 confers susceptibility for CD.

Büning C, Schmidt HH, Molnar T, De Jong DJ, Fiedler T, Bühner S, Sturm A, Baumgart DC, Nagy F, Lonovics J, Drenth JP, Landt O, Nickel R, Büttner J, Lochs H, Witt H. · Department of Gastroenterology, Hepatology and Endocrinology, Charité, Campus Mitte, Universitätsmedizin Berlin, Berlin, Germany. · Aliment Pharmacol Ther. · Pubmed #17877509 No free full text.

Abstract: BACKGROUND: A recent study reported that a non-synonymous single nucleotide polymorphism (rs11209026, p.Arg381Gln) located in the IL23R gene is a protective marker for inflammatory bowel disease. AIM: To analyse the frequency of p.Arg381Gln in three independent European inflammatory bowel disease cohorts and to evaluate how this variant influences disease behaviour. METHODS: We assessed a European cohort of 919 inflammatory bowel disease patients and compared the IL23R p.Arg381Gln genotype frequency with 845 healthy controls. Inflammatory bowel disease patients originated from Germany [Crohn's disease (CD): n = 318; ulcerative colitis (UC): n = 178], Hungary (CD: n = 148; UC: n = 118) and the Netherlands (CD: n = 157). Ethnically matched controls were included. We performed subtyping analysis in respect to CARD15 alterations and clinical characteristics. RESULTS: The frequency of the glutamine allele of p.Arg381Gln was significantly lower in inflammatory bowel disease patients compared with controls in a pooled analysis of all three cohorts (P < 0.000001) as well as in the individual cohorts (Germany: P = 0.001, Hungary: P = 0.02 and the Netherlands: P = 0.0002). The p.Arg381Gln genotype distribution was similar between CD and UC. We did not observe either statistical interactions between p.Arg381Gln and CARD15 variants or any significant associations between p.Arg381Gln genotype and subphenotypes. CONCLUSIONS: The p.Arg381Gln IL23R variant confers a protective effect against both CD and UC, but does not determine disease phenotype.

Fiedler T, Büning C, Reuter W, Pitre G, Gentz E, Schmidt HH, Büttner J, Ockenga J, Gerloff T, Meisel C, Lochs H, Roots I, Köpke K, Johne A. · Department of Gastroenterology, Hepatology & Endocrinology, Charité - Universitätsmedizin Berlin, CCM, Charitéplatz 1, Berlin, 10117, Germany. · Eur J Clin Pharmacol. · Pubmed #17665184 No free full text.

Abstract: BACKGROUND: The role of the single nucleotide polymorphisms (SNPs) on positions 2677G>T/A and 3435C>T of the multi-drug-resistance gene 1 (MDR1) in inflammatory bowel disease (IBD) remains unclear. AIMS: To further elucidate the potential impact of MDR1 two-locus genotypes on susceptibility to IBD and disease behaviour. PATIENTS AND METHODS: Three hundred eighty-eight German IBD patients [244 with Crohn's disease (CD), 144 with ulcerative colitis (UC)] and 1,005 German healthy controls were genotyped for the two MDR1 SNPs on positions 2677G>T/A and 3435C>T. Genotype-phenotype analysis was performed with respect to disease susceptibility stratified by age at diagnosis as well as disease localisation and behaviour. RESULTS: Genotype distribution did not differ between all UC or CD patients and controls. Between UC and CD patients, however, we observed a trend of different distribution of the combined genotypes derived from SNPs 2677 and 3435 (chi(2) = 15.997, df = 8, p = 0.054). In subgroup analysis, genotype frequencies between UC patients with early onset of disease and controls showed significant difference for combined positions 2677 and 3435 (chi(2) = 16.054, df = 8, p = 0.034 for age at diagnosis >or=25, lower quartile). Herein the rare genotype 2677GG/3435TT was more frequently observed (odds ratio = 7.0, 95% confidence interval 2.5 - 19.7). In this group severe course of disease behaviour depended on the combined MDR1 SNPs (chi(2) = 16.101, df = 6, p = 0.017 for age at diagnosis >or=25). No association of MDR1 genotypes with disease subgroups in CD was observed. CONCLUSIONS: While overall genotype distribution did not differ, combined MDR1 genotypes derived from positions 2677 and 3435 are possibly associated with young age onset of UC and severe course of disease in this patient group.

Norman K, Kirchner H, Lochs H, Pirlich M. · Klinik mit Schwerpunkt Gastroenterologie, Hepatologie und Endokrinologie, Charité-Universitätsmedizin Berlin Campus Mitte, Germany. · World J Gastroenterol. · Pubmed #16733855 links to  free full text

Abstract: AIM: To investigate the association between malnutrition and quality of life in patients with benign gastrointestinal disease. METHODS: Two hundred patients (104 wellnourished and 96 malnourished) were assessed according to the Subjective Global Assessment, anthropometric measurements and bioelectrical impedance analysis. Quality of life was determined with the validated Medical Outcomes Study 36-item Short-Form General Health Survey (SF 36). Muscle function was assessed by hand grip strength and peak flow. RESULTS: Body mass index, body cell mass, arm muscle area and hand grip strength were significantly lower in the malnourished patients. Quality of life was generally lower when compared to norm values. Seven out of eight quality of life scales (excluding bodily pain) were significantly reduced in the malnourished patients. Comparing patients with liver cirrhosis and inflammatory bowel disease (IBD), patients with IBD experienced significantly lower values in the perception of bodily pain,social functioning and mental health. Malnourished liver cirrhotics suffered reductions in more scales (six out of eight) than malnourished IBD patients did (four out of eight). CONCLUSION: Quality of life is generally low in benign gastrointestinal disease and is further reduced in patients who are classified as malnourished. It appears that liver cirrhosis patients experience a higher quality of life than IBD patients do, but the impact of malnutrition seems to be greater in liver cirrhosis than in IBD.

Prantera C, Lochs H, Campieri M, Scribano ML, Sturniolo GC, Castiglione F, Cottone M. · Operative Unit of Gastroenterology, St Camillo-Forlanini Hospital, Rome, Italy. · Aliment Pharmacol Ther. · Pubmed #16611272 No free full text.

Abstract: BACKGROUND: Clinicians often employ antibiotics in Crohn's disease. Rifaximin is active against bacteria frequently found in the intestinal mucosa of Crohn's disease patients. AIM: To evaluate the difference in efficacy between once and twice/daily oral administration of rifaximin and placebo in the treatment of active Crohn's disease. METHODS: We enrolled 83 patients with mild-to-moderate Crohn's disease and randomized to three treatments for 12 weeks: Group A (rifaximin 800 mg o.d. + placebo), Group B (rifaximin 800 mg b.d.) and Group C (placebo b.d.). RESULTS: Clinical remission was achieved by 52% of Group B, 32% (A) and 33% (C). Clinical response was seen in 67% (B), 48% (A) and 41% (C), without reaching a statistically significant difference. Treatment failures were: 4% (B), 12% (A) and 33% (C), (P = 0.010). Remission and response rates of rifaximin 800 mg b.d. were significantly higher than those of placebo and rifaximin 800 mg o.d. in patients with elevated C reactive protein values (P < 0.05). CONCLUSIONS: Rifaximin 800 mg b.d. was superior to placebo in inducing clinical remission of active Crohn's disease. Although this difference was not statistically significant, the number of the failures in the placebo group was significantly higher than those who received rifaximin 800 mg b.d.

Büning C, Geerdts L, Fiedler T, Gentz E, Pitre G, Reuter W, Luck W, Buhner S, Molnar T, Nagy F, Lonovics J, Dignass A, Landt O, Nickel R, Genschel J, Lochs H, Schmidt HH, Witt H. · Department of Gastroenterology, Hepatology & Endocrinology, Charité, Campus Mitte, Universitätsmedizin Berlin, Berlin, Germany. · Am J Gastroenterol. · Pubmed #16494592 No free full text.

Abstract: OBJECTIVES: Genetic variants within DLG5 were recently reported to be associated with inflammatory bowel disease (IBD). The aim of our study was to test for allelic and haplotype associations of six DLG5 variants in 668 IBD patients from two European populations. Furthermore, we evaluated whether DLG5 variants alter gastrointestinal permeability in Crohn's disease (CD). METHODS: Six DLG5 variants (p.R30Q, p.P1371Q, p.G1066G, rs2289308, DLG_e26, p.D1507D) were genotyped in two study populations: (1) German IBD patients (CD n = 250; ulcerative colitis (UC) n = 150) and German healthy controls (n = 422); (2) Hungarian IBD patients (CD n = 144; UC n = 124) and Hungarian healthy controls (n = 205). Subtyping analysis was performed in respect of CARD15 mutations and clinical characteristics. We also tested for differences within DLG5 genotypes in German CD patients with respect to gastroduodenal and intestinal permeability measured by triple-sugar-test. RESULTS: Allele as well as genotype frequencies of DLG5 variants did not differ between IBD patients and controls in either study population. Indeed, the p.R30Q polymorphism was found more frequently in controls than in patients. The distribution of DLG5 genotypes in German and Hungarian CD patients with CARD15 mutations was not different from patients without mutated CARD15. We did also not observe any association between DLG5 variants and clinical parameters. Importantly, DLG5 variants were not associated with gastroduodenal or intestinal permeability. CONCLUSIONS: We could not replicate that DLG5 is a relevant disease susceptibility gene for IBD in German or Hungarian subjects. In addition, we have no evidence that DLG5 variants are involved in altered gastrointestinal permeability in CD.

Caprilli R, Gassull MA, Escher JC, Moser G, Munkholm P, Forbes A, Hommes DW, Lochs H, Angelucci E, Cocco A, Vucelic B, Hildebrand H, Kolacek S, Riis L, Lukas M, de Franchis R, Hamilton M, Jantschek G, Michetti P, O'Morain C, Anwar MM, Freitas JL, Mouzas IA, Baert F, Mitchell R, Hawkey CJ, Anonymous00006. · John Radcliffe Hospital, Oxford OX3 9DU, UK. · Gut. · Pubmed #16481630 links to  free full text

Abstract: This third section of the European Crohn's and Colitis Organisation (ECCO) Consensus on the management of Crohn's disease concerns postoperative recurrence, fistulating disease, paediatrics, pregnancy, psychosomatics, extraintestinal manifestations, and alternative therapy. The first section on definitions and diagnosis reports on the aims and methods of the consensus, as well as sections on diagnosis, pathology, and classification of Crohn's disease. The second section on current management addresses treatment of active disease, maintenance of medically induced remission, and surgery of Crohn's disease.

Buhner S, Buning C, Genschel J, Kling K, Herrmann D, Dignass A, Kuechler I, Krueger S, Schmidt HH, Lochs H. · Department of Gastroenterology, Hepatology, and Endocrinology, Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Schumannstr 20-21, 10117 Berlin, Germany. · Gut. · Pubmed #16000642 links to  free full text

Abstract: BACKGROUND AND AIMS: A genetically impaired intestinal barrier function has long been suspected to be a predisposing factor for Crohn's disease (CD). Recently, mutations of the capsase recruitment domain family, member 15 (CARD15) gene have been identified and associated with CD. We hypothesise that a CARD15 mutation may be associated with an impaired intestinal barrier. METHODS: We studied 128 patients with quiescent CD, 129 first degree relatives (CD-R), 66 non-related household members (CD-NR), and 96 healthy controls. The three most common CARD15 polymorphisms (R702W, G908R, and 3020insC) were analysed and intestinal permeability was determined by the lactulose/mannitol ratio. RESULTS: Intestinal permeability was significantly increased in CD and CD-R groups compared with CD-NR and controls. Values above the normal range were seen in 44% of CD and 26% of CD-R but only in 6% of CD-NR, and in none of the controls. A household community with CD patients, representing a common environment, was not associated with increased intestinal permeability in family members. However, 40% of CD first degree relatives carrying a CARD15 3020insC mutation and 75% (3/4) of those CD-R with combined 3020insC and R702W mutations had increased intestinal permeability compared with only 15% of wild-types, indicating a genetic influence on barrier function. R702W and G908R mutations were not associated with high permeability. CONCLUSIONS: In healthy first degree relatives, high mucosal permeability is associated with the presence of a CARD15 3020insC mutation. This indicates that genetic factors may be involved in impairment of intestinal barrier function in families with IBD.

Swidsinski A, Weber J, Loening-Baucke V, Hale LP, Lochs H. · Innere Klinik, Gastroenterologie, Charité Humboldt Universität, 10098 Berlin, Germany. · J Clin Microbiol. · Pubmed #16000463 links to  free full text

Abstract: The composition and spatial organization of the mucosal flora in biopsy specimens from patients with inflammatory bowel disease (IBD; either Crohn's disease or ulcerative colitis), self-limiting colitis, irritable-bowel syndrome (IBS), and healthy controls were investigated by using a broad range of fluorescent bacterial group-specific rRNA-targeted oligonucleotide probes. Each group included 20 subjects. Ten patients who had IBD and who were being treated with antibiotics were also studied. Use of nonaqueous Carnoy fixative to preserve the mucus layer was crucial for detection of bacteria adherent to the mucosal surface (mucosal bacteria). No biofilm was detectable in formalin-fixed biopsy specimens. Mucosal bacteria were found at concentrations greater than 10(9)/ml in 90 to 95% of IBD patients, 95% of patients with self-limiting colitis, 65% of IBS patients, and 35% of healthy controls. The mean density of the mucosal biofilm was 2 powers higher in IBD patients than in patients with IBS or controls, and bacteria were mostly adherent. Bacteroides fragilis was responsible for >60% of the biofilm mass in patients with IBD but for only 30% of the biofilm mass in patients with self-limiting colitis and <15% of the biofilm mass in patients with IBS. In contrast, bacteria which positively hybridized with the probe specific for Eubacterium rectale-Clostridium coccoides accounted for >40% of the biofilm in IBS patients but for <15% of the biofilm in IBD patients. In patients treated with (5-ASA) or antibiotics, the biofilm could be detected with 4,6-diamidino-2-phenylindole but did not hybridize with fluorescence in situ hybridization probes. A Bacteroides fragilis biofilm is the main feature of IBD. This was not previously recognized due to a lack of appropriate tissue fixation. Both 5-ASA and antibiotics suppress but do not eliminate the adherent biofilm.