Crohn Disease: Hoffmann JC

Hoffmann JC, Preiss JC, Autschbach F, Buhr HJ, Häuser W, Herrlinger K, Höhne W, Koletzko S, Krieglstein CF, Kruis W, Matthes H, Moser G, Reinshagen M, Rogler G, Schreiber S, Schreyer AG, Sido B, Siegmund B, Stallmach A, Bokemeyer B, Stange EF, Zeitz M. · Medizinische Klinik I, St. Marienkrankenhaus, Ludwigshafen. · Z Gastroenterol. · Pubmed #18810679 No free full text.

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Hoffmann JC, Autschbach F, Bokemeyer B, Buhr HJ, Herrlinger K, Höhne W, Krieglstein C, Kruis W, Moser G, Preiss JC, Reinshagen M, Rogler G, Schreiber S, Schreyer AG, Siegmund B, Stallmach A, Stange EF, Zeitz M. · Medizinische Klinik I, St. Marienkrankenhaus Ludwigshafen. · Dtsch Med Wochenschr. · Pubmed #18788069 No free full text.

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Hoffmann JC, Zeitz M. · Medizinische Klinik I, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Hindenburgdamm 30, 12200 Berlin. · Internist (Berl). · Pubmed #12524918 No free full text.

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Westermann J, Engelhardt B, Hoffmann JC. · Institute of Anatomy, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany. · Ann Intern Med. · Pubmed #11511143 links to  free full text

Abstract: T cells play an important role in the pathogenesis of chronic and autoimmune inflammatory diseases. They are found in high numbers in involved tissues, such as the lamina propria of the gut in patients with Crohn disease. Modifying T-cell number and function may therefore be of therapeutic value. In principle, two mechanisms may be responsible for the development of such T-cell infiltrates: 1) an increased rate of T-cell immigration into involved tissues or 2) an increased proliferation rate, decreased T-cell death (apoptosis) rate, and prolonged retention of T cells already in the tissue. Based on the theory that T cells selectively target affected tissues through organ-specific adhesion-molecule pathways, current anti-adhesion-molecule therapy aims to interfere selectively with T-cell entry to stop tissue damage. However, the traffic of labeled T cells in unmanipulated animals shows that the entry of T-cell subsets into tissues is not organ-specific, even under conditions of differing adhesion molecule and chemokine receptor expression. In contrast, within various tissues, both movement and survival of T-cell subsets differ considerably. These observations suggest that the differential expression of adhesion molecules and chemokine receptors on T cells serves at least two functions in vivo. First, during migration of T cells out of the bloodstream, the different adhesion-molecule pathways provide redundancy, which guarantees that T-cell subsets are able to enter the different tissues in sufficient numbers (security). Second, adhesion molecules and chemokine receptors mediate T-cell interactions within the tissue that are characteristic for each subset and each microenvironment and determine the nature of the ensuing immune response (selectivity). Shifting the focus of anti-adhesion-molecule therapy toward the T cells in diseased tissue may lead to new treatment options.

Hoffmann JC, Zeitz M. · Innere Medizin II, Universitätskliniken des Saarlandes, Homburg, Germany. · Hepatogastroenterology. · Pubmed #10690589 No free full text.

Abstract: The treatment of Crohn's disease depends on disease location and disease activity. It can be divided into medical and surgical treatment. While surgery is reserved for complications such as abscesses or failure of pharmacological treatment (fistulae, perianal disease, or strictures) medical treatment aims at induction and maintenance of remission. In order to achieve these goals supportive and therapeutic strategies must be used. Supportive measures include substitution of vitamins, particularly fat-soluble vitamins, and minerals in deficiencies due to resection or disease involvement of the small bowel. All patients on long-term steroids should receive calcium and vitamin D in order to prevent osteoporosis. Therapeutic options include drug treatment (corticosteroids, antibiotics, salicylates, and immunosuppressives), nutrition (parenteral or enteral), and endoscopy (dilatation of strictures). Depending on disease location different pharmacologic preparations of salicylates or corticosteroids should be used, e.g., enemas for distal colitis. The most potent drugs for long-term control are immunosuppressive agents, particularly azathioprine. It is the most widely investigated immunosuppressive agent in Crohn's disease and should be the first line treatment for patients with steroid refractory, chronic steroid dependent, fistulating, and stenosing courses. In the future, more potent drugs and better risk stratification criteria should improve the treatment of Crohn's disease.

Hoffmann JC, Heller F, Faiss S, von Lampe B, Kroesen AJ, Wahnschaffe U, Schulzke JD, Zeitz M, Bojarski C. · Medizinische Klinik I mit Schwerpunkt Gastroenterologie, Infektiologie, Rheumatologie, Charité, Campus Benjamin Franklin, 12200 Berlin, Germany. · Int J Colorectal Dis. · Pubmed #18338175 No free full text.

Abstract: BACKGROUND/AIMS: About half of all Crohn's disease (CD) patients undergo surgery at some point, many because of strictures. An alternative possibility is to dilate strictures endoscopically. However, little is known about prognostic factors. PATIENTS AND METHODS: Thirty-two patients with primary CD (n=2), radiogenic strictures (n=1), or postoperative strictures (27 because of CD; 2 after resection because of cancer), were planned to undergo colonoscopic dilatation of which 25 patients were dilated (10 men; 15 women; median age 48). Length of stenosis, diameter of stricture, balloon size, smoking status, ulcer in the stricture, passage postdilatation, hemoglobin level, complications, redilatation, and subsequent surgery were recorded. Only patients with at least 6 months follow up were included. RESULTS: Five out of 32 patients had no stenosis, marked inflammation, or fistulas adjacent to the stricture. One patient each had a long stricture (8 cm) or a filiform stenosis ruling out dilatation [technical success, 25/27 (92.6%)]. Among these 25 patients, 39 colonoscopies with 51 dilatations were performed. After a single dilatation, 52% were asymptomatic while 48% needed another intervention, half of them surgery. Bleeding without need for transfusion occurred in 3 out of 39 colonoscopies and one perforation required surgery. Significant prognostic factors were smoking and ulcers in the stricture (P<0.05 each). Some ulcers led to intussusception requiring surgery in spite of good dilatation results. CONCLUSION: Through the endoscope balloon stricture dilatation is a relatively safe and often effective treatment modality in ileocolonic strictures. The presence of ulcers in the stricture have a worse outcome as do smokers.

Sina C, Schreiber S, Hoffmann JC, Rogler G, Schölmerich J, Zeitz M, Fölsch UR. · Klinik für Allgemeine Innere Medizin, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel. · Med Klin (Munich). · Pubmed #16501914 No free full text.

Abstract: The competence network chronic inflammatory bowel disease (KN-CED) is one of 17 networks of competence initiated by the German Federal Ministry of Education and Research (BMBF). These networks are concerned with disease patterns which are characterized by their high frequency, high mortality rate or which present a large expense factor. The project-executing organization is the German Center for Air and Space Travel (DLR e. V.). The central structure of organization is the Telematic Platform for medical Networks (TMF e. V.).Aim of the KN-CED is to investigate, in their complexity, the incurable chronic diseases ulcerative colitis and Crohn's disease, particularly with regard to the causes of disease, the establishment of new therapy standards as well as patient care.To achieve this goal, the competence network is integrated into both national and international research associations and is also backed by the national self-help group DCCV and the pharmaceutical industry.Principal items of the competence network are the core facilities and their main focus on molecular genetics, animal and cell models and serum markers. Having stored the data of more than 4,000 patients so far, the central database of the competence network is one of the largest databases worldwide with regard to inflammatory bowel disease (IBD).The successful cooperation within the network is reflected in numerous publications. Thus, two of the three known genes of Crohn's disease were identified. Also with the participation of the competence network national guidelines for the diagnosis and therapy of IBD were generated.Furthermore, the competence network operates study centers where significant therapeutic developments in the field of biotechnological drugs are taking place.The analysis of existing structures of care as well as the development of standards of organization for patients with IBD top the research within the competence network and emphasize the claim to find comprehensive answers to the questions connected with IBD.

Scherübl H, Wittig BM, Hoffmann JC, Zeitz M. · Charité -- Universitätsmedizin Berlin, Campus Benjamin Franklin, Medizinische Klinik I -- Gastroenterologie, Infektiologie und Rheumatologie. · Dtsch Med Wochenschr. · Pubmed #15368182 No free full text.

This publication has no abstract.

Hoffmann JC. · Medizinische Klinik I mit Schwerpunkt Gastroenterologie/Infektiologie/Rheumatologie, Charité, Universitätsmedizin Berlin, Campus Benjamin Franklin. · Dtsch Med Wochenschr. · Pubmed #15368175 No free full text.

This publication has no abstract.

Kühl AA, Loddenkemper C, Westermann J, Hoffmann JC. · Medizinische Klinik I, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Berlin, Deutschland. · Pathobiology. · Pubmed #12571419 No free full text.

Abstract: gammadelta T cells have previously been shown to play a protective role in various animal models of chronic inflammation (e.g., experimental autoimmune encephalomyelitis, collagen-induced arthritis, and non-obese diabetes). This immunoregulatory potential is exerted by synthesizing various anti-inflammatory cytokines and growth factors (e.g., transforming growth factor-beta). As the normal balance between inflammatory and regulatory cytokines is perturbed in inflammatory bowel disease (IBD) a protective effect of gammadelta T cells seems likely. This notion is supported by our finding of increased mortality of rats with 2,4,6-trinitrobenzene sulfonic acid-induced colitis following gammadelta T cell depletion. In contrast, no effect was observed after depletion of gammadelta T cells in a Crohn's disease animal model with terminal ileitis (TNF(DeltaARE) mice). Therefore, future studies must further define where in the intestinal immune system gammadelta T cells exert their protective function and how this can be used in the treatment of IBD.