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Perianal fistulas and abscesses are a common manifestation in Crohn's disease (CD), seen in about 30 - 40 % of the patients. Often they are combined with CD of the anal canal and occur as a complex system of fistulas. The evaluation of these fistulas can be done with endoscopic ultrasound or magnetic resonance imaging, the conceptual accuracy of both methods is high. There are accepted therapeutic concepts for surgery and for the conventional drug therapy according to the classification of the fistulas. In contrast, the therapeutic regimens for a complex perianal fistulising CD are not convincing, especially not for maintainance therapy. However, several studies about therapy with anti-TNF-alpha antibodies have shown good results while long-time results with other recent anti-TNF-alpha antibodies apart from infliximab are still lacking. In this review article we analyse the current literature and develop a stage-adapted therapy for the use of biologicals and surgery in fistulising perianal CD.

Nanofabricated pores in 20 nm-thick silicon nitride membranes were used to probe various protein analytes as well as to perform an antigen-antibody binding assay. A two-compartment electrochemical cell was separated by a single nanopore, 28 nm in diameter. Adding proteins to one compartment caused current perturbations in the ion current flowing through the pore. These perturbations correlated with both the charge and the size of the protein or of a protein-protein complex. The potential of this nanotechnology for studying protein-protein interactions is highlighted with the sensitive detection of β-human chorionic gonadotropin, a hormone and clinical biomarker of pregnancy, by monitoring in real time and at a molecular level the formation of a complex between hormones and antibodies in solution. In this form, the assay compared advantageously to immunoassays, with the important difference that labels, immobilization, or amplification steps were no longer needed. In conclusion, we present proof-of-principle that properties of proteins and their interactions can be investigated in solution using synthetic nanopores and that these interactions can be exploited to measure protein concentrations accurately. © 2008 American Chemical Society.

Introduction Neuroendocrine tumors of the gastroenteropancreatic system (GEP) are heterogeneous regarding hormone production, localisation and biological behaviour making the prognostic evaluation of these rare tumors difficult. Capella et al. proposed a new classification that combines for the first time both biological and prognostic characteristics. This study aimed to evaluate the prognostic value of Capella's classification in the patients treated at our hospital. Methods 86 from 1975-1999 surgically treated and histologically confirmed neuroendocrine tumors were retrospectively classified as benign (B), uncertain behavior (UB), low grade malignant (LG) or high grade malignant (HG) following the Capella classification. These data were correlated with the long-term outcome of the patients 8.5 (range: 1-24) years after surgery. Results 43 % of tumors were localised in the pancreas, the others were equally distributed in the remaining GEP. Most tumors were classified as B (42 %) or LG (41 %), few were UB (10 %) or HG (7 %). 61 patients survived free of disease, 25 patients died, 13 of them not tumor related. Tumor related deaths were only observed in 6 patients with inoperable LG- and 6 patients with HG-neuroendocrine tumors within 3 years after surgery. Conclusion The Capella classification reliably reflects the heterogeneity and the biological behaviour of GEP-neuroendocrine tumors and can therefore be recommended for clinical use.

The role of the tumor suppressor gene p53 and proto-oncogenes mdm-2, waf-1,and bcl-2 in sporadic colorectal carcinoma (CRC) has been well investigated. However, little is known about the role of these genes in the development of ulcerative colitis-associated colorectal carcinoma (CAC). Colectomy specimens from patients with CAC, patients with ulcerative colitis (UC) and dysplasia, patients with long-standing UC without carcinoma or dysplasia, and patients with CRC were investigated in comparison to normal colon (NC) specimens from patients with diverticulosis without histologic signs of inflammation. Immunohistochemistry was performed with antibodies against p53, mdm-2, waf-1, and bcl-2; and staining was evaluated semiquantitatively with an expression of more than 20% of tumor cell nuclei or epithelial cell nuclei in nontumor specimens considered "positive." Statistical analysis was performed using Fisher's exact test. In carcinomas, p53 was positive in 50% of CRC tissues and 60% of CAC tissues without statistical difference. Positive expression of p53 was found in most high-grade dysplasia but not in low-grade dysplasia (p0.01). Whereas mdm-2 and bcl-2 were only sporadically expressed, waf-1 was observed in most specimens, with a high prevalence in UC without carcinoma or dysplasia (11/15). NC specimens were always negative for all antibodies. Immunohistochemical expression of p53, mdm-2, waf-1, and bcl-2 is similar for CAC and CRC. The malignant potential of dysplasia in UC is partially confirmed by a high prevalence of p53 and waf-1 expression, suggesting that CAC may develop along pathways that are different from CRC. High expression of waf-1 in nonmalignant long-standing UC has to be proved over a long-term course in its role as an independent cancer risk factor in UC patients.

Objective Cell-matrix interactions are important regulators of cellular functions, including matrix synthesis, proliferation and differentiation. This is well exemplified by the characteristically labile phenotype of chondrocytes that is lost in monolayer culture but is stabilized in suspension under appropriate conditions. We were interested in the role of collagen suprastructures in maintaining or destabilizing the cartilage phenotype of chondrocytes. Design Primary sternal chondrocytes from 17-day-old chick embryos were cultured in gels of fibrils reconstituted from soluble collagen I from various sources. The culture media either contained or lacked FBS. Cells were cultured for up to 28 days and the evolution of the phenotype of the cells was assessed by their collagen expression (collagens II and X for differentiated chondrocytes and hypertrophic chodrocytes, repectively; collagen I for phenotypically modulated cells), or by their secretion of alkaline phosphatase (hypertrophic cartilage phenotype). Results The cells often retained their differentiated phenotype only if cultured with serum. Under serum-free conditions, cartilage characteristics were lost. The cells acquired a fibroblast-like shape and, later, synthesized collagen I instead of cartilage collagens. Shape changes were influenced by β1-integrin-activity, whereas other matrix receptors were important for alterations of collagen patterns. Heterotypic fibrils reconstituted from collagens II, IX, and XI did not provoke this phenotypic instability. Conclusions Chondrocytes sensitively recognize the suprastructures of collagen fibrils in their environment. Cellular interactions with fibrils with appropriate molecular organizations, such as that in cartilage fibrils, result in the maintenance of the differentiated cartilage phenotype. However, other suprastructures, e.g. in reconstituted fibrils mainly containing collagen I, lead to cell-matrix interactions incompatible with the cartilage phenotype. The maintenance of the differentiated traits of chondrocytes is pivotal for the normal function of, e.g., articular cartilage. If pathologically altered matrix suprastructures lead to a dysregulation of collagen production also in vivo compromised cartilage functions inevitably will be propagated further.

We demonstrate high resolution imaging with microfabricated, cantilevered probes, consisting of solid quartz tips on silicon levers. The tips are covered by a 60-nm thick layer of aluminium, which appears to be closed at the apex when investigated by transmission electron microscopy. An instrument specifically built for cantilever probes was used to record images of latex bead projection patterns in transmission as well as single molecule fluorescence. All images were recorded in constant height mode and show optical resolutions down to 32 nm.

Als funktionell orientiertes Verfahren ermoglicht die Positronenemissionstomographie mit [18F]Fluordesoxyglukose ([18F]FDG-PET) die Untersuchung der Stoffwechselaktivitat eines Gewebes in vivo. Da maligne Prozesse meist eine erhohte Stoffwechselaktivitat im Vergleich zu nicht maligne transformiertem Gewebe aufweisen, bietet sich die [18F]FDG-PET als Stagingverfahren und bei der Rezidivdiagnostik verschiedener Tumorentitaten an. Fur den onkologisch tatigen Chirurgen betrifft dies vor allem die Diagnostik des Pankreascarcinoms, colorectalen Carcinoms, Bronchialcarcinoms und Oesophaguscarcinoms. In der vorliegenden kurzen Ubersicht wird nach Darstellung der physikalischen Grundlagen der aktuelle Stand der klinischen Wertigkeit der [18F]FDG-PET fur die Diagnostik dieser Tumoren kritisch beleuchtet.

SUMMARYIntestinal epithelial cells seem to play a key role during IBD. The network of cellular interactions between epithelial cells and lamina propria mononuclear cells is still incompletely understood. In the following co-culture model we investigated the influence of intestinal epithelial cells on cytokine expression of T cytotoxic and T helper cells from patients with IBD and healthy controls. Peripheral blood mononuclear cells (PBMC) were purified by a Ficoll–Hypaque gradient followed by co-incubation with epithelial cells in multiwell cell culture insert plates in direct contact as well as separated by transwell filters. We used Caco-2 cells as well as freshly isolated colonic epithelia obtained from surgical specimens. Three-colour immunofluorescence flow cytometry was performed after collection, stimulation and staining of PBMC with anti-CD4, anti-CD8, anti-IFN-γ and anti-IL-4. Patients with IBD (Crohn's disease (CD), n = 12; ulcerative colitis (UC), n = 16) and healthy controls (n = 10) were included in the study. After 24 h of co-incubation with Caco-2 cells we found a significant increase of IFN-γ-producing CD8+ lymphocytes in patients with IBD. In contrast, healthy controls did not respond to the epithelial stimulus. No significant differences could be found between CD and UC or active and inactive disease. A significant increase of IFN-γ+/CD8+ lymphocytes in patients with UC was also seen after direct co-incubation with primary cultures of colonic crypt cells. The observed epithelial–lymphocyte interaction seems to be MHC I-restricted. No significant epithelial cell-mediated effects on cytokine expression were detected in the PBMC CD4+ subsets. Patients with IBD—even in an inactive state of disease—exert an increased capacity for IFN-γ induction in CD8+ lymphocytes mediated by intestinal epithelial cells. This mechanism may be important during chronic intestinal inflammation, as in the case of altered mucosal barrier function epithelial cells may become targets for IFN-γ-producing CD8+ lymphocytes.

The pro-inflammatory cytokine interleukin (IL)-6 (refs. 1-5) can bind to cells lacking the IL-6 receptor (IL-6R) when it forms a complex with the soluble IL-6R (sIL-6R) (trans signaling). Here, we have assessed the contribution of this system to the increased resistance of mucosal T cells against apoptosis in Crohn disease (CD), a chronic inflammatory disease of the gastrointestinal tract. A neutralizing antibody against IL-6R suppressed established experimental colitis in various animal models of CD mediated by type 1 T-helper cells, by inducing apoptosis of lamina propria T cells. Similarly, specific neutralization of sIL-6R in vivo by a newly designed gp130-Fc fusion protein caused suppression of colitis activity and induction of apoptosis, indicating that sIL-6R prevents mucosal T-cell apoptosis. In patients with CD, mucosal T cells showed strong evidence for IL-6 trans signaling, with activation of signal transducer and activator of transcription 3, bcl-2 and bcl-xl. Blockade of IL-6 trans signaling caused T-cell apoptosis, indicating that the IL-6-sIL-6R system mediates the resistance of T cells to apoptosis in CD. These data indicate that a pathway of T-cell activation driven by IL-6-sIL-6R contributes to the perpetuation of chronic intestinal inflammation. Specific targeting of this pathway may be a promising new approach for the treatment of CD.

The objective of this work is to fabricate a scanning probe sensor that combines the well-established method for atomic force microscopy, employing a micro-machined Si cantilever and integrated tip, with a probe for the optical near field. A photosensitive pn-junction is integrated into the tip for that purpose and an Al coating is applied to the tip. It comprises an aperture of 50-70 nm in diameter at the apex of the tip in order to spatially limit the interaction of the tip to the optical near field of the sample. Characterization of the tip and first results of simultaneously recorded force and photon images are presented.

Die chronisch entzundlichen Darmerkrankungen (CED: Morbus Crohn, Colitis ulcerosa) sind durch schubartig verlaufende destruierende Entzundungsreaktionen der Darmschleimhaut gekennzeichnet. In den letzten Jahren konnte gezeigt werden, das bei diesen Erkrankungen eine pathologische Aktivierung des intestinalen Immunsystems durch mucosale Antigene auftritt. In der chronischen Phase der Erkankungen sowie bei der Entwicklung postoperativer Rezidive sind Anderungen in der Zellmigration sowie der Cytokinproduktion intestinaler Zellen wahrscheinlich von entscheidender Bedeutung. Basierend auf diesen neuen pathogenetischen Erkenntnissen werden zur Zeit innovative klinische Behandlungsstrategien getestet, die rekombinante antiinflammatorische Cytokine (IFN-α, IL-10, IL-11) und Inhibitoren von Adhasionsmolekulen (ICAM), proinflammatorischen Cytokinen (TNF, IL-12) und deren Rezeptoren (TNF, IL-6R) umfassen.

Aspects of Intensive Care Therapy in Patients with Fecal Peritonitis Local fecal peritonitis may have severe systemic implications associated with high mortality. Progress has been

Leukocyte emigration from blood to sites of inflammation involves sequential interaction of specific adhesion molecules expressed by both leukocytes and endothelial cells. The central steps in leukocyte-endothelial adhesive interactions are leukocyte rolling, sticking, and transmigration. This study investigated the effect of monoclonal antibodies against CD54 (ICAM-1) and CD11b (alphaM-chain of MAC-1) on intestinal inflammation. Anti-CD54 and anti-CD11b were tested in rats with indomethacin-induced chronic ileitis. Macroscopic changes were assessed by a modified version of the Wallace et al. score. Leukocyte rolling and sticking were investigated by intravital microscopy. Results show that indomethacin administration led to a chronic inflammatory response characterized by significant increase (P0.05) in rolling (from 5.41+/-2.87 to 32.41+/-15.03 100 microm(-1) s(-1)) and sticking (from 0.16+/-0.18 to 9.11+/-5.3 100 microm(-1) s(-1)) leukocytes. After antibody treatment only the anti-CD11b group showed significant (P0.05) reduction in rolling (from 32.41+/-15.03 to 6.6+/-2.7 100 microm(-1) s-1) and sticking (from 9.11+/-5.3 to 0.07+/-0.09 100 microm(-1) s-1) leukocytes. This was also the case for macroscopic changes. Indomethacin led to a rise in the Wallace score from 0 to 4.29+/-0.76 points (P0.05) and anti-CD11b to a reduction from 4.29+/-0.76 to 1.29+/-1.11 points (P0.05). Anti-CD54 and combined anti-CD11b/CD54 administration was not followed by significant changes. Therefore we suggest that leukocyte-based CD11b but not endothelial-based CD54 contributes most to leukocyte adhesion in the setting of indomethacin-induced ileitis in rats.

Several approaches are described with the aim of producing near-field optical probes with improved properties. Focused ion beam milling allows the fabrication of small apertures in a controlled fashion, resulting in probes with excellent polarization properties and increased transmission. Microfabrication processes are described that allow the production of apertures of 30-50 nm, facilitating the mass-fabrication of apertured tip structures that can be used in a combined force/near-field optical microscope. Finally, possible future developments are outlined.

Since there are no data concerning the results/efficiency of research stipends in foreign countries, the aim of this study was to analyze the experience of German surgeons doing research work abroad. Seventy-four fellows (residents) in surgical training who conducted research outside Germany between 1986 and 1995 were interviewed using a detailed questionnaire. Back in Germany, the results and experience gained from research abroad led in the majority of cases to a PhD degree ("habilitation"), a high number of publications, and intensified research efforts in the same field using the methods learned abroad. In Germany, better support for researchers in terms of better clinical and scientific perspectives is urgently needed according to numerous comments.

The surgical treatment of patients suffering from peritonitis with an open abdomen is commonplace. However scheduled as well as required dressing changes and peritoneal lavages mean a time- and costs-intensive challenge for the nursing and medical personnel. Since the introduction of the abdominal dressing-kit (KCI, Walluf, Germany) in the management of diffuse peritonitis one expects to influence the patients' recovery in a positive way due to the continuous evacuation of intraabdominal infectious fluids, augmentation of tissue's granulation, prevention of fascial retraction and prevention of an abdominal compartment syndrome. First on trial we established 2004 in our surgical department the use of the abdominal dressing-kit as a routine procedure in the management of diffuse peritonitis.

Background and aim—Some of the recently observed functional features characteristic of immunocompetent cells residing in the human intestinal lamina propria could be mediated by interleukin- 10 (IL-10). To investigate the role of IL-10 in the human intestinal mucosa, the regulation of IL-10 production by lamina propria T lymphocytes (LPL-T) was determined and compared with that of peripheral blood T lymphocytes (PBL-T).Methods—Following activation by using different stimuli, IL-10 release by LPL-T and PBL-T into the supernatant was measured by enzyme linked immunosorbent assay (ELISA). In parallel, cell growth was determined by [3H]-thymidine incorporation.Results—Neither LPL-T nor PBL-T release IL-10 constitutively. Triggering through CD2 or the T cell receptor (TCR)/CD3 complex in the presence of autologous monocytes induces significantly greater IL-10 secretion by LPL-T than by PBL-T. Engagement of the CD45 receptor enhances IL-10 release and proliferation of CD2 triggered CD45RO+ PBL-T. In contrast, it reduces CD2 induced IL-10 production by LPL-T without altering cell growth significantly .Conclusions—Activated LPL-T release relatively high amounts of IL-10. Enhanced IL-10 production by activated LPL-T, in comparison with activated PBL-T, is not only related to the presence of a higher proportion of CD45RO+ T cells in the intestinal lamina propria, but is also caused by increased sensitivity of LPL-T to CD2 co-stimulation. The differential responsiveness of LPL-T, compared with PBL-T, to CD45 engagement demonstrates that CD45 could be involved in the altered CD2 reactivity of LPL-T.

This article reviews the molecular basis of cell adhesion and its possible implications in surgery. Adhesion of circulating cells to endothelial cells is mediated by a variety of celladhesion molecules. The first steps in the cell adhesion cascade (rolling, tethering) are regulated by selectins (P, E, L selectin). Stable adhesion and transmural migration predominantly involve integrins (LFA-1, etc.) and members of the immunoglobulin supergene family (ICAM-1, etc). The mechanisms of leucocyte-endothelial interaction are markedly similar in various organs under both physiological and pathophysiological conditions. However, it is likely that cell trafficking to specific tissues/organs (e.g., homing) is regulated by additional organ-specific, topical adhesion molecules (e.g., MAdCAM-1). In surgery, cell adhesion molecules are involved in organ-transplantation pathology (ischemia/reperfusion injury, rejection), inflammation (e.g., chronic inflammatory bowel diseases), tumor metastasis. Animal experiments with anti-adhesive substances show that blocking the leukocyte-endothelial interaction reduces the cellular inflammatory infiltrate and organ rejection. The transfer of experimental data into clinical practice requires further understanding of the regulators of cell adhesion (cytokines, chemoattractant substances, etc.) and the specificity of the process. Current experimental data suggest that early intervention in cell-adhesion mechanisms may offer innovative therapeutic strategies.

SUMMARY Human intestinal lamina propria T lymphocytes (LPL-T) physiologically exhibit minimal proliferation in response to antigen receptor stimulation in vitro. This is thought to occur as a consequence of regulatory influences which are exerted by the mucosal microenvironment. The present study is aimed at investigating whether proliferative responses of intestinal LPL-T to antigen receptor stimulation are altered in patients with inflammatory bowel disease. Accordingly, proliferative responses of LPL-T in patients with Crohn's disease and ulcerative colitis to stimulation with CD3 MoAb plus IL-2 were examined and compared with controls. In addition, T cell receptor (TCR) repertoires of LPL-T and peripheral blood T lymphocytes were determined by indirect immunofluorescenee using a panel of 11 TCR Vβ specific antibodies. In most patients with inflammatory bowel disease, LPL-T showed enhanced proliferation to antigen receptor stimulation compared with controls. Moreover, perhaps as a consequence, an enhanced frequency of in vivo preactivated T cells was seen as judged from an increased spontaneous proliferative response to low concentrations of exogenous IL-2. LPL-T and peripheral blood T lymphocytes exhibited similar percentages of TCR Vβ gene usage both in controls and in patients. In summary, polyclonal activation of LPL-T due to impairment of local adjustment, i.e. insufficient down-regulation of TCR/CD3-dependent signalling processes, may contribute to the pathogenesis of inflammatory bowel disease.

Background: Compared with T cells in peripheral blood, lamina propria T lymphocytes have a low proliferative response to stimulation via the T-cell antigen receptor/CD3 complex or by protein kinase C activators yet largely preserve or even show an enhanced reactivity to CD2 and CD28 triggering. Coculture of peripheral blood T lymphocytes with intestinal mucosa supernatant leads to a similar functional behavior as found in freshly recovered lamina propria T lymphocytes. The aim of this study is to characterize the nature of substances in the mucosal supernatant responsible for downregulation of T-cell receptor-dependent signals. Methods: Mucosal supernatant was produced, dialyzed, digested with proteinase K, reduced by 2-mercaptoethanol or dithiothreitol, and tested for its activity on peripheral blood T lymphocytes. Results: Supernatant lost its activity after dialysis through a membrane (pore size 12,000–14,000). Digestion with proteinase K does not abolish its activity suggesting that the substances are neither proteins nor peptides. However, its effects on T lymphocyte proliferation can be reversed by reducing agents like 2-mercaptoethanol or dithiothreitol, suggesting that oxidative substances are contained in mucosal supernatants. Conclusions: Our data support the view that mucosal substances that down-regulate antigen receptor-induced T lymphocyte proliferation are small, nonprotein, nonpeptide molecules with oxidative properties.

Scintigraphy with a radiolabelled somatostatin analog represents a new highly specific approach in the diagnostic work-up of receptor-positive APUD tumours and their metastases. We present our preliminary results with somatostatin receptor scintigraphy in 15 patients with histologically proven midgut carcinoid. 5 out of 6 primary tumour sites (83%) and 90% of the known metastatic lesions could be detected; unknown metastatic lesions were seen in 5 patients. Compared with other nuclear medicine procedures somatostatin receptor scintigraphy is able to detect all tumour sites within hours. This advantage will promote the acceptance of this sensitive and specific imaging modality by the clinicians with regard to preoperative work-up and symptomatic therapy with a somatostatin analog.

Crohn's disease (CD) and ulcerative colitis (UC) show an intestinal activation of T cells and macrophages within the inflamed lesions. The aim of the present prospective study was to determine whether circulating interleukins (IL) represent useful markers of immune activation in vivo and to characterize their respective roles in monitoring disease activity. Serum concentrations of the soluble IL-2 receptor (sIL-2R), IL-6 and IL-1 beta were measured in 10 patients with CD and 10 patients with UC before, at day 10 and 2 years after resection of inflamed bowel segments. The data were correlated with neopterin, C-reactive protein and other standard parameters of disease activity. Preoperatively, mean sIL-2R concentration was 495 +/- 62 U/ml (mean +/- SEM; healthy controls; 210 +/- 25 U/ml; p less than 0.02) in CD and 705 +/- 120 U/ml (p less than 0.00002) in UC. The corresponding IL-6 serum concentrations were 37 +/- 6 U/ml in CD (controls: 11 +/- 0.6 U/ml; p less than 0.0036) and 33 +/- 6 U/ml (p less than 0.04) in UC. Two years postoperatively, sIL-2R was still elevated in 6 out of 9 patients in both disease groups. These patients did not differ from the remaining group with respect to disease activity. Serum IL-6, elevated in 7 patients with CD and in 6 patients with UC at day 10 postoperatively, had returned to normal in all patients by this time.(ABSTRACT TRUNCATED AT 250 WORDS)

Note: 204 Reference SAMLAB-ARTICLE-1999-020doi:10.1002/(SICI)1096-9918(199905/06)27:5/6 3.0.CO;2-V Record created on 2009-05-12, modified on 2016-08-08

Perianal fistulas and abscesses are a common manifestation in Crohn's disease (CD), seen in about 30 - 40 % of the patients. Often they are combined with CD of the anal canal and occur as a complex system of fistulas. The evaluation of these fistulas can be done with endoscopic ultrasound or magnetic resonance imaging, the conceptual accuracy of both methods is high. There are accepted therapeutic concepts for surgery and for the conventional drug therapy according to the classification of the fistulas. In contrast, the therapeutic regimens for a complex perianal fistulising CD are not convincing, especially not for maintainance therapy. However, several studies about therapy with anti-TNF-alpha antibodies have shown good results while long-time results with other recent anti-TNF-alpha antibodies apart from infliximab are still lacking. In this review article we analyse the current literature and develop a stage-adapted therapy for the use of biologicals and surgery in fistulising perianal CD.

Human lamina propria lymphocytes were recovered from surgical specimens of unaffected large bowel and compared with peripheral blood lymphocytes (PBL) from the same individual. We investigated their capacities to respond to triggering stimuli delivered by mitogenic monoclonal antibodies directed at the T cell receptor/CD3 complex or, alternatively, the CD2 glycoprotein. In marked contrast to PBL, expression of the interleukin 2/interleukin 2 receptor system was markedly reduced in LPL following activation through the CD3/T cell receptor. Perhaps, more important, responses to CD2 triggering were similar or even stronger in LPL as opposed to PBL. This indicates that the CD2-dependent alternative pathway of T cell activation might serve a functional role in local immunity in the gut.

The morphology, clinical parameters and treatment of the popliteal artery entrapment syndrome (PAES) are presented on the basis of 13 of our own cases and from the literature. PAES is based on a segmental vascular compression due to an anatomical anomaly of the popliteal region and a new classification is presented distinguishing three variants according to the different anatomical conditions. PAES is mostly found in young sportsmen with well-developed muscles. Clinical symptoms are acute or chronic, and the diagnosis is made by physical examination, angiography and Doppler ultrasound, both in neutral position and in plantar flexion. Although thromboendarterectomy in some cases leads to good results, the preferred surgical therapy is decompression of the entrapped artery and reconstruction of the arterial pathway by vein graft interposition. The results were excellent in nine of 13 cases. In two patients, a recurrent thrombosis necessitated a femoro-crural bypass and in two others the entrapment was only diagnosed during reoperation for aneurysms of the venous graft.

The surgical treatment of patients suffering from peritonitis with an open abdomen is commonplace. However scheduled as well as required dressing changes and peritoneal lavages mean a time- and costs-intensive challenge for the nursing and medical personnel. Since the introduction of the abdominal dressing-kit (KCI, Walluf, Germany) in the management of diffuse peritonitis one expects to influence the patients' recovery in a positive way due to the continuous evacuation of intraabdominal infectious fluids, augmentation of tissue's granulation, prevention of fascial retraction and prevention of an abdominal compartment syndrome. First on trial we established 2004 in our surgical department the use of the abdominal dressing-kit as a routine procedure in the management of diffuse peritonitis.

Cantilevers with integrated tip and piezoelectric layer (zinc oxide, ZnO) for actuation and detection have been microfabricated using monocrystalline silicon as the bulk material. Arrays of five levers and cantilevers with two independent ZnO layers have also been obtained. The levers have been mechanically and electrically characterized. Dynamic mode and contact mode atomic force microscopy (AFM) images were achieved using the integrated piezoelectric layer of these levers as a vertical deflection sensor.

Arrays of cantilevers with integrated self-sharpening tips and self-exciting piezoelectric sensors have been fabricated using monocrystalline silicon micromachining. During the fabrication process, tips are first formed with a wet etching technique allowing a good homogeneity of tip shape over a whole wafer and then protected with a local thick silicon dioxide layer. Single cantilevers have been used to achieve atomic force microscopy images of grids with periods of 0.25, 1, and 5 μm and with height differences of 100, 15, and 180 nm, respectively.

Endothelins, a group of polyfunctional cytokines, induce the adhesion of circulating leucocytes to venous endothelium, an initial step in the pathogenesis of a cellular infiltrate in inflammatory bowel disease (IBD). The effect of bosentan, a non-selective endothelin receptor antagonist, on leucocyte adhesion and inflammation in a murine model of IBD was studied.Thirty BALB/c mice were divided into three groups of 10 animals: untreated controls, chronic colitis [dextran sodium sulphate (DSS), 3% w/v for 30 days], and treatment with bosentan (30 mg/kg i.p. daily on days 26-30). On day 30, adherent and rolling leucocytes and the average rolling velocity were assessed by intravital microscopy. Clinical and histological activity of inflammation were assessed by the disease activity index and modified Dieleman score, respectively.Kruskal-Wallis test was used, followed by Dunn's method. A value of p0.05 was considered significant.Compared to healthy controls, mice treated with DSS showed pronounced clinical and histological inflammation, and a higher number of rolling and adhering leucocytes in colonic submucosal venules. Therapy with bosentan significantly reduced clinical and histological inflammation. Adherent leucocyte levels were markedly lower (1.2+/-0.3 vs 23.7+/-2.8 adherent cells per 0.01 mm2, p0.05). The number of rolling leucocytes was lower but not significantly different. However, rolling velocity was significantly higher (91.5+/-14.0 vs 19.0+/-1.6 microm/s, p0.05).Bosentan reduces the adhesion of leucocytes in colonic submucosal venules and reduces inflammation in this mouse model of IBD. By inhibiting leucocyte adhesion, a crucial step in the recruitment of leucocytes to the inflamed tissue, bosentan is a potent therapeutic drug in this animal model. Further studies are necessary to investigate the role of bosentan as a novel drug in human IBD.

Morbus Crohn ist eine chronisch entzundliche Darmerkrankung, die in den westlichen Industrienationen eine Inzidenz von 4-6 und eine Pravalenz von 30–90 pro 100.000 Einwohner hat. Ein Erkrankungsgipfel besteht in der 3. Dekade, ein zweiter kleinerer Peak liegt jenseits des 6. Lebensjahrzehnts (Kolonbefall). Die Erkrankung wurde von den amerikanischen Autoren Crohn, Clinzberg und Oppenheimer am Mount Sinai Hospital in New York 1932 erstmals charakterisiert (Tabelle 1). (Der masgebliche Chirurg A. Berg wollte in der Publikation unerwahnt bleiben; ansonsten ware er — bei alphabetischer Reihenfolge der Autoren — namensgebend gewesen!). Morbus Crohn kann den gesamten Gastrointestinaltrakt befallen, bei 10–20% der Patienten kommt es zusatzlich zu extraintestinalen Manifestationen (Abb. 1). Es besteht eine transmurale Entzundung mit einem zellreichen Entzundungsinfiltrat und diskontinuierlichem, segmentalem Befallsmuster. Als atiopathogenetische Faktoren werden Umwelteinflusse, genetische Pradisposition, Ernahrungsgewohnheiten, eine gestorte Immunregulation, Permeabilitatsstorungen und vaskular-ischamische Aspekte diskutiert.

Intravital microscopy was performed in normal and indomethacin-induced intestinal inflammation at serosal postcapillary venules of the small bowel in rats. Standard parameters of microcirculation as red blood cell velocity, diameter of venules, blood flow and adherent leucocytes were successfully investigated using FITC-labelled red blood cells. Since postcapillary venules are responsible for the venous drainage of the inflammed small bowel segments this method is reliable and effective for further investigation of intestinal microcirculation under special conditions such as intestinal inflammation.

Neuroendocrine tumors of the gastroenteropancreatic system (GEP) are heterogeneous regarding hormone production, localisation and biological behaviour making the prognostic evaluation of these rare tumors difficult. Capella et al. proposed a new classification that combines for the first time both biological and prognostic characteristics. This study aimed to evaluate the prognostic value of Capella's classification in the patients treated at our hospital.86 from 1975-1999 surgically treated and histologically confirmed neuroendocrine tumors were retrospectively classified as benign (B), uncertain behavior (UB), low grade malignant (LG) or high grade malignant (HG) following the Capella classification. These data were correlated with the long-term outcome of the patients 8.5 (range: 1-24) years after surgery.43 % of tumors were localised in the pancreas, the others were equally distributed in the remaining GEP. Most tumors were classified as B (42 %) or LG (41 %), few were UB (10 %) or HG (7 %). 61 patients survived free of disease, 25 patients died, 13 of them not tumor related. Tumor related deaths were only observed in 6 patients with inoperable LG- and 6 patients with HG-neuroendocrine tumors within 3 years after surgery.The Capella classification reliably reflects the heterogeneity and the biological behaviour of GEP-neuroendocrine tumors and can therefore be recommended for clinical use.