Downregulation of the ubiquitin-proteasome system in normal colonic macrophages and reinduction in inflammatory bowel disease.

BACKGROUND: In normal mucosa, intestinal lamina propria macrophages (IMACs) maintain tolerance against food antigens and the commensal bacterial flora. Several mechanisms have been identified that mediate tolerance. The ubiquitin-proteasome system (UPS) is a large multiprotein complex that degrades cellular proteins. As the UPS may modulate immune functions of IMACs, we performed a detailed investigation of UPS expression and function under normal conditions and in cells derived from patients suffering from inflammatory bowel disease (IBD). METHODS: IMACs were isolated from intestinal mucosa. mRNA expression of macrophages differentiated in vitro (i.v. MACs) and IMACs was compared by Affymetrix® oligonucleotide arrays. Quantitative Taqman-PCR was performed on five exemplary proteasomal and five ubiquitinylation genes each. Proteins were analyzed by immunohistochemistry and Western blotting. Proteasome function was assessed by a fluorimetric test. RESULTS: Affymetrix analysis showed downregulation of mRNA expression of almost all represented proteasomal and of 22 ubiquitination-associated genes in IMACs as compared to i.v. MACs and monocytes. By quantitative PCR, up to tenfold higher mRNA expression of 10 exemplary genes of the UPS (UBE2A, UBE2D2, UBE2L6, USP14, UBB and ATPase2, ß2, ß5, ß2i/MECL-1, ß5i/LMP7) was demonstrated in i.v. MACs as compared to IMACs. Immunohistochemistry and Western blots confirmed these findings in intestinal mucosa of controls and patients suffering from diverticulitis. In contrast, a significant increase in protein amounts was found in mucosa of patients with IBD. CONCLUSION: Reduced expression of subunits of the UPS in IMACs of normal mucosa supports the concept of the presence of a nonreactive, anergic macrophage phenotype in the gut under normal conditions. Reinduction in IMACs of IBD mucosa reflects activated IMACs which can present antigenic peptides and thus support inflammation.

[Indications for magnetic resonance imaging in Internal Medicine. When do we really need this technology?]. / Internistische Indikation zur Magnetresonanztomographie. Wann brauchen wir sie wirklich?

Due to further technical developments in recent years, magnet resonance imaging (MRI) is now recognized as one of the primary diagnostic imaging modalities in the field of Internal Medicine. This review describes relevant indications for MRI in the different subspecialties of Internal Medicine and compares the diagnostic yield of MRI to other established modalities such as computed tomography and ultrasound.

(GT)N dinucleotide repeat polymorphism of haem oxygenase-1 promotor region is not associated with inflammatory bowel disease risk or disease course.

Haem oxygenase-1 (HO-1) up-regulation was suggested to reduce mucosal tissue damage in inflammatory bowel disease (IBD) and an up-regulation of HO-1 expression in patients with Crohn's disease (CD) and ulcerative colitis (UC) was demonstrated. A HO-1 gene promoter microsatellite (GT)(n) dinucleotide repeat polymorphism was associated with regulation of HO-1 in response to inflammatory stimuli. We therefore hypothesized that IBD patients might segregate into phenotypes with high or low HO-1 inducibility. Ethylenediamine tetraacetic acid blood samples were obtained from 179 CD patients, 110 UC patients and 56 control patients without inflammation. Genomic DNA was purified and the 5'-flanking region of the HO-1 gene containing the (GT)(n) dinucleotide repeat was amplified. Polymerase chain reaction (PCR) products were purified and the length of the PCR fragments was analysed. The number of (GT)(n) repeats in the population studied ranged from 13 to 42. The distribution of the allele frequencies was comparable in patients and controls for both the short and the long alleles. The frequencies of short-, middle- and long-sized alleles were not changed among the groups studied. No correlation was found between IBD and microsatellite instability detected in five individals. Our data indicate that (GT)(n) dinucleotide repeats of the HO-1 promotor region have no significance for the pathophysiology and disease course of IBD.

Normal luminal bacteria, especially Bacteroides species, mediate chronic colitis, gastritis, and arthritis in HLA-B27/human beta2 microglobulin transgenic rats.

Genetic and environmental factors are important in the pathogenesis of clinical and experimental chronic intestinal inflammation. We investigated the influence of normal luminal bacteria and several groups of selected bacterial strains on spontaneous gastrointestinal and systemic inflammation in HLA-B27 transgenic rats. Rats maintained germfree for 3-9 mo were compared with littermates conventionalized with specific pathogen-free bacteria. Subsequently, germfree transgenic rats were colonized with groups of five to eight bacteria that were either facultative or strictly anaerobic. Transgenic germfree rats had no gastroduodenitis, colitis, or arthritis, but developed epididymitis and dermatitis to the same degree as conventionalized rats. Colonic proinflammatory cytokine expression was increased in transgenic conventionalized rats but was undetectable in germfree and nontransgenic rats. Colitis progressively increased over the first 4 wk of bacterial exposure, then plateaued. Only transgenic rats colonized with defined bacterial cocktails which contained Bacteroides spp. had colitis and gastritis. Normal luminal bacteria predictably and uniformly induce chronic colonic, gastric and systemic inflammation in B27 transgenic F344 rats, but all bacterial species do not have equal activities.

Irinotecan plus gemcitabine and 5-fluorouracil in advanced pancreatic cancer: a phase II study.

AIMS: The aim of the present study was to evaluate the 6-month survival rate of patients with inoperable or metastatic pancreatic cancer treated with irinotecan and gemcitabine plus 5-fluorouracil. Secondary efficacy end points included response rate, time to progression (TTP), overall survival (OS) and toxicity. PATIENTS AND METHODS: 30 patients with histologically proven pancreatic carcinoma and at least one bidimensionally measurable lesion were enrolled. Of the patients, 83% had metastatic and 17% locally advanced disease. One cycle, lasting 21 days, comprised treatment on days 1 and 8 consisting of 75 mg/m(2) irinotecan i.v. for 90 min, 1,000 mg/m(2) gemcitabine i.v. for 30 min and 2,000 mg/m(2) fluorouracil (5-FU) for 24 h. A total of six cycles was planned for each patient. RESULTS: 28 patients competed at least one treatment cycle and were therefore assessable for efficacy, and 75% of them achieved the primary end point of the study (survival after 6 months). One-year survival was 25%. Stabilization (partial response and stable disease) was observed in 35.7% (10/28) and partial remission in 7.1% (2/28). The objective response rate was 7.1% (2/28) after completion of the six cycles. Median TTP was 3.4 months (1.2-11.5), and median OS was 8.3 months (2.1-36.2). Regarding severe hematological toxicities, only neutropenia was observed (grade 3 20.7%, 6/29, and grade 4 3.5%, 1/29). In spite of anti-emetic supportive care, nausea affected most of the patients: 79.3% (23/29). Grade 3 vomiting was observed in 4 of the 29 patients (13.8%) and grade 4 in 1 patient (3.5%). Only 1 patient experienced diarrhea grade 3 (3.5%) and 1 patient (3.5%) suffered from a grade 3 peroneal nerve enervation. CONCLUSIONS: A combination of irinotecan, gemcitabine and 5-FU is feasible and shows considerable efficacy in patients with inoperable or metastatic pancreatic cancer. Due to its low toxicity, this combination might be an interesting cytotoxic regimen in addition to targeted therapies.

Calcitriol analog ZK191784 ameliorates acute and chronic dextran sodium sulfate-induced colitis by modulation of intestinal dendritic cell numbers and phenotype.

AIM: To investigate the effects of ZK1916784, a low calcemic analog of calcitriol on intestinal inflammation. METHODS: Acute and chronic colitis was induced by dextran sodium sulfate (DSS) according to standard procedures. Mice were treated intraperitoneally with ZK1916784 or placebo and colonic inflammation was evaluated. Cytokine production by mesenterial lymph node (MLN) cells was measured by ELISA. Immunohistochemistry was performed to detect intestinal dendritic cells (DCs) within the colonic tissue, and the effect of the calcitriol analog on DCs was investigated. RESULTS: Treatment with ZK191784 resulted in significant amelioration of disease with a reduced histological score in acute and chronic intestinal inflammation. In animals with acute DSS colitis, down-regulation of colonic inflammation was associated with a dramatic reduction in the secretion of the proinflammatory cytokine interferon (IFN)-gamma and a significant increase in intereleukin (IL)-10 by MLN cells. Similarly, in chronic colitis, IL-10 expression in colonic tissue increased 1.4-fold when mice were treated with ZK191784, whereas expression of the Th1-specific transcription factor T-beta decreased by 81.6%. Lower numbers of infiltrating activated CD11c+ DCs were found in the colon in ZK191784-treated mice with acute DSS colitis, and secretion of proinflammatory cytokines by primary mucosal DCs was inhibited in the presence of the calcitriol analog. CONCLUSION: The calcitriol analog ZK191784 demonstrated significant anti-inflammatory properties in experimental colitis that were at least partially mediated by the immunosuppressive effects of the derivate on mucosal DCs.

Genomic structure of human omentin, a new adipocytokine expressed in omental adipose tissue.

Genomic structure, promoter region, amino acid sequence and exon-specific primer combinations of the human omentin gene are presented. Omentin mRNA expression differs between omental adipose tissue probes from patients with chronic inflammatory bowel diseases such as Crohn's disease. Sequence comparisons revealed a 100% identity of omentin with human intelectin. Based on this, omentin might be a new adipocytokine playing a role in the defense against intestinal bacterial translocation in the context of Crohn's disease.

Genomic organization, chromosomal localization and adipocytic expression of the murine gene for CORS-26 (collagenous repeat-containing sequence of 26 kDa protein).

The murine gene for CORS-26 shows striking homologies to the adipocyte-specific secretory protein adiponectin (belonging to the newly discovered C1q/TNF molecular superfamily) and its expression has been reported to be restricted to fibroblasts, cartilage and kidney. However, the present data demonstrate specific induction of CORS-26 mRNA expression in hormonally differentiated 3T3-L1 adipocytes, but not in preadipocytes. Furthermore, CORS-26 mRNA expression could be demonstrated in human synovial adipocytes of the knee by in situ hybridization. Since the genes for CORS-26 and adiponectin are homologous for their COOH-terminal globular domain and of their N-terminal collagenous domain, they might have originated by divergence from an innate mesenchymal precursor molecule directing the development of myocytes, adipocytes and chondrocytes from a mesenchymal stem cell. Here, the complete genomic organization with exon/intron boundaries together with exon-specific primer combinations are presented. Additionally, approximately 1 kb of the TATA-box-containing promoter region was cloned and analyzed for putative transcription factor binding sites. The chromosomal localization of the murine CORS-26 gene was mapped to mouse chromosome 15 A2 by fluorescence in situ hybridization (FISH). Since the linkage loci for proteoglycan-induced arthritis and MRL/lpr arthritis in mice have been mapped to that chromosomal region, CORS-26 might represent the underlying mechanism of disease. The present data provide the basis for further investigation of the CORS-26 gene regulation in the context of mesenchymal tissue development, chondrocyte/adipocyte function and bone or skeletal disease.

Genomic organization, promoter, amino acid sequence, chromosomal localization, and expression of the human gene for CORS-26 (collagenous repeat-containing sequence of 26-kDa protein).

The murine gene for CORS-26 is located on mouse chromosome 15A2 and its expression has been reported to be restricted to fibroblasts, cartilage and kidney. Here, the complete genomic organization of the corresponding human CORS-26 gene with exon/intron boundaries and exon-specific primer combinations is presented. Additionally, a 1.2 kb fragment of the TATA box-containing promoter region was cloned and analyzed for putative transcription factor binding sites. The deduced amino acid sequence is presented completely. Northern blot analysis using a human multiple-tissue cDNA panel demonstrated expression of human CORS-26 mRNA in colon and small intestine. Additionally, RT-PCR analysis revealed expression of CORS-26 mRNA in placenta, fibroblasts and white adipose tissue. The chromosomal localization of the human CORS-26 gene was mapped to human chromosome 5p by fluorescence in situ hybridization (FISH). In humans, chromosomal imbalances on chromosome 5p were reported to be involved in the pathogenesis of osteosarcoma. Therefore, a human bone tumor cDNA panel was investigated and a strong CORS-26 mRNA expression was found in osteosarcoma, chondroblastoma and giant cell tumor. The present data provide the basis for further investigation of CORS-26 gene regulation in the context of mesenchymal tissue development and in the pathogenesis of bone or skeletal disease.

Role of specificity protein-1, PPARgamma, and pituitary protein transcription factor-1 in transcriptional regulation of the murine CORS-26 promoter.

The collagenous repeat-containing sequence of 26-kDa protein (CORS-26) was recently described as a new gene that is induced during adipocyte differentiation. Since the transcription factors specificity protein-1 (SP-1) and PPARgamma have been demonstrated to modulate transcriptional activation of adipocytic genes, we investigated the putative role of SP-1 and PPARgamma in the regulation of the murine CORS-26 promoter. Computer-based sequence analysis revealed two putative SP-1 binding sites and binding sites for PPARgamma and Pit-1 within the TATA-box containing promoter. Electrophoretic mobility shift assays (EMSA) with nuclear extracts from 3T3-L1 adipocytes and appropriate promoter fragments demonstrated that SP-1 binds specifically to both SP-1 binding sites. Specificity was demonstrated by (i) the appearance of supershift bands, (ii) competition experiments and, (iii) by using oligonucleotides carrying mutated SP-1 binding sites. Functional promoter activity was analyzed by Luciferase reporter gene assays and SP-1 was shown to exert inhibitory effects on the transcriptional activation of the murine CORS-26 gene. Additionally, specific binding activity of PPARgamma and Pit-1 to the CORS-26 promoter was demonstrated. Taken together, the present data demonstrate the functionality of the proximal murine CORS-26 promoter, which is regulated specifically by two SP-1 binding sites via SP-3-independent repressive effects of SP-1 on transcriptional activation. Pit-1 and PPARgamma can bind specifically to the promoter and might play an additive functional role in gene regulation of murine CORS-26.

Bacterial Cell Wall Polymer-Induced Granulomatous Inflammation

Local or systemic injection of peptidoglycan-polysaccharide polymers, which are the primary structural components of cell walls of nearly all bacteria, leads to acute inflammation, which can develop into chronic, spontaneously relapsing, granulomatous inflammation in a number of organs. Evolution into chronic granulomatous inflammation is dependent upon persistence of poorly biodegradable cell wall polymers within tissues, genetically determined host susceptibility, and generation of a T-lymphocyte-mediated immune response. Intraperitoneal injection of peptidoglycan-polysaccharide fragments from group A streptococci or selected intestinal bacteria into susceptible Lewis rats leads to chronic, spontaneously reactivating erosive arthritis and hepatic granulomas. Subserosal (intramural) injection of poorly biodegradable cell wall fragments into the distal intestine of Lewis rats induces chronic, spontaneously relapsing granulomatous enterocolitis with associated arthritis, hepatic granulomas, anemia, and leukocytosis. Chronic inflammation does not occur in T-lymphocyte-deficient rats and is prevented by cyclosporin-A therapy and degradation of peptidoglycan by the muralytic enzyme, mutanolysin. Moreover, resistant Buffalo and Fischer F344 rats, the latter sharing identical MHC antigens with Lewis rats, develop only acute inflammation with no chronic granulomatous response. Peptidoglycan-polysaccharide polymers activate almost every limb of the inflammatory response. Blockade of specific pathways suggests that interleukin-1, transforming growth factor-beta, plasma kallikrein, and T lymphocytes are dominant mediators of peptidoglycan-polysaccharide-induced arthritis, hepatic granulomas, and enterocolitis. Because of the similarity of immune mechanisms of these rat models to human disease, bacterial cell wall-induced inflammation provides unique opportunities to study pathogenic mechanisms of granuloma formation in response to ubiquitous microbial agents and to test novel therapeutic agents.

Monocyte differentiation in intestine-like macrophage phenotype induced by epithelial cells.

Macrophages in normal colonic mucosa show a specific and distinct phenotype with low expression of the typical monocyte/macrophage surface antigens CD14, CD16, and CD11b and T-cell costimulatory molecules. A method for the in vitro induction of a macrophage phenotype similar to this intestinal phenotype is presented. Multicellular spheroids (MCSs) of intestinal epithelial cell (IEC) and control cell lines were cocultured with elutriated monocytes. Surface antigen expression was analyzed by immunohistochemistry and flow cytometry. Interleukin (IL)-1beta mRNA was measured by quantitative PCR. Monocytes adhered and infiltrated the MCSs within 24 h. In the MCSs of all IEC lines, the typical monocyte/macrophage surface antigens CD14, CD16, CD11b, and CD11c, which are detectable after 24 h of coculture by immunohistochemistry and flow cytometry, were down-regulated after 7 days (e.g., for CD14 at 24 h, expression was 86% of CD33+ cells; at day 7, it was 11%). A clear decrease of lipopolysaccharide (LPS)-stimulated IL-1beta transcription in monocytes cocultured with IEC MCSs could be observed during the 7-day period. For the first time an intestine-like macrophage-phenotype could be induced in vitro. Interactions with IECs play an essential role during this differentiation, which is of functional relevance, e.g., for LPS-induced cytokine secretion.

Adiponectin represents an independent cardiovascular risk factor predicting serum HDL-cholesterol levels in type 2 diabetes.

UNLABELLED: Low levels of high-density lipoprotein (HDL)-cholesterol represent an independent cardiovascular risk factor and, besides reduced physical activity, mechanisms leading to decreased HDL-cholesterol levels are not known. We aimed to test the hypothesis, that adiponectin provides a missing link between type 2 diabetes and low levels of HDL-cholesterol, independent from common metabolic risk factors. 523 patients with type 2 diabetes were investigated for adiponectin serum levels and parameters of lipid metabolism. Even after correction for age, gender, BMI and fasting insulin concentration, serum levels of adiponectin were highly significant (P<0.0001) and positively (regression analysis: r=0.86) associated with HDL-cholesterol levels in type 2 diabetes. CONCLUSION: adiponectin seems to predict HDL-cholesterol levels in patients with diabetes mellitus type 2. Low levels of adiponectin are associated with low levels of HDL-cholesterol independently from common metabolic risk factors and therefore represent an independent cardiovascular risk factor in type 2 diabetes. Thus, adiponectin is a potentially new drug target in the treatment of dyslipidaemia.

Plasminogen activator inhibitor-1 promoter activity in adipocytes is not influenced by the 4 G/5 G promoter polymorphism and is regulated by a USF-1/2 binding site immediately preceding the polymorphic region.

Plasminogen activator inhibitor-1 (PAI-1) levels were found to be associated with obesity indicating that adipocytes influence PAI-1 plasma levels. In addition, the 4 G/5 G promoter polymorphism of the PAI-1 gene may modulate PAI-1 transcription. We investigated the transcriptional regulation of the human PAI-1 gene in adipocytes and analyzed the genetic contribution of the 4 G/5 G polymorphism. The PAI-1 promoter was analyzed using electrophoretic mobility shift assays (EMSAs) and luciferase reporter gene assays. A putative binding site for the upstream stimulatory factor-1/2 (USF-1/2) at the polymorphic region of the PAI-1 promoter was identified. The binding of USF-1/2 was studied using nuclear extracts prepared from adipocytes and was similar in all the promoter variants as analyzed by EMSA. A 257 bp PAI-1 promoter fragment including the 4 G/5 G site was transcriptionally active in adipocytes and was not influenced by the polymorphism. The present data indicate for the first time that USF-1/2 is transcriptionally active in differentiated adipocytes. However, USF-1/2 binding activity and PAI-1 transcription are not influenced by the 4 G/5 G-allele. These data possibly explain the observation that PAI-1 secretion from adipose tissue is not influenced by the PAI-1 promoter polymorphism.

Polymorphism of CC chemokine receptors CCR2 and CCR5 in Crohn's disease.

Crohn's disease (CD) is a chronic inflammatory disease of the intestine that is characterized by mononuclear cell infiltration and a predominant Th1 lymphocyte response. We tested the hypothesis that CC chemokine receptors CCR2 and CCR5 might be important in the regulation of the intestinal immune response in this disease, and we speculated that carriers of a defective 32 base pair deletion mutant of CCR5, CCR5Delta32, which results in a non-functional receptor, might be protected from CD. Using polymerase chain reaction (PCR) and PCR restriction fragment length polymorphism (PCR-RFLP) gene frequencies of CCR5Delta32 and of CCR2-641 (replacement of valine-64 by isoleucine in the CCR2 gene) in healthy controls (n=346) and in CD patients (n=235) were determined. In CD patients, subgroup phenotypic analyses were performed according to the Vienna classification. The overall gene frequency of CCR5Delta32 (9.8%) and CCR2-641 (7.6%) in CD patients did not deviate significantly from healthy controls (9.2 and 8.2%, respectively), nor did we observe a significant deviation from the predicted Hardy-Weinberg distribution. No significant differences in the CD phenotype classification for the different CCR5 and CCR2 alleles were observed, except for a trend to disease sparing of the upper gastrointestinal tract (carrier frequency 0 versus 19.6%, Delta=1 9.6%, P=0.079) as well as a more stricturing disease behaviour (23.5 versus 16.2%, Delta=7.3%, P=0.136) in carriers of the mutant CCR5Delta32 allele. These results indicate that the different CCR5 but not CCR2 alleles may influence disease behaviour and thereby contribute to the observed heterogeneity of CD. However, the associations observed are limited and await replication in other datasets. CCR2 and CCR5 polymorphisms are unlikely to be important determinants of overall disease susceptibility.

Intracellular polyamine levels of intestinal epithelial cells in inflammatory bowel disease.

Polyamines and their acetylated derivatives are a prerequisite for cellular metabolism and considered to be essential for proliferation and differentiation of the rapidly renewing intestinal mucosa. However, their role during mucosal inflammation is less clear. Polyamine concentrations were determined in isolated colonic epithelial cells (CECs) from endoscopic biopsies from 26 patients with inflammatory bowel disease (IBD) and 40 controls as well as colon samples from mice with and without acute or chronic dextran sodium sulfate (DSS)-induced colitis. In patients with ulcerative colitis, CEC spermidine and N8-acetylspermidine levels were significantly enhanced and spermine levels were reduced compared with healthy controls. A correlation of polyamine levels of patients with IBD with their corresponding inflammatory index revealed that increased concentrations of spermidine, N8-acetylspermidine, and N1-acetylspermine were found in CECs from the most severe inflamed mucosal areas. Using acute and chronic DSS colitis as a model of mucosal inflammation, we found enhanced levels of spermidine and spermine in acute colitis, whereas in chronic inflammation, CEC spermine concentrations were decreased. Our data indicate a lack of the anti-inflammatory polyamine spermine in severe ulcerative colitis and chronic DSS colitis, which may aggravate the disease. Increased spermidine and N8-acetylspermidine levels reflect increased uptake and metabolism likely due to accelerated proliferation and regeneration of CECs.

Identification of influencing variables on adiponectin serum levels in diabetes mellitus type 1 and type 2.

BACKGROUND: Adiponectin represents an adipocyte-specific secretory protein that has been discussed recently as candidate gene and promising new drug target to restore insulin sensitivity in diabetes mellitus type 2. AIM: The aim of the present study was to define influencing variables on adiponectin serum levels in a large cohort of caucasian patients with type 1/type 2 diabetes and healthy controls. Additionally, adiponectin gene polymorphisms (Tyr111His and Gly15Gly) were investigated for possible associations with adiponectin serum levels. METHODS: Adiponectin serum concentrations were measured in a metabolically well characterized cohort of 892 caucasian patients (556 with type 2 diabetes, 118 with type 1 diabetes, 218 controls) by ELISA. Gene polymorphisms were determined by PCR-based RFLP. RESULTS: 1) Adiponectin values are dependent on gender with higher levels in diabetic females than in diabetic males. This gender-specific effect was only restricted to patients with diabetes and cannot be observed in controls. 2) In contrast to previous studies, the presence of diabetes does not influence adiponectin serum levels after correction for BMI. In addition, age has no influence on adiponectin levels. 3) Adiponectin levels are dependent on renal function at a creatinine clearance < 45 ml/min. 4) Regression analysis showed a significant, but only weak correlation between BMI and adiponectin in patients with diabetes mellitus type 2 (r = 0.47) and type 1 (r = 0.57). 5) Adiponectin gene polymorphisms (Tyr111His and Gly15Gly) do not influence adiponectin levels. CONCLUSIONS: Adiponectin serum concentrations can only be interpreted after careful correction for gender and renal function, whereas the genetic variants Tyr11His and Gly15Gly do not seem to play a role. The correlation between BMI and adiponectin was weaker than expected in diabetic patients.

[Diagnosis and therapy of obstructive jaundice]. / Diagnostik und Therapie des obstruktiven Ikterus.

Obstructive jaundice is a sign of intra- or posthepatic blockage of bile flow. This diagnosis has to be differentiated from various other diagnoses such as disorders of bilirubin metabolism or hepatocellular causes of jaundice. An accurate evaluation of the past medical history and clinical examination of the patient can already establish obstruction as the cause of jaundice in most cases. For prevention of a cholangitis further imaging procedures should focus on rapidly establishing the cause and the location of obstruction. Further therapeutic procedures are dependent on the type of obstruction and the condition of the patient. Most importantly there should be a decompression of the biliary tree with ES or PTBD.

[Extraintestinal manifestations in chronic inflammatory bowel diseases]. / Extraintestinale Manifestationen bei chronisch entzündlichen Darmerkrankungen.

60-80% of patients with inflammatory bowel diseases (IBD) develop extraintestinal manifestations. These complications are mostly the result of the underlying disease, deficiencies, or drug therapy and can significantly reduce the quality of life of patients with IBD. The most evident manifestations affect the perianal region, joints, skin, and eyes. Regular check-ups and early substitution in addition to a consistent therapy of the chronic intestinal inflammation usually lead to a significant reduction of the extraintestinal symptoms.