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H Vogelsang

Publications and source records attributed to H Vogelsang.

At least 73 records · Page 4Linked to original sources

Aberrant esophageal HLA-DR expression in a high percentage of patients with Crohn's disease.

Esophageal histology is not well studied in patients with Crohn's disease (CD). We, therefore, analyzed the histologic and immunohistologic appearance of esophageal mucosa in CD. Biopsy specimens taken from the esophagus of 57 consecutive patients with known CD of the large and/or small bowel, of 200 Crohn's-free controls, of 15 cases with ulcerative colitis, and of 5 cases with viral esophagitis were evaluated. In controls, most patients had either HLA-DR negative esophageal epithelium or showed focal or diffuse basal staining. HLA-DR expression of all epithelial layers (transepithelial staining) was observed in only four (2%) control subjects, in one case with herpes esophagitis, but not in patients with ulcerative colitis. In contrast, transepithelial HLA-DR expression was found in 19 (33%) patients with CD (p < 0.0001). In CD patients, it was associated with a significantly increased epithelial content in T-cells (CD3+, TIA-1+, granzyme B+), B-cells (CD79a+), natural killer cells (CD57+), and macrophages (CD68+). There was no correlation with either histological findings elsewhere in the upper gastrointestinal tract or with laboratory findings, symptoms, CDAI, or medication. Transepithelial esophageal HLA-DR expression is common in CD. Immunohistochemistry may prove useful in supporting the histologic diagnosis of CD in staging procedures, for initial diagnosis as well as in doubtful cases.

Adolescent↗

Prevalence and clinical importance of hypertransaminasaemia in coeliac disease.

OBJECTIVE: To assess the prevalence and potential pathogenetic factors of hypertransaminasaemia in patients with coeliac disease prior to initiation of a gluten-free diet (GFD) and to assess the course of transaminases on a GFD. PATIENTS: A retrospective study was made of 178 patients with coeliac disease (130 women, 48 men; median age 36 years; range 17-84 years) at the gastroenterological department of a university hospital. METHODS: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured prior to initiation of a GFD and at 3, 6 and 12 months of GFD. Intestinal permeability, a test for functional integrity of the small bowel, was investigated before starting a GFD in 116 patients by an oral test using lactulose and mannitol. RESULTS: In 72 patients (40.4%) AST and/or ALT were increased prior to initiation of a GFD. Within 1 year on a GFD ALT and AST normalized except in eight cases (4.6%). The intestinal permeability index (% lactulose/% mannitol in 5 h urine) was higher in patients with elevated (median 0.34; range 0.03-1.43) than in patients with normal transaminases (0.11; 0.02-1.28) (P < 0.0001) and correlated with AST (tau = 0.34; P < 0.0001) and ALT (tau = 0.32; P < 0.0001). In five cases with hypertransaminasaemia a liver biopsy was performed prior to initiation of a GFD. Two patients had mild to moderate hepatitis with septal fibrosis. The other three had minimal lymphocytic infiltrates of the portal tracts. Inflammatory alterations of the bile ducts were not found. CONCLUSION: Hypertransaminasaemia before GFD is frequent in coeliac patients, correlates with intestinal permeability and normalizes on a GFD in most patients. In cases of persistently elevated liver function tests of unknown origin underlying coeliac disease should be considered.

Adolescent↗

The histopathology of coeliac disease: time for a standardized report scheme for pathologists.

In this paper, we review the histological features of coeliac disease and propose a standardized report scheme based on the Marsh classification. Furthermore, terms used by pathologists are defined. The most important histological differential diagnoses are given, as well as a definition of the different clinical forms of coeliac disease such as symptomatic, silent, latent, potential, treated and refractory coeliac disease.

Biopsy↗

Thromboembolism and resistance to activated protein C in patients with inflammatory bowel disease.

OBJECTIVE: Thromboembolic events are serious complications in patients with inflammatory bowel disease (IBD). Resistance of factor V to degradation by activated protein C (APC) is a major cause for venous thrombosis and is found in approximately 30% of patients with thromboembolism. The aim of the present study was to assess the prevalence of APC resistance and clinical risk factors in patients with IBD. METHODS: One-hundred-two patients with IBD (64 women and 38 men; median age, 35 yr; range, 17-77 yr; 77 with Crohn's disease, 25 with ulcerative colitis) and 102 gender- and age-matched healthy control subjects were investigated prospectively for the presence of APC resistance. None of the healthy controls but 16 patients with IBD had a history of thromboembolism. RESULTS: Patients with IBD and thromboembolism were young, with a median age of 37 yr (range, 17-61 yr). Five (31.3%) of them had APC resistance, which was more common than in patients with IBD without thromboembolism (7%) and in controls (5.9%) (p < 0.01). Three patients had two thromboembolic events, the other 13 each had one. Deep vein thrombosis of the leg and pulmonary emboli were the most common thromboembolic complications (84.2%). Active disease, fistula, or bowel stenosis were found in 10 (52.6%) of 19 thromboembolic events; in three (15.8%) cases thromboembolism happened postoperatively. CONCLUSIONS: APC resistance is not associated with IBD but, when present, increases the risk of thromboembolism. Patients with IBD and thromboembolism are mostly young and clinical risk factors can be found in one-half of cases.

Activated Protein C Resistance↗

In vitro production of endomysial antibodies in cultured duodenal mucosa from patients with celiac disease.

OBJECTIVE: Endomysial antibodies (EMAs) had been found recently after in vitro gluten challenge of duodenal mucosa from treated celiac patients. This was a promising result for diagnosis of potential/latent celiac disease. Therefore, we tested the usefulness of the production of EMAs of in vitro-challenged mucosa for diagnosis of celiac disease and determined the location of EMA production. METHODS: We investigated EMAs in the serum, in the supernatants of in vitro gliadin-challenged duodenal mucosa specimens in 68 patients, and in homogenized native duodenal and gastric specimens in seven patients. Twenty-one of the 68 patients served as nonceliac controls, 11 as candidates for potential celiac disease, 23 celiac patients were on glutenfree diet, and 13 were newly diagnosed. RESULTS: EMAs were just found in the supernatants of duodenal biopsies of those celiac patients who had demonstrable EMAs in serum, independent of gliadin challenge. In these patients EMAs were also found in homogenized native duodenal biopsies, but not in gastric biopsies. CONCLUSIONS: EMAs seem to be produced in the small bowel mucosa of celiac patients, but not in other tissues such as gastric mucosa. The production of EMAs could not be initiated under standard in vitro conditions and therefore, such as in vitro challenge cannot be used for diagnostic purposes.

Adult↗

Clinical relevance of serum interleukin-6 in Crohn's disease: single point measurements, therapy monitoring, and prediction of clinical relapse.

OBJECTIVE: To investigate the clinical relevance of interleukin-6 (IL-6) serum levels in patients with Crohn's disease (CD), single point IL-6 measurements in sera from consecutive CD patients and healthy donors (HD), as well as longitudinal measurements during the course of steroid therapy for active CD were performed. Patients with steroid-induced remission were followed until clinical relapse. METHODS: One hundred thirty-six CD patients without steroid or other immunosuppressive treatment within 2 months and surgical procedures within 3 months before study entry were investigated; 63 patients with active CD were enrolled into the follow-up program. Clinical activity was evaluated by the Crohn's disease activity index (CDAI) and serum IL-6 levels measured by enzyme-linked immunosorbent assay. RESULTS: IL-6 serum levels were significantly elevated in CD patients compared to HD (p < 0.001). In individual patients serum IL-6 levels correlated with corresponding CDAI scores in a subgroup referred to as primarily inflammatory patients presenting without bowel stenosis, previous intestinal resection, or concomitant inflammatory disorders (r = 0.72, p < 0.001). Primarily inflammatory patients displayed higher serum IL-6 levels (median: 6.0 pg/ml; range: 1.3-25) than CD patients with bowel stenosis (median: 2.0; range: 1.3-4.9; p < 0.01) or extensive intestinal resection (median: 1.5; range: 1.3-13.7; p < 0.001). Longitudinally measured serum IL-6 levels reflected the clinical response during steroid therapy and predicted clinical relapse after steroid-induced remission at week 9 of the treatment protocol. CONCLUSIONS: Serum IL-6 is a clinically relevant parameter for CD that correlates with inflammatory activity and implies a prognostic value after steroid-induced remission.

Adult↗

Influence of Helicobacter pylori infection on the phenotype of Crohn's disease.

OBJECTIVE: Very little is known about the impact of Helicobacter pylori (H. pylori) infection on Crohn's disease. In this study we investigated a possible influence of H. pylori on the phenotype of Crohn's disease. METHODS: Patients with Crohn's disease who had gastric biopsy between 1990 and 1994 and a clinical follow-up in our outpatient clinic for at least 2 yr were included in the study. The mean number of flare-ups per year of follow-up, the mean numbers of intestinal resections per year of disease duration, and primary disease location were compared in H. pylori-positive and -negative patients. Various regression models were calculated to test the influence of H. pylori status on these parameters, correcting for smoking habits and disease duration. RESULTS: Of 131 patients, 50 (38.2%) were H. pylori positive and 62 (47.3%) were smokers. Due to a significant interaction between smoking habits and H. pylori infection, regression models were calculated separately for smokers and nonsmokers. Nonsmokers without H. pylori infection had more flare-ups than nonsmokers with H. pylori infection (0.77 [0.57-0.97] vs 0.29 [0.16-0.42]; p < 0.01; mean [95% confidence interval]). In contrast, nonsmokers without H. pylori infection had less intestinal resections than nonsmokers infected with H. pylori (0.08 [0.04-0.12] vs 0.11 [0.07-0.15]; p < 0.05). These differences were not significant for smokers (p < 0.41 and p < 0.07). There was a predominance of small bowel disease in H. pylori-positive patients, which did not reach statistical significance. CONCLUSIONS: Our data indicate that H. pylori influences the phenotype of Crohn's disease, especially in nonsmokers.

Adult↗

Jeg-3 human choriocarcinoma-induced immunosuppression: downregulation of interleukin-2, interleukin-2 receptor alpha-chain, and its Jak/Stat signaling pathway.

PROBLEM: The mechanisms of the immunosuppressive and immunosuppression-inducing capacities of Jeg-3 human choriocarcinoma cell line supernatants (HCSs) are not yet completely understood. The influence on interleukin (IL)-2, IL-4 and interferon (IFN)-gamma production; IL-2 receptor (IL-2R) alpha-, beta-, and gamma-chain; and the signaling pathway molecules Janus kinase (Jak)1, Jak3, signal transducers and activators of transcription (Stat)1, Stat3, and Stat5 should be investigated. METHOD OF STUDY: For assessment of IL production, whole peripheral venous blood from healthy donors was stimulated with phorbol-myristate-acetate and ionomycine. Secretion of ILs was blocked with monensine. Intracellular ILs were analyzed by flow cytometry. For IL-2R and signaling pathway molecule analysis, peripheral blood lymphocytes were stimulated with phytohemagglutinin (PHA). IL-2R chains were measured by flow cytometry, and Jaks/Stats by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot. RESULTS: Phorbol-myristate-acetate and ionomycine strongly increase the percent-age of IL-2+ cells; an additional 50% HCSs significantly suppresses the percentage to, or below the level of unstimulated cells. IFN-gamma production is strongly decreased by HCSs in some cases, but not in others. PHA stimulates IL-2R alpha-, beta-, and gamma-chain expression and their signaling pathway molecules Jak1, Jak3, Stat1, Stat3, and Stat5. 50% HCS downregulates the alpha-chain and slightly upregulates the beta-chain. Jak1, Jak3, Stat1, Stat3, and Stat5 expression is suppressed approximately to, or below the level of unstimulated cells. CONCLUSIONS: HCS forcefully blocks the production of IL-2; the IL-2R alpha-chain; and Jak1, Jak3, Stat1, Stat3, and Stat5 expression. The observed phenomena might be caused by downregulation of an IL-2R regulation gene, and might play a key role in the expansion of choriocarcinoma, and possibly in the survival of the fetal allograft.

Adult↗

Outcome prediction by traditional and new markers of inflammation in patients with sepsis.

Patients (n=242) admitted to intensive care unit for longer than 48 hours were categorised for sepsis according to American College of Chest Physicians/Society of Critical Care Medicine (ACCP/SCCM) Consensus Conference criteria. Body temperature, leukocyte count, C-reactive protein (CRP) and procalcitonin (PCT) as well as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-8, IL-10 and HLA-DR expression on monocytes were determined. Data of one randomly chosen day per patient entered analysis. Immunologic mediators contributing significantly to outcome were determined by logistic regression analysis. Area under the curves (AUC) of receiver operating characteristic curves of clinical markers of inflammation predicting prognosis were compared with AUC of relevant immunologic mediators. TNF-alpha, IL-6 and HLA-DR expression on monocytes were significantly associated with outcome; the AUC's were 0.835, 0.844 and 0.761 respectively. AUC's for clinical markers were 0.878, 0.811, 0.620 and 0.614 for PCT, CRP, leukocyte count and body temperature respectively. PCT had the highest AUC compared to other clinical markers. These data indicate that PCT might be a better marker than the classic criteria of inflammation, CRP, leukocyte count, and body temperature to identify patients endangered by severe infection or sepsis.

Adult↗

Anti-TNF antibody in Crohn's disease--status of information, comments and recommendations of an international working group.

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.

Antibodies, Monoclonal↗

Familial gastric cancer: overview and guidelines for management.

Families with autosomal dominant inherited predisposition to gastric cancer have been described. More recently, germline E-cadherin/CDH1 mutations have been identified in hereditary diffuse gastric cancer kindred. The need to have protocols to manage and counsel these families in the clinic led a group of geneticists, gastroenterologists, surgeons, oncologists, pathologists, and molecular biologists to convene a workshop to produce consensus statements and guidelines for familial gastric cancer. Review of the available cancer pathology from people belonging to families with documented germline E-cadherin/CDH1 mutations confirmed that the gastric cancers were all of the diffuse type. Criteria to define the different types of familial gastric cancer syndromes were agreed. Foremost among these criteria was that review of histopathology should be part of the evaluation of any family with aggregation of gastric cancer cases. Guidelines for genetic testing and counselling in hereditary diffuse gastric cancer were produced. Finally, a proposed strategy for clinical management in families with high penetrance autosomal dominant predisposition to gastric cancer was defined.

Cadherins↗

[Cyclosporin A therapy in steroid-refractory patients with chronic inflammatory bowel diseases].

About eighty percent of patients with severe ulcerative colitis refractory to steroids are responsive to intravenous cyclosporine therapy within a few days. However, no controlled data are available on intravenous cyclosporine therapy in steroid refractory Crohn's disease. In this study 7 patients with severe ulcerative colitis and 4 patients with active Crohn's disease unresponsive to prednisone were treated with high dose intravenous cyclosporine. A response was estimated by a decrease of Crohn's disease activity index (Best) and colitis activity index (Rachmilewitz). Six of 7 patients with ulcerative colitis showed a significant decrease in colitis activity index (index before therapy: 15 +/- 2; one week later: 7 +/- 1; p < 0.001). In these patients prednisone could be tapered to a dose less than 20 mg/day within 6 months during oral cyclosporine and concomitant azathioprine therapy. Cyclosporine medication was withdrawn within a few weeks and the clinical response could be preserved for another 6 months. In 3 of 4 patients with Crohn's disease intravenous cyclosporine led to a temporary improvement of the Crohn's disease activity index (before treatment: 343 +/- 43, after one week: 194 +/- 20; p < 0.05). Nevertheless, all of these patients had an early relapse under oral cyclosporine therapy. Our data confirm the efficacy of intravenous cyclosporine as a rapid acting drug for severe ulcerative colitis. Maintenance therapy with azathioprine preserved the clinical response for one year. In patients with steroid refractory Crohn's disease intravenous cyclosporine showed only a short term effect.

Administration, Oral↗

[Carbohydrate-deficient transferrin (CDT) as preoperative alcohol marker in surgical risk patients].

In a prospective study the preoperative risk of alcohol addiction was evaluated in 46 patients with squamous cell carcinoma of the esophagus. In all patients the alcohol marker carbohydrate-deficient transferrin (CDT) was measured prior to esophagectomy and correlated with the incidence of postoperative withdrawal symptoms (yes/no) and the postoperative course (good/moderate/poor/fatal). Withdrawal symptoms were more frequently observed in cases of elevated CDT values (median of CDT with withdrawal 17.0 U/l vs without withdrawal 10.7 U/l; P = 0.0006). CDT values were significantly increased in case of a complicated postoperative course (median of CDT for moderate/poor/fatal postoperative course 14.0 U/l vs good course 10.8 U/l; P = 0.02). The CDT value correlated (P = 0.04) with the patient's history of preoperative alcohol consumption (normal/increased/high). In a multivariate logistic regression analysis CDT and preoperative alcohol consumption were independent parameters to predict significantly the postoperative course and withdrawal. The sensitivity was 71.4% and the specificity 84.4% selecting the parameter "postoperative withdrawal" and a CDT cut-off point of < 15.3 U/l. CDT can effectively identify patients with high alcohol consumption prior to esophagectomy.

Alcohol Withdrawal Delirium↗

Chromatographic resolution of ciprofibrate and interaction of the racemate and both enantiomers with rat liver microsomes in vitro.

The enantiomers of ciprofibrate may be achieved by enantioselective HPLC separation of its methylesters using a OD - Daicel column. Ciprofibrates (racemate and both enantiomers) bind to oxidized cytochrome P-450 in rat liver microsomes according type II like aniline or most probably as inversed type I, but less pronounced and with a general shift to the left. Ethylmorphine N-demethylation, ethoxycoumarin and ethoxyresorufin O-deethylation are all inhibited by the ciprofibrates, most effectively ethoxyresorufin O-deethylation by S(-)-ciprofibrate even in microM concentrations. Microsomal luminol and lucigenin amplified chemiluminescence indicating the formation of reactive oxygen species, microsomal hydrogen peroxide formation and NADPH/Fe stimulated lipid peroxidation were inhibited in a concentration dependent manner in concentration ranges between mM and microM. This might be due to distinct scavenger activities of all 3 compounds: the zymosan stimulated chemiluminescence of whole blood was completely inhibited in mM concentrations and influenced significantly down to concentrations of 10 microM, whereas burst and phagocytosis tests with human polynuclear leucocytes were not influenced.

Aniline Compounds↗

Gastroduodenal permeability in Crohn's disease.

BACKGROUND: Gastric permeability was prospectively investigated by determination of sucrose excretion in 100 patients with Crohn's disease. Results were compared with histological findings and the lactulose-mannitol ratio as a measure of intestinal permeability. METHODS: All subjects underwent oesophagogastroduodenoscopy with biopsies of all investigated parts. Thirty-two Helicobacter pylori-positive patients were excluded from further analyses. RESULTS: Gastroduodenal permeability was significantly higher in patients with Crohn's disease than in control subjects (P < 0.00001). Sucrose excretion alone did not predict microscopic inflammation of the upper gastrointestinal tract. Increased gastroduodenal permeability with a concomitant rise in intestinal permeability predicted histological upper gastrointestinal involvement of Crohn's disease with a likelihood of 86%. The negative predictive value was 43%. CONCLUSION: In parallel with findings in the small intestine, gastroduodenal permeability is increased in a high proportion of patients with Crohn's disease. In patients with an increased lactulose-mannitol ratio, elevated sucrose excretion is highly predictive of histological gastroduodenal involvement.

Adolescent↗

Conflicting results of ileoscopy and small bowel double-contrast barium examination in patients with Crohn's disease.

BACKGROUND AND STUDY AIMS: Ileoscopy has become a routine procedure for the diagnosis of Crohn's disease of the terminal ileum. The aim of this study was to compare the diagnostic accuracy of small bowel barium examination with that of ileoscopy. PATIENTS AND METHODS: In a retrospective study the two methods were compared in 55 patients with Crohn's disease. First, routine radiology reports and second, reevaluation of the small bowel barium study by gastrointestinal radiologists with scoring of examination quality were compared with the results of ileoscopy. RESULTS: Using routine radiology reports, 66% sensitivity and 82% specificity were reached for inflammatory changes of the terminal ileum by small bowel barium study. Sensitivity and specificity increased to 68% and 91% with double reading by experienced radiologists. Disagreement between endoscopic and radiologic results changed from 31% to 27% and were mainly because of false-negative barium studies. Sensitivity and specificity of barium studies were influenced by the quality of the examination with a sensitivity of 91% and specificity of 100% when the quality was good. CONCLUSIONS: In patients in whom the terminal ileum is successfully intubated, ileoscopy is superior to barium examination in the evaluation of Crohn's disease of the terminal ileum. Results of the barium study were strongly influenced by the quality of the examination.

Adolescent↗

High proportion of granzyme B-positive (activated) intraepithelial and lamina propria lymphocytes in lymphocytic gastritis.

Intraepithelial lymphocytes (IELs) and lamina propria lymphocytes (LpLs) have not been well studied in gastric mucosa, particularly in lymphocytic gastritis. Therefore, they were immunohistologically characterized with antibodies recognizing CD3, CD8, CD57, T cell-restricted intracellular antigen (TIA-1), and granzyme B (GrB). The TIA-1 labels cytotoxic granules of resting and activated T-cells, whereas GrB decorates activated cytotoxic T cells. Thirty patients with celiac disease, including 20 taking gluten and 10 on a gluten-free diet, 15 patients with nonceliac disease-associated lymphocytic gastritis, and 20 controls were studied. Stained cells were counted and results were given as IELs/100 epithelial cells or percentage of lamina propria cells. Sixty percent to 90% of CD3+ IELs and up to 12% of lamina propria cells contained TIA-1-positive cytotoxic granules. The number of GrB+ IELs and LpLs was increased in Helicobacter pylori-positive controls (p < 0.03 vs. H pylori-negative controls) and celiac disease patients taking gluten (p < 0.05 vs. controls). The highest number of GrB+ IELs and LpLs was found in nonceliac disease-associated lymphocytic gastritis (p < 0.009 vs. controls, p < 0.05 vs. celiac disease). This study shows that a high proportion of gastric IELs and LpLs is potentially cytotoxic in nature. Through stimuli not yet identified, a proportion of them becomes activated after H pylori infestation and in lymphocytic gastritis.

Adolescent↗