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C Gasche

Publications and source records attributed to C Gasche.

32 records · Page 2Linked to original sources
PubMed2000

Anemia in IBD: the overlooked villain.

During the past decade relevant progress has been made in the understanding and treatment of IBD-associated anemia. Effective replacement of iron deficits has become safe by using novel intravenous iron preparations such as iron sucrose. The ability of erythropoietin to interfere with key mechanisms of myelosuppression in anemia of chronic diseases also benefits patients with IBD-associated anemia. Concerns about cost effectiveness have been raised and weighed against the potential improvement in quality of life. Gastroenterologists who are caring for IBD patients should be concerned with low hemoglobin levels, since the quality of life in these patients can be as low as in anemic patients with advanced cancer. Also provided is a structured approach to cost-effective therapy.

Anemia↗
PubMed2000

In vivo effects of recombinant human interleukin-10 on lymphocyte phenotypes and leukocyte activation markers in inflammatory bowel disease.

BACKGROUND: Interleukin-10 (IL-10) exhibits potent anti-inflammatory and immunosuppressive activities in vitro. Recent data indicate that treatment with recombinant human IL-10 (rHuIL-10) Crohn's disease is safe and may induce clinical and endoscopic remission. The present study investigates the in vivo immunomodulatory properties of rHuIL-10 in inflammatory bowel disease (IBD). METHODS: As part of two randomized, double-blinded, placebo-controlled trials, repeated flow cytometric analyses of lymphocyte phenotypes (CD3, CD4, CD8, CD16 + 56, CD19) and activity markers (human leukocyte antigen [HLA]-DR; intercellular adhesion molecule-1 [ICAM-1]; IL-2-receptor alpha [IL-2R alpha]; high affinity receptor for immunoglobulin G [IgG; Fc gamma RI]) on T cells, monocytes, and neutrophils were performed in 17 patients with IBD who received rHuIL-10 (5, 10, or 20 micrograms/kg) or placebo, administered subcutaneously, once daily for 28 days. RESULTS: Minor changes were noted in CD3+, CD8+, and CD3+/CD16 + 56+ lymphocyte phenotypes, whereas absolute numbers of CD4+ lymphocytes and CD19+ cells increased. T-cell activation markers HLA-DR and IL-2R alpha were downregulated. rHuIL-10 did not influence HLA-DR expression on monocytes. ICAM-1 modulation on monocytes and neutrophils was mild and inconsistent. Fc gamma RI expression was upregulated on both neutrophils and monocytes. CONCLUSIONS: These data indicate that the immunosuppressive effects of rHuIL-10 treatment are partly different from its in vitro observed actions. The increase of the cytotoxicity-mediating Fc gamma RI points to potential immunostimulating properties of this cytokine.

Adult↗
PubMed1999

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↗
PubMed1999

Transabdominal bowel sonography for the detection of intestinal complications in Crohn's disease.

BACKGROUND: The course of Crohn's disease is characterised by the occurrence of intestinal complications such as strictures, intra-abdominal fistulas, or abscesses. Standard diagnostic procedures may fail to show these complications, in particular fistulas. AIMS: To test the value of transabdominal bowel sonography (T) for the detection of intestinal complications in Crohn's disease. METHODS: T was prospectively performed in 213 patients with Crohn's disease in a university based inflammatory bowel disease referral centre. Thirty three underwent resective bowel surgery and were included in this study. The accuracy of T to detect strictures, intra-abdominal fistulas, or abscesses was compared with surgical and pathological findings. RESULTS: T was able to identify strictures in 22/22 patients and to exclude it in 10/11 patients (100% sensitivity, 91% specificity). Fistulas were correctly identified in 20/23 patients and excluded in 9/10 patients (87% sensitivity, 90% specificity). Intra-abdominal abscesses were correctly detected in 9/9 patients and excluded in 22/24 patients (100% sensitivity, 92% specificity). CONCLUSIONS: In experienced hands T is an accurate method for the detection of intestinal complications in Crohn's disease. T is thus recommended as a primary investigative method for evaluation of severe Crohn's disease.

Abdominal Abscess↗
PubMed1999

Sequential treatment of anemia in ulcerative colitis with intravenous iron and erythropoietin.

BACKGROUND: Intravenous iron and erythropoietin have been shown to be effective in Crohn's disease-associated anemia. The aim of this study was to test the sequential treatment of anemia in ulcerative colitis with intravenous iron in the first phase and erythropoietin in the second. PATIENTS AND METHODS: Twenty patients with ulcerative colitis-associated anemia (hemoglobin < or = 10.5 g/dl) entered this open-label trial. In the first phase all patients received intravenous iron saccharate for 8 weeks. A response was defined as an increase in hemoglobin > or = 2.0 g/dl; a final hemoglobin >10.5 g/dl was regarded as full response, < or = 10.5 g/dl as partial response. A hemoglobin increase < 2.0 g/dl was regarded as nonresponse. In the second phase (n = 4) erythropoietin was initiated in patients without response. Patients with partial response were continued on iron saccharate for another 8 weeks. RESULTS: During the first phase the hemoglobin increased from 8.3 to 11.9 g/dl (mean hemoglobin difference 3.6+/-2.3 g/dl, p < 0.001). Fifteen patients (75%) showed a full response (mean hemoglobin difference 4.5+/-1.5 g/dl), 1 (5%) a partial response (hemoglobin difference 2.1 g/dl) and 4 no response (mean hemoglobin difference 0.4+/-1.8 g/dl) with a need for blood transfusions in a single patient. In the second study phase erythropoietin was highly effective in previous nonresponders (mean hemoglobin difference 3.3+/-1.9 g/dl). The single patient with partial response had a minor hemoglobin increase (hemoglobin difference 1.0 g/dl). CONCLUSION: Most patients with ulcerative colitis-associated anemia improve on intravenous iron alone. Erythropoietin is effective in those who do not respond.

Adult↗
PubMed1999

Autologous blood donation for surgery in inflammatory bowel disease--a report of six cases.

BACKGROUND: Surgery in inflammatory bowel disease (IBD) is frequently associated with need for perioperative blood transfusions carrying the potential risk of infection. Autologous blood donation is often limited by IBD-associated anemia which is reversible by intravenous iron and erythropoietin. We therefore tested the feasibility of autologous blood donation in IBD. METHODS: Six patients (five Crohn's disease, one ulcerative colitis) with indication for elective bowel resection were treated after informed consent was obtained. Two to four blood donations were scheduled during four weeks prior to surgery. Once a week 350-450 ml of blood were collected from patients with a hemoglobin level above 11.0 g/dl. After each donation 200 mg of iron saccharate diluted in 0.9% saline were given to all patients intravenously as substitute for donation-related iron loss. Patients with preexisting anemia or C-reactive protein above 2.0 mg/dl received concomitant erythropoietin. RESULTS: The scheduled number of packed red cells was donated successfully by four patients. Due to low hemoglobin levels two patients donated one unit less than intended. Four patients received autologous blood transfusions intra- or postoperatively. No patient needed homologous blood. No serious adverse events were observed during blood donations, perioperatively, and during the one year follow-up period. CONCLUSION: Preoperative autologous blood donation is save and feasible in IBD patients with elective bowel resection.

Adult↗
PubMed1998

Different missense mutations in histidine-108 of lysosomal acid lipase cause cholesteryl ester storage disease in unrelated compound heterozygous and hemizygous individuals.

Cholesteryl ester storage disease (CESD) and Wolman disease (WD) are both autosomal recessive disorders associated with reduced activity of lysosomal acid lipase (LAL), that leads to the tissue accumulation of cholesteryl esters in endosomes and lysosomes. WD is caused by genetic defects of LAL that leave no residual enzymatic activity, while in CESD patients a residual LAL activity can be identified. We have analyzed the LAL cDNA in three CESD patients from two nonrelated families and identified the mutations responsible for the disease. The associated genetic defects characterized revealed compound heterozygosity for a splice defect leading to skipping of exon 8, due to a G-->A transition at position -1 of the exon 8 splice donor site, and a point mutation leading to a Hisl08Pro change (CAT-->CCT) in two patients (siblings) with mild CESD phenotype. A further CESD patient was hemizygous for a His108-->Arg missense mutation (CAT-->CGT) in combination with a partial deletion of the LAL gene and was affected more severely. Expression of the LAL enzymes with the His108-->Pro and His108-->Arg mutation in insect cells revealed residual enzymatic activities of 4.6% versus 2.7%, respectively, compared with controls. Therefore, His108 seems to play a crucial role in folding or catalytic activity of the lysosomal acid lipase. This is the first description of two different, naturally occurring mutations involving the same amino acid residue in the lysosomal acid lipase in unrelated CESD patients. Moreover, our results demonstrate that the variable manifestation of CESD can be explained by mutation-dependent, variable inactivation of the LAL enzyme.

Amino Acid Substitution↗
PubMed1998

Influence of topically and systemically active steroids on circulating leukocytes in Crohn's disease.

OBJECTIVE: Budesonide, although only topically active, is effective in the treatment of Crohn's disease. This study was performed to compare the clinical efficacies of budesonide and prednisolone in relation to the activation status of circulating leukocytes. METHODS: Twenty-four patients with active Crohn's disease were randomized to treatment with either budesonide or 6-methylprednisolone. Clinical response was monitored by the Crohn's disease activity index, C-reactive protein, and orosomucoid. Expression of CD25 and CD71 on T cells and CD64 on neutrophils was determined by flow cytometry. The release of TNF-alpha and IL-1beta by peripheral blood mononuclear cells was measured by ELISA. RESULTS: After 2 wk of treatment a clinical response was observed in both groups, but it was more accentuated in patients treated with prednisolone. At baseline an upregulation of CD71 and CD64, but not CD25, was found in active patients. Prednisolone significantly decreased the expression of CD64 and the release of TNF-alpha and IL-1beta, but did not alter the expression of CD25 and CD71. Budesonide treatment failed to exert any effect on circulating leukocytes. CONCLUSIONS: The inability of budesonide to downregulate activated circulating leukocytes may contribute to the somewhat lower clinical efficacy of this topical steroid in the treatment of active Crohn's disease.

Adult↗
PubMed1998

[Diagnosis in chronic inflammatory bowel diseases--report of the Austrian Chronic Inflammatory Bowel Disease Study Group].

Diagnostic procedures in inflammatory bowel diseases (IBD) serve to secure the diagnosis and to optimize treatment. Upon initial diagnosis endoscopy up to the terminal ileum is mandatory including multiple step biopsies. When diagnostic guidelines are followed and adequate clinical information is available, IBD will be correctly classified in about 80 to 90% of cases upon first examination. In contrast endoscopic studies are only of limited value in monitoring treatment. The decision if and when to perform endoscopy during exacerbation of disease must be an individual one. When disease activity is evaluated, a distinction must be made between degree of activity as reflected by laboratory parameters and severity of illness as reflected by the clinical presentation with abdominal complaints, fistulas, abscesses, etc. Distinct activity indices are useful in clinical studies to obtain an objective evaluation of activity and severity of disease. At clinical routine visits questions should not only concern the basic illness but also ask for quality of life and psychosocial status. Only a small number of laboratory tests are needed for basic diagnosis and follow-up. A small bowel enteroclysis should always be performed upon primary diagnosis of Crohn's disease and during the course of disease when there is suspicion of small-bowel involvement. Double contrast barium enema should be limited to special indications as incomplete colonoscopy e.g. due to stenosis or suspected fistula. Sonography is the primary investigation when complications are suspected. CT is useful as an adjunct or when the afore mentioned methods do not show clear findings. NMR is the procedure of choice for detection of pararectal fistulas and abscesses. Transrectal endosonography is comparably good but limited to the experience of the investigators and by patient's tolerability.

Biopsy↗
PubMed1997

Altered mononuclear phagocyte differentiation associated with genetic defects of the lysosomal acid lipase.

Multiparameter flow cytometry reveals a complex heterogeneity of mononuclear phagocyte differentiation within the peripheral blood compartment. In this study, the relation of abnormal cellular lipid metabolism to the phenotype of peripheral blood mononuclear phagocytes, which finally may be related to atherogenesis, was analyzed using recently characterized autosomal recessive defects of lysosomal acid lipase (LAL) expression as model system. The reduction of LAL activity in nine heterozygote, disease free carriers of mutations from two cholesteryl ester storage disease (CESD) pedigrees and the family of a patient with Wolman disease was associated with an increased fraction of monocytes which expressed CD56 (N-CAM) (4.1 +/- 2.7% of monocytes, compared to 2.2 +/- 0.5% in ten controls, P < 0.05), an antigen characteristic of immature myeloid cells, suggesting an increased turnover of monocytes. Furthermore, a trend was observed towards an enhanced blood pool of more mature mononuclear phagocytes which show decreased expression of the 55 kD lipopolysaccharide receptor (CD14) together with either expression of the Fc-gamma-receptor III (CD16) or a high expression of CD33. A similar phenotype of peripheral mononuclear phagocytes was observed in the two CESD patients analyzed. In conclusion, our data suggest that these monogenetic defects of lysosomal lipoprotein metabolism are associated with complex alterations of mononuclear phagocyte differentiation and extravasation.

Adolescent↗
PubMed1997

A novel variant of lysosomal acid lipase in cholesteryl ester storage disease associated with mild phenotype and improvement on lovastatin.

Cholesterol ester storage disease (CESD) is a rare congenital disorder of lipid metabolism, with mutation of the lysosomal acid lipase gene, causing chronic liver disease, usually before adolescence. We here describe three adult siblings with CESD diagnosed by light microscopic demonstration of excessive lysosomal storage of lipids with accumulation of foamy cells in liver biopsies and by a decrease in acid lipase activity (2-3% of controls). One patient (male, 46a) had extensive liver fibrosis, another (female, 58a) had cirrhosis of the liver. The third patient had died from variceal haemorrhage (female, 56a). Using sequence analysis of RT-PCR products of LAL mRNA, the patients were identified as compound heterozygotes for a G-->A substitution at position -1 of the exon 8 splice donor site and a point mutation at the second allele, resulting in a His108-->Pro shift. In two patients, therapy with lovastatin was initiated, which led to normalisation of serum cholesterol and triglyceride levels. After 12 months, liver biopsy demonstrated a significant decrease in vacuolisation of hepatocytes, with fewer and smaller droplets. Semi-automated computer-assisted image analysis of electron microscopic sections demonstrated a decrease in the hepatocellular lysosomal area from 20.5+/-7.1% to 11.7+/-6.5% (p<0.05) and 41.7+/-5.1% to 33.4+/-4.4% (p<0.01). We conclude that in two siblings with a novel LAL variant and mild phenotype of CESD, lovastatin decreased both serum lipid concentrations and hepatocellular lysosomal content.

Anticholesteremic Agents↗
PubMed1994

Functional characterization of cytokine autoantibodies in chronic renal failure patients.

We have recently reported on an increase of IL-1 alpha and IL-6 autoantibodies in patients maintained on chronic hemodialysis treatment. The aim of the present study was to evaluate functional properties of these autoantibodies. Serum samples of more then 500 chronic renal failure patients with and without replacement therapy were screened for the presence of IL-1 alpha and IL-6 autoantibodies by second antibody precipitation. The neutralizing capacity of IL-1 alpha autoantibody serum was studied by immunofluorescence flow cytometry analysis of IL-1 alpha induced expression of E-selectin (ELAM-1, CD62e) on HUVEC (human umbilical vein endothelial cells). Results of these inhibition studies were confirmed with IgG preparations from antibody positive sera, purified by affinity chromatography. Functional studies on IL-6-dependent B9 cell proliferation were performed with IL-6 autoantibody positive sera, and quantitated with the colorimetric MTT assay. IL-1 alpha induced expression of E-selectin on HUVEC (considered 100% positive cells) was inhibited by each IL-1 alpha autoantibody positive serum sample (N = 13; anti-IL-1 alpha activity: 7.62 to 57.52% binding). Inhibition of E-selectin expression by IL-1 alpha autoantibodies ranged from 0.11 to 80.22% positive cells (0.15 to 92.31% mean fluorescence intensity). A strong correlation of E-selectin expression with IL-1 alpha autoantibody concentration was observed (P < 0.005). Furthermore, IgG eluates from autoantibody positive patients inhibited E-selectin expression to 41.0 +/- 23.1% positive cells if compared with 83.7 +/- 5.7% positive cells of the IgG depleted serum samples.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗
PubMedDate not supplied

Complications of inflammatory bowel disease.

Complications in inflammatory bowel disease determine the severity of disease as well as the complexities of medical or surgical treatment opportunities. Therefore, in known inflammatory bowel disease, the prevention, the early detection and the adequate therapeutic response to certain complications are important goals in the follow-up of inflammatory bowel disease patients. Disease complications are separated into intestinal and extraintestinal complications. Intestinal complications are somewhat disease specific, which means that they occur exclusively in either Crohn's disease or ulcerative colitis (e.g., enteric fistulas are particularly found in Crohn's disease and toxic megacolon in ulcerative colitis). Most extraintestinal complications occur in both forms of inflammatory bowel disease (e.g., anemia, thromboembolic events or osteoporosis). The current knowledge on pathogenesis, diagnostic tools, prevention and treatment of certain intestinal and extraintestinal complications is reviewed.

Anemia↗