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Biomedical subjects

H Vogelsang

Publications and source records attributed to H Vogelsang.

At least 109 records · Page 6Linked to original sources
PubMed1996

Course of pseudocholinesterase isozymes during an acute phase in Crohn's disease.

We have previously shown that the percentage distribution of the pseudocholinesterase isozymes (C1, C2, C3 and C4) is significantly altered in patients with active Crohn's disease (CD). The aim of the present study was to assess the time course and the clinical meaning of the pseudocholinesterase isozymes during an acute phase in CD. Ten healthy volunteers and 10 patients with active CD (Crohn's disease activity index, CDAI, > 200) were examined. In CD patients an acute phase treatment with prednisolone was administered for 7 weeks reaching an improvement (CDAI < 200) in 7 patients. Before initiation of steroid treatment, the isozymes C1 (controls: median 19.7%, interquartile range 16-22.2%; CD: 6.2%, 5-8%; p < 0.001) and C4 (controls: 63.5%, 59-71%; CD 81.7%, 72.9-84.7%; p < 0.001) were decreased and increased, respectively, and did not change significantly during the time of acute phase treatment. The isozymes C2 and C3 did not show any difference between controls and CD patients. Five of the patients were followed up for the subsequent 3 months of remission (CDAI < 150). During the period C1 and C4 normalized and no difference between controls and CD patients was obtained (C1: 16.4%, 15.5-20.2%; C4: 59.4%, 55.8-60.5%). Therefore, pseudocholinesterase isozymes are useful parameters in CD to to indicate active CD or long-term remission.

Acute Disease↗
PubMed1996

Evidence that intestinal intraepithelial lymphocytes are activated cytotoxic T cells in celiac disease but not in giardiasis.

To further define intraepithelial lymphocytes (IELs) in celiac disease (CD) and giardiasis, IELs were probed for the presence of cytolytic granules containing granzyme B (GrB) and T-cell-restricted intracellular antigen (TIA)-1. The expression of TIA-1, GrB, CD3 (T-cell-receptor-associated complex), and Leu-7 (subset of natural killer cells) was studied by a sensitive three-step immunoperoxidase technique. Stained IELs were determined quantitatively, and results were expressed as number of stained IELs per 100 epithelial cells (ECs). The relative content in labeled lamina propria lymphocytes was determined and expressed as the percentage of all lamina propria cells counted. When compared with controls, CD3+ and GrB+ IELs were significantly increased (P < 0.0004) in CD paralleled by an increase in TIA-1+ IELs (P < 0.0004). In CD, the highest numbers of IELs containing GrB were found in subjects with a flat mucosa (median, 38 IELs/100 ECs, P < 0.0004), followed by cases with shortened and blunted villi (median, 8 IELs/100 ECs, P < 0.0004) and, finally, CD patients with an intact villous architecture (median, 0.5 IELs/100 ECs, P < 0.02). Except for cases with giardiasis, Leu-7+ IELs were virtually absent in all groups as were GrB+ IELs in the controls and in subjects with giardiasis. In the lamina propria of CD subjects, GrB+ lymphocytes were also significantly increased (P < 0.001), whereas controls and cases with giardiasis were essentially free of GrB+ cytotoxic T lymphocytes. The percentage of CD3+ lamina propria lymphocytes was nearly equal in all groups. In humans and mice, extensive studies revealed a GrB expression to be absolutely restricted to activated cytotoxic T lymphocytes and natural killer cells. TIA-1, on the other hand, is considered a marker of resting T lymphocytes possessing cytolytic potential. We therefore conclude that IELs are cytotoxic T cells that are in a resting state in the normal small bowel and in giardiasis. In CD, they become activated as suggested by the GrB positivity of their granules.

Adolescent↗
PubMed1995

Prospective evaluation of interferon-alpha in treatment of chronic active Crohn's disease.

Several case reports suggested good effects of interferon-alpha in patients with Crohn's disease. In addition, a decreased production of interferon-alpha in Crohn's disease has been shown in vitro. Treatment with interferon-alpha may activate intestinal natural killer cells and down-regulate the overproduction of inflammatory cytokines like interleukin-6 in Crohn's disease. To evaluate the clinical efficacy of interferon-alpha, we treated 12 patients with a chronic active course of Crohn's disease with recombinant human interferon-alpha prospectively for 24 weeks. Prednisolone was continuously tapered and discontinued at week 12. The end point of the study was the prevention of worsening of clinical symptoms defined with the Crohn's disease activity index and was monitored by acute-phase proteins, interleukin-6 serum concentrations, and endoscopy. The biochemical activity of interferon-alpha was measured by 2',5'-oligo adenylate serum levels. The end point of the study was reached in four patients (33%). In these patients the final Crohn's disease activity index was above 150, which means that they did not achieve clinical remission. All other patients (66%) did not respond to interferon-alpha and had to be withdrawn prematurely. Interferon-alpha did not show any beneficial effect on interleukin-6 or acute-phase protein concentrations and on endoscopic activity. The 2',5'-oligo adenylate levels continuously increased during interferon therapy. Considerable side effects were noted. These results fail to demonstrate a therapeutic role of interferon-alpha in chronic active Crohn's disease.

Adenine Nucleotides↗
PubMed1995

Dietary vitamin D intake in patients with Crohn's disease.

In search for the reasons of vitamin D deficiency in Crohn's disease (CD), dietary records were evaluated over 7 days in 30 uninformed out-patients with CD (but no current flare-up) by the help of food tables and compared with those of 30 age- and sex-matched healthy controls. The study was undertaken in December. The nutritional status (height-weight index) was similar in both groups. The dietary vitamin D intake was as low in patient with CD (1.0 microgram/d; 0.5-1.3) as in the controls (1.1; 0.4-1.6) whereas the recommended daily intake is 5 micrograms/d. Vitamin D intake correlated with serum 25-hydroxyvitamin D (25-OHD) levels in patients with low 25-OHD levels (tau = 0.45, p = 0.04). Bone mineral content (BMC)-measured by single photon absorptiometry on the radius- was decreased in 9 patients (31%) with CD. Patients with CD tended to have a lower sun exposure in summer (p = 0.10), which also correlated with BMC (p = 0.03). Hence, a specific diet with a high vitamin D content, or vitamin D supplementation is recommended in patients with CD to overcome the negative effects of low sun exposure on bone mineral density.

Adult↗
PubMed1995

Screening for celiac disease in first-degree relatives of patients with celiac disease by lactulose/mannitol test.

OBJECTIVES: In first-degree relatives of celiac patients, the risk of oligosymptomatic celiac disease is elevated. These individuals therefore also have a higher potential for malignancy or nutritional deficiencies. Lactulose/mannitol permeability is increased in untreated celiac patients and has been recommended to screen for celiac disease. We investigated the usefulness of a lactulose/mannitol home test kit for screening first-degree relatives home test kit for screening first-degree relatives of celiac patients. METHODS: The lactulose/mannitol test was performed at home by 111 first-degree relatives. These subjects received the test kit from celiac index patients, were instructed by an information sheet how to carry out the test, and were asked about their symptoms by questionnaire. When lactulose/mannitol permeability was abnormal, endomysial antibodies were tested by immunofluorescence. Any relatives with positive endomysial antibodies were then biopsied. To investigate the specificity of the lactulose/mannitol test for celiac disease, 40 patients with nonspecific gastrointestinal symptoms were tested. RESULTS: Lactulose/mannitol permeability was elevated in 34 (31%) relatives, but only nine (8%) of those relatives showed positive endomysial antibodies. Flat mucosa was found in all nine relatives after biopsy. The prevalence of celiac disease was much higher (42%) among 12 relatives who contacted the outpatient clinic themselves because of symptoms. Seventy-one percent of the remaining 21 relatives with elevated permeability demonstrated normal intestinal permeability at a control test within 1 yr. CONCLUSION: By combining the lactulose/mannitol test with endomysial antibody testing, we have developed a good strategy for use in screening for celiac disease among first-degree relatives.

Adolescent↗
PubMed1995

Budesonide in glucocorticoid dependent chronic active Crohn's disease; a pilot study.

Patients with chronic active Crohn's disease are dependent on systemic glucocorticosteroids. The aim of the study was to investigate the efficacy of budesonide, a topically selective glucocorticosteroid, as therapy in these patients. We investigated 20 patients with chronic active Crohn's disease. During the last 6 months prior to the study the patients had a median Crohn's disease activity index (CDAI) of 193 (interquartile range: 122-230) (monthly controls) with a median prednisolone dosage of 14 mg per day (9-20). Budesonide was given 3 to 6 mg daily and prednisolone was weaned within one month. The patients were seen monthly for 6 months. Treatment was considered not successful, if under budesonide therapy CDAI was above 200 and increased more than 60 points despite weaning of prednisolone. Only 5 patients remained in the study for 6 months without deterioration. All other patients (75%) dropped out. The reasons for drop out of the study were worsening in 11 cases, the occurrence of extraintestinal manifestations without signs of severe intestinal inflammation in one case and noncompliance in 3 cases. Worsening could be confirmed by an increase not only of CDAI but also of biochemical parameters of inflammation in all cases. Our data show clearly, that in the dosage investigated budesonide was not effective in chronic active Crohn's disease. Further investigations are needed to evaluate higher dosages of budesonide versus conventional glucocorticosteroids.

Administration, Oral↗
PubMed1995

Microsatellite instability in adenocarcinomas of the upper gastrointestinal tract. Relation to clinicopathological data and family history.

We analyzed 66 adenocarcinomas arising in the upper gastrointestinal tract for microsatellite instability at eight microsatellite loci to investigate the role of these genetic alterations in the etiology of these tumors. We identified alterations in at least one locus in 11/46 adenocarcinomas of the stomach, in 2/15 adenocarcinomas arising in Barrett's esophagus, and in 1/5 adenocarcinomas of the duodenum and jejunum. Microsatellite instability in gastric tumors was found in 5/22 of intestinal, 1/3 of mixed, and 5/21 of diffuse type tumors. No relationship to the tumor stage (TNM), age, and survival time of the patients was observed. One patient had two synchronous gastric tumors both exhibiting microsatellite instability at multiple loci. His family history revealed four individuals in the maternal line afflicted with gastric carcinoma in three generations. Our data show that microsatellite instability is a genetic event in 11 to 24% of tumors of the upper gastrointestinal tract. The observation of microsatellite instability and a familial clustering of gastric tumors may suggest a genetic predisposition for a subset of gastric tumors, which may be identified by microsatellite analysis.

Adenocarcinoma↗
PubMed1995

Screening for celiac disease: a prospective study on the value of noninvasive tests.

OBJECTIVE: Celiac disease is frequently diagnosed in patients with nonspecific abdominal symptoms. Therefore, highly sensitive, specific, and simple noninvasive screening tests are needed. METHODS: This study compared the usefulness of IgG- and IgA-antigliadin antibodies, IgA-endomysial antibodies, and intestinal permeability in diagnosing celiac disease in 102 adult patients with nonspecific abdominal symptoms. In addition, all patients underwent small bowel biopsy as a gold standard for the diagnosis of celiac disease. RESULTS: Forty-nine patients were ultimately diagnosed as having celiac disease because of flat mucosa. Flatulence and signs and symptoms dating back to childhood were more frequent and abdominal pain less frequent (p < 0.05) in celiac disease but were not helpful for screening. IgA-endomysial antibodies showed a sensitivity and specificity of 100%; an altered intestinal permeability had also a 100% sensitivity, but only 55% specificity. IgG- and IgA-antigliadin antibodies' sensitivity (73% and 82%, respectively) and specificity (74% and 83%, respectively) were much lower. Combining the two antigliadin antibodies did not significantly improve the sensitivity and specificity. CONCLUSIONS: Our data show the advantage of IgA-endomysial antibodies for screening of celiac disease except in the case of patients with IgA-deficiency or dermatitis herpetiformis. In these patients, the permeability test could improve noninvasive differential diagnosis.

Adult↗
PubMed1995

Disease-related worries and concerns: a study on out-patients with inflammatory bowel disease.

OBJECTIVE: To investigate the relationship between inflammatory bowel disease (IBD) patients' disease-related worries and concerns and their disease-related data, sociodemographic variables and perceived information level with respect to IBD. STUDY DESIGN: Prospective evaluation of disease-related concerns. SETTING: Out-patient IBD clinic of a university hospital. STUDY POPULATION: The study included 105 patients with IBD (72 with Crohn's disease and 33 with ulcerative colitis). MEASUREMENTS: Worries and concerns were measured using the standardized 25-item rating form of IBD patient concerns; actual disease activity was assessed by physicians using the Crohn's disease and clinical activity indices. Sociodemographic and other disease-related data were collected using a structured questionnaire. Patients' perceived information level was measured using a visual analogue scale. RESULTS: The issues of greatest concern to our patients were, in descending order of importance, having an ostomy bag (mean score +/- SD 63.6 +/- 38), the effects of medication (53.1 +/- 34), having surgery (51.6 +/- 36), the uncertain nature of the disease (46.5 +/- 32) and energy level (41.5 +/- 34). Patients with ulcerative colitis scored higher with respect to concern about loss of bowel control (P < 0.03). Disease-related worries and concerns correlated poorly with disease-related data (actual disease activity, severity of the course of IBD, diagnosis, disease duration or location, medication) but showed a significant negative correlation with patients' perceived information level about IBD (t = 0.2, P < 0.004). Lower information-level scores were associated with greater concerns. CONCLUSION: We conclude that the patients' information level about IBD and disease-related concerns have to be considered in clinical practice. Better information about IBD and psychosomatic counselling for patients who show high levels of concern may improve their quality of life and clinical care.

Adolescent↗
PubMed1995

Prevention of bone mineral loss in patients with Crohn's disease by long-term oral vitamin D supplementation.

OBJECTIVE: To determine whether long-term dietary supplementation with low doses of vitamin D helps to prevent bone loss and the development of osteoporosis or osteomalacia in out-patients with Crohn's disease. DESIGN: A randomized controlled study. SETTING: The out-patient clinic of a tertiary centre (university hospital). PATIENTS: Seventy-five out-patients (31 men and 44 women, aged 16-77 years) with Crohn's disease. INTERVENTIONS: All patients were randomly assigned to receive either an oral supplement of 1000 IU/day vitamin D for 1 year or no supplement. Bone mineral density, assessed in the distal part of the nondominant forearm using single photon absorptiometry, and serum levels of 25-hydroxyvitamin D, assessed using a competitive protein binding assay, were measured before and after the period of dietary supplementation. MAIN OUTCOME MEASURE: Relative change of bone mineral density. RESULTS: Serum levels of 25-hydroxyvitamin D increased in 57% of patients who received a supplement (compared with 37% of control patients). Bone mineral density decreased significantly in control patients [median -7%, interquartile range -12.6-(+0.4%)] but not in patients who received a supplement [median -0.2%, interquartile range -3.8-(+14%); P < 0.005]. Increases in bone mineral density were especially prevalent among patients who received the supplement and had normal serum levels of 25-hydroxyvitamin D (68%), whereas increases occurred in only 18% of patients with low serum levels of 25-hydroxyvitamin D (P = 0.008). Patients without an intestinal resection and receiving the vitamin D supplement had a marginally greater increase in bone mineral content than patients who had undergone a resection (P = 0.05). CONCLUSION: Long-term oral vitamin D supplementation seems to be an efficient means of preventing bone loss in patients with Crohn's disease and could be recommended, especially for patients at high risk of osteoporosis.

Absorptiometry, Photon↗
PubMed1994

Prognostic impact of urokinase-type plasminogen activator and its inhibitor PAI-1 in completely resected gastric cancer.

The prognostic impact of the proteolytic factors urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) was evaluated in 76 completely resected gastric cancer patients enrolled in a prospective study. All patients underwent macroscopically and microscopically residual tumor-free resection (category R0, Union International Contre Cancer, 1987). uPA and PAI-1 levels were quantified in detergent-extracted (Triton X-100) specimens of primary gastric tumors by enzyme-linked immunosorbent assays. Median values of 1.57 ng uPA/mg protein were determined in tumor tissue extracts compared to 0.14 ng uPA/mg protein in normal mucosa. For PAI-1, 0.93 ng PAI-1/mg protein versus 0.09 ng PAI-1/mg protein was calculated. uPA levels in tumor tissue extracts were significantly correlated with vascular invasion, Laurén classification, and WHO classification, whereas PAI-1 levels showed a significant correlation with advanced lymph node involvement, depth of invasion, tumor stage, site of tumor, and the Laurén, Borrmann, and WHO classifications. Elevated uPA and PAI-1 levels were found to be associated with poor prognosis. The optimal cutoff values indicating a group of patients with shorter survival were 1.5 ng uPA/mg protein and 1.25 ng PAI-1/mg protein, respectively (Classification and Regression Tree analysis). Patients with either high uPA or PAI-1 values were significantly associated with decreased survival (median time of survival was 23 months (high) versus 44 months (low). By univariate Cox regression analysis, it was shown that TNM categories, WHO classification, size of tumor, uPA and PAI-1 levels were all significantly associated with survival. However, in multivariate Cox regression analysis of these grouped variables, nodal status, PAI-1 levels, and WHO classification were the only independent prognostic factors. The relative risks of failure were 5-, 2.9-, and 2.4-fold, respectively. We conclude that PAI-1 and uPA positivity may serve as new prognostic factors in gastric cancer, predicting shorter survival even in clinically important subgroups of patients.

Adult↗
PubMed1994

On interleukins 4, 6 and 10 and their interrelationship with immunoglobulins G and M in common variable immunodeficiency.

Following culture of human peripheral blood mononuclear cells (PBMNC) from 25 normal donors and 15 patients with common variable immunodeficiency (CVID), we were unable to identify any IL10-defective patients. Clear-cut effects of IL4 could be demonstrated in controls, while in CVID all effects are less pronounced. While in both controls and CVID baseline levels of IL6, IgG and IgM were found to be correlated, this was altered by the addition of either IL4 or Poke Weed Mitogen (PWM). We therefore conclude that the inability of PBMNC to produce IL10 is not the cause of CVID in our patients. In CVID, the regulating circuitry triggered by IL4 remains principally intact, however, some subgroups of CVID behave significantly differently.

Adult↗
PubMed1994

Ileal and colonic fatty acid profiles in patients with active Crohn's disease.

In patients with active Crohn's disease and in a control group the fatty acid profiles in the whole lipid fraction of ileal and colonic mucosal biopsy specimens were determined by capillary gas chromatography. The biopsy specimens in Crohn's disease patients were taken from the inflamed terminal ileum as well as from the inflamed and macroscopically normal colon. Compared with controls the fatty acid distribution in the inflamed ileal mucosa was significantly characterised by (a) a decrease of 18:2 n6 and 18:3 n3 accompanied by a substantial increase of the highly polyunsaturated fatty acids 20:4 n6, 22:4 n6, and 22:6 n3 and (b) a higher unsaturation index of total fatty acids compared with controls. These changes were similar in the inflamed colon. Additionally, both the inflamed and the macroscopically normal colonic mucosa showed an increase of saturated (18:0) and a decrease of monounsaturated fatty acids (18:1 n9). Fatty acid profiles of ileum and colon showed side variations in controls, but not in the Crohn's disease group. These data suggest that in Crohn's disease changes in the distribution of polyunsaturated fatty acids seem to be the general feature of inflamed mucosa in small and large intestine. Results further suggest that colonic fatty acid metabolism in Crohn's disease is altered by degrees, showing changes in saturated and monounsaturated fatty acids as an additional, primary event.

Acute Disease↗
PubMed1994

Folate absorption in Crohn's disease.

An oral folate absorption test was performed in 100 consecutive patients with Crohn's disease (CD) and 20 healthy individuals to investigate the frequency of abnormal folate absorption in regard to the site of the disease and to investigate the possibility of defining a subgroup of patients requiring parenteral folate supplementation. The described oral folate absorption test can be performed quickly on an outpatient basis and is capable of distinguishing patients with altered folate absorption from those with normal folate absorption. In 25 patients, abnormal folate absorption was detected. 16 patients showed impaired folate absorption as indicated by a marked but insufficient increase in serum folate levels after oral folate intake, whereas no increase of the serum folate levels was detected in the remaining 9 patients. Abnormal folate absorption was not correlated with disease extent or activity. In patients with only impaired folate absorption, it might be sufficient to increase dietary intake of folates. In the remaining patients with no measurable increase of serum folate levels after oral folate intake, i.e. about 10% of all patients with CD, parenteral folate supplementation could be considered.

Administration, Oral↗