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Biomedical subjects

O Fausa

Publications and source records attributed to O Fausa.

At least 73 records · Page 4Linked to original sources

Secretory immunity in celiac disease: cellular expression of immunoglobulin A subclass and joining chain.

Two-color immunofluorescence staining in situ demonstrated increased proportions of immunoglobulin A2 subclass-producing cells in jejunal mucosa from adult patients with untreated (47%, P less than 0.01) or treated (37%, P less than 0.05) celiac disease compared with controls (28%). Costaining was also performed for joining chain, which is a key factor in the epithelial transport of secretory antibodies; its expression by immunoglobulin A2 cells was only marginally reduced in untreated patients (96%) compared with treated patients and controls (98%). Also, immunoglobulin A1 cells showed similar joining chain positivity (89%) in all three groups. Considering the expanded total jejunal immunoglobulin A-cell population and the subclass-associated joining chain expression, it could be calculated that the potential of immunoglobulin A2 cells for contribution to secretory immunity was increased 3.9 times in untreated (P less than 0.01) and 1.8 times in treated (P less than 0.05) patients and that of immunoglobulin A1 cells was increased 1.7 times in untreated (P less than 0.05) but remained unaltered in treated patients. The estimated relative contributions of locally produced immunoglobulin A2 to secretory immunoglobulin A would thus be 51% and 37% in the two patient categories, respectively, compared with 31% in the controls. These data suggested enhanced secretory immunity in celiac disease and might reflect a protective, possibly antimicrobial, immune response. It could not be excluded, however, that increased generation of secretory immunoglobulin A at the same time contributes to the gluten-induced pathogenesis of celiac disease.

Adult↗

Omeprazole or high-dose ranitidine in the treatment of patients with reflux oesophagitis not responding to 'standard doses' of H2-receptor antagonists.

Ninety-eight patients (26 females), who presented with erosive and/or ulcerative oesophagitis, despite at least a 3-month period of treatment with standard doses of cimetidine (greater than or equal to 1200 mg daily) or ranitidine (greater than or equal to 300 mg daily), were included in a double-blind, randomized trial to compare omeprazole (40 mg o.m.) with a high dose of ranitidine (300 mg b.d.). The treatment was given for 4-12 weeks; endoscopy assessment and laboratory screening were performed on entry to the trial and thereafter every fourth week. Endoscopic healing was defined as complete epithelialization of all macroscopic erosions or ulcers in the squamous epithelium. An 'intention-to-treat' analysis of the clinical data revealed omeprazole to be superior to ranitidine: 63% of those patients who were given omeprazole were healed endoscopically after a 4-week period of treatment, compared with only 17% of those given ranitidine. This difference in healing rate persisted during the 12-week study period (90% vs 47% after 12 weeks; P less than 0.0001). Reflux symptoms were more rapidly and completely relieved with omeprazole: heartburn resolved completely in 86% of patients treated with omeprazole for 4 weeks compared with 32% in the ranitidine group (P less than 0.0001). The mean basal gastrin concentrations increased only in those given omeprazole from 18.9 pmol/L at pre-entry to a mean value of 31.7 pmol/L on the last day of omeprazole administration. In ranitidine-treated patients no significant increase in basal gastrin concentration was observed. Both drugs were well tolerated with few adverse events, which were mainly mild and transient. These results demonstrate the superiority of omeprazole over a high dose of ranitidine in the treatment of resistant reflux oesophagitis.

Adult↗

Hepatic lesions in adult coeliac disease.

In the period 1970 to 1987, 171 patients with small-intestinal mucosal atrophy have been hospitalized in our department. Of these, 132 patients fulfilled the diagnostic criteria of coeliac disease on the basis of histologic findings and clinical improvement on a gluten-free diet. Aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), and alkaline phosphatase (ALP) were chosen as markers of hepatic involvement. Elevation above the normal range in one or more of these tests was seen in 62 patients (47.0%, group I). In 70 patients (53.0%, group II) of similar age the levels of these variables were normal. In group I, 14 (10.6%) patients had an elevation of ALP only, leaving 48 (36.4%) patients with pathologic values for one or both transaminases. In group I, 32 patients had their ASAT, ALAT, and ALP reexamined after at least 6 months of gluten-free diet. Among the patients with increased values of one or both transaminases 18 patients were tested before and at least 6 months after start of gluten-free diet. The variables were significantly reduced in all patients. Liver biopsies were performed in 37 patients, and findings were normal in 5. In 25 patients the changes were classified as non-specific. Chronic active hepatitis was demonstrated in five patients. In one of these patients primary sclerosing cholangitis and ulcerative colitis were also diagnosed. Concomitant malignant disease was found in 22 patients, of whom 16 had malignant lymphoma. Malignant disease was seen more often in group I than group II (p less than 0.01). In conclusion, liver lesions were found in a great proportion of the patients with coeliac disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The significance of anti-hepatitis C virus antibodies measured in chronic liver disease.

The frequency of hepatitic C virus (HCV) antibodies was determined in two different laboratories in stored sera from 128 consecutive patients with chronic liver disease and from 41 healthy blood donors. Repeated measurements were performed in most patients. At the first determination the frequency of HCV antibodies was 7% in primary sclerosing cholangitis, 42% in primary biliary cirrhosis, 40% in autoimmune chronic active hepatitis, and 27% in alcoholic liver disease. The reproducibility of the determinations was rather poor, with a within-assay variation of 9.9%, whereas the between-assay variation was 34% and 47% in the two laboratories. There was a significant difference in the results obtained in the controls, depending on the handling of the sera. Freezing and thawing and, possibly, protracted storing of sera had a major impact on the assay and may have invalidated the results obtained in many studies. A significant association between IgG levels and titers of HCV antibodies was found in the total group of patients (p less than 0.005), in autoimmune chronic active hepatitis (p less than 0.005), and in primary biliary cirrhosis (p less than 0.01). It may be questioned whether the assay really is specific for anti-HCV antibodies in these patients. Whether HCV has anything to do with the etiology and pathogenesis of chronic liver disease apart from NANB-hepatitis is still undetermined.

Adolescent↗

Intraepithelial TcR alpha/beta+ lymphocytes express CD45RO more often than the TcR gamma/delta+ counterparts in coeliac disease.

Expression of CD45RO on intraepithelial lymphocytes (IEL) bearing the T-cell receptor (TcR) alpha/beta or gamma/delta was studied in situ by three-colour immunofluorescence on jejunal tissue sections from 21 patients with coeliac disease and eight controls. CD45RA-TcR alpha/beta+ IEL expressed CD45RO significantly more often (75%) than the preferentially expanded TcR gamma/delta+ counterpart (59%). Triple staining for CD3, CD4/8 and CD45RA or CD45RB revealed that all CD3 + 4 - 8 - IEL (taken to be TcR gamma/delta+) expressed CD45RB and none were CD45RA. CD45RO positivity was of the same magnitude (66%) on the predominating monoclonal antibody delta TCS1-reactive fraction of TcR gamma/delta+ cells as on the remainder of the TcR gamma/delta+ subset. These results suggest that gluten exposition in patients with coeliac disease leads to accumulation of CD45RA-, putative antigen-primed memory cells of both TcR phenotypes. The less marked CD45RO expression within the preferentially expanded TcR gamma/delta+ subset of IEL may be of particular biological interest.

Adolescent↗

Measurements of serum IgA and IgG activities to dietary antigens. A prospective study of the diagnostic usefulness in adult coeliac disease.

Serum samples from 458 consecutive adult patients with intestinal symptoms and/or suspected food intolerance were examined for IgG and IgA antibody activities to gluten, egg, and cow's milk antigens by an enzyme-linked immunosorbent assay (ELISA). Increased IgA and/or IgG activities to gluten were seen in 61 patients: 35 had coeliac disease (CD) as suggested by jejunal villous atrophy and subsequent histologic and/or clinical improvement on a gluten-free diet; 4 were previously diagnosed CD patients with clinically suspected dietary failure; 2 had dermatitis herpetiformis with a CD-like intestinal morphology; and 3 had possible gluten intolerance without villous atrophy. The rest had other disorders that might have affected the permeability of the gastrointestinal mucosa or the hepatic IgA catabolism. When the IgA activity to gluten was increased, neither the IgA/IgG activities to nongluten antigens nor the ratio of nongluten to gluten antibodies could discriminate between CD patients and those without CD. However, the median IgA activity to gluten was significantly higher in the CD group. The probability for CD thus increased from 33% in patients with IgA activity to gluten between 0.4 and 0.8 OD units to 90% in those with such activity above 2.4 OD units. Nevertheless, seven untreated CD patients had IgG and IgA activities to gluten within the normal range. ELISA determinations of serum antibodies to gluten antigens are a valuable adjunct in the diagnosis of adult CD, but a negative test does not exclude this disorder.

Adolescent↗

[Diet among patients with celiac disease. Do patients comply with a gluten-free diet?].

We studied dietary compliance retrospectively among 28 coeliac patients, 18 adults (15-68 years) and 10 children (1-14 years) by means of a self-administered frequency questionnaire. 50% of the participants ate foods that were not guaranteed to be gluten-free. Four adult patients (22%) with certainty did not keep to a strictly gluten-free diet. Lack of dietary compliance was not detected among children. The patients had received information on diet shortly after the disease had been diagnosed during the period 1964-81. The most frequent source of information about gluten-free diet was the physician, but information from the Norwegian Coeliac Association and from clinical nutritionists was rated as more useful. 24 patients reported experiencing social and practical problems related to the gluten-free diet.

Adolescent↗

Raised number of jejunal IgG2-producing cells in untreated adult coeliac disease compared with food allergy.

The subclass distribution of IgG-producing immunocytes was studied by two colour immunohistochemistry with monoclonal antibodies in jejunal biopsy specimens from 10 adults with untreated coeliac disease, 11 coeliac disease patients on a gluten free diet, and seven patients with established food allergy. Paired immunofluorescence staining was performed with subclass specific murine monoclonal antibodies in combination with polyclonal rabbit antibody reagent to total IgG; the proportion of cells belonging to each subclass could thereby be determined. The ratio of IgG2 immunocytes was significantly higher (p less than 0.05) in untreated coeliac disease patients (median, 35.2%; range, 26.7-65.2%) than in those on a gluten free diet (median, 7.3%; range, 0-31.9%) or those having food allergy (median, 12.5%; range, 0-36.5%). The disparity in the local IgG2 response between patients with untreated coeliac disease and those with food allergy might be due to differences in the nature of the antigenic stimuli, dissimilar genetic 'make-up' of the subjects, or both.

Adolescent↗

Deposits of terminal complement complex (TCC) in muscularis mucosae and submucosal vessels in ulcerative colitis and Crohn's disease of the colon.

Extensively washed, ethanol fixed and paraffin embedded colonic specimens from 15 patients with ulcerative colitis (UC) and nine patients with Crohn's disease (CD) of the colon, ileal specimens from six patients with CD of the ileum, and histologically normal control specimens obtained from 10 patients operated for colonic carcinoma, were examined by immunohistochemistry with a monoclonal antibody specific for a neoepitope in the C9 part of the terminal complement complex (TCC). The submucosal blood vessels in inflammatory bowel disease (IBD) showed significantly more TCC positivity than the controls, and vascular TCC deposition was statistically related (p less than 0.001) to degree of inflammation. Five of the six ileal CD specimens contained likewise vascular TCC deposits. In addition, five UC specimens and one colonic CD specimen contained TCC-positive fibrils in the muscularis mucosae or submucosa. There was no significant difference in vascular TCC deposits between UC and CD. The results suggested that terminal complement activation takes place in the intestinal lesions of IBD.

Adolescent↗

J-chain expression is more prominent in immunoglobulin A2 than in immunoglobulin A1 colonic immunocytes and is decreased in both subclasses associated with inflammatory bowel disease.

Paired immunofluorescence staining demonstrated reduced J-chain positivity of both immunoglobulin A1 (IgA1)- and IgA2-producing cells in colonic mucosa from patients with ulcerative colitis and Crohn's colitis compared with controls (p less than 0.002). J-chain expression was generally higher in IgA2 than in IgA1 immunocytes. The median proportion in normal mucosa was 100% for IgA2 vs. 88% for IgA1 (p less than 0.005); in ulcerative colitis, 69% vs. 46% (p less than 0.004); and in Crohn's colitis, 74% vs. 46% (p less than 0.004). Taken together with the overall IgA-subclass distribution, however, these results showed that the proportion of J-chain-positive IgA2 cells in the total IgA-cell population was lower for ulcerative colitis (20%) and Crohn's colitis (32%) than for normal mucosa (63%) (p less than 0.002). In relation to the total J-chain-positive IgA-cell population, which contributes to the secretory IgA system, an increased proportion (p less than 0.002) belonged to IgA1 in ulcerative colitis (61% vs. normal, 27%), whereas IgA2 was reduced (39% vs. normal, 73%). Similar but smaller trends were noted in Crohn's colitis. The disease-associated reduction of J chain might be compensated by the previously reported twofold numeric increase of IgA cells in colitis. Our study, therefore, did not suggest that the secretory IgA-cell system was quantitatively impaired in inflammatory bowel disease.

Adolescent↗

Bacteria of the gastric antrum and their relation to chronic gastritis.

Biopsy samples from the gastric antrum were taken from 61 patients. On bacteriological culture, Campylobacter pylori was isolated in 27 subjects. Thirty-four patients had chronic gastritis, as seen in routine-stained histological sections. By means of the May-Grünwald-Giemsa (MGG) staining technique, bacteria were demonstrated in sections from 26 subjects. Of these, 22 had gastritis histologically. In 13 subjects, structures similar to Campylobacter pylori were found in MGG-stained sections, 11 of these having chronic active gastritis histologically. Scanning electron microscopy demonstrated bacteria with the typical appearance of Campylobacter pylori, but other types of bacteria were also found, both on electron microscopy and on bacteriological culture. The study confirms that there is an increased frequency of histological gastritis when Campylobacter pylori is present in the samples (p = 0.009). However, a causative role of the bacteria could not be demonstrated in this study, and bacterial penetration into the epithelium was not observed.

Adult↗

Campylobacter pylori infection and its relation to chronic gastritis. An endoscopic, bacteriologic, and histomorphologic study.

Campylobacter pylori was isolated from 27 of 61 gastric antral biopsy specimens and from 8 of 61 duodenal biopsy specimens. A significant correlation between the occurrence of C. pylori and chronic active gastritis was demonstrated. However, the presence of the bacterium on normal mucosa weakens the theory of C. pylori as a primary causal organism. There was a significant correlation between isolation of C. pylori and erosive lesions in the antral mucosa as diagnosed by endoscopy. No correlation was found between endoscopic findings and histologically verified chronic active gastritis. The microbiologic examinations in this study showed a high degree of homogeneity between the isolated strains of C. pylori. A 3-OH-octadecanoic acid of the bacterial cell wall seemed to be specific for this organism and was identified in all our isolates and in the type strain of C. pylori. We therefore conclude that all Campylobacter-like organisms isolated in this study belonged to one taxonomic unit.

Adolescent↗

Omeprazole or ranitidine in the treatment of reflux esophagitis. Results of a double-blind, randomized, Scandinavian multicenter study.

One hundred and fifty-two patients with endoscopically verified erosive and/or ulcerative esophagitis entered a double-blind, randomized study comparing 20 mg omeprazole given once daily and ranitidine 150 mg twice daily. The efficacy and safety of 4 to 8 weeks' treatment were studied. Macroscopic healing of esophagitis was defined as complete epithelialization of all esophageal erosive and/or ulcerative lesions. One hundred and forty-four patients completed the first 4 weeks of treatment in accordance with the protocol. The healing rate was 67% in the omeprazole group and 31% in the ranitidine group (p less than 0.0001). The corresponding figures after 8 weeks' treatment were 85% and 50%, respectively (p less than 0.0001). The higher healing rate for omeprazole was also accompanied by a significantly faster and more substantial improvement in reflux symptoms. In the patient's own overall evaluation of symptoms, these had resolved in 51% of the omeprazole-treated patients already at the end of the 1st week of treatment, compared with 27% of those given ranitidine (p = 0.009). Both omeprazole and ranitidine were well tolerated, and there were no adverse events or clinically significant changes in the laboratory values attributable to the trial medication.

Adult↗

Immunological studies of patients with Down's syndrome. Measurements of autoantibodies and serum antibodies to dietary antigens in relation to zinc levels.

Recurrent diarrhoea and weight loss in many adult patients with Down's syndrome (DS), initiated a search for malabsorption based on determination of serum IgG and IgA antibody levels to dietary antigens. The results were compared with measurements of autoantibodies and serum zinc levels. DS patients had increased IgG and IgA activities to gluten proteins, casein and ovalbumin compared with an age- and sex-matched group of other mentally retarded patients in the same institution. Intestinal biopsy was performed in six of the 38 patients; one had total and one partial villous atrophy. Serum zinc was significantly lower in DS patients (median 14.7 mumol/l, range 5.5-20 mumol/l) than in the controls (median 16.4 mumol/l, range 12.7-19.5 mumol/l). DS patients with increased IgA activity to gluten weighed less and had lower concentrations of zinc in serum than DS patients with normal IgA activity. Twenty-eight per cent of the DS patients had autoantibodies to the thyroid gland. Our results suggest intestinal malfunction in DS, perhaps related to a defect of immune regulation caused by reduced levels of zinc in serum.

Adolescent↗

T cell distribution is different in follicle-associated epithelium of human Peyer's patches and villous epithelium.

Immunohistochemical analyses performed on specimens of normal human ileum showed a significantly raised number of T cells in the follicle-associated epithelium (FAE) of Peyer's patches compared with the epithelium of distant villi. The T cells tended to be clustered in all layers of the FAE and were significantly more numerous adjacent to interruptions of the brush border (revealed by lack of staining for alkaline phosphatase). Such interruptions were taken to indicate 'membrane' (M) cells. Our findings therefore suggested a spatial relationship between M cells and the aggregation of T cells. The ratio of CD4+ to CD8+ T cells (approximately 4:10) was significantly higher in the FAE than in the villous epithelium (approximately 0.6:10). This suggested that the FAE may be involved to a greater extent in induction of 'helper' T cell functions, perhaps depending on luminal antigens transported by M cells, whereas the villous epithelium may be more involved in stimulation of 'suppressor' T cell functions as indicated by recent studies in vitro.

Alkaline Phosphatase↗

Protection by misoprostol against naproxen-induced gastric mucosal damage.

The protective effect of misoprostol against naproxen-induced gastric mucosal damage was the subject of a double-blind, randomized, parallel-group study. Thirty-two healthy subjects were treated with naproxen 500 mg twice daily and either misoprostol 200 micrograms or matching placebo twice daily for seven days. Gastroscopy was performed before and after the treatment period and the mucosa was assessed for erosive and petechial lesions according to a predetermined scoring scheme. Of 25 evaluable subjects, 12 were treated with misoprostol and 13 were treated with placebo. The mean overall endoscopic score was 1.24 +/- 0.09 with placebo and 0.26 +/- 0.07 with misoprostol. The difference, 0.98, was highly significant (p less than 0.001), with 95 percent confidence limits of 0.74 to 1.22. All subjects in the placebo group had higher mean scores than any in the misoprostol group. The scores for erosive and bleeding lesions in the antrum and corpus/fundus of the stomach were all reduced by administration of misoprostol. In conclusion, the results clearly demonstrate that misoprostol protects the gastric mucosa of humans against naproxen-induced damage.

Adolescent↗