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M Stolte

Publications and source records attributed to M Stolte.

At least 163 records · Page 9Linked to original sources
PubMed2000

Effects of long-term treatment with proton pump inhibitors in gastro-oesophageal reflux disease on the histological findings in the lower oesophagus.

BACKGROUND: The application of hyperplasia of the basal cell layer and elongation of the papillae in the squamous epithelium of the distal oesophagus, as histological criteria for the diagnosis of gastro-oesophageal reflux disease (GORD), continues to be controversial. An unanswered question is whether these changes may regress under long-term treatment with proton pump inhibitors (PPI). This fact prompted us to investigate the effect of PPI treatment on the histological changes observed in the lower oesophagus. METHODS: 295 patients with endoscopically confirmed erosive GORD were investigated by endoscopy/biopsy prior to and during the course of a 12-month PPI treatment regimen (8 weeks acute treatment with 30 mg lansoprazole/day followed by long-term treatment with 15 or 30 mg lansoprazole or 20 mg omeprazole/day). The parameters studied were the frequency of ulcers and erosions and the hyperplasia of the basal cell layer and elongation of the papillae prior to treatment and on day 56 (D56), after 6 months (M6) and after 12 months (M12) of treatment. RESULTS: In the various treatment groups, the results showed no statistically significant differences. Ulcers and erosions (prior to treatment 21% and 31%, respectively) were detected statistically significantly less frequently under PPI treatment (ulcers, D56: 1%, M6 and M12, 0%; erosions, D56: 2%, M6: 4%, M12, 3%). While high-grade hyperplasia of the basal cell layer and elongation of the papillae was found in 51% of the cases prior to treatment, the corresponding figures were only 3% (D56, M6) and 2% (M12). In contrast, the percentage of cases with normal oesophageal epithelium increased from 8% before treatment to 55% (D56), 66% (M6) and 63% (M12). CONCLUSIONS: Our study shows not only that erosions and ulcers heal under PPI treatment, but also that hyperplasia of the basal cell layer and elongation of papillae in the squamous epithelium of the oesophageal mucosa may normalize, and are thus presumably not 'normal physiological variants'.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

The effect of ammonia on omeprazole-induced reduction of gastric acidity in subjects with Helicobacter pylori infection.

OBJECTIVE: Omeprazole produces a higher intragastric pH during Helicobacter pylori (H. pylori) infection than after cure. We tested the hypothesis that this difference is due to the production of ammonia by H. pylori. METHODS: Gastric acidity and acid output (AO) were measured overnight in 12 subjects, with and without omeprazole, before and 1 and 6 months after cure of H. pylori infection. Gastric ammonia ([NH3]), total bile acid ([TBA]) and protein concentrations and plasma omeprazole levels were measured. RESULTS: During omeprazole, median AO were 0.0 mmol/h before, 0.86 mmol/h (p = 0.003 vs before cure) at 1 month, and 0.34 mmol/h (p = 0.02) at 6 months after cure; median NH3 output was 0.17 mmol/h before, 0.03 mmol/h (p = 0.002) at 1 month, and 0.02 mmol/h (p = 0.005) at 6 months after cure. AO and NH3 output were similar 1 and 6 months after cure. When corrected for [NH3], AO and gastric pH curves were similar before and after cure. Omeprazole plasma levels increased after cure and gastric [TBA] were unchanged. CONCLUSIONS: The higher pH observed before cure of H. pylori during omeprazole administration is attributable, in large part, to ammonia production. Other acid-neutralizing substances and changes in acid secretion may also be important, but duodenogastric reflux and omeprazole pharmacokinetics are not involved.

Adult↗
PubMed2000

Mesalazine inhibits activation of transcription factor NF-kappaB in inflamed mucosa of patients with ulcerative colitis.

OBJECTIVES: The salicylate mesalazine is commonly used for the treatment of inflammatory bowel diseases, yet its precise mechanism of action is unknown. Because transcription factor NF-kappaB plays an important role in inflammatory bowel diseases, we investigated the effects of mesalazine therapy on NF-kappaB activation in patients with ulcerative colitis. METHODS: A total of 20 patients with moderately active ulcerative colitis received mesalazine for 8 wk. Biopsies were taken before and after drug administration and analyzed for NF-kappaB activation using an antibody specific for active NF-kappaB. RESULTS: In biopsies of active ulcerative colitis but not in noninflamed mucosa, activation of NF-kappaB was detected predominantly in macrophages. Mesalazine therapy resulted, in a strong abrogation of NF-kappaB activation in situ. CONCLUSIONS: Our results suggest that the therapeutic properties of mesalazine rely at least in part on the inhibition of NF-kappaB activation, resulting in the suppression of proinflammatory gene expression in the inflamed mucosa.

Adult↗
PubMed2000

alpha-catenin expression is decreased in human gastric cancers and in the gastric mucosa of first degree relatives.

BACKGROUND AND AIMS: The role of altered cell adhesion is critical for the development of epithelial cancers. E-cadherin plays an important role in the maintenance of cell-cell adhesion and its function is thought to be regulated by its associated cytoplasmic proteins, such as alpha-catenin and beta-catenin. To determine the role of alpha-catenin expression in gastric carcinogenesis, we studied its expression in human gastric cancer and in the gastric mucosa of first degree relatives with no clinical disease. METHODS: alpha-Catenin expression was assessed by immunohistochemical analysis and reverse transcriptase-polymerase chain reaction (RT-PCR) using gastric tissue specimens from patients with gastric cancer and from the gastric mucosa of first degree relatives of gastric cancer patients and healthy controls. RESULTS: mRNA levels of alpha-catenin were reduced or absent in 13 of 19 gastric cancer tissues, which differed significantly from levels found in the tumour free gastric mucosa of cancer patients (p<0.05). Of the cancer samples with altered alpha-catenin mRNA levels, alpha-catenin expression was negative in seven and decreased in six cases. Interestingly, decreased alpha-catenin mRNA expression also occurred in the mucosa of the corpus (11/18) and antrum (4/18) of first degree relatives. In the corpus biopsies alpha-catenin expression was more often decreased or lost compared with the antrum biopsies in first degree relatives and healthy controls (p<0.05). Immunohistochemical analysis revealed membranous expression of alpha-catenin in gastric cancer cells and the non-malignant gastric epithelium. However, some cancers also exhibited loss of membranous staining. Generally, loss or downregulation of alpha-catenin mRNA in the gastric mucosa was associated with Helicobacter pylori infection (p<0.05). CONCLUSION: Our findings suggest that loss or downregulation of alpha-catenin expression may be an early event in gastric carcinogenesis and may be associated with H pylori infection.

Adult↗
PubMed2000

The Vienna classification of gastrointestinal epithelial neoplasia.

BACKGROUND: Use of the conventional Western and Japanese classification systems of gastrointestinal epithelial neoplasia results in large differences among pathologists in the diagnosis of oesophageal, gastric, and colorectal neoplastic lesions. AIM: To develop common worldwide terminology for gastrointestinal epithelial neoplasia. METHODS: Thirty one pathologists from 12 countries reviewed 35 gastric, 20 colorectal, and 21 oesophageal biopsy and resection specimens. The extent of diagnostic agreement between those with Western and Japanese viewpoints was assessed by kappa statistics. The pathologists met in Vienna to discuss the results and to develop a new consensus terminology. RESULTS: The large differences between the conventional Western and Japanese diagnoses were confirmed (percentage of specimens for which there was agreement and kappa values: 37% and 0.16 for gastric; 45% and 0.27 for colorectal; and 14% and 0.01 for oesophageal lesions). There was much better agreement among pathologists (71% and 0.55 for gastric; 65% and 0.47 for colorectal; and 62% and 0.31 for oesophageal lesions) when the original assessments of the specimens were regrouped into the categories of the proposed Vienna classification of gastrointestinal epithelial neoplasia: (1) negative for neoplasia/dysplasia, (2) indefinite for neoplasia/dysplasia, (3) non-invasive low grade neoplasia (low grade adenoma/dysplasia), (4) non-invasive high grade neoplasia (high grade adenoma/dysplasia, non-invasive carcinoma and suspicion of invasive carcinoma), and (5) invasive neoplasia (intramucosal carcinoma, submucosal carcinoma or beyond). CONCLUSION: The differences between Western and Japanese pathologists in the diagnostic classification of gastrointestinal epithelial neoplastic lesions can be resolved largely by adopting the proposed terminology, which is based on cytological and architectural severity and invasion status.

Adenoma↗
PubMed2000

Short course acid suppressive treatment for patients with functional dyspepsia: results depend on Helicobacter pylori status. The Frosch Study Group.

BACKGROUND AND AIMS: Treatment of functional dyspepsia with acid inhibitors is controversial and it is not known if the presence of Helicobacter pylori infection influences the response. METHODS: After a complete diagnostic workup, 792 patients with functional dyspepsia unresponsive to one week of low dose antacid treatment were randomised to two weeks of treatment with placebo, ranitidine 150 mg, omeprazole 10 mg, or omeprazole 20 mg daily. Individual dyspeptic and other abdominal symptoms were evaluated before and after treatment according to H pylori status. RESULTS: The proportions of patients considered to be in remission (intention to treat) at the end of treatment with placebo, ranitidine 150 mg, omeprazole 10 mg, and omeprazole 20 mg were, respectively, 42%, 50%, 48%, and 59% in the H pylori positive group and 66%, 73%, 64%, and 71% in the H pylori negative group. In H pylori positive patients, the therapeutic gain over placebo was significant for omeprazole 20 mg (17.6%, 95% confidence intervals (CI) 4.2-31.0; p<0.014 using the Bonferroni-adjusted p level of 0.017) but not for omeprazole 10 mg (6.8%, 95% CI -6.7-20.4) or ranitidine 150 mg (8.9%, 95% CI -4.2-21. 9). There was no significant therapeutic gain from active treatment over placebo in H pylori negative patients. Complete disappearance of symptoms and improvement in quality of life also occurred most frequently with omeprazole 20 mg and was significant in both H pylori positive and H pylori negative groups. The six month relapse rate of symptoms requiring treatment was low (<20%) in all groups. CONCLUSIONS: Omeprazole 20 mg per day had a small but significant favourable effect on outcome in H pylori positive patients. The differential response in these patients may be explained by an enhanced antisecretory response in the presence of H pylori. The effect of weaker acid inhibition was unsatisfactory.

Adolescent↗
PubMed2000

Helicobacter pylori infection: protection against Barrett's mucosa and neoplasia?

BACKGROUND: Since Helicobacter pylori (Hp) infection provokes intestinal and gastric metaplasia, the question arises whether the specialized metaplasia (Barrett's mucosa (BM)) and dysplasia or carcinoma in Barrett's epithelium seen in gastro-oesophageal reflux disease (GORD) might not also be correlated with Hp infection, or whether the latter offers protection against Barrett's oesophagus and Barrett's adenocarcinoma. PATIENTS: Gastric and oesophageal biopsies obtained from a total of 2,201 patients were analysed retrospectively. 297 of these patients had GORD (age 53.5 +/- 13.4 years; m:f ratio 2.1:1), 1,192 patients had BM (age 62.8 +/- 14.6 years; m:f 2.3:1) with or without neoplasia. 1,054 of these patients were diagnosed as having BM alone, 138 patients having BM neoplasia (high-grade dysplasia or adenocarcinoma). Patients with BM and low-grade dysplasia were excluded from this study because of the uncertainty in differentiating low-grade dysplasia from regenerative epithelium. A total of 712 patients with non-ulcer dyspepsia (NUD; average age 40.0 +/- 16.1 years; m:f 0.3:1) served as a control group. RESULTS: The percentage of Hp infection did not differ between patients with GORD with (53.3%)/without BM (51.4%) and neoplasia (47.8%), but is statistically significantly lower than in patients with NUD (65.7%). CONCLUSION: Our analysis shows that patients with GORD and Hp infection have no increased risk for the development of BM or neoplasia in BM. Since Hp infection is significantly less frequent in GORD than in NUD patients, a protective effect of the Hp infection is a possibility worth discussing.

Adenocarcinoma↗
PubMed2000

Treatment with lansoprazole also induces hypertrophy of the parietal cells of the stomach.

The aim of the present study was to investigate whether not only omeprazole but also lansoprazole leads to hypertrophy of the parietal cells of the gastric mucosa. We investigated the gastric mucosa of 295 patients with gastro-esophageal reflux disease prior to therapy, after 8 weeks of treatment with 30 mg lansoprazole/day, and after 6 and 12 months of long-term treatment with 15 or 30 mg lansoprazole, or 20 mg omeprazole/day. In a small group of 48 patients, a follow-up examination was carried out 3 months after termination of the study. Following acute treatment with 30 mg lansoprazole/day, 84% of the patients revealed parietal cell hypertrophy, while under long-term treatment this figure rose to 89%. The grade of the parietal cell hypertrophy increased continuously under long-term treatment. With regard to the incidence and grading of parietal cell hypertrophy, no significant differences were found among the three groups receiving long-term treatment. Three months after termination of treatment with these proton-pump inhibitors, the hypertrophy of the parietal cells had largely disappeared again. This study shows that hypertrophy of the parietal cells in the gastric mucosa occurs not only under treatment with omeprazole, but also under therapy with lansoprazole, and is reversible when the proton pump inhibitors are discontinued.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

Helicobacter pylori gastritis of the gastric carcinoma phenotype: is histology capable of identifying high-risk gastritis?

Several studies have shown that Helicobacter pylori infection implies an increased risk for developing gastric carcinoma. However, it has to be considered that only a few among those infected with H. pylori develop gastric cancer. It is therefore desirable to identify risk indicators of H. pylori gastritis in the presence of which gastric carcinoma is most likely to occur. In our view, the risk indicators intestinal metaplasia and atrophy, frequently cited in the literature, are not suitable, as they are focal changes whose detection at the routine diagnostic workup may be confounded by sampling error and because early carcinoma (in particular of the diffuse type) is often not associated with intestinal metaplasia or atrophy. For this reason we investigated the diffuse gastritis parameters "grade of gastritis" and "activity of gastritis" for their suitability as risk indicators. We found that H. pylori gastritis, particularly in the corpus, is significantly more pronounced in gastric carcinoma patients or individuals with a family history of gastric cancer than in matched controls. Hence, a simple comparison of the grade of gastritis and activity of gastritis in the antrum and corpus might help identify patients with H. pylori gastritis with an increased cancer risk. Currently. we are testing this hypothesis in an ongoing gastric cancer prevention study in Germany, Austria, and Czechia.

Cell Transformation, Neoplastic↗
PubMed2000

International comparability of the pathological diagnosis for early cancer of the digestive tract: Munich meeting.

Large differences have been found between Western and Japanese pathologists' diagnosis of adenoma/dysplasia versus early carcinoma for gastric, esophageal. and colorectal epithelial neoplastic lesions. In this study we examined whether differences in experience in gastrointestinal pathology can to some extent explain these differences in diagnostic practice. Three Japanese, one British, and two German pathologists with much experience and one North American pathologist with less experience in routine diagnostic work reviewed 52 microscopic slides: 16 gastric, 24 esophageal, and 12 colorectal biopsy and resection specimens obtained from patients with lesions ranging from early carcinoma to adenoma, dysplasia, and regenerative epithelium. The extent of agreement between the diagnoses of the four individual Western pathologists and the most common Japanese diagnoses was assessed by kappa statistics. For the 16 gastric lesions, a diagnosis of suspected or definite carcinoma was made by the Japanese pathologists in 69%-75% of the slides, by three experienced Western pathologists in 56%-63% (high kappa values: 0.61, 0.64, 0.65), and by the less experienced Western pathologist in only 31% of the slides (low kappa value: 0.10). For the 24 specimens of esophageal squamous lesions, carcinoma in situ and suspected or definite carcinoma were diagnosed by the Japanese in 96%-100% and by the Western pathologists in 63%-88% of the slides (low kappa values: 0.17, 0.25, 0.25, 0.27). For the 12 colorectal lesions, the Japanese diagnosed suspected or definite carcinoma in 58%-83%, whereas all Western pathologists followed the World Health Organization definition of colorectal carcinoma and diagnosed suspected or definite carcinoma in only 0-42% of the slides (kappa values: 0.04, 0.10,0.12, 0.49). In conclusion, there were few differences in diagnoses between experienced Western and Japanese pathologists for gastric lesions but considerable differences for esophageal and colorectal lesions. The differences in the diagnosis of adenoma/dysplasia versus early carcinoma between Western and Japanese pathologists found in previous studies may in large part be attributable to differences in experience with regard to gastric neoplasia and to differences in interpretation and nomenclature with regard to esophageal and colorectal neoplasia.

Biopsy↗
PubMed2000

Ablation of Barrett's epithelium by endoscopic argon plasma coagulation in combination with high-dose omeprazole.

BACKGROUND: Barrett's esophagus is a premalignant condition induced by gastroesophageal reflux. The aim of this prospective study was to assess the efficacy of argon plasma coagulation in combination with high-dose omeprazole therapy to ablate nondysplastic Barrett's epithelium. METHODS: In 73 patients with histologically confirmed Barrett's epithelium, argon plasma coagulation was used in combination with maximal acid suppression (omeprazole 40 mg three times a day). Histologic and endoscopic changes were evaluated at 6- and 12-month intervals. RESULTS: In 69 of 70 patients (98.6%) complete squamous regeneration was achieved after a median of 2 argon plasma coagulation sessions (range 1 to 5). During a median follow-up of 12 months (range 2 to 51 months) there has been no relapse or evidence of the development of dysplasia under continuous acid suppression. Three patients (4.3%) developed a mild stricture of the distal esophagus that resolved after a single session of bougie dilation. CONCLUSIONS: In our experience, argon plasma coagulation in combination with high-dose omeprazole treatment is an effective and safe technique for complete ablation of nondysplastic Barrett's epithelium. Restoration of squamous mucosa after argon plasma coagulation appears to be long-lasting.

Adult↗