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Biomedical subjects

M Vieth

Publications and source records attributed to M Vieth.

At least 37 records · Page 2Linked to original sources
PubMed2003

Genome wide array comparative genomic hybridisation analysis of premalignant lesions of the stomach.

BACKGROUND: Gastric cancer is one of the most frequent malignancies in the world, ranking fifth in the Netherlands as a cause of cancer death. Surgery is the only curative treatment for advanced cases, but results of gastrectomy largely depend on the stage of the disease. A better understanding of the mechanisms of progression from a preneoplastic condition through intraepithelial neoplasia to invasive cancer may provide information relevant to designing focused prevention strategies. METHODS: Because the pattern of chromosomal aberrations in precursors of gastric cancer is unclear, 11 gastric polyps with intraepithelial neoplasia (three hyperplastic polyps and eight adenomas) were analysed by microarray comparative genomic hybridisation to study chromosomal instability in precursors of gastric cancer. RESULTS: Chromosomal aberrations were detected in all specimens. Adenomas showed no more chromosomal aberrations than did the hyperplastic polyps. The most frequent aberrations were gain of 7q36 and 20q12, and loss of 5q14-q21 in the adenomas, and loss of 15q11-14, 1p21-31, and 21q11-21.2 in the hyperplastic polyps. The most frequent chromosomal aberration in common to both types was loss of 9p21.3. CONCLUSION: Hyperplastic polyps showed many chromosomal aberrations, confirming that neoplastic transformation can occur in these lesions. These observations are consistent with the existence of two morphologically and genetically distinct pathways to gastric cancer-the hyperplastic polyp pathway and the (intestinal type) adenoma pathway. The relative contribution of each to gastric carcinogenesis in general, and how they compare to patterns of chromosomal aberrations in the more prevalent flat foci of intraepithelial neoplasia remain to be determined.

Adenoma↗
PubMed2002

Intraepithelial high-grade neoplasia and early adenocarcinoma in short-segment Barrett's esophagus (SSBE): curative treatment using local endoscopic treatment techniques.

BACKGROUND AND STUDY AIMS: In recent years, short-segment Barrett's esophagus (SSBE) has attracted increasing attention in the context of reflux disease. However, there is continuing controversy regarding its potential for malignant transformation. PATIENTS AND METHODS: Between October 1996 and September 1999, 50/115 patients (43 %) with intraepithelial high-grade neoplasia or early Barrett's adenocarcinoma, who underwent local endoscopic treatment, had developed a malignant lesion in an (SSBE). In the framework of a prospective observational study, 28 patients were treated with endoscopic mucosal resection (EMR), 13 with photodynamic therapy, and three with argon plasma coagulation; six patients received combinations of these treatments. RESULTS: Complete local remission was achieved in 48/49 patients (98 %). One patient switched to surgery after the first EMR, because there was submucosal tumor infiltration, and in one patient out of 50 local endoscopic treatment failed. A mean of 1.7 +/- 1.4 treatment sessions was required for local endoscopic treatment. The method-associated mortality was 0 %. The rate of relevant complications (stenosis, bleeding) was 6 % (3/50 patients). No cases of severe hemorrhage (Hb fall >2 g/dl) or perforation occurred. During a mean follow-up period of 34 +/- 10 months, metachronous intraepithelial high-grade neoplasms or early adenocarcinomas were seen in 11/48 patients (23 %), who received further successful endoscopic treatment. Four patients died during the follow-up period, but in only one patient was this due to his Barrett's adenocarcinoma (this was the patient who underwent esophageal resection). CONCLUSIONS: The malignant potential of short-segment Barrett's esophagus must not be underestimated. Organ-preserving local endoscopic treatment shows good acute-phase and long-term results. Local endoscopic treatment represents an alternative to esophageal resection in the case of intraepithelial high-grade neoplasia and selected early adenocarcinomas in Barrett's esophagus.

Adenocarcinoma↗
PubMed2002

Can the diagnosis of NSAID-induced or Hp-associated gastric ulceration be predicted from histology?

We studied the question whether NSAID/ASA-induced ulcerations can be identified in human gastric biopsy material on the basis of ischaemic necrosis. Biopsies of 208 patients with gastric ulcers were assessed histologically. 29 patients were excluded from the study. NSAID/ASA ulcers were diagnosed when a homogeneous eosinophilic ischaemic necrosis was found. Helicobacter pylori-(Hp-) induced ulcers were diagnosed when non-homogeneous fibrinoid necrotic material containing granulocytes and cell debris was noted. The histological diagnosis was compared with the data on medication use, endoscopy and clinical history. 121 of the 179 patients included had a medical history on NSAIDS/ASA. From the 60 patients taking NSAIDS/ASA with no histologic evidence of Hp all (100 %) were identified by the histology of the necrosis. From the 61 patients taking NSAID/ASA and histologic evidence of H. pylori 40 (66 %) were identified by histology. From the 58 patients with no such medication 41 were Hp-positive and correctly identified by histology in 31 cases (76 %). The sensitivity of the histologic diagnosis of NSAID/ASA-induced ulceration was 85 %, and its specificity 53 %. The results of our study show that a high percentage of the NSAID/ASA-induced ulcers of the stomach can indeed be correctly diagnosed at histology. In conclusion the underlying aetiopathogenesis of gastric ulcerations (NASID/ASA vs. Hp) can be uncovered in a large proportion of patients based on histological examination.

Aged↗
PubMed2002

Fundic gland polyps (Elster's cysts) of the gastric mucosa. A marker for colorectal epithelial neoplasia?

The results of several retrospective studies allow us to conclude that the detection of fundic gland polyps (Elster's cysts) is associated with an increased incidence of colorectal tumors. In this survey, we present the results of a prospective study investigating such a possible relationship. A total of 144 patients were investigated, of whom 80 had fundic gland polyps of the gastric corpus mucosa. Sixty-four of these patients underwent a colonoscopy, whereas the other 64 patients belonged to a sex- and age-matched control group with no fundic gland polyps. In the group with known fundic gland polyps, colorectal neoplasias were found in 29 (45.3%) patients. Eight of these patients had (12.5%) adenocarcinomas, 3 (4.7%) had high-grade intraepithelial neoplasia, and 18 (28.1%) had tubular adenomas. In one patient, a synchronous carcinoma of the rectum and the colon was detected. In comparison, 6 patients of the control group (9.3%) developed tubular adenomas and 9 (14.1%) had hyperplastic polyps of the colonic and rectal mucosa. Our results suggest that it is necessary to conduct a careful diagnostic work-up of the colon in patients with gastric fundic gland polyps.

Biomarkers, Tumor↗
PubMed2001

[50 years of Barrett esophagus. Current diagnostic possibilities in pathology].

The most important differential diagnosis of specialized intestinal columnar cell metaplasia (Barrett's-mucosa) is the intestinal metaplasia of the cardia mucosa (possibly caused by Helicobacter infection). Furthermore it happens from time to time that Barrett's regenerative epithelium is overdiagnosed as low-grade dysplasia (unequivocal intraepithelial neoplasia). This might explain the disappearance of many low-grade dysplasias during further follow-up. Mucosal adenocarcinomas are often underdiagnosed as dysplastic lesions. Therefore many authors tried to establish molecular methods for improvement of the diagnostic possibilities. Immunohistochemistry or PCR with p53 and HER 2-neu might give at least some help but a negative reaction does not exclude a neoplasia in every case. The gold standard is careful endoscopy and biopsy taking with good documentation of the endoscopical findings and most important still the routine H&E stain are the only reliable diagnostic tools.

Adenocarcinoma↗
PubMed2001

Down-regulation of Akt/PKB in senescent cardiac fibroblasts impairs PDGF-induced cell proliferation.

OBJECTIVE: Cardiovascular diseases are the leading cause of death in the Western World, especially in the elder population. One pathophysiological component of cardiovascular disease is myocardial fibrosis, primarily derived from cardiac fibroblasts. Here we investigated the regulation of proliferation of fibroblasts from hearts of adult rats by platelet derived growth factor AA (PDGF-AA). METHODS: Cardiac fibroblasts were isolated from adult Wistar rats. PDGF-induced cell proliferation was analysed by FACS. PDGF-receptor numbers were analysed by receptor binding assays. Using differential display, differentially expressed kinases were identified during ageing in vitro and confirmed by Northern and Western blotting. Transient overexpression of IRES-GFP constructs was used to analyse the role of the akt kinase on proliferation by FACS. RESULTS: During in vitro senescence/aging of primary fibroblasts, the growth response to PDGF-AA was greatly reduced without alterations in its receptor number or affinity and without changes in downstream signalling via the MAP-kinase pathway. By using a differential display strategy selective for protein kinases, we identified reduced expression of Akt-1 kinase (PKB-alpha) in senescent rat cardiac fibroblasts. These findings were supported by data showing reduced expression of Akt-1 in heart samples from old humans. Overexpression of activated Akt-1 almost completely reconstituted PDGF-AA dependent cell proliferation in aged fibroblasts. CONCLUSION: These results support an important role for Akt in senescence and regulation of cardiac fibroblast cell proliferation.

Animals↗
PubMed2001

Red streaks in the oesophagus in patients with reflux disease: is there a histomorphological correlate?

BACKGROUND: The Los Angeles classification of reflux oesophagitis includes sharply demarcated areas of erythema without any associated slough within the definition of reflux-induced mucosal breaks, though there is uncertainty as to whether these "red streaks" actually represent such a mucosal lesion. This study evaluates the histopathology of these red streaks. METHODS: Forty patients with one or more red streaks on the tops of the mucosal folds in the distal oesophagus were included in a multinational, multicentre prospective study. All patients were referred for upper gastrointestinal endoscopy to investigate chronic heartburn and acid regurgitation. Biopsies were taken from the red streaks and from control biopsies from more normal appearing mucosa 1 cm lateral to the red streaks. A two-sided probability test using normal approximation assessed differences in the histological findings at the two biopsy locations. RESULTS: Compared to control biopsies, biopsies of red streaks had a significantly thicker basal cell layer (mean +/- s 41% +/- 32% versus 18% +/- 23% of mucosal thickness, P=0.001) and longer papillae (mean +/- s 71% +/- 19% versus 49% +/- 24% of mucosal thickness, P= 0.001). Of the red streak biopsies, 25% had either newly re-epithelized lesions or granulation tissue beneath squamous epithelium. Only 10% of the control biopsies had moderate or more marked regenerative changes (based on elongation of papillae and basal cell hyperplasia), compared to 65.1% of red streak biopsies. Of the biopsies from the red streak itself, 7% showed no abnormality and 27.9% only slight changes. In comparison, 25% of the biopsies from control biopsies showed no regenerative changes and 62.5% only slight change due to gastro-oesophageal reflux disease. CONCLUSION: The histomorphological counterpart to the endoscopically visible red streaks of the distal oesophagus is marked regenerative changes of the squamous epithelium and/or capillary rich granulation tissue beneath the squamous epithelium. Red streaks are validated as being indicative of acid/peptic mucosal injury, but they do not satisfy a strict definition of a mucosal break.

Biopsy↗
PubMed2001

Acute measles gastric infection.

We describe the case of a 44-year-old man who was referred for gastroscopy because of abdominal pain. During endoscopy, inflammatory changes of the antrum and corpus mucosa were clearly visible, and biopsy samples from the antrum and corpus mucosa were taken. At histology, routine hematoxylin and eosin staining showed characteristics indicative of so-called ex-Helicobacter pylori-gastritis that had developed after antibiotic treatment 2 years ago. Additional large, bizarre inclusion bodies and clusters of multinucleated giant cells were located in the surface epithelium and within the lamina propria. These giant cells had an appearance similar to that of Warthin-Finkeldey cells, which can be found during the prodromal phase of measles infection. Anti-measles virus immunochemistry showed a strong positivity for measles virus antigen within the giant cells. Based on these results, the final diagnosis of morbilliform gastritis was made. To our knowledge, no case of measles gastritis has been described in the literature. Our case report confirms the systemic character of measles virus infection and confirms that measles viral replication can involve the gastric mucosa in addition to the conjunctiva, lung, and intestina.

Acute Disease↗
PubMed2001

The AMOR study: a randomized, double-blinded trial of omeprazole versus ranitidine together with amoxycillin and metronidazole for eradication of Helicobacter pylori.

BACKGROUND: Besides antibiotics, additionally effective acid inhibition is necessary for the eradication of Helicobacter pylori. OBJECTIVE: To assess the significance of acid suppression and, in particular, treatment with proton pump inhibitors (PPIs) compared with H2 receptor antagonists (H2 RAs). The primary target parameter for the study was H. pylori eradication. In addition, the ulcer healing rate, speed of pain reduction, score for gastritis in the antrum and gastric body, and rate of side effects were recorded. DESIGN: Randomized, double-blinded, multicentre study. PARTICIPANTS: A total of 456 patients between the ages of 18 and 80 years with H. pylori-positive duodenal ulcers were included in the study. METHODS: Using a randomization list, patients were assigned either to a treatment group receiving omeprazole 40 mg once daily, amoxycillin 750 mg three times a day, and metronidazole 500 mg three times a day (OAM), or to a group receiving ranitidine 300 mg once daily, amoxycillin 750 mg three times a day, and metronidazole 500 mg three times a day (RAM). The treatment period was 7 days in both groups. Long-term acid-suppressant treatment was not given. RESULTS: The eradication rate was 87.1% (169/194, intention to treat [ITT]) in the OAM group and 77% (137/ 178, ITT) in the RAM group. The difference of 10.1% (95% CI 2.5-18%) is statistically significant (P= 0.0104). The ulcer healing rate was 93.3% in the OAM group (181/194, ITT) and 92.1% in the RAM group (164/178, ITT, NS). With regard to the speed and intensity of pain reduction, the OAM group was superior to the RAM group. In patients in whom H. pylori eradication was successful, the reduction in the antral and gastric body gastritis score was significantly greater than in patients without eradication. In the OAM group, 39.1% of the patients (n = 90) reported one or more side effects, compared with 44.7% (n = 101) in the RAM group (P= 1.5449, NS). CONCLUSION: Omeprazole (40 mg once daily in the morning) is significantly more effective than ranitidine (300 mg once daily in the morning) with respect to H. pylori eradication when used together with amoxycillin (750 mg three times a day) and metronidazole (500 mg three times a day) for a 7-day treatment period.

Adolescent↗
PubMed2001

Specific detection and prevalence of Helicobacter heilmannii-like organisms in the human gastric mucosa by fluorescent in situ hybridization and partial 16S ribosomal DNA sequencing.

Gastric infection with Helicobacter heilmannii (previously known as Gastrospirillum hominis) is invariably linked with the presence of chronic gastritis and the risk of developing low-grade mucosa-associated lymphoid tissue lymphoma in humans. In contrast to Helicobacter pylori, various H. heilmannii species colonize the stomachs of domestic animals, which might be a reservoir for transmission to humans (zoonosis). To identify the number and prevalence of different H. heilmanni types in humans, we analyzed 89 gastric biopsy samples histologically identified as H. heilmannii positive by fluorescence in situ hybridization. Of these gastric specimens, 84 (94.4%) contained a single H. heilmannii type. In five samples, however, two different H. heilmannii types were detected. The most prevalent species in monoinfected samples is H. heilmannii type 1, found in 78.5% (66 of 84) of the specimens, followed by a novel H. heilmannii-like organism (HHLO), HHLO type 4, identified in 9.6% (8 of 84) of tissue sections. H. heilmannii type 2 and a further HHLO type not described before, type 3, were found in 8.3% (7 of 84) and 1.2% (1 of 84) of the monoinfected samples, respectively. Additionally, HHLO type 5 with a 16S ribosomal DNA sequence identical to that of Helicobacter salomonis was found with a prevalence of 2.4% (2 of 89). Thirteen of these biopsy samples were also investigated by a PCR approach developed for this study that allows a Helicobacter-specific amplification of a variable portion of the 16S rRNA gene and subsequent sequencing. In total, five different types of HHLOs could be identified within these samples. We conclude that humans can be infected by at least five different HHLO types, which presumably have their origin in animal species like dogs, cats, and pigs.

Biopsy↗
PubMed2001

Fundic gland polyps are not induced by proton pump inhibitor therapy.

It is still unclear whether proton pump inhibitors (PPIs) could cause fundic gland polyps (FGPs) in patients without Helicobacter pylori infection. The frequency of FGPs in patients during PPI therapy has not been compared, however with a control group of patients who did not have H. pylori infection and were not undergoing PPI treatment. In a retrospective 12-month study, the frequency of FGPs in 2,251 patients without H. pylori infection receiving PPI therapy (duration of treatment at least 4 weeks) was compared with a control group of 28,096 patients who did not have H. pylori infection and were not receiving PPI therapy. FGPs were identified with an identical frequency in both groups (5.0% in the control and 5.2% in the PPI group). No significant differences were present between the groups with respect to the presence of gastritis or age or sex. Our study shows that a causal pathogenetic relationship between PPI therapy and FGPs is unlikely.

Enzyme Inhibitors↗
PubMed2000

DoMCoSAR: a novel approach for establishing the docking mode that is consistent with the structure-activity relationship. Application to HIV-1 protease inhibitors and VEGF receptor tyrosine kinase inhibitors.

DoMCoSAR is a novel approach for statistically determining the docking mode that is consistent with a structure-activity relationship. The approach establishes the binding mode for the compounds in a chemical series with the assumption that all molecules exhibit the same binding mode. It involves three stages. In the first stage all molecules that belong to a given chemical series are docked to the active site of the protein target. The only bias used in the docking at this stage involves the location of the protein binding site. Coordinates of the common substructure (CS) that results from the unbiased docking are then clustered to establish the major substructure docking modes. In the second stage all molecules are docked to the major docking modes (MDMs) with constraints based on the common substructure. The third stage generates, for the major docking modes, interaction-based descriptors that include electrostatic, VDW, strain, and solvation contributions. The problem of docking mode evaluation is now reduced to the question of which descriptor set is more predictive. To establish a quantitative comparison of the descriptor sets associated with the major docking modes, we use 50 instances of random 4-fold cross-validation. For each 4-fold cross-validation the predictive squared correlation coefficient (R(2)) is computed. t-Tests are applied to establish significance of the differences in mean R(2) for one docking mode versus another. We test the methodology on two test cases: HIV-1 protease inhibitors (Holloway et al. J. Med. Chem. 1995, 38, 305-317) and vascular endothelial growth factor (VEGF) receptor tyrosine kinase oxoindoles (Sun et al. J. Med. Chem. 1998, 41, 2588-2603). For both test cases there is statistically significant preference for the binding mode consistent with the X-ray structure. The appeal of this methodology is that researchers gain the objectivity of statistical justification for the selected docking mode. The methodology is relatively insensitive to subtle variations of the protein structure that include, but are not limited to, side chain and small backbone rearrangement during binding. In addition, predictive models that result from the approach can be used to further optimize chemical series.

Crystallography, X-Ray↗
PubMed2000

Endoscopic mucosal resection of early cancer and high-grade dysplasia in Barrett's esophagus.

BACKGROUND & AIMS: In view of the mortality and morbidity rates of esophagectomy and the relatively large group of inoperable patients, local therapeutic techniques are required for high-grade dysplasia and early Barrett's cancer. METHODS: A prospective investigation of endoscopic mucosal resection was conducted in 64 patients (mean age, 65 +/- 10 years) who had early carcinoma (61 patients) or high-grade dysplasia (3 patients) in Barrett's esophagus. Thirty-five patients met the criteria for low risk: macroscopic types I, IIa, IIb, and IIc; lesion diameter up to 20 mm; mucosal lesion; and histological grades G1 and G2 and/or high-grade dysplasia (group A). The remaining 29 patients were included in group B (high risk). RESULTS: A total of 120 resections were performed, with no technical problems encountered. The mean number of treatment sessions per patient was 1. 3 +/- 0.6 in group A and 2.8 +/- 2.0 in group B (P < 0.0005). Only one major complication occurred, a case of spurting bleeding, which was managed endoscopically. Complete local remission was achieved significantly earlier (P = 0.008) in group A than in group B. In May 1999, complete remission had been achieved in 97% of the patients in group A and in 59% of those in group B; however, 1 patient in group A and 9 in group B are still undergoing treatment or awaiting the first check-up. During a mean follow-up of 12 +/- 8 months, recurrent or metachronous carcinomas were found in 14%. CONCLUSIONS: Endoscopic mucosal resection of early carcinoma in Barrett's esophagus is associated with promisingly low morbidity and mortality rates. The procedure may offer a new minimally invasive therapeutic alternative to esophagectomy, especially in low-risk situations. Comparisons with surgical results will need to be done when the long-term results of this procedure become available.

Adult↗
PubMed2000

Ocular findings in Fryns syndrome.

PURPOSE: To demonstrate the ocular histopathologic findings in Fryns syndrome, a multiple congenital anomaly syndrome, with characteristic features including Dandy-Walker malformation, cleft palate, diaphragmatic hernia, lung hypoplasia, distal limb anomalies and polyhydramnios. The prevalence is about 0.7 per 10,000 births. Reported ocular features include microphthalmus, "cloudy cornea", irregularities of Bowman's layer, thickened posterior lens capsule and retinal dysplasia. METHODS: Case report. The ocular histopathologic and ultrastructural findings in a male fetus with Fryns syndrome who died immediately after his birth at 26th week of gestation are shown. RESULTS: An abnormal Descemet's membrane was found in addition to "cloudy corneae". Electron microscopy demonstrated absence of the banded collagen fibrils in Descemet's membrane, indicating corneal endothelial dysfunction. Otherwise, the eye was morphologically normal for its age; none of the other reported ocular features of Fryns syndrome were found. CONCLUSION: Corneal endothelial dysfunction might cause abnormal composition of anterior Descemet's membrane and could contribute to the "cloudy cornea" known to occur in Fryns syndrome.

Abnormalities, Multiple↗
PubMed2000

Barrett's mucosa, Barrett's dysplasia and Barrett's carcinoma: diagnostic endoscopy without biopsy-taking does not suffice.

Many gastroenterologists are of the opinion that endoscopic diagnosis of gastro-oesophageal reflux disease (GORD) suffices and that additional biopsies are not necessary. The data obtained from 1068 consecutive patients with histologically confirmed Barrett's oesophagus were analysed retrospectively. In 37.9% of the patients, the histological diagnosis of Barrett's oesophagus was an incidental finding, whereas 32.7% of Barrett's carcinomas were diagnosed only at histology but not during endoscopy. Of the Patients with dysplasia, 92.4% were diagnosed only by the pathologist. Our analysis shows that an endoscopic diagnosis suspicious for Barrett's mucosa is made in 62.1% of the cases, carcinoma in 70%, and dysplasia in only 7.6% of the cases. Also, because neoplasia is detected for the most part at the invasive carcinoma state, but not in the dysplasia stage, the diagnosis of Barrett's oesophagus, with and without dysplasia, needs to be improved by additional biopsies for histopathological investigation.

Aged↗