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Biomedical subjects

M Vieth

Publications and source records attributed to M Vieth.

At least 55 records · Page 3Linked to original sources
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↗
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

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

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

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↗
PubMed1999

Differential expression of mucins and trefoil peptides in native epithelium, Barrett's metaplasia and squamous cell carcinoma of the oesophagus.

BACKGROUND AND AIMS: In humans, trefoil peptides (TFF peptides) and some mucins have been reported to be expressed in a cell-specific manner at mucosal surfaces of normal gastrointestinal tissues. Neoplastic conditions cause characteristic changes of these expression patterns. To study such patterns in Barrett's metaplasia and squamous cell carcinoma of the oesophagus (SCC), the distribution of MUC1, MUC2, MUC5AC and the three TFF peptides (TFF1, TFF2 and TFF3) was investigated. METHODS: In 40 archival samples of SCC and in 21 samples of Barret's metaplasia, expression of the three mucins and two TFF peptides (TFF1 and TFF2) was assessed by specific antibodies. Reverse transcriptase/polymerase chain reaction amplification (RT-PCR) was performed on frozen tissue samples from the 11 biopsies of SCC for the three TFF peptides. RESULTS: Immunohistochemical tests for MUC2 and TFF2 were negative both in samples of Barret's metaplasia and in SCC. MUC1 expression was detected in 57.5% of the tumour samples, while TFF1 and MUC5AC were found in 10% and 7.5% of the cases respectively. In Barrett's metaplasia MUC1 was detected in 90.5% of the cases and TFF1 and MUC5AC in all of them. RT-PCR analysis revealed a more complex pattern: TFF1 and TFF3 expressed the corresponding mRNA in all samples investigated; the third member, TFF2, was active in 45.5% of the carcinoma biopsies and not in the corresponding native tissue. CONCLUSIONS: This finding in oesophageal carcinoma contrasts with the situation found in normal and neoplastic stomach epithelium where TFF1 and TFF2 are found co-expressed and TFF3 remains silent. Interestingly, MUC1 is expressed in a significant proportion of SCC. Both in Barett's metaplasia and in SCC the expression of MUC5AC mirrors the TFF1 synthesis in intensity and spatial distribution.

Adult↗
PubMed1999

The differentiation of true adenomas from colitis-associated dysplasia in ulcerative colitis: a comparative immunohistochemical study.

Adenomas in areas involved by ulcerative colitis (UCA) are difficult to identify because of their morphological similarity to ulcerative colitis-associated dysplasia (UCD) and have an uncertain biology. Recently, a set of morphopathologic criteria were published for the diagnosis of UCA versus UCD. As a first step to analyze these criteria, we studied p53 and bcl-2 expression in groups of UCA and UCD along with a sporadic adenoma control group. Ninety lesions from UC areas (62 patients) were examined, including 24 UCA without high-grade dysplasia (HGD) and 66 UCD consisting of 43 polypoid and 23 flat dysplastic lesions (29 with HGD). Immunohistochemical p53 and bcl-2 expression were evaluated semiquantitatively. P53-positive cases were significantly less frequent in the UCA (4%) versus the UCD group (30%, P = .01) and the polypoid UCD subgroup (35%, P = .005). Moderate or strong bcl-2 expression was significantly more frequent in the UCA than in the UCD group (96% v 70%, P = .01) and in the UCA versus both polypoid and flat UCD subgroups. Comparison of UCA with low-grade dysplastic polypoid UCD cases alone showed a difference just below significance for p53 (P = .07). p53 and bcl-2 expression rates were very similar in the UCA group and the sporadic adenoma (n = 25) control group. These results show that UCA has phenotypic features more similar to sporadic adenomas than UCD and supports the concept that adenomas in UC have a biology different from UC-associated dysplasia.

Adenoma↗
PubMed1999

Short Barrett: prevalence and risk factors.

BACKGROUND: The incidence of adenocarcinoma at the gastro-oesophageal junction is on the increase. These carcinomas are usually diagnosed too late and thus have a poor prognosis. Only early diagnosis can improve the situation. Classical Barrett oesophagus (length, >3 cm) is a known precancerous condition. There is also specialized columnar epithelium (SCE) in the grossly unremarkable gastro-oesophageal transitional zone (short Barrett). METHODS: To determine the frequency of SCE, 370 patients were investigated by gastroscopy (OGD) consecutively between September 1995 and February 1996. RESULTS: Classical Barrett oesophagus was found to have an incidence of 4.6%. In contrast, microscopic evidence of SCE was observed in 13.6% of the cases. Patients with short Barrett presented with reflux symptoms (odds ratio (OR), 4.7), irregular zona serrata ('tongues') in the cardia (OR, 2.8), and reflux oesophagitis significantly more frequently. Patients with reflux symptoms and concomitant 'tongues', however, had an OR of 13.16. Careful history-taking, together with a subtle histologic work-up of the gastro-oesophageal transitional zone can improve the rate of detecting patients with short Barrett. CONCLUSION: Patients with reflux symptoms and irregular zona serrata should be selectively biopsied at the gastro-oesophageal junction, even when the latter presents a grossly normal appearance, with the aim of detecting patients at risk of developing a Barrett carcinoma.

Adenocarcinoma↗
PubMed1998

[Short-term triple therapy with pantoprazole, amoxicillin and metronidazole in Helicobacter pylori infection].

BACKGROUND: The present study was conducted to investigate the efficacy and tolerability of a 7-day treatment with pantoprazole, amoxicillin and metronidazole for the eradication of Helicobacter pylori (H. pylori) infection. PATIENTS AND METHODS: Fifty patients (26 male, 24 female, age 18 to 86, mean 54 years) with an active duodenal (n = 25) or gastric ulcer (n = 25) were recruited into the study, 48 patients being H. pylori positive at the study start. Patients were treated with pantoprazole (40 mg bid), amoxicillin (1 g bid) and metronidazole (500 mg bid) for 7 days and for another 21 days with pantoprazole (40 mg/od). Four weeks after the end of study medications the patients were re-examined endoscopically and their H. pylori status was re-assessed using urease test, histology and 13C-urea-breath test. RESULTS: In 39 of 48 intention to treat patients, H. pylori infection was cured, according to 81% (95%-CI = 67 to 91%). In the per protocol population in 35 of 41 patients H. pylori was eradicated, which results in an eradication rate of 85% (95%-CI = 71 to 94%). Ulcer healing was endoscopically confirmed in 45 of 48 patients (94%; 95%-CI = 83 to 99%) after 8 weeks. Six of 50 patients (12%) reported mild to moderate probable side-effects of the study medication. Cure of the infection was associated with a distinct reduction of the gastritis grade and activity. CONCLUSION: A 7-day triple therapy using pantoprazole, amoxicillin and metronidazole is an effective and cost-effective alternative to regimens including clarithromycin for the treatment of H. pylori infection.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1998

Adenocarcinoma in an ileal pouch after prior proctocolectomy for carcinoma in a patient with ulcerative pancolitis.

We report the first known case of pouch carcinoma in a 35-year-old female patient following proctocolectomy for adenocarcinoma in ulcerative pancolitis with backwash ileitis. Pouch cancer was diagnosed 2 years after the pelvic pouch procedure, illustrating that there might be a risk of pouch cancer in such patients. Adenocarcinoma arising in an ileoanal reservoir is rare. Two other cases have been reported: both patients concerned were believed to have developed cancer in small areas of residual remaining rectal mucosa.

Adenocarcinoma↗
PubMed1998

Do active site conformations of small ligands correspond to low free-energy solution structures?

We compare the low free energy structures of ten small, polar ligands in solution to their conformations in their respective receptor active sites. The solution conformations are generated by a systematic search and the free energies of representative structures are computed with a continuum solvation model. Based on the values of torsion angles, we find little similarity between low energy solution structures of small ligands and their active site conformations. However, in nine out of ten cases, the positions of 'anchor points' (key atoms responsible for tight binding) in the lowest energy solution structures are very similar to the positions of these atoms in the active site conformations. A metric that more closely captures the essentials of binding supports the basic premise underlying pharmacophore mapping, namely that active site conformations of small flexible ligands correspond to their low energy structures in solution. This work supports the efforts of building pharmacophore models based on the information present in solution structures of small isolated ligands.

Binding Sites↗
PubMed1997

Dramatic increase of alpha-hydroxyaldehydes derived from plasmalogens in the aged human brain.

Plasmalogens-substantial compounds of brain tissue--suffer degradation either by hydrolysis under production of aldehydes or by oxidation with lipid peroxylradicals by generation of plasmalogen epoxides. The latter react by addition of pentafluorobenzylhydroxylamine HCl (PFBHA HCL) under hydrolysis to alpha-hydroxyaldehydes which are immediately transformed to pentafluorobenzyloximes (PFBO). Likewise, free aldehydes are transformed to PFBO-derivatives. PFBO-derivatives of free aldehydes and PFBO-derivatives of alpha-hydroxyaldehydes were extracted and after trimethylsilylation quantified by GC/FID and by GC/MSD. The remaining aqueous phase, containing plasmalogens besides other lipids, was hydrolyzed by treatment with acid. The hydrolysis products of plasmalogens, long chain aldehydes, react with PFBHA HCl to produce PFBO-derivatives. These were also quantified by GC/FID. This method allows the quantification of plasmalogens, free aldehydes and plasmalogenepoxides in human brain samples to study changes in the relation of these compounds with increasing age. While the ratio of plasmalogens in respect to derived aldehydes seems to remain constant during life time, the quotient of plasmalogenepoxides to plasmalogens increases with age, indicating that lipid peroxidation processes are involved in the damage of plasmalogens in the brain of aged individuals, starting at an age of about 70 years.

Adolescent↗