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Biomedical subjects

G Wallner

Publications and source records attributed to G Wallner.

At least 19 recordsLinked to original sources

Esomeprazole 20 mg vs. pantoprazole 20 mg for maintenance therapy of healed erosive oesophagitis: results from the EXPO study.

BACKGROUND: Following initial healing of erosive oesophagitis, most patients require maintenance therapy to prevent relapse. AIM: To compare endoscopic and symptomatic remission rates over 6 months' maintenance therapy with esomeprazole or pantoprazole (both 20 mg once daily) in patients with healed erosive oesophagitis. METHODS: Patients with symptoms of gastro-oesophageal reflux disease and endoscopically confirmed erosive oesophagitis at baseline were randomized to receive esomeprazole 40 mg or pantoprazole 40 mg for up to 8 weeks. Patients with healed erosive oesophagitis and free of moderate/severe heartburn and acid regurgitation at 4 weeks or, if necessary, 8 weeks entered the 6-month maintenance therapy phase of the study. RESULTS: A total of 2766 patients (63% men; mean age 50 years) received esomeprazole 20 mg (n = 1377) or pantoprazole 20 mg (n = 1389) and comprised the intention-to-treat population. Following 6 months of treatment, the proportion of patients in endoscopic and symptomatic remission was significantly greater for those receiving esomeprazole 20 mg (87.0%) than pantoprazole 20 mg (74.9%, log-rank test P < 0.0001). Esomeprazole 20 mg produced a higher proportion of patients free of moderate to severe gastro-oesophageal reflux disease symptoms and fewer discontinuations because of symptoms than pantoprazole 20 mg (92.2% vs. 88.5%, P < 0.001). CONCLUSIONS: Esomeprazole 20 mg is more effective than pantoprazole 20 mg for maintenance therapy following initial healing of erosive oesophagitis and relief of gastro-oesophageal reflux disease symptoms.

2-Pyridinylmethylsulfinylbenzimidazoles↗

A randomized comparative study of esomeprazole 40 mg versus pantoprazole 40 mg for healing erosive oesophagitis: the EXPO study.

AIM: To assess the efficacy of the 8-week therapy with esomeprazole 40 mg vs. pantoprazole 40 mg for healing erosive oesophagitis (EE) as part of a management study. METHODS: Patients had a history of gastro-oesophageal reflux disease symptoms (> or =6 months) and had suffered heartburn on at least 4 of the 7 days preceding enrollment. Endoscopies were performed to grade EE severity using the Los Angeles (LA) classification system at baseline, 4 and 8 weeks (if unhealed at 4 weeks). Heartburn severity was recorded by patients on diary cards. The primary end point was healing of EE by week 8 of treatment. RESULTS: Of 3170 patients randomized, the intent-to-treat population consisted of 3151 patients (63% male, mean age: 50.6 years, 27% Helicobacter pylori-positive). Esomeprazole 40 mg healed a significantly greater proportion of EE patients than pantoprazole 40 mg at both 4 weeks (life table estimates: esomeprazole 81%, pantoprazole 75%, P < 0.001) and 8 weeks (life table estimates: esomeprazole 96%, pantoprazole 92%, P < 0.001). The median time to reach sustained heartburn resolution was 6 days in patients receiving esomeprazole and 8 days with pantoprazole (P < 0.001). CONCLUSION: Esomeprazole 40 mg is more effective than pantoprazole 40 mg for healing EE and providing resolution of associated heartburn.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Restorative impact of rabeprazole on gastric mucus and mucin production impairment during naproxen administration: its potential clinical significance.

Rabeprazole augments gastric mucus and mucin production in humans. However, its potential restorative impact on gastric mucus and mucin production impairment, resulting from administration of naproxen, remained to be explored. Therefore, we measured the content of mucus and mucin in gastric juice (GJ) before and after administration of naproxen with rabeprazole or placebo. The study was approved by HSC at KUMC and conducted in 21 asymptomatic, H. pylori-negative volunteers in a double-blind, placebo-controlled, crossover design. The content of gastric mucus in GJ, after exhaustive dialysis and complete lyophilization, was assessed gravimetrically, whereas the content of mucin was measured after its purification with equilibrium density-gradient ultracentrifugation in CsC1. Gastric mucus secretion during administration of naproxen with placebo declined significantly both in basal (by 44%; P < 0.001) and in pentagastrin-stimulated (by 35%; P < 0.001) conditions. Coadministration of rabeprazole significantly restored the naproxen-induced impairment in mucus production in basal conditions (by 47%; P < 0.01) and by 22% during stimulation with pentagastrin. Gastric mucin secretion during naproxen/placebo administration also declined significantly in both basal (by 39%; P < 0.01) and stimulated (by 49%; P = 0.003) conditions. Rabeprazole also significantly restored the naproxen-induced decline of gastric mucin output during pentagastrin-stimulated conditions (by 67%; P = 0.003) and by 40% in basal conditions (P = 0.05). The restorative capacity of rabeprazole on the quantitative impairment of gastric mucus and mucin during administration of naproxen may translate into a clinical benefit of protection of the upper alimentary tract from NSAID-related mucosal injury.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Selected biochemical parameters and ultrastructural picture of pancreas due to Ulinastatin treatment of experimental acute pancreatitis.

Urinary trypsin inhibitor (UTI, Ulinastatin) is a protease inhibitor that has not been yet used in Europe in any experimental trial of severe acute pancreatitis. We have combined the experimental model of severe, hemorrhagic form of acute pancreatitis, and pharmacological treatment with a protease inhibitor. Male Wistar rats were divided into four experimental groups: healthy controls, operated, operated with experimentally induced acute pancreatitis, and animals with acute pancreatitis--treated with UTI preparations. Subjects in the last group were administered UTI intraperitoneally 1 h after pancreatitis induction in an average standard dose of 3000 units/animal. Additionally, four subgroups were created in this treated group, based on the UTI administration time--number of standard doses received: 2 h - 1 standard dose, 6 h - 5 standard doses, 12 h - 11 doses, 24 and 48 h - 15 doses. Statistically significant differences in the serum amylase and lipase activity between the UTI-treated and non-treated subjects were found. In the group of non-treated animals, there a profound destruction of cellular organelles was observed with a total degradation of nuceli, endoplasmatic reticulum and zymogen granules. However, in the UTI-treated subjects, pathological processes proceeded with the significantly slower pace and in much smaller quantities.

Amylases↗

Assessment of prognostic significance of cytoplasmic survivin expression in advanced oesophageal cancer.

Survivin is a member of the family of proteins, which inhibit apoptosis (inhibitor of apoptosis proteins - IAP). Expression of survivin was found in colorectal cancer, neuroblastoma, bladder cancer, non-small cell lung cancer, and breast cancer. There is some recent data indicating the correlation of poor prognosis and worse response to chemotherapy in patients with oesophageal squamous cell carcinoma (OSCC) expressing survivin. The aim of the present study was to assess survivin expression in cancerous tissue of patients with advanced OSCC and to test the potential correlation between survivin expression and clinicopathological data. Forty two patients (mean age 58.36+/-8.97 yrs), who were oesophagectomised due to squamous cell carcinoma of the thoracic oesophagus between 1998 and 2000, were retrospectively analysed. Cytoplasmic survivin expression, examined immunohistochemically, was found in 35 (83.33%) cases. No statistically significant correlation between survivin expression in the tumour and patients' gender, TNM stage, or vascular involvement was noted. The mean survival of patients with cytoplasmic survivin expression (17.81+/-5.51 months) was not statistically different to those with negative survivin staining (16+/-6.28 months) as assessed by Mantel-Cox test (p=0.49). Univariate regression analysis revealed UICC staging as the only predictor of survival in the analysed group (p<0.05). These results indicate that the cytoplasmic survivin expression does not seem to be the prognostic factor in advanced cases of OSCC.

Adult↗

Biochemical and immunohistochemical study on physiological activity and distribution of hepatic cathepsin D.

Cathepsin D (EC 3.4.23.5) is a lysosomal endopeptidase physiologically present at very low concentration in different tissues. The aim of the study was to estimate the physiological activity and distribution of cathepsin D in the liver. Four groups of ten-week-old male Wistar rats were raised without xenobiotics and sacrificed on day 4, 42, 47 and 84 of the experiment, and their livers were taken for immunohistochemical and biochemical investigation. Immunostaining for cathepsin D was evaluated by light microscope. Activity of the free and bound fractions of hepatic cathepsin D was measured spectrophotometrically. Immunohistochemical staining for cathepsin D was positive in Browicz-Kupffer cells in some but not in all rat liver specimens of each experimental group. The staining pattern was cytoplasmic and granular. Occasionally the positive stained endothelial cells were also found. No activity of cathepsin D in hepatocytes was detected. The positive immunostaining was found in livers with high enzyme activity in the biochemical investigation. No significant differences in activity of the free and bound fractions of cathepsin D among the different age groups were noted. However, the higher, age-dependent activity (p>0.05) of the free fraction was observed in the youngest and the two-middle groups of rats that were sacrificed on day 42 and 47 than in the oldest one. The bound fraction did not reveal such changes. It could be concluded that there were no differences in the activity of hepatic free and bound fractions of cathepsin D in male Wistar rats of various reproductive age. The rat Browicz-Kupffer cells revealed the highest activity of cathepsin D.

Animals↗

Diethylnitrosamine may induce esophageal dysplasia after local intramural administration.

PURPOSE: To assess the possibility of promoting esophageal squamous cell carcinoma after direct administration of diethylnitrosamine (DEN) into the wall of the esophagus. MATERIAL AND METHODS: Adult male Wistar rats weighing 250-300 g were used in the studies. Via laparotomy, solution of DEN (at the volume of 0.1 ml) was injected directly into the esophageal wall. Animals were divided into 3 groups: CONTROL group--injected with saline, DEN1 group--injected with DEN 100 mg, DEN2 group--injected twice with DEN at the dose of 100 mg with 7 days interval (total dose of 200 mg). RESULTS: Microscopic evaluation after 180 days revealed signs of esophagitis in 20% and 30% subjects in DEN1 and DEN2 group respectively. In 30% of animals from DEN1 and 50% animals from DEN2 group, low-grade dysplasia was recognized. The difference between DEN2 and control animals was statistically significant with p < 0.03. Neither high-grade dysplasia nor invasive carcinoma were found in both experimental groups. None of the liver specimens showed the evidence of pathology. CONCLUSIONS: These initial results may indicate the possibility of development of premalignant lesions after local administration of carcinogen into esophageal wall. Observed changes were limited exclusively to esophagus which became the "target organ" in this model.

Alkylating Agents↗

Reinvestigation of airborne 210Pb, 137Cs and 207Bi in Vienna (Austria) after atmospheric nuclear weapons tests.

Reconstruction of atmospheric 210Pb and 137Cs activity concentrations occurring in Vienna immediately after the atmospheric nuclear weapons tests shall answer the question, whether artificial 210Pb has been produced by fusion devices using lead materials. If so, 207Bi also can be expected. In 1962, weekly average values for 210Pb were between 0.08 +/- 0.02 and 1.31 +/- 0.30 mBq/m2, 137Cs amounts up to 5.1 +/- 0.6 mBq/m3. 207Bi remains below the detection limit, viz. < 0.5 mBq/m3. Bimonthly averages for the periods 1962-1964 and 1974-1975 show 137Cs activity concentrations with typical springtime maxima occurring together with low 210Pb values and 207Bi < 0.02 mBq/m3. Annual averages of 210Pb are varying between 0.27 and 0.53 mBq/m3, independent of whether atmospheric tests have been performed or not. Comparison of the activity ratios 207Bi/210Pb, 207Bi/137Cs and 210Pb/137Cs with published data, leads to the conclusion that no evidence exists for a significant production of 210Pb by nuclear explosions, neither after the Soviet tests in 1961-1962 nor after the Chinese tests in 1973-1976.

Air Pollutants, Radioactive↗

Visualisation of diverticula of the upper part of the alimentary tract; comparison of roentgenologic and endoscopic techniques.

Diverticula of the upper part of the alimentary tract, irrespective of their etiology, are frequently observed benign changes of the pharynx, oesophagus, stomach and duodenum. In the present work, patients of the II General Surgery Department of the Medical University of Lublin, with radiologically or endoscopically proved diverticula of the upper part of the alimentary tract, were examined. The presence of diverticula of such localisation was an indication for supplementary endoscopic or radiological examination. The localisation, size, diameter of the opening, mucosal relief of diverticula and its contiguity were checked and analysed. Our data suggest that both medical procedures are complementary to each other. All previously observed changes in diverticula of the thoracic part of the oesophagus and the infradiaphragm part of the alimentary tract were fully proved. The radiological examination gave a better view of Zenker's diverticulum, especially in short and obese patients. Sampling and better visualisation of the diverticula opening testify to the unquestionable superiority of endoscopy. However, precise evaluation by radiological process fully completes the diagnostic protocol. Both diagnostic procedures are usually supplemented by manometric examination of the oesophagus and superior and inferior oesophageal sphincters. This enables the accurate diverticula etiology to be stated.

Adult↗

Vascular endothelial growth factor and basic fibroblast growth factor in patients with squamous cell oesophageal cancer.

It is suggested that vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) play an important role in tumor-induced angiogenesis. The purpose of this study was to estimate the correlation between VEGF and bFGF levels and tumor pathological status according to pTNM classification in patients with squamous cell oesophageal cancer. A group of 25 healthy controls and 32 consecutive patients with oesophageal cancer were included in this study. Serum VEGF and bFGF levels were determined by enzyme-linked immunosorbent assay (Quantikine R&D Systems). Serum VEGF and bFGF levels were significantly elevated in the patient groups (VEGF: 146.0 pg/ml, 79.0-386.3 pg/ml vs. 38.0 pg/ml, 6.5-135.1 pg/ml, p<0.005, and bFGF: 5.2 pg/ml, 1.2-10.6 pg/ml vs. 2.06 pg/ml, 0.07-4.0 pg/ml, p<0.02 Fisher test). The highest correlation between serum VEGF and bFGF levels were found in patients with advanced cancers, especially with: T4, N1, and M1 factors. The VEGF and bFGF levels were significantly higher in patients with pT4 (p<0.01). Patients with N1 lymph node invasion, compared with N0 factor, have higher levels of angiogenetic factors (p<0.04). Also in patients with advanced cancers with liver metastases the serum levels VEGF and bFGF were significantly higher (M1 vs. M0, VEGF p<0.001 and bFGF p<0.05). Consecutive monitoring of VEGF and bFGF serum levels may be a useful prognostic marker for patients with squamous cell oesophageal cancer.

Adult↗

Circulating anti-p53 antibodies in esophageal cancer patients.

Circulating anti-p53 protein antibodies (p53-Abs) have been detected in some cancer patients. The aim of the study was to determine the presence of circulating anti-p53 protein antibodies and their clinical significance in patients with esophageal carcinoma. Serum specimens from 75 consecutive patients with squamous cell carcinomas and 10 healthy subjects were studied. Enzyme linked immunosorbent assay (ELISA--Pharma Cell) was used to detect p53-Abs. At the time of diagnosis 20 (26.6%) of 75 analyzed patients had positive result in the p53-Abs test, but not any of the healthy subjects. The positive rate was 25% (1/4) cases in stage I, 41% (10/24) cases in stage IIA, 0% (0/8) cases in stage IIB, 28% (8/28) cases in stage III and 9% (1/11) cases in stage IV. In respect of tumour differentiation, cases graded as G1, G2 and G3 were positive in 28.5% (4/14), 25.9% (7/27) and 26.4% (9/34), respectively. There was no correlation between presence of p53-Abs and stage, rumour differentiation, lymph nodes metastases, tumour size, patient age and sex. In conclusion, the results of the present study indicate that serum p53-Abs did not correlate with cliniocopathologic feature of esophageal carcinoma.

Adult↗

Bleeding from gastro-intestinal tract caused by benign tumours of the small bowel.

The paper discusses three cases of mass bleeding from the upper section of gastrointestinal tract caused by benign tumours od the small bowel. The technique of the intraoperative endoscopic examination of gastrointestinal tract has been described. The authors stress the usefulness of this technique in the case when the source of bleeding is difficult to localise.

Aged↗

Proliferating nuclear antigen (PCNA) as a prognostic factor of squamous cell carcinoma of the oesophagus.

Proliferating nuclear antigen (PCNA) plays an important role both in the process of replication and repair of DNA. The aim of the carried out investigations was to find out if there was any correlation between the depth of malignant infiltration, invasion of lymph nodes, presence of metastases in extra-regional lymph nodes, the length of patients' survival, and the value of PCNA proliferating index analysed in biopsy specimens before the operation, taken from 60 patients with oesophageal squamous cell carcinoma. In the groups with advanced squamous cell carcinoma of the oesophagus the following statistic correlation was found between PCNA proliferating index and: invasion of lymph nodes--p < 0.04; degree of carcinoma progression--p < 0.01; and blood vessels infiltration--p < 0.001. The survival of patients with carcinomas of high (> 50%) and low (< 50%) PCNA index did not differ significantly. It results from the above investigations that high values of PCNA index may indicate the presence of metastases in lymphatic nodes and the degree of progression of oesophageal carcinoma.

Biomarkers, Tumor↗

p35 protein as a prognostic factor of squamous cell carcinoma of the oesophagus.

Communications show that in squamous cell carcinoma of the oesophagus one can often observe overexpression of p53 protein. Wild type p53 protein suppresses cells' growth, and mutated p53 acts as onkogene. Gene p53 mutations usually lead to stabilization and accumulation of p53 protein, and, as a result they become detectable by immunochemical methods. Overexpression of p53 has been observed in 28 (46.7%) out of 60 collected specimens. It has no connection with sex, age, histological differentiation, category (pT) of tumour, infiltration (pN) of lymph nodes and extent of metastases (pMlym+). p53 protein expression has no correlation with survival predictability.

Bacterial Outer Membrane Proteins↗

Range of serum bile acid concentrations in neonates, infants, older children, and in adults.

BACKGROUND: Serum total bile acids (tBA) determination is a non-invasive, simple and very sensitive diagnostic test in evaluation of liver disorders. However, its usefulness is limited by lack of the data on normal value range of serum tBA concentrations in children, especially neonates and infants. The aim of the study was evaluation of serum tBA concentrations according to the age and gender of children, and their comparison with the values found in adults. MATERIAL AND METHODS: Serum tBA concentration measurements were performed using enzymatic-colorimetric test Enzabile (Nycomed Pharma, N) in blood samples collected 3 hours after last meal in newborns and infants, and fasting in children over 1 year of age. The studied children were healthy, without any abnormalities on physical examination. In adults, the measurements were performed in fasting patients with inguinal hernia without any other concomitant diseases scheduled for elective surgery. Two hundred seventy eight children (145 females and 133 males) of ages ranging from the 1st day of life to 16 years, and 63 adults (39 males and 24 females) were investigated. RESULTS: Serum tBA concentrations in newborns (mean (SD: 19.6 +/- 5.2 mumol/l) were significantly higher than the values found in adults (5.1 +/- 2.9 mumol/l). Serum tBA concentrations increased gradually after delivery, with peak values occurring at the age of 1 month (22.2 +/- 5.1 mumol/l), which then gradually declined to nearly adult levels. No gender-related differences were observed in serum tBA concentrations in children. CONCLUSIONS: It is mandatory to refer to the age of the patient, interpreting values of serum tBA concentration in children.

Adolescent↗

Interleukin-2 gene-modified allogeneic melanoma cell vaccines can induce cross-protection against syngeneic tumors in mice.

Vaccination using well-characterized allogeneic tumor cell lines expressing standardized doses of immunostimulatory cytokines is an attractive alternative for autologous gene-transfected tumor cell vaccines. In the present study, we show that vaccination with irradiated allogeneic K1 735 (H-2k) or B16F10 (H-2b) melanoma cells induces a moderate degree of cross-protection against the M-3 melanoma (H-2d) in DBA/2 mice. Cross-protection against the syngeneic tumor was markedly improved when the allogeneic vaccines were transfected with the interleukin-2 (IL-2) gene. The IL-2 gene-modified allogeneic vaccines were effective for prophylactic vaccination against subsequent tumor challenge and for therapeutic vaccination against pre-existing tumor deposits, with efficacies that were comparable with that of the IL-2 gene-modified syngeneic vaccines. Cross-protection correlated with the cytotoxic activity of splenocytes against M-3 targets. Allogeneic vaccination was not effective in another model, against the B16F10 melanoma in C57BL/6 mice, irrespective of genetic modification with the IL-2 or granulocyte-macrophage colony-stimulating factor genes.

Animals↗

Esophageal motility impairment--the cause or consequence of gastroesophageal reflux disease?

There are at least three, well-known, different groups of motor activity disturbances of the upper part of alimentary tract which can induce the development of gastroesophageal reflux disease (GERD) and enlarge the risk of excessive exposure of the esophageal mucous membrane on gastric juice and/or biliary contents. Most important is insufficiency of the lower esophageal sphincter (LES), which causes gastroesophageal reflux at 50-60% of patients suffering from GERD. Other reasons include impairment of stomach function (increase of intra-gastric pressure, late emptying and/or hypersecretion), and impairment of esophageal clearance. The question: does motility impairment of the esophagus occur primary or secondary to the gastroesophageal reflux, is still not enough clarified. Motor activity of the esophagus before and after the antireflux operation was prospectively assessed in 57 patients. Motility of the esophagus was determined by estimation: the efficacy of LES, general motor activity of the body of the esophagus and motor activity of the body during the reflux episodes, basing on 24-h manometry. Comparison of general pre- and postoperative data revealed significantly positive influence of Nissen-Rossetti fundoplication on improvement of motor activity of the esophagus, but the results differed in relation to the height of the measurements. Moreover comparison of the data during gastroesophageal reflux episodes revealed negative changes of the manometric parameters in the upper and middle esophagus. We conclude that post-operative improvement of esophageal motility confirms the secondary dysfunction in the peristalsis, connected with pathological reflux. However, lack of the complete normalization in motor activity after operation suggests that disorder may partially occur as primary impairment of motor activity or as the secondary dysfunction, which is fixed in the course of GERD.

Esophageal Motility Disorders↗

Phylogeny and in situ identification of a morphologically conspicuous bacterium, Candidatus Magnospira bakii, present at very low frequency in activated sludge.

A morphologically conspicuous bacterium that constituted a very small fraction (< 0.01%) of the total microbial community of activated sludge was enriched and analysed phylogenetically by a combination of cultivation-independent molecular and physical methods. The large, corkscrew-shaped, filamentous bacteria were first detected in municipal activated sludge by light microscopy owing to their unusual rotating gliding motility. Various attempts at microbiological enrichment and pure culture isolation with traditional techniques failed, as did attempts to retrieve the morphotype of interest by micromanipulation. In situ hybridization with the group-specific, rRNA-targeted oligonucleotide probe CF319a indicated a phylogenetic affiliation to the Cytophaga-Flexibacter group of the Cytophaga-Flavobacterium-Bacteroides phylum. Based on strong morphological resemblance to members of the genus Saprospira, additional 16S rRNA-targeted oligonucleotides with more narrow specificity were designed and evaluated for in situ hybridization to the morphotype of interest. Flow cytometric cell sorting based on the fluorescence conferred by probe SGR1425 and forward scatter enabled a physical enrichment of the helical coiled cells. Subsequent polymerase chain reaction (PCR) amplification of 16S rDNA fragments from whole fixed sorted cells with a primer pair based on probes CF319a and SGR1425 resulted in the retrieval of 12 almost identical partial 16S rDNA fragments with sequence similarities among each other of more than 99.2%. In situ hybridizations proved that the sequences that showed the highest similarity (88.4%) to the 16S rRNA of Saprospira grandis were indeed retrieved from the corkscrew-shaped filaments. The bacterium is likely to be a member of a genus of which no species has been cultured hitherto. It was consequently tentatively named 'Magnospira bakii' and has the taxonomic rank of Candidatus Magnospira bakii, as the ultimate taxonomic placement has to await its cultivation. In this study, it was demonstrated that even bacteria occurring at very low frequencies in highly complex environmental samples can be retrieved selectively without cultivation for further molecular analysis.

Cloning, Molecular↗