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Biomedical subjects

Z Tulassay

Publications and source records attributed to Z Tulassay.

At least 55 records · Page 3Linked to original sources

Increased cell proliferation in chronic Helicobacter pylori positive gastritis and gastric carcinoma--correlation between immuno-histochemistry and Tv image cytometry.

BACKGROUND: [corrected] Epithelial cell proliferation activity has been reported both to be unaltered and increased in Helicobacter pylori (H. pylori) associated chronic gastritis. The proliferation rate decreased following H. pylori eradication, but results are controversial whether this change is dependent on the success of eradication. We compared the cell proliferation activity of H. pylori positive and negative gastric epithelial biopsies in chronic gastritis with and without intestinal metaplasia (IM) and gastric cancer by the expression of proliferation cell nuclear antigen (PCNA) and Tv image cytometry, and assessed the effect of H. pylori eradication on the cell proliferation rate in the gastric epithelium. METHODS: Brush smears and antral biopsies were taken from 70 patients (42 men, 28 women, mean age 58+/-15 y.o.) on routine endoscopy. Patients were divided into four groups according to the histology; normal epithelia (n = 10), chronic gastritis without IM (n = 24), chronic gastritis with IM (n = 20), and gastric carcinoma (n = 16). Thirty-three patients were H. pylori positive, and success of eradication was controlled in 24 cases. Cell proliferation was measured by immunohistochemistry using PCNA labeling index (LI) and by Tv image cytometry evaluating 12 morpho- and densitometric parameters of each nuclei and 6 additional parameters of each smear. RESULTS: PCNA LI, DNA index and S + G2 ratio were all higher in chronic gastritis than in the normal epithelium, and were further increased in carcinoma. The lower PCNA LI observed in chronic gastritis with IM corresponds to the lower S phase ratio determined by Tv image analysis. In H. pylori positive cases, the proliferation activity was 69.3+/-13.05% prior to the eradication and it decreased to 55.8+/-23.31% after the successful eradication therapy. When immunohistochemistry was compared with Tv image cytometry, PCNA LI significantly correlated with the percentage of cells in GL phase (r = -0.415) and S phase (r = 0.385), Integrated Optical Density mean (r = 0.598), density maximum (r'= 0.608), surface (r = 0.670), layers (r = 0.638), diameter minimum (r = 0.619), diameter maximum (r = 0.730) and perimeter (r = 0.501), respectively (p < 0.05). CONCLUSIONS: Epithelial cell turnover is increased in chronic gastritis with or without IM, and in gastric carcinoma. The lower PCNA LI observed in chronic gastritis with IM corresponds to the lower S phase ratio determined by Tv image analysis. Cell proliferation decreases after successful H. pylori eradication. Both methods proved to be reliable for the determination of epithelial cell proliferation.

Adult↗

Determination of H+/K+-ATPase activity in human gastric biopsy specimens.

The aim of our work was to develop a method to determine the the H+/K+-ATPase activity of human gastric biopsy samples. Our method is based on the phosphatase activity and the K+-inducible property of the enzyme. K+-inducible pNPPase activity was determined from homogenated corpus and antrum biopsy samples. H+/K+-ase activity was calculated as the difference between the corpus and antrum K+-inducible pNPPase activities. Quality control measurements were done during 20 successive days from pooled homogenates. The total, between-day and between-run, within-day and within-run coefficients of variations were between 10 and 16%. The healthy mean and reference range of K+-inducible pNPPase activity in the corpus was 95.8 (95% CI: 83.4-108.2 mU/mg protein); in the antrum it was 28.3 (21.6-35.0) mU/mg protein. The calculated H+/K+-ATPase activity was 67.2 (56.9-77.5) mU/mg protein. The measured activities were independent of the age and gender. Summarizing our results we have concluded, that our novel method might be a potential tool to gather data about the functional acid producing capability of human gastric mucosa.

Adolescent↗

Circulating plasma endothelin-1, plasma lipids and complications in Type 1 diabetes mellitus.

UNLABELLED: The damage of endothelial integrity is an important step in the atherogenic process. To evaluate the role of circulating endothelin-1 (ET-1) in Type 1 diabetes mellitus (T1DM), plasma ET-1 levels were evaluated in T1DM patients either with (n=9) or without hyperlipidaemia (n=11), or with (n=9) and without (n=11) late diabetic complications, in non-diabetic hyperlipidaemic patients (n=17) and in healthy volunteers. Groups were matched for age, sex and body mass index. RESULTS: Serum total cholesterol and apolipoprotein B were significantly higher in the diabetic group (p<0.05). Plasma ET-1 level was similar in controls and in non-diabetic hyperlipidaemic subjects (5.77+/-1.74 ng/l vs 4.97+/-1.58 ng/l); however, diabetic hyperlipidaemic patients had a significantly higher plasma ET-1 concentration compared to control subjects (6.67+/-2.44 ng/l vs 4.97+/-1.58 ng/l, p<0.05). Diabetic patients with vascular complications had a significantly higher plasma ET-1 concentration than found in diabetic patients without complications (6.99+/-2.17 ng/l vs 4.74+/-1.27 ng/l, p<0.01) and in controls (6.99+/-2.17 ng/l vs 4.97+/ 1.58 ng/l, p<0.01). Patients with diabetic complications also had a significantly higher apolipoprotein B level compared to healthy controls (0.94+/-0.37 g/l vs 0.66+/-0.12 g/l, p<0.005). CONCLUSION: The susceptibility of T1DM patients to the development of atherosclerosis might be attributed to the relationship between elevated lipid levels and ET-1.

Adolescent↗

[Effective demeclocycline therapy in a patient with over-secretion of antidiuretic hormone following head trauma].

The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is a common cause of hyponatremia. In this study a case of SIADH caused by head trauma is reported, in which severe hyponatraemia, escorted by life-threatening neurological symptoms was observed that could only be managed by parenteral sodium chloride infusions. Severe hyponatraemia was accompanied by elevated urinary sodium excretion, a characteristic sign of SIADH. After introducing the therapy with demeclocycline, a tetracycline type antibiotic that inhibits the renal action of antidiuretic hormone, serum sodium levels began to rise gradually, and the urinary sodium excretion slowly decreased. These observations show the effectiveness of demeclocycline in the treatment of SIADH.

Craniocerebral Trauma↗

The role of cysteine and serine proteases in colorectal carcinoma.

BACKGROUND: Cathepsin B (CATB) and cathepsin L (CATL), which are cysteine proteases, urokinase-(UPA) and tissue-type plasminogen activator (TPA), both serine proteases, and their inhibitor type-1 (PAI-1) are believed to play an important role in colorectal carcinoma (CRC) invasion and metastasis. The objective of this study was to measure CATB, CATL, UPA, TPA, and PAI-1 in the same cancerous tissue (CANCER) and in tissues obtained from a tumor free area (NORMAL) to compare their respective prognostic roles in patients with CRC. METHODS: CANCER and NORMAL samples were obtained from 60 CRC patients undergoing surgery (36 males and 24 females; mean age, 63.8 years [range, 27-85 years]). The antigen concentrations were measured using an enzyme-linked immunoadsorbent assay method. The CANCER tissue also was examined in terms of major histomorphologic parameters such as differentiation, vascular invasion, degree of necrosis, and mucus production. RESULTS: Significantly higher antigen levels were found: 1) in CANCER versus NORMAL (with respect to CATL, UPA, and PAI-1, with significantly lower levels for TPA); 2) in CRC with versus without metastasis (CATB, CATL, and PAI-1); 3) in poorly versus well differentiated CRC (UPA and PAI-1); and 4) in advanced Dukes stages (PAI-1). CATB and CATL significantly correlated with UPA and PAI-1. Finally, CATL (P = 0.0001), UPA (P = 0.006), PAI-1 (P = 0.006), Dukes stage (P = 0.0001), presence of metastases (P = 0.003), and vascular invasion (P = 0.03) had a significant prognostic impact. CONCLUSIONS: The simultaneous up-regulation of cysteine and serine proteases in CRC confirms their role in colorectal tumor biology and particularly in the process of invasion and metastasis. Together with Dukes stage, determinations of CATL, UPA, and PAI-1 have a major prognostic impact in patients with CRC.

Adult↗

[The role of cathepsins and the plasminogen activator/inhibitor system in colorectal cancer].

Cysteine proteases [Cathepsin B and L (CATB, CATL)] and the serine protease urokinase type plasminogen activator (UPA) with its inhibitor type-1 (PAI-1) are thought to play an important part in colorectal cancer invasion and metastasis. To our knowledge, however, cathepsins and plasminogen activator/inhibitor system have not been evaluated in the same study. The authors using the ELISA method, determined the protease antigen concentrations in colorectal cancer tissue and in normal tissue distant from tumour, in 35 patients with colorectal cancer. They also evaluated the relationship that these proteases may have with the major histomorphological parameters and tumour staging. Significantly higher antigen levels were found: 1. in cancerous tissue vs. tumour free tissue (CATB, CATL, UPA, PAI-1); in colorectal cancer with vs. without metastasis (CATB, CATL, UPA, PAI-1); 3. in poorly vs. well differentiated tumours (CATB, UPA, PAI-1); 4. in advanced Dukes' stages (CATB, UPA, PAI-1). The simultaneous activation of cathepsins and plasminogen activator/inhibitor system in colorectal cancer confirms their role in colorectal tumor biology and particularly in the process of invasion and metastasis. Our results suggest the possible prognostic impact of these proteases in colorectal cancer.

Cathepsins↗

[Ret-protooncogene mutation, verified by molecular genetic methods, in a Hungarian MEN Type 2a family].

Multiple endocrine neoplasia Type 2 (MEN2) is a hereditary tumour syndrome characterized by the association of medullary thyroid cancer, phaeochromocytoma and hyperparathyroidism. It is inherited as an autosomal dominant trait. During the past few years the cloning of the gene responsible for the syndrome, the ret protooncogene, made the molecular genetic diagnosis of the disease possible. In this study we demonstrate the results of the MEN2 mutation analysis performed in three members of a Hungarian MEN2A family. The mutation analysis was carried out according to the method of Dr. W. Hoppner's Laboratory (Hamburg) that is the main centre for MEN2 genetic diagnosis in Germany. Two Members of the family are affected, one suffered from both medullary thyroid cancer and phaeochromocytoma, the other (the first patient's daughter) had only medullary thyroid cancer. We found a ret exon 11 codon 634 mutation, that resulted in the change of TGC to TAC, a cysteine-tyrosine amino acid exchange. We found no mutation in the youngest member of the family. This result is of great clinical significance, because the carrier status of this individual can thus be excluded and, therefore, there is no need for prophylactic thyroidectomy and further clinical screening tests. As molecular genetic diagnosis of MEN2 becomes possible, the uncertain clinical examinations used for MEN2 diagnosis seems to be less important.

Adult↗

IL1B gene polymorphisms influence the course and severity of inflammatory bowel disease.

There is evidence of a disbalance in the inflammatory regulation of patients with inflammatory bowel diseases (IBD). Interleukin-1 beta plays an important role in the pro-inflammatory response. Our aim was to study the influence which IL1B gene polymorphisms may have on the severity and course of these diseases. Ninety-six patients with ulcerative colitis (UC), 98 patients with Crohn's disease (CD), and 132 ethnically matched healty individuals (HC) were typed for the polymorphic sites in the promoter region (position -511) and in exon 5 (position +3953) of the IL1B gene, using polymerase chain reaction (PCR)-based methods. In the CD group a significant association (P = 0.009) was found in this pair of genes. Homozygotes for allele 1 at position +3953 were more often present (69% vs 31%) in the subgroup of patients carrying at least one copy of allele 2 at position -511. This association was significant in patients with non-perforating disease (P = 0.002), but was not present in patients with perforating-fistulizing disease. The distribution of both allelic pairs in the non-fistulizing group proved to be significantly different from HC (P < 0.05), UC (P < 0.03), and the fistulizing group (P < 0.05). There was a similar association in non-operated patients (P = 0.024), whereas no such association was found in surgically treated patients. Among carriers of allele 2 at position -511, UC patients with more severe bleeding symptoms (P = 0.006) were less frequently found. These results suggest that IL1B gene polymorphisms participate in determining the course and severity of inflammatory bowel disease and contribute to explain the heterogeneity of these diseases.

Adolescent↗

Significant differences in the interleukin-1beta and interleukin-1 receptor antagonist gene polymorphisms in a Hungarian population with inflammatory bowel disease.

BACKGROUND: There is growing evidence of the importance of genetic predisposition and the activation of the mucosal immune system in the pathogenesis of inflammatory bowel disease. Thus, genes involved in the regulation of inflammation are receiving increased attention. We have studied whether Crohn's disease (CD) or ulcerative colitis (UC) is associated with certain allelic combinations of IL1B/IL1RA gene polymorphisms in a different European population than the ones studied so far. METHODS: Ninety-six patients with UC, 97 with CD, and 132 healthy individuals (HC) were typed for the polymorphic regions in exon 5 of the IL1B gene and in intron 2 of the IL1RA gene, using polymerase chain reaction-based methods. RESULTS: In CD homozygotes for allele 1 in IL1B gene polymorphism were more often present (72% versus 28%; P = 0.01) in the subgroup of patients carrying at least one copy of allele 2 in IL1RA gene polymorphism. This association was not found in HC (HC versus CD; P = 0.03) or UC. However, in UC patients with pancolitis a similar trend was observed (75% versus 25%). Several genotype combinations characterized by the presence of allele 2 of the IL1RA gene polymorphism were more common in CD (P = 0.001) and UC (P = 0.049) than in HC. CONCLUSIONS: Our data support the concept that CD and severe UC have a genetic disequilibrium in the distribution of IL1B and IL1RA gene polymorphisms. These findings together with functional studies will contribute to the understanding of the pathogenesis of the chronicity of inflammation in these diseases.

Adolescent↗

Automated prozone effect detection in ferritin homogeneous immunoassays using neural network classifiers.

The application of turbidimetric homogeneous immunoassays made the determination of several plasma components widely available. The sensitivity and accuracy of these assays are appropriate enough for routine laboratory use; however, in the case of many pathologically high concentration samples, prozone effect (high dose hook effect) can be observed, that leads to false-negative determination. Up to the present there are no cost-effective algorithms available for the safe detection of the prozone effect. Pathological serum ferritin values can be elevated up to 5000 ng/ml, while the measuring range covers only the 0-440 ng/ml range by a commercial assay. The determination of samples with ferritin concentration higher than 1500 ng/ml results in false-negative values because of the overlapping measuring range and prozone effect range. The prozone effect can be recognised by analysis of reaction kinetics after measurement. We have developed a neural network classifier system to analyse reaction kinetics of the measurements and check the prozone effect. One thousand five hundred determinations and 77 patient samples were used for neural network training and test. Using the trained neural networks, false-negative results can be filtered immediately after the determination, without re-run; thus, the sensitivity of plasma ferritin determination may become reliable enough, even in the case of high concentration samples. Applying this new technology, false-negative serum ferritin determinations can be avoided, thus even a relatively high hook effect rate (5-12% in different patient groups) can be handled safely.

Blood Chemical Analysis↗

[Importance of endocrine imaging methods in multiple endocrine neoplasia type 2A proved by mutation analysis].

Multiple endocrine neoplasias are rare, inherited disorders. The authors describe a case history of a patient with multiple endocrine neoplasia type 2A, who presented with unusual clinical manifestations. The diagnosis of phaeochromocytoma, which was the first manifestation of the disorder, was greatly facilitated with radiologic imaging methods. The authors review, on the basis of recent data from the literature, the importance of radiologic methods, which improved due to methodological advance. Finally, the authors emphasize the importance of follow-up for early diagnosis.

Diagnostic Imaging↗

Randomised controlled trial of Helicobacter pylori eradication in patients on non-steroidal anti-inflammatory drugs: HELP NSAIDs study. Helicobacter Eradication for Lesion Prevention.

BACKGROUND: The effect of Helicobacter pylori in patients receiving non-steroidal anti-inflammatory drugs (NSAIDs) is unclear. We investigated the effects of H. pylori eradication in patients with current or previous peptic ulceration, dyspepsia, or both who continued to use NSAIDs. METHODS: 285 patients were randomly assigned omeprazole 20 mg, amoxycillin 1000 mg, and clarithromycin 500 mg, twice daily (n=142, H. pylori eradication treatment), or omeprazole with placebo antibiotics (n=143, controls) for 1 week. All patients received omeprazole 20 mg once daily for 3 weeks until endoscopy, and, if the ulcer was not healed, 40 mg once daily until repeat endoscopy at 8 weeks. Ulcer-free patients with mild dyspepsia continued NSAIDs but not antiulcer treatment. We investigated ulcers with endoscopy at 1, 3, and 6 months and with carbon-13-labelled urea breath test at 3 months. FINDINGS: The estimated probability of being ulcer-free at 6 months was 0.56 (95% CI 0.47-0.65) on eradication treatment and 0.53 (0.44-0.62) on on control treatment (p=0.80). Time to treatment failure did not differ between groups for ulcers or dyspepsia alone, per-protocol analysis, or final H. pylori status. 66% (58-74) of the eradication group compared with 14% (8-20) of the control group had a final negative H. pylori result (p<0.001). Fewer baseline gastric ulcers healed among eradication-treatment patients than among controls (72 vs 100% at 8 weeks, p=0.006). INTERPRETATION: H. pylori eradication in long-term users of NSAIDs with past or current peptic ulcer or troublesome dyspepsia led to impaired healing of gastric ulcers and did not affect the rate of peptic ulcers or dyspepsia over 6 months.

Adolescent↗

[Biologic detection methods in the comparison of circulating tumor cells and micrometastases].

Early studies could not prove any diagnostic or prognostic value of the presence of tumor cells in the circulation. Recent knowledge in the field of molecular and cellular pathology provided better understanding of mechanisms of metastasis formation therefore advanced detection of circulating cancer cells has been suggested as a supplementary method of staging metastatic cancer. Beside the widely used immunocytochemical methods the reverse transcriptase-polymerase chain reaction (RT-PCR) is now the most relevant technique in studying micrometastases of solid tumors. Magnetic activated cell sorting (MACS) is a recently developed method for the enrichment of different cells from suspensions by magnetic labelling of their surface antigens. RT-PCR seems to be the most sensitive to detect circulating cancer cells or micrometastases, but it is possible by MACS to purify cells for further immunological, biochemical or genetic analysis. The aim of this review is to give a brief summary of recently used methods and to discuss the clinical relevance of the attainable results.

Biomarkers, Tumor↗

[Incidence and elimination of false-negative results of ferritin determination].

Introduction of turbidimetric homogeneous immunoassays made the determination of plasma ferritin concentration wide-ranging available. However, high-dose hook effect or prozone effect occurring at samples with high ferritin concentration can lead to false-negative results. According to the authors, this phenomenon has considerable clinical significance, in patients with iron-overload disorders false-negative laboratory values may result in inaccurate diagnosis. The prozone effect can be eliminated by reaction kinetic analysis of measurements. The authors developed a neural network classification procedure based on artificial intelligence technology for the recognition of the reactions with differing kinetic flow, and made a computer software for helping the application of the classification system. False-negative results can be filtered using this new technology following the laboratory determination, thus sensitivity of plasma ferritin determination may become safe enough even in case of high concentration samples.

False Negative Reactions↗

[Computerized speech recognition-based endoscopic findings].

Discrete, Hidden Markov model based speech recognition and phoneme based speech synthesis techniques were applied for gastroscopy reporting and machine control. The authors developed a special program for grammatical analysis of the sentences. Altogether 100 patient findings were grammatically analysed. The sentences were grouped according to the topographical order of the investigation: oesophagus, cardia, fundus, corpus, antrum, pylorus, bulbus, postbulbar section, and the pathological findings: erosion, ulceration, malignancy. Speech samples from 3 deep voiced male investigators were collected. The recognition rate was above 95%. A simulation program was also developed for dictation and controlling of the different equipment (monitor, printer, video, endoscope) in the gastroscopy laboratory by speech recognition. Speech synthesis was applied for the evaluation of understanding. This module artificially synthesizes the answer of the system giving backup for the understood information. With additional developments the discrete word speech 'recognition' achieved the level of routine application in medical reporting. However, ready-to-use developments need the joint activity of speech technology and endoscopy industry with end-user teams.

Diagnosis, Computer-Assisted↗