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Biomedical subjects

Zsolt Tulassay

Publications and source records attributed to Zsolt Tulassay.

At least 37 records · Page 2Linked to original sources
PubMed2006

Prevention of ulcers by esomeprazole in at-risk patients using non-selective NSAIDs and COX-2 inhibitors.

OBJECTIVES: Proton pump inhibitors reduce ulcer recurrence in non-steroidal anti-inflammatory drug (NSAID) users, but their impact in at-risk ulcer-free patients using the current spectrum of prescribed agents has not been clearly defined. We assessed esomeprazole for ulcer prevention in at-risk patients (> or = 60 yr and/or ulcer history) taking NSAIDs, including COX-2 inhibitors. Such studies are particularly relevant, given that concerns regarding adverse cardiovascular outcomes among COX-2 inhibitor users may prompt re-evaluation of their use. METHODS: We conducted two similar double-blind, placebo-controlled, randomized, multicenter studies; VENUS (United States) and PLUTO (multinational). A total of 844 and 585 patients requiring daily NSAIDs, including COX-2 inhibitors were randomized to receive esomeprazole (20 or 40 mg) or placebo, daily for 6 months. RESULTS: In the VENUS study, the life table estimated proportion of patients who developed ulcers over 6 months (primary variable, intent-to-treat population) was 20.4% on placebo, 5.3% on esomeprazole 20 mg (p < 0.001), and 4.7% on esomeprazole 40 mg (p < 0.0001). In the PLUTO study, the values were 12.3% on placebo, 5.2% with esomeprazole 20 mg (p = 0.018), and 4.4% with esomeprazole 40 mg (p = 0.007). Significant reductions were observed for users of both non-selective NSAIDs and COX-2 inhibitors. Pooled ulcer rates for patients using COX-2 inhibitors (n = 400) were 16.5% on placebo, 0.9% on esomeprazole 20 mg (p < 0.001) and 4.1% on esomeprazole 40 mg (p= 0.002). Esomeprazole was well tolerated and associated with better symptom control than placebo. CONCLUSIONS: For at-risk patients, esomeprazole was effective in preventing ulcers in long-term users of NSAIDs, including COX-2 inhibitors.

Aged↗
PubMed2006

[Hereditary tumours of the endocrine pancreas].

The pathogenesis, diagnosis and therapy of tumours originating from the endocrine pancreas represent one of the most exciting challenges of contemporary medicine. Some of these tumours appear as part of four hereditary syndromes (multiple endocrine neoplasia type 1 (MEN1), von Hippel-Lindau disease (VHL), neurofibromatosis type 1 and tuberous sclerosis) that are all inherited as autosomal dominant traits and result from mutations of tumour suppressor genes. Considering its clinical relevance, MEN1 appears to be the most important among these four syndromes. Tumours of the endocrine pancreas develop in 30-80% of patients carrying mutations of the MEN1 gene. Gastrinomas are the most frequent functioning tumours in MEN1 patients, followed by insulinomas, whereas other tumors e.g. glucagonoma, VIP-oma, GRF-oma and somatostatinoma occur very rarely. Tumours of the endocrine pancreas are infrequent in patients suffering from VHL, neurofibromatosis and tuberous sclerosis. In this review article, the authors present a synopsis of tumours of the endocrine pancreas related to these hereditary syndromes underlining the clinical characteristics, diagnostical and therapeutical possibilities.

Gastrinoma↗
PubMed2006

[The genetics of obesity].

Obesity is a major health problem. It increases the risk of cardiovascular diseases, 2-type diabetes mellitus, cancers, and premature mortality. Apart from some monogenic forms, it's a polygenic disorder, the result of interaction of genes and environmental factors. Genetic variants of proteins taking part in the regulation of food intake or thermogenesis and tissue mediators produced by the adipose tissue are responsible the genetic components of obesity. Identification of the genetic background of the obesity will help to understand the exact molecular mechanism of the pathogenesis, make possible the prevention, as well as individual therapeutic interventions.

Animals↗
PubMed2006

[Diagnosis and treatment outcome in primary aldosteronism based on a retrospective analysis of 187 cases].

INTRODUCTION: Primary aldosteronism is the most common form of mineralocorticoid hypertension. The disease has been described by Jerome W. Conn in 1955; since that time there has been a great progress in the knowledge concerning the prevalence, diagnostics and treatment of the disease. AIMS: The authors retrospectively analyzed the efficacy of diagnostic procedures and the outcome of treatment by the analysis of data of 187 patients with primary aldosteronism examined between 1958 and 2004 at the 2nd Department of Medicine of Semmelweis University. METHODS: The efficacy of different methods used for the diagnosis, the frequency of the different subtypes of primary aldosteronism, as well as the surgical outcomes in patients with surgically treated subtypes of primary aldosteronism were studied. RESULTS: Aldosterone-producing adenoma was detected in more than two thirds of patients (n = 135), whereas idiopathic hyperaldosteronism was found in 46 patients. Other subtypes of primary hyperaldosteronism occurred less frequently (unilateral primary adrenocortical hyperplasia in 5 patients and adrenocortical carcinoma in one patient). For the diagnosis of familial hyperaldosteronism type I, molecular biological studies of the aldosterone-synthase/11beta-hydroxylase gene chimera were carried out in 30 patients but none of them showed the presence of the chimeric gene. When comparing the clinical parameters of patients with aldosterone-producing adenoma and idiopathic hyperaldosteronism, no significant differences were found in the time period between the diagnosis of hypertension and the diagnosis of primary aldosteronism, or in the systolic and diastolic blood pressure values. The mean of the lowest documented serum potassium concentration was slightly lower in patients with aldosterone-producing adenoma (2.8 +/- 0.1 mmol/l) compared to those with idiopathic hyperaldosteronism (3.1 +/- 0.2 mmol/l), but the difference was not significant. Normokalemic primary hyperaldosteronism was found in 7 cases. The ratio of plasma aldosterone concentration (ng/dl) to plasma renin activity (ng/ml/h) was above 20 in all patients with aldosterone-producing adenoma and in all but 5 cases with idiopathic hyperaldosteronism. To confirm the diagnosis and to differentiate the subtypes of primary aldosteronism, the postural test combined with furosemide administration was performed in the majority of patients. When cases showing an elevation of plasma cortisol level during the test were excluded, this test differentiated patients with aldosterone-producing adenoma from those with idiopathic hyperaldosteronism with a sensitivity of 69% and a specificity of 92%. In cases of adrenocortical adenomas not or not clearly detectable by radiological imaging techniques, as well as in cases with bilateral adrenocortical adenomas, selective adrenal vein sampling was performed (n = 55). All but 4 patients with aldosterone-producing adenoma underwent adrenalectomy. Histology and postoperative hormone results confirmed the preoperative diagnosis in all operated patients. After surgery serum potassium concentration returned to normal in all patients showing low serum potassium levels before surgery. Also, the moderate to severe preoperative hypertension disappeared or improved after surgery. CONCLUSIONS: These observations are in contrast with the results of international studies which showed a high frequency of normokalemic primary aldosteronism and a more frequent occurrence of idiopathic hyperaldosteronism well treatable with aldosterone-antagonists. Therefore, it can be presumed that a significant number of primary aldosteronism cases that are not accompanied with severe hypokalemia remain undetected in Hungary.

Adenoma↗
PubMed2006

Automated four-color analysis of leukocytes by scanning fluorescence microscopy using quantum dots.

BACKGROUND: Scanning fluorescence microscope (SFM) is a new technique for automated motorized microscopes to measure multiple fluorochrome labeled cells (Bocsi et al., Cytometry A 2004, 61:1-8). AIMS: We developed a four-color staining protocol (DNA, CD3, CD4, and CD8) for the lymphocyte phenotyping by SFM. METHODS: Organic (Alexa488, FITC, PE-Alexa610, CyChrom, APC) and inorganic (quantum dot (QD) 605 or 655) fluorochromes were used and compared in different combinations. Measurements were performed in suspension by flow cytometer (FCM) and on slide by SFM. RESULTS: Both QDs were detectable by the appropriate Axioplan-2 and FCM filters and the AxioCam BW-camera. CD4/CD8 ratios were highly correlated (P = 0.01) between the SFM and FCM. CONCLUSION: Automated SFM is an applicable tool for CD4/CD8 ratio determination in peripheral blood samples with QDs.

Benzimidazoles↗
PubMed2006

Secretory leukocyte protease inhibitor expression in various types of gastritis: a specific role of Helicobacter pylori infection.

OBJECTIVES: Secretory leukocyte protease inhibitor (SLPI) represents a multifunctional protein of the gastrointestinal mucosa exerting antimicrobial and anti-inflammatory effects. SLPI expression is generally induced during inflammation; however, Helicobacter pylori-mediated gastritis is associated with significantly decreased antral SLPI levels. The aim of the study was to investigate whether SLPI downregulation of gastric mucosa represents a specific phenomenon of H. pylori infection or is generally linked to gastric inflammation. METHODS: SLPI expression was retrospectively analysed by immunohistochemistry in 85 paraffin-embedded samples: H. pylori-induced (n=13), non-steroidal anti-inflammatory drug (NSAID)-enhanced (n=18), autoimmune (n=11), lymphocytic gastritis (n=26) and H. pylori-negative controls (n=17). The intensity of the staining was semiquantitatively analysed using an immunoreactivity score. Statistical analysis of differences was performed using an analysis of variance test. RESULTS: In comparison with the control group, the SLPI expression of antral mucosa in H. pylori-mediated and lymphocytic gastritis was significantly lower (P<0.001), whereas epithelial SLPI expression was not affected in NSAID-enhanced and autoimmune gastritis either in the antrum or corpus, respectively. Both the H. pylori-mediated and lymphocytic gastritis revealed a significantly lower expression of SLPI in infiltrating immune cells (P<0.01), whereas immune cells infiltrating the corpus in autoimmune gastritis showed higher SLPI levels than the immune cells of other groups (P<0.03). CONCLUSION: The local downregulation of SLPI in antral mucosa is specifically linked to H. pylori infection and is not a general phenomenon of gastric inflammation.

Adult↗
PubMed2006

DLG5 R30Q is not associated with IBD in Hungarian IBD patients but predicts clinical response to steroids in Crohn's disease.

BACKGROUND: Recent data suggest that haplotypic variants of the DLG5 gene on 10q23 are associated with susceptibility to inflammatory bowel disease (IBD) in Germany. In view of the geographical differences in frequency of genetic markers and the absence of data in Central European patients, our aim was to determine the DLG5 R30Q variant in Hungarian IBD patients. MATERIALS AND METHODS: We investigated 773 unrelated IBD patients (age 38.1 +/- 10.3 years; duration, 8.8 +/- 7.5 years; Crohn's disease [CD]: 639; male/female, 309/330; duration, 8.4 +/- 7.1 years; ulcerative colitis [UC]: 134; male/female, 63/71; duration, 10.6 +/- 8.9 years) and 150 healthy subjects. DLG5 R30Q and TLR4 D299G variants were tested by polymerase chain reaction/restriction fragment length polymorphism. DNA was screened for NOD2/CARD15 mutations by denaturing high-performance liquid chromatography. Detailed clinical phenotype was determined by reviewing the medical charts. RESULTS: The frequency of the R30Q variant allele was not significantly different in IBD (22.0%), CD (20.8%), and UC (27.6%) patients compared with healthy control subjects (28.0%). In CD, the 113A variant allele was associated with steroid resistance (16.3% vs noncarriers, 7.6%; odds ratio [OR], 2.4; 95% CI 1.3-4.5; P = 0.013). In a logistic regression model carriage of DLG5 R30Q, perianal involvement and frequent relapses were independently associated with steroid resistance. No phenotype-genotype associations were found in UC patients, although a trend toward more extensive disease was observed in carriers of the variant allele (OR = 2.1; 95% CI 0.95-4.4; P = 0.07). CONCLUSIONS: The present data strongly contrast previous data from Germany. DLG5 113A is not associated with disease susceptibility, but there was a tendency for this allele to confer resistance to steroids. Further studies are required to evaluate the significance of DLG5 in other populations from geographically diverse regions.

Adult↗
PubMed2006

Infliximab therapy improves the bone metabolism in fistulizing Crohn's disease.

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) plays a pivotal role in the pathogenesis of inflammatory bowel diseases and bone resorption as well. Limited data exist about the effect of anti-TNF-alpha infliximab on bone metabolism in inflammatory-type Crohn's disease (CD). AIM: Our aim was to evaluate the effect of infliximab treatment on rapid changes of bone metabolism in fistulizing CD patients. METHODS: 27 patients with fistulizing CD were treated with three series of infliximab. Serum osteocalcin (OC) and beta-CrossLaps (bCL) were measured before administration of each infliximab infusion. 54 patients with inactive CD were controls. RESULTS: In treated patients, there were significant differences in bCL concentrations on days 0 and 14 (p < 0.01) and days 0 and 42 (p < 0.05). OC levels increased significantly between day 0 and 42 (p < 0.05). The values of bCL and OC of control groups differed from serum levels in active patients before the treatment, but not on day 42. Bone markers improved significantly in responder patients, but not in non-responders. CONCLUSION: The beneficial effect of infliximab to the bone metabolism is more expressive in patients whose fistulizing disease improves with this therapy. Our results suggest that TNF-alpha has an important role in the alteration of bone metabolism in fistulizing CD patients.

Adult↗
PubMed2005

[The Human Genome Project, genetic viability and genetic epidemiology].

The goal of the Human Genome Project to elucidate the complete sequence of the human genome has been achieved. The aims of the "post-genome" era are explaining the genetic information, characterisation of functional elements encoded in the human genome and mapping the human genetic variability as well. Two unrelated human beings also share 99.9% of their genomic sequence. The difference of 0.1% is the result of genetic polymorphisms: single nucleotide polymorphisms, repetitive sequences and insertion/deletion. The genetic differences, coupled with environmental exposures will determine the phenotypic variation we observe in health or disease. The disease-causing genetic variants can be identified by linkage analysis or association studies. The knowledge of human genome and application of multiple biomarkers will improve our ability to identify individuals at risk, so that preventive interventions can be applied, earlier diagnosis can be made and treatment can be optimized.

Early Diagnosis↗
PubMed2005

[Possible treatment modalities of primary sclerosing cholangitis].

Primary sclerosing cholangitis (PSC) is a chronic progressive liver disease with the segmental inflammation, obliterative fibrosis and cholestasis of intra- and extrahepatic biliary ducts which leads to secondary biliary cirrhosis. Its aetiology is unknown. The disease is accompanied with ulcerative colitis in 70-80 percent. Its clinical progress is variable, the average duration of the disease is between the diagnosis and the final stage (liver transplantation) about 18 years. The prevalence of PSC is 1-5/100 000 inhabitants. Mainly it occurs in male patients (70 %), male-female rate is 2:1. The authors summarise the treatment modalities after reviewing the pathogenesis, clinical picture and the diagnostic procedures. The pathomechanism of the basis therapy with ursodeoxycholic acid (UDCA) is discussed in details, especially its effects on the clinical picture and the laboratory data. The authors review the results of the immunosuppressive therapy and the treatments of specific complications in PSC. They underline the importance and opportunities of the early diagnosis of cholangiocarcinoma, which is very frequent in this disease.

Cholangitis, Sclerosing↗
PubMed2005

Plasma carnitine ester profile in adult celiac disease patients maintained on long-term gluten free diet.

AIM: To determine the fasting plasma carnitine ester in patients with celiac disease. METHODS: We determined the fasting plasma carnitine ester profile using ESI triple quadrupol mass spectrometry in 33 adult patients with biopsy-confirmed maturity onset celiac disease maintained on long term gluten free diet. RESULTS: The level of free carnitine did not differ as the celiac disease patients were compared with the healthy controls, whereas the acetylcarnitine level was markedly reduced (4.703 +/- 0.205 vs 10.227 +/-0.368 nmol/mL, P<0.01). The level of propionylcarnitine was 61.5%, butyrylcarnitine 56.9%, hexanoylcarnitine 75%, octanoylcarnitine 71.1%, octenoylcarnitine 52.1%, decanoylcarnitine 73.1%, cecenoylcarnitine 58.3%, lauroylcarnitine 61.5%, miristoylcarnitine 66.7%, miristoleylcarnitine 62.5% and oleylcarnitine 81.1% in the celiac disease patients compared to the control values, respectively (P<0.01). CONCLUSION: The marked decrease of circulating acetylcarnitine with 50-80 % decrease of 11 other carnitine esters shows that the carnitine ester metabolism can be influenced even in clinically asymptomatic and well being adult celiac disease patients, and gluten withdrawal alone does not necessarily normalize all elements of the disturbed carnitine homeostasis.

Adult↗
PubMed2005

[Clinical symptoms, diagnosis and treatment of multiple endocrine neoplasia type 1. Results of genetic screening in Hungarian patients].

Multiple endocrine neoplasia type 1 syndrome is an autosomal dominant disorder characterized by endocrinopathies involving the parathyroid glands, anterior pituitary gland, and pancreas. Also, it may be associated with foregut carcinoid, adrenocortical tumors and non-endocrine tumors. After reviewing the prevalence, genetic background, clinical symptoms, diagnosis and treatment of the disorder, the authors present their genetic screening method used for the detection of mutations of the MEN1 gene (prescreening of polymerase chain reaction amplified exons using temporal temperature gradient gel electrophoresis followed by direct DNA sequencing). Using this method, the authors identified disease-causing MEN1 gene mutations in 9 probands (small deletions in 2 cases, insertion in 2 cases, nonsense mutations in 2 cases and missense mutations in 3 cases). Of the 9 mutations, 4 proved to be novel mutation not reported in the literature. Family screening indicated de novo mutations in 2 probands. In addition to mutations, several sequence polymorphisms were also detected. The authors conclude that one of the major advantages of genetic screening in families with MEN1 syndrome was the identification of family members carrying the mutation who should be regularly screened for disease manifestations and those not carrying the mutation in whom clinical screening is unnecessary. Also, genetic screening may be useful in cases when MEN1 syndrome is suspected, but the clinical manifestations do not fully establish the diagnosis of MEN1 syndrome.

Adrenal Cortex Neoplasms↗
PubMed2005

[Genetics of primary biliary cirrhosis].

The primary biliary cirrhosis is a chronic cholestatic liver disease, which is characterised by non-suppurative destruction of interlobular bile ducts. The precise etiopathogenesis of primary biliary cirrhosis remains unknown. Evidence suggest that genetic and environmental factors seem to be important. It shows strong heritability according to familial occurrence and monozygotic twins concordance. There is an increase in the degree of monosomy of the X chromosome in female subjects with PBC. There is an association with HLA-DR8 (DR1*08) antigen at least in some populations. Correlation the PBC with polymorphisms of HLA class I, II, III alleles, genes encoding for molecules influencing immune tolerance, apoptosis, cytokine expression, will require additional studies.

ATP-Binding Cassette Transporters↗
PubMed2005

[Genotype-phenotype associations in inflammatory bowel disease].

Inflammatory bowel disease has traditionally been categorized as either ulcerative colitis or Crohn's disease on the basis of clinical, radiological and histological criteria. Emerging data suggest that inflammatory bowel disease comprises a heterogenous family of inflammatory disorders in which the specific clinical manifestations of disease are determined by the interaction of genetic and environmental factors. Interactions of susceptibility and modifying genes influence the specific features of disease phenotype, penetrance, location, behavior, and complication. CARD15/NOD2 mutations are significantly associated with ileal location, whereas certain HLA haplotypes are associated with colonic disease. The associations with CARD15/ND2 mutations and early age at onset, as well as disease behavior (stricturing, fistulizing type) are less consistent. Distinct HLA alleles contribute to the occurrence of extraintestinal manifestation. With the increasing number of genotype-phenotype relationship, it is hoped that a molecular classification can be created, in which various disease subtypes are categorized according to their specific genotypes. In the future, such sheme may permit early, accurate diagnosis, prediction of disease course, complications, prognosis, as well as treatment response.

Age of Onset↗
PubMed2005

Long-term omeprazole and esomeprazole treatment does not significantly increase gastric epithelial cell proliferation and epithelial growth factor receptor expression and has no effect on apoptosis and p53 expression.

AIM: To study the effect of proton pump inhibitor (PPI) treatment on patients with reflux esophagitis and its in vivo effect on apoptosis, p53- and epidermal growth factor receptor (EGFR) expression. METHODS: After informed consent was obtained, gastric biopsies of the antrum were taken from patients with reflux oesophagitis prior to and after 6 mo of 20 mg omeprazole (n = 14) or 40 mg esomeprazole (n = 12) therapy. Patients did not take any other medications known to affect the gastric mucosa. All patients were Helicobacter pylori negative as confirmed by rapid urease test and histology, respectively. Cell proliferation, apoptosis, EGFR, and p53 expression were measured by immunohistochemical techniques. At least 600 glandular epithelial cells were encountered and results were expressed as percentage of total cells counted. Was considered statistically significant. RESULTS: Although there was a trend towards increase of cell proliferation and EGFR expression both in omeprazole and esomeprazole treated group, the difference was not statistically significant. Neither apoptosis nor p53 expression was affected. CONCLUSION: Long-term PPI treatment does not significantly increase gastric epithelial cell proliferation and EGFR expression and has no effect on apoptosis and p53 expression.

Adult↗
PubMed2005

[Hypercalcemia in neoplastic and granulomatous diseases: pathogenesis and treatment options].

Hypercalcemia is a frequently observed laboratory phenomenon in clinical practice. It can occur in several diseases, among which it is associated most frequently with neoplasms, hyperparathyroidism and disorders of vitamin D metabolism. The appearance of hypercalcemia in neoplastic diseases is related to a poor prognosis in general. In most cases, malignant hypercalcemia is related to the secretion of parathormone-related protein, but other causes have also been described. Granulomatous diseases are associated with the hypersecretion of vitamin D metabolites. Fluid volume repletion, forced diuresis can be regarded as cornerstones in the therapy of acute hypercalcemia independent of its etiology, in addition, medications including bisphosphonates, calcitonin, gallium nitrate and glucocorticoids can be applied. In this review article, the authors present a brief synopsis of the pathogenesis of hypercalcemia associated with neoplastic and granulomatous diseases along with the treatment options, underlining the practical aspects.

Animals↗
PubMed2005

[The p53 gene and protein in 2005: new results, promising opportunities].

The p53 gene and protein in 2005: new results, promising opportunities. The p53 gene is one of the most important genes which is involved in the regulation of cell division and tumor formation. The normal function of the p53 protein is to arrest the cell division and to turn the cell towards apoptosis in the case of cell stress and DNA damage, thereby to protect the integrity of the genome. Several p53 gene mutations that have function in carcinogenesis have been found in various tumors, including gastrointestinal carcinomas. The loss of p53 response plays an important role in the malignantly transformed cell proliferation. Promising experiments try to substitute the lost functions of the p53 gene. With their help new anti-tumor therapeutic methods should be developed.

Animals↗