János Fehér

Rearrangement of the T-cell receptor alpha, beta and gamma chain genes in chronic lymphocytic leukemia

Simultaneous expression of mature B-cell and T-cell markers and subsequent abrogation of expression of the T-cell surface markers by cytotoxic chemotherapy was reported earlier in a patient (TG) with chronic lymphocytic leukemia (CLL). In addition to rearrangements of the immunoglobulin (Ig) gene loci correlating with phenotypic data, the T-cell receptor (TCR) alpha, beta and gamma chain genes also displayed clonal rearrangements in peripheral blood lymphocyte DNA of TG. The present case shows that in CLL cells not only the expression of B-cell and T-cell specific differentiation antigens but also the rearrangement of Ig as well as TCR alpha, beta and gamma genes may occur simultaneously.

[Efficacy and safety of ezetimibe/simvastatin combination therapy in patients with type 2 diabetes and nonalcoholic fatty liver disease].

UNLABELLEDnNonalcoholic fatty liver disease is commonly associated with type 2 diabetes, dyslipidemia and obesity all of which are components of the metabolic syndrome.nnnAIMnTo determine the efficacy and safety of ezetimibe/simvastatin 10/20mg combination therapy on patients with type 2 diabetes and nonalcoholic fatty liver disease.nnnMETHODSnWe studied nineteen patients with type 2 diabetes and nonalcoholic fatty liver disease diagnosed and treated between 2005 and 2008 at Health Center of Budaörs. After six months of ezetimibe/simvastatin (10/20mg/day) combination treatment, all patients were assessed for changes serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL) and triglycerides.nnnRESULTSnSix months of ezetimibe/simvastatin administration reduced significantly the serum levels of ALT (63.78+/-5.12 vs 32.57+/-3.92 U/L; p < 0.0001), AST (50.79+/-3.66 vs 23.68+/-3.42 U/L; p < 0.0001), cholesterol (6.26+/-0.46 vs 4.02+/-0.31 mmol/L; p < 0.0001) and LDL-cholesterol (4.24+/-0.37 vs 2.22+/-0,1 mmol/L; p < 0.0001). Combination therapy reduced significantly serum triglyceride level (2.62+0.48 vs 1.33+0.20 mmol/L; p < 0.0001) and increased the level of HDL-cholesterol (1.02+/-0.12 vs 1.18+/-0.07 mmol/L; p < 0.0001).nnnCONCLUSIONSnThese findings indicate that ezetimibe/simvastatin combination therapy is safe and effective in patients with type 2 diabetes and nonalcoholic fatty liver disease.

[Metabolic therapy for early treatment of age-related macular degeneration].

Currently, age-related macular degeneration is one of the most common eye diseases causing severe and permanent loss of vision. This disease is estimated to affect approximately 300-500 thousand Hungarians. While earlier no treatment was available, in the recent decade an antioxidant therapy became very popular using combinations of high dosage antioxidant vitamins C, E, beta carotene and zinc. Based on theoretical concepts and mostly in vitro experiences, this combination was thought to be effective through neutralizing reactive oxygen species. According to a large clinical trial (AREDS) it reduced progression of intermediate state disease to advanced state, but did not influence early disease. This original combination, due to potential severe side effects, is not on the market anymore. However, the efficacy of modified formulas has not been proved yet. Recently, the metabolic therapy, a combination of omega-3 fatty acids, coenzyme Q10 and acetyl-L-carnitine has been introduced for treating early age-related macular degeneration through improving mitochondrial dysfunction, specifically improving lipid metabolism and ATP production in the retinal pigment epithelium, improving photoreceptor turnover and reducing generation of reactive oxygen species. According to a pilot study and a randomized, placebo-controlled, double blind clinical trial, both central visual field and visual acuity slightly improved after 3-6 months of treatment and they remained unchanged by the end of the study. The difference was statistically significant as compared to the base line or to controls. These functional changes were accompanied by an improvement in fundus alterations: drusen covered area decreased significantly as compared to the base line or to control. Characteristically, all these changes were more marked in less affected eyes. A prospective case study on long-term treatment confirmed these observations. With an exception that after slight improvement, visual functions remained stable, drusen regression continued for years. Sometimes significant regression of drusen was found even in intermediate and advanced cases. All these findings strongly suggested that the metabolic therapy may be the first choice for treating age-related macular degeneration. Currently, this is the only combination of ingredients corresponding to the recommended daily allowance, and at the same time, which showed clinically proved efficacy.

[Common occurrence of non-alcoholic fatty liver disease and cholecystolithiasis].

INTRODUCTIONnNon-Alcoholic Fatty Liver Disease is an acquired metabolic disease of the liver caused by accumulation of triglycerides in hepatocytes that is followed by necrobiotic inflammatory reaction, fibrosis and cirrhosis. Obesity, insulin resistance, diabetes mellitus and hyperlipidaemia are important pathogenetic factors of the process. It is known that among patients with cholecystolithiasis and diabetes mellitus in their anamnesis complications of cholecystolithiasis occur much more frequently like among patients without diabetes.nnnAIMnThe aim of the study is observation of the incidence of cholecystolithiasis and its complications in patients with Non-Alcoholic Fatty Liver Disease and comparison of cholecystolithiasis incidence between healthy population and population with Non-Alcoholic Fatty Liver Disease.nnnMETHODSnAbdominal ultrasonographical findings were analysed in patients hospitalised at our department and in outpatients, patients with severe accompanied diseases were excluded of the analysis. The analysed basic file of patients could be considered as a selected file. The independence of the two examined variables was measured by chi(2) test.nnnRESULTSnSteatosis was described in 38% of the examined patients, cholecystolithiasis was described in 16% of patients. Cholecystolithiasis and its complications occur two times more frequently in patients with Non-Alcoholic Fatty Liver Disease (33%) like Non-Alcoholic Fatty Liver Disease in patients with cholecystolithiasis (16%). Complications of cholecystolithiasis occur more frequently among patients with Non-Alcoholic Fatty Liver Disease like in healthy individuals. The chi(2) test did not bring significant results concerning the independence of cholecystolithiasis and Non-Alcoholic Fatty Liver Disease.nnnCONCLUSIONnPathogenetic factors of Non-Alcoholic Fatty Liver Disease participate in the pathogenesis of cholecystolithiasis. Their common pathogenetic factors bring about that the formation of cholecystolithiasis is probably faster than the progression of steatosis.χ 2 test. Results: Steatosis was described in 38% of the examined patients, cholecystolithiasis was described in 16% of patients. Cholecystolithiasis and its complications occur two times more frequently in patients with Non Alcoholic Fatty Liver Disease (33%) like Non Alcoholic Fatty Liver Disease in patients with cholecystolithiasis (16%). Complications of cholecystolithiasis occur more frequently among patients with Non Alcoholic Fatty Liver Disease like in healthy individuals.The χ 2 test did not bring significant results concerning the independence of cholecystolithiasis and Non Alcoholic Fatty Liver Disease. Conclusion: Pathogenetic factors of Non Alcoholic Fatty Liver Disease participate in the pathogenesis of cholecystolithiasis. Their common pathogenetic factors bring about that the formation of cholecystolithiasis is probably faster than the progression of steatosis.

The beneficial effect of metadoxine (pyridoxine-pyrrolidone-carboxylate) in the treatment of fatty liver diseases

Abstract Hepatic steatosis involves an imbalance between the processes of the hepatocytes’ lipid uptake and lipid elimination, an overproduction results in the accumulation of excess triglycerides in the cells of the liver. Normally about 5% of the cells contain triglyceride; in steatosis this may exceed 50%. Under 50% the condition is called fatty infiltration, and over 50% it is called fatty liver. In mild forms this does not necessarily lead to disorders in cell functions, but in more severe forms it does; it often precedes the death of the cell. Fatty liver can be considered a pathologic condition which makes the liver more susceptible to other toxic influences. It is not a genuine disease; in most cases it is associated with a noxious state or other pathologic process. Alcohol-induced fatty liver is a current epidemie. The abnormal accumulation of fat in parenchymal organs, including the liver, is called fatty transformation or steatosis. Alone and limited to a certain degree of severity (the appeara...

Levels of carbohydrate-deficient transferrin according to gender and age in a small town in Hungary.

Abstract Abstract The estimated amounts of alcohol consumed regularly are data recorded on the basis of patients’ self-report at history-taking. In many instances, however, patients do not genuinely inform their physician on the extent of their alcohol consumption, and in some cases they simply conceal it. In such cases determination of the amount of carbohydrate-deficient transferrin (CDT) can be helpful. Objective To determine the levels of carbohydrate-deficient transferrin in a healthy population. Methods The authors performed examinations among inhabitants of a small Hungarian town (Enese). Data of 409 individuals (average age: 49.7 years) have been processed. They included 204 men (average age: 49.3 years) and 205 women (average age: 50.3 years). Subjects were divided into two groups: 1) those who consumed no alcohol or only small quantities (< 40 g/day) and 2) the so-called social drinkers who consumed an amount corresponding to 40 to 60 g alcohol/day. Levels of carbohydrate-deficient transferrin w...

Role of gastrointestinal inflammations in the development and treatment of depression

Recent studies have revealed that inflammation, among other factors, may be involved in the pathogenesis of depression. One line of studies has shown that depression is frequently associated with manifest gastrointestinal inflammations and autoimmune diseases as well as with cardiovascular diseases, neurodegenerative diseases, type 2-diabetes and also cancer, in which chronic low-grade inflammation is a significant contributing factor. Thus depression may be a neuropsychiatric manifestation of a chronic inflammatory syndrome. Another line of studies has shown that the primary cause of inflammation may be the dysfunction of the gut-brain axis. Although, this is a bidirectional mechanism, life style factors may primarily affect the symbiosis between host mucous membrane and the microbiota. Local inflammation through the release of cytokines, neuropeptides and eicosanoids may also influence the function of the brain and of other organs. Role of metabolic burst due to inflammation represents a new aspect in both pathophysiology and treatment of the depression. Finally, an increasing number of clinical studies have shown that treating gastrointestinal inflammations with probiotics, vitamin B, D and omega 3 fatty acids, through attenuating proinflammatory stimuli to brain, may also improve depression symptoms and quality of life. All these findings justify an assumption that treating gastrointestinal inflammations may improve the efficacy of the currently used treatment modalities of depression and related diseases. However, further studies are certainly needed to confirm these findings.

The effectivity and safety of the biological therapy with adalimumab

Adalimumab is a human, recombinant antibody, which is effective in patients with rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriasis, arthritis psoriatica, spondylitis ankylopoetica, as well as with Crohn-disease. Adalimumab has got a high affinity binding to tumor necrosis factor (TNF-alfa), this way it inhibits the interactions with TNF and its receptors (soluble and membrane associated). It is well tolerated and safe, it improves the the quality of life. Possible side effects can be decreased by the careful observation and usual control of patients. The authors discuss in detail the publications on adalimumab in the above mentioned diseases.

Carbohydrate-Deficient Transferrin as a Marker of Alcohol Consumption

At history-taking, the assessment of the amount of regular alcohol consumption means data to be recorded on the basis of the patient’s self-report. In many cases, however, patients do not genuinely inform their physician on the extent of their alcohol consumption, and in certain cases they simply conceal it. In order to prove the diagnosis in diseases of alcoholic origin (e.g. hepatic disease), an objective parameter may often be needed to demonstrate concealed alcohol consumption. An objective marker of alcohol consumption is also required in other cases, as at taking out a life insurance policy or when forming a medical expert opinion in forensic medicine. The amount of carbohydrate-deficient transferrin may be such an indicator.The authors review the pathomechanism of carbohydrate-deficient transferrin formation, the methods of determination, the importance of carbohydrate-deficient transferrin in the diagnostics of diseases caused by alcohol consumption, as well as its role in confirming alcohol consu...

Associations of Autoimmune Endocrine Diseases

Abstract Recently, an increasing amount of data on the connection between neuro-endocrine and immune systems has been gathered. Results of molecular genetic research have provided evidence for a common language of these systems including neurotransmitters, hormones and cytokines. It has been proved that the immune system is capable of producing neurotransmitters and hormones and even the endocrine system can prepare cytokines. This integrative (holistic) approach makes possible the investigation of physiological and pathological events as interactions of psychoneuro-endocrine-immune systems. The associations of autoimmune diseases and the autoimmune polyendocrine syndromes constitute a heterogeneous group of disorders characterised by decreased or lost immune tolerance against self-antigens. Molecular genetic research has explored the mechanism of the associations of diseases that are called organ-specific. Autoimmune polyendocrine syndrome type 1 is characterised by the presence of at least two of the th...