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Hungarian Immunology

JANUARY 22, 2008

[Pseudolymphoma orbitae]

VÁNCSA Andrea, GERGELY Lajos, NEMES Zoltán, BÍRÓ Edit, ILLÉS Árpád, BAKÓ Gyula

[INTRODUCTION - Pseudolymphoma orbitae is a rare and difficult entity. The cooperation of the pathologist and clinician is needed to properly manage the patient. CASE REPORT - The authors report the case history of a 38 years old male patient. His disease started at the age of 30. He was previously treated with allergic rhinitis. No definitive diagnosis was made for eight years. Several surgical biopsies were made from nasal mucosa, but no specific histologyical diagnosis was applicable. At the age of 30 he developed an unilateral exophthalmus on the left side. Thyroid associated ophthalmopathy was ruled out several times with laboratory analysis. High dose methylprednisone therapy was repeatedly given with limited results. At the age of 34 orbital CT and MRI scan confirmed the pseudotumour orbitae already compressing the optical nerve. Laboratory analysis again ruled out thyroid associated ophthalmopathy. Churg-Strauss syndrome, Wegener’s granulomatosis or Sjögren’s syndrome could be ruled out. A bone marrow trephine biopsy excluded systemic hematological disease as well. A biopsy was performed from the retrobulbar mass again, which confirmed the lymphoid hyperplasia with B-cell dominance. High dose methylprednisone and local irradiation resulted only moderate decrease of the mass, so systemic chemotherapy was started using CVP (cyclophosphamide, vincristin, prednisone) then CHOP (CVP + anthrycycline) polychemotherapy for eight cycles and subcutaneous interferon-α for 20 months. CONCLUSIONS - This resulted a complete regression of the disease, and the patient is well for 48 months now.]

Lege Artis Medicinae

OCTOBER 20, 2003

[NEW MODALITIES IN THE TREATMENT OF CHRONIC VIRAL HEPATITIS C: PEGYLATED INTERFERONS]

GERVAIN Judit, NEMESÁNSZKY Elemér, CSEPREGI Antal

[Interferon-α proved to be the most effective therapy of chronic hepatitis C. Its combination with ribavirin enhances the antiviral activity and this modality has become the therapeutic standard recommended worldwide during the past few years. Metaanalysis of the international studies revealed that only 12-19% of the patients became virus-free following a 48-week long course of α interferon monotherapy. The combination treatment with ribavirin for 48 weeks increased the proportion of sustained responders to 35-45%. The introduction of pegylated interferons resulted in significantly higher response rates. The new therapeutic possibilities are due to the modified pharmacokinetic characteristics of the drug by changing the size and the structure of the molecules. Multicentre studies investigating the clinical effectiveness of the 40 kD sized pegylated interferon α-2a as well as the 12 kD sized pegylated interferon α-2b in combination with ribavirin reported 56% and 54% response rate, respectively. However, there is significant heterogeneity in the results according to the type of drug administered and to the genotype of the hepatitis C virus, as well as in the basal viral level and the stage of hepatic fibrosis, respectively. The message and the conclusion of the viral kinetic studies are worth remembering: if the result of the HCV nucleic acid test is still positive at week 12 or 24, therapy should be ceased due to the patient non-responder status. Since pegylated interferons are also available in Hungary the authors felt useful to give an overview of the current knowledge, summarizing the results of the relevant studies and provide a suggested state-of-the-art therapeutic protocol based on international consensus.]

Clinical Neuroscience

MARCH 10, 2005

[Application of the Multiple Sclerosis Functional Composite in Debrecen]

MEZEI Zsolt, BERECZKI Dániel, CSIBA László, CSÉPÁNY Tünde

[Introduction - The Multiple Sclerosis Functional Composite (MSFC) has been recommended by the National Multiple Sclerosis Society as a new clinical outcome measure. It is based on measurements in three clinical dimensions: leg function/ambulation (timed 25-foot walk), arm function (9-hole peg test), and cognitive function (paced auditory serial addition test). Scores on component measures are converted to standard scores (Z-scores) that reflect patient performance. This method has not yet been introduced into routine clinical practice. Patients and method - MSFC calculation was applied to 17 patients with relapsing-remitting multiple sclerosis (age mean: 37.4±10.8 years; duration of the disease: 5.5±4.9 years, EDSS: 2.7±1.4) seen at the neuroimmunological outpatient clinic to evaluate its usefulness and its correlation with the traditionally applied Expanded Disability Status Scale (EDSS) and with patient-reported quality of life. Fifteen patients received immunomodulatory treatment (interferon beta and glatiramer acetate). MSFC and EDSS were measured at 0, 3, 6, 9, 12, 18 months, and questionnaires on quality of life were filled in by the patients at 0, 6, 12, 18 months of follow- up. Results - The prospective study confirmed a strong correlation between EDSS and MSFC (Spearman correlation test, p=0.03, 0.004, 0.002, 0.004, 0.0008, 0.002; R=-0.54, -0.66, -0.68, -0.65, -0.73, -0.69) in multiple sclerosis. The MSFC was more sensitive to clinical changes than EDSS. The extent of changes on the two scales correlated only after 18 months (p<0.005, R=-0.65). The arm/hand function was the most sensitive measure for disease progression. There was no correlation between the quality of life and either of the two other clinical parameters. Conclusion - MSFC is a simple method, suitable for followup of multiple sclerosis patients in everyday clinical practice.]

Hungarian Immunology

OCTOBER 20, 2007

[Altered rate and absolute count of Th1/Th2 and Tc1/Tc2 lymphocytes in whole blood of patients with psoriasis]

ANTAL-SZALMÁS Péter, ALEKSZA Magdolna, GONDA Andrea, HERÉDI Emese, SIPKA Sándor, HUNYADI János, SZEGEDI Andrea

[BACKGROUND - Psoriasis is a chronic inflammatory skin disorder characterised by an altered rate of interferon (IFN)-γ and interleukin (IL)-4 producing lesional and peripheral blood CD4+ and CD8+ T cells. To further characterise the imbalance of these cells and cytokines the rate and as a novel approach the absolute cell count (ACC) of IFN-γ+, IL-4+ and IL-10+ Thelper and Tcytotoxic cells was determined in the peripheral blood of psoriatic individuals. MATERIALS AND METHODS - Cell-associated cytokine expression was determined using intracellular cytokine staining and flow cytometry, serum cytokine levels were measured by enzyme linked immunosorbent assays (ELISAs) in the samples of 35 psoriatic patients and 15 controls. RESULTS - Significantly elevated rate (p<0.008) and ACC (p<0.009) of CD4+/IFN-γ+ cells was observed in the patients (28.3±8.8% and 237,216±134,154 cells/ml) compared to the healthy controls (21.0+ 6.8% and 135,772±50,212 cells/ml). In contrast the rate and the ACC of CD4+/IL-4+ cells decreased significantly in psoriasis (0.45±0.67% vs. 1.01± 0.48%, p<0.0001; 3,229±3,724 vs. 5,117±4,171 cells/ml, p<0.05). In the case of CD8+ T cells only the rate and the ACC of CD8+/IL-10+ cells increased significantly in patients compared to controls (5.49±5.42% vs. 1.59±0.78%, p<0.003 and 19,799±17,412 vs. 5,564±2,794 cells/ml, p<0.03). Though higher IFN-γ and lower IL-4 and IL-10 serum concentrations were detected in psoriasis these differences between patients and controls were not significant. Comparing the different cytokine parameters the serum cytokine levels showed some correlation only with the ACC and not with the rate of cytokine positive cells. CONCLUSIONS - These results further prove the presence of an altered balance in cytokine regulation towards the Thelper 1 cytokines in psoriasis, besides indicate that application of the ACC of cytokine positive helper and cytotoxic T cells as a novel parameter can help in the characterisation of these changes in different disorders.]

Lege Artis Medicinae

JANUARY 27, 2009

[Efficacy of peginterferon alfa-2a and -2b plus ribavirin in the routine treatment of patients with chronic hepatitis C]

TUSNÁDI Anna, SZABÓ Anna

[INTRODUCTION - Combination of peginterferon plus ribavirin is the standard treatment for chronic hepatitis C virus (HCV) infection. Two types of peginterferon are available. The aim of this retrospective study was to find out whether the choice of peginterferon influenced the patient’s chance of recovery. PATIENTS AND METHODS - Between 2004 and 2007, 142 patients with HCV genotype 1 hepatitis with or without cirrhosis (107 treatmentnaive, 35 previously treated) were treated with 180 ug/week peginterferon alfa-2a (Group A) or 1.5 ug/kg/week peginterferon alfa-2b (Group B) plus ribavirin. Examination and treatment of patients followed the rules of the national guideline. Patients were not randomized in any way. Group A consisted of 78 patients and Group B included 64 patients. Eight patients dropped out for various reasons (5 from Group A, 3 from Group B). There was no statistically significant difference in the baseline characteristics and the cumulative doses of the drugs between Group A and B, so the treatment results were comparable. RESULTS - Sustained virological response (undetectable HCV ribonucleic acid serum levels 24 weeks after the end of treatment) occurred in 42.5% of patients from Group A and 37.7% from Group B. When focusing on treatment-naive patients only, sustained virological response was found in 48.2% of patients in Group A and 46.7% in Group B. Result of the treatment was better if the patient was treatment-naive, if there was no cirrhosis, and if early virological response at 12 weeks was achieved. CONCLUSION - Patients treated with peginterferon alfa-2a plus ribavirin achieved sustained virological response at a higher rate than those with peginterferon alfa-2b plus ribavirin, however, the difference was not statistically significant.]

Lege Artis Medicinae

JULY 14, 2008

[IMMUNE-MEDIATED NEUROLOGICAL DISORDERS]

CSÉPÁNY Tünde

[Multiple sclerosis, myasthenia gravis and chronic inflammatory neuropathies share the common feature of chronic course with potential development of disability due to the damage caused by immunological processes. Early detection and precise diagnosis is very important, because most patients respond well to proper immunomodulatory treatment. The diagnosis requires extensive knowledge of the disease and is based on the clinical symptoms recognised by the GP, as well as on complex assessment of the results of special neurophysiological, radiological and laboratory examinations. The present paper reviews the major immune-mediated neurological disorders and discusses their targeted immunological treatment.]

Hungarian Immunology

OCTOBER 10, 2005

[Plasmacytoid dendritic cells - type I interferon producing cells]

MAGYARICS Zoltán, RAJNAVÖLGYI Éva

[Dendritic cells represent a multifunctional cell population classified to myeloid (mDC) and plasmacytoid (pDC) types. Both subsets circulate in the peripheral blood and are found in lymphoid and also in non-lymphoid tissues, where they act as sensors of environmental changes. Upon activation by a wide range of stimuli they undergo morphological and functional transition and give rise to professional antigen presenting cells, which migrate to lymphoid organs. A newly identified precursor subset of human dendritic cells has recently been identified as professional type I interferon producing cells (IPC) with multiple functional activities. With their capacity of priming, instructing and regulating various pathogen- and tumor-specific immune responses, IPC/pDC act as a link between innate and adaptive immunity. The role of pDC in the pathogenesis of various diseases is well established, and these cells also emerge as novel candidates of immunomodulation.]

Lege Artis Medicinae

NOVEMBER 19, 2006

[TREATMENT APPROACHES OF CHRONIC HEPATITIS B IN HUNGARY]

TORNAI István, NEMESÁNSZKY Elemér

[Today, there are less patients with active chronic hepatitis B requiring treatment than patients with chronic hepatitis C. However, the course and outcome of chronic hepatitis B is usually more severe, therefore, the disease has not lost importance. The most dangerous risks are the development of liver cirrhosis and hepatocellular carcinoma. The disease may present in various forms. Symptom-free carriers only need follow-up and hepatologic care. In the active stages with elevated liver enzymes and high level of viral nucleic acid (either HBeAg negative or positive), however, antiviral treatment is strongly indicated. There are two main forms of treatment. Alfa-interferon-based therapy, which is applied for a defined period of time, has a direct antiviral and immunomodulatory effect, but has several adverse effects. Long-term nucleoside analogue treatment represent the other treatment modality. These drugs are administered orally, have minimal side effects, but after some time resistant mutants may develop. Traditional interferon has recently been replaced by pegylated interferon alfa-2a with much better pharmacokinetic properties. Lamivudine has been in use for the longest time of the nucleoside analogues. Its efficacy is high, but after 3 to 4 years of treatment, resistant mutants appear in about 70% of cases. Of the most recent compounds, adefovir dipivoxil has recently become available in Hungary; it is primarily recommended in cases with lamivudine resistant mutants. There are promising new drugs in the stages of clinical trial; of these, entecavir has already been approved in the United States.]

Lege Artis Medicinae

SEPTEMBER 20, 2002

[Drug treatment possibilities in chronic liver diseases]

HAGYMÁSI Krisztina, LENGYEL Gabriella, FEHÉR János

[Alcoholic and drug induced liver diseases, nonalcoholic steatohepatitis, hepatitis C and B chronic hepatitis, autoimmune diseases (primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis) and metabolic disorders (hemochromatosis, Wilson's disease) are the main chronic liver diseases. Authors summarize, based on the latest literature data, the medications of chronic liver diseases, emphasizing the treatment of the everyday practice. Natural and synthetic antioxidants are approved for the treatment of chronic alcoholic liver diseases besides abstinence, with diet of adequate quality and quantity. Nucleoside analogues (lamivudin) are recommended for the first-line therapy of the treatment of chronic hepatitis B. Interferon is presently considered the optimal treatment for only certain patients. Interferon and ribavirin combined therapy is well-established in the treatment of chronic hepatitis C. Ursodeoxycholic acid is the beneficial treatment option for primary biliary cirrhosis and primary sclerosing cholangitis. Prednisolon and azathioprine constitute the basic therapy of autoimmune hepatitis. Presumably, in the future, new strategies based on immunosuppressive combinations will play a crucial role. The chelating deferoxamine has less important part in the treatment of hemochromatosis. D-penicillamine still plays principle role in the medication of Wilson's disease.]

Lege Artis Medicinae

MAY 26, 2008

[RETREATMENT OF CHRONIC HEPATITIS C IN PREVIOUS NONRESPONDERS]

TORNAI István

[Only approximately 50% of patients with chronic hepatitis C virus (HCV) genotype 1, the prevailing genotype in Hungary, show a sustained virologic response (SVR) when treated with the combination of peginterferon alfa and ribavirin. The number of patients who do not respond to this treatment is continuously increasing. The appearance of increasingly efficient treatment modalities was seen in the past 15 years, but now no new drugs are expected for a few years. There is a growing need for retreatment to prevent possible progression of the disease. The best candidates for retreatment are identified based on the data of the previous treatment; the dosage of the drugs used, dose reductions and their causes, the kinetics of the virologic response, the patient’s compliance, and every correctable and non-correctable factor should be carefully analysed. When the previous treatment with peginterferon and ribavirin failed to induce response, retreatment is only recommended if correctable factors can be identified. Repeated treatment may result in sustained virologic response usually if a longer duration and/or higher dose of ribavirin is applied. Since the best possible outcome of retreatment is sustained virologic response in 10 to 30% of patients, which is significantly lower than the results achieved in naive patients, every effort has to be made to increase the efficacy of the first treatment. For patients in whom no sustained virologic response can be achieved, a maintenance therapy with low dose interferon may be considered, although its benefit is yet to be proven. New small molecules are under development, which may bring further hope for nonresponders to current standard therapy.]