Hungarian Immunology

[50th Anniversary of the Hungarian Society of Microbiology, Section of Immunology]

KÁVAI Mária

JANUARY 22, 2008

Hungarian Immunology - 2008;7(01-02)

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Hungarian Immunology

[“Simply the BeSt”]

SZEKANECZ Zoltán

Hungarian Immunology

[The role of endothelium, cell migration, chemokines and angiogenesis in inflammatory rheumatic diseases]

BESENYEI Tímea, PÁKOZDI Angéla, VÉGVÁRI Anikó, SZABÓ Zoltán, SZEKANECZ Zoltán

[Endothelial cells, leukocyte-endothelial interactions and angiogenesis are highly involved in the pathogenesis of inflammation and thus in that of inflammatory rheumatic diseases. As this research area is very progressive, one needs to review novel molecular mechanisms and new therapeutic approaches in this respect. Authors review the most important functions of endothelial cells, the process of leukocyte extravasation, tissue infiltration and their cellular and molecular basis. Endothelial cells themselves produce a number of inflammatory mediators including interleukin-1 (IL-1), IL-6, IL-8, chemokines and others. Among cell adhesion molecules, β1 and β3 integrins, as well as E-, L- and P-selectins and their respective ligands have been implicated in leukocyte-endothelial adhesion. In recent years, numerous inflammatory mediators, cytokines, chemokines and proteases have been implicated in angiogenesis and angiostasis. Hypoxia, the vascular endothelial growth factor (VEGF)-angiopoietin system and mechanisms driven by β3 integrins are of major importance during angiogenesis. Significant amount of data have become available of the regulation of cell adhesion, migration and neovascularisation. Adhesion, chemokine and angiogenesis research has important clinical, practical aspects for antirheumatic and anti-cancer therapy. VEGF antagonists, anti-integrin antibodies, chemokine and chemokine receptor inhibitors, as well as thalidomide are currently in the first line of development.]

Hungarian Immunology

[Etanercept in early rheumatoid arthritis]

SZEKANECZ Zoltán

Hungarian Immunology

[MCP-1 (monocyte chemoattractant protein-1) G/A and T-bet (T-helper promoter factor) C/G polymorphisms in primary Sjögren’s syndrome and systemic lupus erythematosus]

KOVÁCS Attila, KONCZ Ágnes, ENDREFFY Emőke, ARANKA László, PETRI Ildikó, ELLER József, SZALAI Csaba

[INTRODUCTION - Monocyte chemoattractant protein- 1 (MCP-1) is a β-chemokine involved in the attraction and accumulation of mononuclear granulocytes towards the site of inflammation. One of the transcriptional factors of T-cells is called T-bet. PATIENTS AND METHODS - The authors investigated the MCP-1-2518 G/A and T-bet 310 C/G (His33Gln) polymorphisms evaluating the distribution of the specific genotypes in 45 patients with primary Sjögren's syndrome (pSS), 51 patients with systemic lupus erythematosus (SLE), and in 320 healthy blood donors as the control group. MCP-1-2518 G/A and T-bet 310 C/G polymorphisms were detected with molecular genetic methods from the purified genomic DNA. RESULTS - The frequency of the MCP-1-2518 AG heterozygous genotype decreased tendentiously only in SLE patients, while the frequency of the MCP-1 AA homozygous genotype increased comparing to the control group (13.7% vs. 5.9%; Pearson’s χ2 test=6.125, ns.). Analyzing the genotype frequency for the MCP-1 wild (GG) and AA homozygous genotypes in pSS group, the MCP-1 AA homozygous genotype proved to be more frequent comparing to the control group (82.8%:17.2% vs. 90.7%:9.3%; Pearson’s χ2 test 1.755, ns). These relations showed only tendentious association in the SLE group (81.6%:18.7% vs. 90.7%:9.3%; Pearson’s χ2 2.811, p=0.094, ns.) There was not any significant correlation between the investigated MCP-1- 2518 G/A and the T-bet 310 C/G polymorphisms and the TNF-α -308 G/A and -238 allele polymorphisms. The frequency of T-bet was equal in relation with heterozygous (CG) to wild CC genotype in the investigated two autoimmune disorders. The GG homozygous genotype for T-bet could not be found in SLE and pSS groups, likely to be a protective factor. CONCLUSIONS - The above mentioned polymorphisms didn’t show any significant correlation with TNF-α -308 and -238 allele polymorphisms. The further research of the MCP-1 G/A and T-bet C/G polymorphisms is important, because of their possible prognostic importance for SLE and pSS.]

Hungarian Immunology

[EULAR]

SZEKANECZ Zoltán

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[Advanced Parkinson’s disease characteristics in clinical practice: Results from the OBSERVE-PD study and sub-analysis of the Hungarian data]

TAKÁTS Annamária, ASCHERMANN Zsuzsanna, VÉCSEI László, KLIVÉNYI Péter, DÉZSI Lívia, ZÁDORI Dénes, VALIKOVICS Attila, VARANNAI Lajos, ONUK Koray, KINCZEL Beatrix, KOVÁCS Norbert

[The majority of patients with advanced Parkinson’s disease are treated at specialized movement disorder centers. Currently, there is no clear consensus on how to define the stages of Parkinson’s disease; the proportion of Parkinson’s patients with advanced Parkinson’s disease, the referral process, and the clinical features used to characterize advanced Parkinson’s disease are not well delineated. The primary objective of this observational study was to evaluate the proportion of Parkinson’s patients identified as advanced patients according to physician’s judgment in all participating movement disorder centers across the study. Here we evaluate the Hungarian subset of the participating patients. The study was conducted in a cross-sectional, non-interventional, multi-country, multi-center format in 18 countries. Data were collected during a single patient visit. Current Parkinson’s disease status was assessed with Unified Parkinson’s Disease Rating Scale (UPDRS) parts II, III, IV, and V (modified Hoehn and Yahr staging). Non-motor symptoms were assessed using the PD Non-motor Symptoms Scale (NMSS); quality of life was assessed with the PD 8-item Quality-of-Life Questionnaire (PDQ-8). Parkinson’s disease was classified as advanced versus non-advanced based on physician assessment and on questions developed by the Delphi method. Overall, 2627 patients with Parkinson’s disease from 126 sites were documented. In Hungary, 100 patients with Parkinson’s disease were documented in four movement disorder centers, and, according to the physician assessment, 50% of these patients had advanced Parkinson’s disease. Their mean scores showed significantly higher impairment in those with, versus without advanced Parkinson’s disease: UPDRS II (14.1 vs. 9.2), UPDRS IV Q32 (1.1 vs. 0.0) and Q39 (1.1 vs. 0.5), UPDRS V (2.8 vs. 2.0) and PDQ-8 (29.1 vs. 18.9). Physicians in Hungarian movement disorder centers assessed that half of the Parkinson’s patients had advanced disease, with worse motor and non-motor symptom severity and worse QoL than those without advanced Parkinson’s disease. Despite being classified as eligible for invasive/device-aided treatment, that treatment had not been initiated in 25% of these patients.]

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Evaluation of anxiety, depression and marital relationships in patients with migraine

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Aim - The aim of this study was to evaluate the frequency and characteristics of attacks in patients with migraine, to determine the effects of anxiety or depressive symptoms, and to evaluate the marital relationships of patients with migraine. Method - Thirty patients who were admitted to the neurology outpatient clinic of our hospital between July 2018 and October 2018 and were diagnosed with migraine according to the 2013 International Headache Society (IHS) diagnostic criteria were included in this cross-sectional study. Age, sex, headache frequency and severity, depressive traits, marital satisfaction and anxiety status were examined. We used the Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI), Maudsley Marital Questionnaire (MMQ) and Visual Analogue Scale (VAS) for measuring relevant parameters. Results - The mean severity of migraine pain according to VAS scale was 6.93 ± 1.41 and the mean number of migraine attacks was 4.50 ± 4.24. The mean BDI score of the patients was 12.66 ± 8.98, the mean MMQ-M score was 19.80 ± 12.52, the mean MMQ-S score was 13.20 ± 9.53, the mean STAI-state score was 39.93 ± 10.87 and the mean STAI-trait score was 45.73 ± 8.96. No significant correlation was found between age, number of migraine attacks, migraine duration, migraine headache intensity, and BDI, STAI and MMQ scores (p>0.05). But there was a positive correlation between MMQ-S and scores obtained from the BDI and STAI-state scales (p<0.05). Conclusion - In this study more than half of the migraine patients had mild, moderate or severe depression. A positive correlation was found between sexual dissatisfaction and scale scores of depression and anxiety.

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[Complications of infusion treatment with emphasis on extravasation of cytostatics]

HARISI Revekka

[The extravasation of cytostatics is the most signifi cant complication of infusion therapy in cancer treatment. Extravasation refers to the inadvertent infi ltration of cytostatic drugs into subcutaneous or subdermal tissues surrounding the intravenous or intraarterial administration site. According to literature data incidence estimates between 0,01-7%. Extravasated drugs are classifi ed according to their potential for causing damage as vesicant, irritant and nonvesicant. Knowledge of risk factors, the patientrelated and treatment-related ones is important to minimize the occurrence of extravasation. In order to reduce the risk of extravasation, the staff involved in the tumor infusion therapy must be specially trained to implement several preventive and therapeutical protocols. In 2012, ESMO-EONS has put together a new comprehensive treatment protocol on the topic of cytostatics extravasation. Protocol recommended that every oncological department, who administers chemotherapy have to have extravasation trained team and a standby extravasation kit. According to the new ESMO-EONS guideline subcutaneous corticoids are not recommended, anymore. In case of mechloretamine extravasation the recommendation is immediate subcutaneous injection of sodium thiosulfate. After extravasation of anthracyclines, mitomycin C and platin salts the best treatment opportunity is subcutan dimethyl sulfoxide administration. In case of anthracyclines’ extravasation intravenous dexrazoxane treatment is also effective. Hyaluronidase, injected into or under the skin, facilitates absorption of extravasated drugs because of increases connective tissue permeability, promotes the spreading and reduces the local concentration of the extravasated citostatic agents. Hyaluronidase might be effi cacious in preventing skin necrosis by extravasation due to vinca alkaloids. The treatment of unresolved tissue necrosis or pain lasting more than 10 days is surgical debridement. Because of the medical and juristic importance of the extravasation event, it is necessary to establish uniform guidelines for treatment of extravasation, in all Hungarian Oncological Centers.]

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[Decisional collisions between evidence and experience based medicine in care of people with epilepsy]

RAJNA Péter

[Background – Based on the literature and his long-term clinical practice the author stresses the main collisions of evidence and experience based medicine in the care of people with epilepsy. Purpose – To see, what are the professional decisions of high responsibility in the epilepsy-care, in whose the relevant clinical research is still lacking or does not give a satisfactory basis. Methods – Following the structure of the Hungarian Guideline the author points the critical situations and decisions. He explains also the causes of the dilemmas: the lack or uncertainty of evidences or the difficulty of scientific investigation of the situation. Results – There are some priorities of experience based medicine in the following areas: definition of epilepsy, classification of seizures, etiology – including genetic background –, role of precipitating and provoking factors. These are able to influence the complex diagnosis. In the pharmacotherapy the choice of the first drug and the optimal algorithm as well as the tasks during the care are also depends on personal experiences sometimes contradictory to the official recommendations. Same can occur in the choice of the non-pharmacological treatments and rehabilitation. Discussion and conclusion – Personal professional experiences (and interests of patients) must be obligatory accessories of evidence based attitude, but for achieving the optimal results, in some situations they replace the official recommendations. Therefore it is very important that the problematic patients do meet experts having necessary experiences and also professional responsibility to help in these decisions. ]

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[Adherence of Hungarian postmenopausal women with osteoporosis]

LAKATOS Péter, TÓTH Emese, LANG Zsolt, NAGY Bence, SZEKERES László, TAKÁCS István

[INTRODUCTION - Osteoporosis is defined as a loss of bone tissue and bone mass that leads to a compromised trength and quality of bones and thus to an increased risk of fractures. In many women, menopausal hormonal changes are associated with an increased bone loss. This population has postmenopausal osteoporosis. The essence of osteporosis treatment is the adequate calcium and vitamin D supplementation, which, if needed, might be combined with drug therapy to inhibit the process of bone loss. METHODS - We assessed the adherence to therapy of Hungarian patients and its effect on the risk of bone fractures, using data recorded by the National Health Insurance Fund Administration between 2004 and 2010 (n=223068, mean age: 69.9 years). We performed a statistical analyses of the available data. Medication possession ratio (MPR) for each treatment and the ratio of patients receiving continuous treatment in the study period (for 12, 18 and 24 months) were estimated. Medication persistence was investigated using Kaplan-Meier survival analysis. A multivariate Cox proportional hazard model was used to determine the factors influencing the risk of fracture. RESULTS, CONCLUSION - The results of our study show that medication adherence to treatment is low among Hungarian patients [mean MPR: 57.9%; 95% CI (57.7%- 58.0%) and persistence rate: 32.4%; 95% CI (32.2%-32.6%) in the first year]. These parameters are substantially influenced by the administration route and the frequency of treatments [mean MPR ranged 41.5%- 100% and persistence rates ranged 18.8%- 100% in the first year, differences between subgroups were significant (p<0,05)]. Our compliance as well as persistance studies showed that parenteral administration had more beneficial effects. Confirming our preliminary hypotheses, the improvement of patient compliance significantly reduced fracture risk (good compliance was defined as MPR>80%, which was associated with RR: 0.57, p<0.05 for fracture risk). Further improvement might be achieved by parenteral administration [RR for fracture risk 0.60 compared with non-compliant patients and 0.44 compared with compliant subgroups treated with oral and parenteral medications (p<0.05)].]