Hungarian Immunology

[Comparison of disease-modifying drugs in rheumatoid arthritis]

SZŰCS Gabriella, SZEKANECZ Zoltán

JANUARY 22, 2008

Hungarian Immunology - 2008;7(01-02)

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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

[Kinetic measurement on flow cytometer simultaneous monitoring of intracellular progresses]

MÉSZÁROS Gergő, RÓNAI Katalin Zsuzsanna, TOLDI Gergely, KAPOSI Ambrus, VÁSÁRHELYI Barna, TRESZL András

[INTRODUCTION - Flow cytometry provides an opportunity for real-time monitoring of intracellular processes in several cell populations simultaneously. Cells stained with specific fluorescent dyes are sequentially measured during kinetic FACS measurements. Fluorescent light signals obtained in cells are recorded and analyzed to describe the alteration of the investigated parameter(s) over time. The use of kinetic FACS assays is not spread as there was no mathematic algorithm to characterize objectively the distribution of data and kinetic changes. MATERIALS, METHODS, RESULTS - We developed a new approach which fits functions to measured data sets, describes the statistical distribution and forms a basis for statistical comparison between individual kinetic measurements. We created two FACS assays on BD FACS Aria instrument. The first one monitors calcium flux, generation of reactive oxygen species and mitochondrial membrane potential, while the second one monitors mitochondrial calcium flux, nitric oxide generation and plasma membrane potential in CD4+ and CD8+ lymphocytes simultaneously before and after the administration of a lymphocyte activator. CONCLUSIONS - This technique may be used to investigate purposes (i.e. to test the impact of any agent (such as immunmodulatory drugs) on cellular processes in lymphocytes) and to diagnostic purposes (i.e. to test the alteration of lymphocyte activation characteristics in disease).]

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

[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.]

Hungarian Immunology

[EULAR]

SZEKANECZ Zoltán

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Clinical Neuroscience

Late simultaneous carcinomatous meningitis, temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting with mono-symptomatic vertigo – a clinico-pathological case reporT

JARABIN András János, KLIVÉNYI Péter, TISZLAVICZ László, MOLNÁR Anna Fiona, GION Katalin, FÖLDESI Imre, KISS Geza Jozsef, ROVÓ László, BELLA Zsolt

Although vertigo is one of the most common complaints, intracranial malignant tumors rarely cause sudden asymmetry between the tone of the vestibular peripheries masquerading as a peripheral-like disorder. Here we report a case of simultaneous temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting as acute unilateral vestibular syndrome, due to the reawakening of a primary gastric signet ring cell carcinoma. Purpose – Our objective was to identify those pathophysiological steps that may explain the complex process of tumor reawakening, dissemination. The possible causes of vestibular asymmetry were also traced. A 56-year-old male patient’s interdisciplinary medical data had been retrospectively analyzed. Original clinical and pathological results have been collected and thoroughly reevaluated, then new histological staining and immunohistochemistry methods have been added to the diagnostic pool. During the autopsy the cerebrum and cerebellum was edematous. The apex of the left petrous bone was infiltrated and destructed by a tumor mass of 2x2 cm in size. Histological reexamination of the original gastric resection specimen slides revealed focal submucosal tumorous infiltration with a vascular invasion. By immunohistochemistry mainly single infiltrating tumor cells were observed with Cytokeratin 7 and Vimentin positivity and partial loss of E-cadherin staining. The subsequent histological examination of necropsy tissue specimens confirmed the disseminated, multi-organ microscopic tumorous invasion. Discussion – It has been recently reported that the expression of Vimentin and the loss of E-cadherin is significantly associated with advanced stage, lymph node metastasis, vascular and neural invasion and undifferentiated type with p<0.05 significance. As our patient was middle aged and had no immune-deficiency, the promoting factor of the reawakening of the primary GC malignant disease after a 9-year-long period of dormancy remained undiscovered. The organ-specific tropism explained by the “seed and soil” theory was unexpected, due to rare occurrence of gastric cancer to metastasize in the meninges given that only a minority of these cells would be capable of crossing the blood brain barrier. Patients with past malignancies and new onset of neurological symptoms should alert the physician to central nervous system involvement, and the appropriate, targeted diagnostic and therapeutic work-up should be established immediately. Targeted staining with specific antibodies is recommended. Recent studies on cell lines indicate that metformin strongly inhibits epithelial-mesenchymal transition of gastric cancer cells. Therefore, further studies need to be performed on cases positive for epithelial-mesenchymal transition.

Clinical Neuroscience

Alexithymia is associated with cognitive impairment in patients with Parkinson’s disease

SENGUL Yildizhan, KOCAK Müge, CORAKCI Zeynep, SENGUL Serdar Hakan, USTUN Ismet

Cognitive dysfunction (CD) is a common non-motor symptom of Parkinson’s disease (PD). Alexithy­mia is a still poorly understood neuropsychiatric feature of PD. Cognitive impairment (especially visuospatial dysfunction and executive dysfunction) and alexithymia share com­mon pathology of neuroanatomical structures. We hypo­thesized that there must be a correlation between CD and alexithymia levels considering this relationship of neuroanatomy. Objective – The aim of this study was to evaluate the association between alexithymia and neurocognitive function in patients with PD. Thirty-five patients with PD were included in this study. The Toronto Alexithymia Scale–20 (TAS-20), Geriatric Depression Inventory (GDI) and a detailed neuropsychological evaluation were performed. Higher TAS-20 scores were negatively correlated with Wechsler Adult Intelligence Scale (WAIS) similarities test score (r =-0.71, p value 0.02), clock drawing test (CDT) scores (r=-0.72, p=0.02) and verbal fluency (VF) (r=-0.77, p<0.01). Difficulty identifying feelings subscale score was negatively correlated with CDT scores (r=-0.74, p=0.02), VF scores (r=-0.66, p=0.04), visual memory immediate recall (r=-0.74, p=0.01). VF scores were also correlated with difficulty describing feelings (DDF) scores (r=-0.66, p=0.04). There was a reverse relationship bet­ween WAIS similarities and DDF scores (r=-0.70, p=0.02), and externally oriented-thinking (r=-0.77,p<0.01). Executive function Z score was correlated with the mean TAS-20 score (r=-62, p=0.03) and DDF subscale score (r=-0.70, p=0.01) Alexithymia was found to be associated with poorer performance on visuospatial and executive function test results. We also found that alexithymia was significantly correlated with depressive symptoms. Presence of alexithymia should therefore warn the clinicians for co-existing CD.

Clinical Neuroscience

Comparison of direct costs of percutaneous full-endoscopic interlaminar lumbar discectomy and microdiscectomy: Results from Turkey

ÜNSAL Ünlü Ülkün, ŞENTÜRK Salim

Microdiscectomy (MD) is a stan­dard technique for the surgical treatment of lumbar disc herniation (LDH). Uniportal percutaneous full-endoscopic in­terlaminar lumbar discectomy (PELD) is another surgical op­tion that has become popular owing to reports of shorter hos­pitalization and earlier functional recovery. There are very few articles analyzing the total costs of these two techniques. The purpose of this study was to compare total hospital costs among microdiscectomy (MD) and uniportal percutaneous full-endoscopic interlaminar lumbar discectomy (PELD). Forty patients aged between 22-70 years who underwent PELD or MD with different anesthesia techniques were divided into four groups: (i) PELD-local anesthesia (PELD-Local) (n=10), (ii) PELD-general anesthesia (PELD-General) (n=10), (iii) MD-spinal anesthesia (MD-Spinal) (n=10), (iv) MD-general anesthesia (MD-General) (n=10). Health care costs were defined as the sum of direct costs. Data were then analyzed based on anesthetic modality to produce a direct cost evaluation. Direct costs were compared statistically between MD and PELD groups. The sum of total costs was $1,249.50 in the PELD-Local group, $1,741.50 in the PELD-General group, $2,015.60 in the MD-Spinal group, and $2,348.70 in the MD-General group. The sum of total costs was higher in the MD-Spinal and MD-General groups than in the PELD-Local and PELD-General groups. The costs of surgical operation, surgical equipment, anesthesia (anesthetist’s costs), hospital stay, anesthetic drugs and materials, laboratory wor­kup, nur­sing care, and postoperative me­dication diffe­red significantly among the two main groups (PELD-MD) (p<0.01). This study demonstrated that PELD is less costly than MD.

Lege Artis Medicinae

[Diagnosis and treatment of microvascular coronary heart disease. Specialities of conditions in Hungary]

SZAUDER Ipoly

[Invasive investigations show that in two-thirds of patients the myocardial ischaemia persists without obstructive coronary disease and any other heart conditions (INOCA). The underlying cause may be microvascular dysfunction (CMD) with consecutive microvascular coronary disease (MVD) and microvascular or epicardial vasospastic angina (MVA). The modern practice of clinical cardiology while using the developed non-invasive cardiac imaging permits exact measuring of the coronary flow with its characteristic indices. All of these improve the diagnosing of CMD-induced myocardial ischemia and provide opportunity to determine primary MVD cases. Since the recognition and treatment of MVD is significantly underrep­resented in the Hungarian medical care, the primary stable microvascular angina (MVA) is described in detail below with its modern invasive and non-invasive differential diagnosis and treatment, concerning especially its frequency provoked by high blood pressure and female coronary heart diseases. There are highlighted all recommended diagnostic procedures available under domestic conditions.]

Lege Artis Medicinae

[Risk of nonsteroidal antiinflammatory drugs. Focus on aceclofenac]

FARSANG Csaba

[Nonsteroidal antiinflammatory drugs (NSAIDs) are among the most frequently used pharmaceuticals. Nevertheless, a number of studies emphasized that NSAIDs were damaging not only the gastrointestinal (GI), but also the cardiovascular (CV) system, could increase the blood pressure, the frequency of coronary events (angina, myocardial infarction) and stroke incidence, as well as they might deterio­rate renal functions. The National Institute for Health and Care Excellence (NICE) did not find evidence that administering NSAIDs could increase the risk of developing COVID-19 or worsened the condition of COVID-19 patients. However, unwanted effects of specific drugs differ substantially in their occurrence and seriousness as well. It seemed to be for a long time that the NSAIDs provoked higher GI-risk was closely related to the COX1/COX2 selectivity, like the cardiovascular (CV) risk to the COX2/COX1 selectivity, however, the recent data did not prove it clearly. Based on the available literature while pondering the gastrointestinal and cardiovascular adverse events, among all NSAIDs the aceclofenac profile seemed to be the most favourable.]