Hungarian Immunology

[Immune-dysfunctions in patients with Hodgkin’s lymphoma being in a long lasting complete remission]

ALEKSZA Magdolna, KERESZTES Katalin, BARÁTH Sándor, SIPKA Sándor, ILLÉS Árpád

FEBRUARY 20, 2005

Hungarian Immunology - 2005;4(01)

[OBJECTIVES - Immunosuppression has long been known to be associated with Hodgkin’s lymphoma. The authors report on immunologic abnormalities with special focus on cellular immunity in patients with Hodgkin’s disease in complete remission. METHODS - We determined the proportion of the lymphocytes subpopulations, activated T cells, CD4+/CD25+ suppressor T cell population and intracytoplasmic cytokines by flow cytometry. The soluble cytokines were measured by classical ELISA technique. RESULTS - Based on lymphocyte cell surface antigen expression the subpopulations were as described in the literature, however a unique elevation of CD4+/CD25+ cell fraction was detected. The decreased amount of IFN-γ in the serum suggest Th2 dominance, but reduced intracellular IL-4 production in both CD4+ and CD8+ cells results from Th1 dominance. These results somewhat contrary but can not be completely compared as in vivo and in vitro techniques used for the analysis are not identical. However a constant elevation concentration and expression of IL-10 and TGF-β is observed. CONCLUSION - These alterations may reflect the existence of an immunosuppressive state also in the peripheral blood of Hodgkin’s lymphoma patients not only in the lymph nodes.]

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Hungarian Immunology

[Pathomechanism of Crohn’s disease and ulcerative colitis]

GÁL István, CSIKI Zoltán, SZEGEDI László, G. KISS Gyula

[The two archetypes of inflammatory bowel diseases, Crohn’s disease (CD) and ulcerative colitis (UC) have a considerably high prevalence and chronic morbidity, and thereby a striking public health relevance amongst the maladies involving the gastrointestinal tract. Unveiling their pathogenesis can be the key for the development of successful therapeutic approaches. Our view of these diseases has undergone radical changes in the past few years, and the latest discoveries have shed new light upon their pathomechanism. A multifactorial view is appropriate when explaining their pathogenesis, although certain factors are seemingly of particular importance.]

Hungarian Immunology

[Experimental arthritis model]

SZÁNTÓ Sándor, GONDA Andrea, MIKECZ Katalin, GLANT Tibor, SZEKANECZ Zoltán

[Animal models of experimental arthritis can be used to understand pathophysiology of the arthritic processes in patients and provide opportunity to develop new therapeutic approaches. The animal models can be divided into different categories based on the pathomechanism of the model and on the features that resemble human inflammatory joint diseases. This review provides an overview of the most widely used types of experimental arthritis models emphasizing their advantages and limitations in the basic arthritis research.]

Hungarian Immunology

[Functional measurements of the hand’s circulation in Raynaud’s patients]

CSIKI Zoltán, GALUSKA László, GARAI Ildikó, SZABÓ Nóra, GALAJDA Zoltán, VARGA József, ZEHER Margit

[INTRODUCTION - In patients presenting with isolated tissue perfusion disturbance without large vessel involvement the examination of hand microcirculation is of major importance. In our study we present the results of three examination methods used for hand perfusion monitoring which measure the tissue microcirculation in different depths. PATIENTS AND METHODS - We examined 58 primary Raynaud's patients using capillary microscopy, laser doppler perfusion imaging and hand perfusion scintigraphy with Tc-99m-DTPA. From our patients 38 were smokers, 42 patients frequently suffered from headache. For the validation of our laser Doppler results we involved into the study also 16 non-smoker healthy volunteers. For the standardisation of the results the studies were performed in a climatised room. During the laser examination we performed and analysed also the post-occlusion hyperaemia test. RESULTS - In the majority of our patients no morphological alterations were found with capillary microscopy. In primary Raynaud’s patients the perfusion values measured with laser-Doppler scanner in basic condition were significantly lower both in fingers’ and palm’s regions compared to healthy controls. In the primary Raynaud’s group the smokers had significantly lower hyperaemic response than the non-smokers and we measured also significantly lower FPR (finger-to-palm ratio) values with hand perfusion scintigraphy. Both with laser doppler imaging and hand perfusion scintigraphy there was no difference between the values measured in patients with or without headache. CONCLUSIONS - We consider of benefit the functional examination of hand circulation in all diseases involving the hand microcirculation.]

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[History of immunology in Hungary Part VI]

KARASSZON Dénes, CSABA Béla

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[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.]

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

Evaluation of the effectiveness of transforaminal epidural steroid injection in far lateral lumbar disc herniations

EVRAN Sevket, KATAR Salim

Far lateral lumbar disc herniations (FLDH) consist approximately 0.7-12% of all lumbar disc herniations. Compared to the more common central and paramedian lumbar disc herniations, they cause more severe and persistent radicular pain due to direct compression of the nerve root and dorsal root ganglion. In patients who do not respond to conservative treatments such as medical treatment and physical therapy, and have not developed neurological deficits, it is difficult to decide on surgical treatment because of the nerve root damage and spinal instability risk due to disruption of facet joint integrity. In this study, we aimed to evaluate the effect of transforaminal epidural steroid injection (TFESI) on the improvement of both pain control and functional capacity in patients with FLDH. A total of 37 patients who had radicular pain caused by far lateral disc herniation which is visible in their lumbar magnetic resonance imaging (MRI) scan, had no neurological deficit and did not respond to conservative treatment, were included the study. TFESI was applied to patients by preganglionic approach. Pre-treatment Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) scores of the patients were compared with the 3rd week, 3rd month and 6th month scores after the procedure. The mean initial VAS score was 8.63 ± 0.55, while it was 3.84 ± 1.66, 5.09 ± 0.85, 4.56 ± 1.66 at the 3rd week, 3rd month and 6th month controls, respectively. This decrease in the VAS score was found statistically significant (p = 0.001). ODI score with baseline mean value of 52.38 ± 6.84 was found to be 18.56 ± 4.95 at the 3rd week, 37.41 ± 14.1 at the 3rd month and 34.88 ± 14.33 at the 6th month. This downtrend of pa­tient’s ODI scores was found statistically significant (p = 0.001). This study has demonstrated that TFESI is an effective method for gaining increased functional capacity and pain control in the treatment of patients who are not suitable for surgical treatment with radicular complaints due to far lateral lumbar disc hernia.