Hungarian Immunology

[Examination of leukocyte-endothel interactions in inflammatory animal models]

GONDA Andrea, MIKECZ Katalin, HUNYADI János

OCTOBER 20, 2007

Hungarian Immunology - 2007;6(05)

[Leukocyte influx into tissues is one of the hallmarks of physiological reactions to inflammatory stimuli, which is followed by a multistep process, resulting in leukocyte extravasation from the postcapillary venules. The different kinds of adhesion molecules, that play role in the rolling and firm adhesion of the leukocytes, have been investigated very intensively. By the help of animal models of inflammation, numerous individuals, being in the same stage of the disease, can be examined. The requirement for the adhesion molecules for inflammatory responses could be investigated with antibodies or, nowadays more often, gene knock out (KO) or transgenic mice. Beside evaluating the morphological and cytokine profile differences, using intravital microscopy is of great importance in the inflammatory experiments, while it allows observing interactions of virtually any blood cell types with the endothelial wall in vivo. The results are sometimes conflicting, indicating that the process of leukocyte-endothel interactions depends on different kind of other factors than the adhesion molecules, and still not fully understood.]

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Hungarian Immunology

[Waiting for DROP]

SZEKANECZ Zoltán

Hungarian Immunology

[The role of endothelial cells]

CERVENAK László

[The role of endothelial cells is much beyond the well known barrier function between blood and tissues. Several different stimuli converge in the endothelial cells, which in turn regulate a number of vital processes in the organisms. Among these processes one of the most important is the immune response. Endothelial cells modulate the homing of leukocytes by the production of adhesion molecules and cytokines depending on activation state, anatomic location and vessel type. Endothelial cells express MHC and costimulatory molecules, which enables them to present antigens to T cells. Antigen presentation may lead to activation or tolerance of T cells depending on the phenotype of endothelial cells. They also express complement regulatory molecules and produce several complement cascade proteins. Endothelial cells take part in the catabolism of immunoglobulins as well as in the removal of circulating immune complexes. Finally, endothelial cells regulate inflammation at different levels by several mechanisms, which may substantially determinate the progression of the immune response.]

Hungarian Immunology

[Alpha calcidol treatment in patients with psoriatic arthropathy: clinical and immunological effects]

GAÁL János, LAKOS Gabriella, ALEKSZA Magdolna, KISS Judit, HORVÁTH Irén, HORKAY Edit, NAGY Georgina, SZEGEDI Andrea

[OBJECTIVE - Our objective was to describe the functional changes of the immune system also to evaluate the clinical parameters during systemic alphacalcidol (1αOH vitamin D3) treatment in patients with psoriatic arthropathy. PATIENTS AND METHOD - Nineteen patients with peripheral polyarticular form of psoriatic arthropathy were investigated. Ten patients were treated with daily 2×25 mcg alphacalcidol per os for 6 months and the other 9 patients served as controls. Three visits (at start, 3 and 6 months later) were carried out during the study, changes in the laboratory and clinical parameters were examined and analysed statistically in the treated and control groups. RESULTS - In the peripheral blood of the treated group a statistically significant decrease in the percentage of CD3/CD69 positive activated and CD8 positive IFNγ producing T cells was observed and the serum level of IFNγ also showed a significant decrease during the first 3 months. Another three months later no change in the above mentioned variables could be detected. Additionally, there was a significant decrease in the clinical activity of the disease using DAS28 score during the whole 6 months follow up period. In the control group no significant changes were observed. CONCLUSION - Our results show that systemic alphacalcidol treatment has a notable immune modulatory effect on patients with psoriatic arthropathy. This effect is manifested in short-term temporary decrease of type 1 immune responses and continuous decrease in the disease activity.]

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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

[What happens to vertiginous population after emission from the Emergency Department?]

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[Background – Dizziness is one of the most frequent complaints when a patient is searching for medical care and resolution. This can be a problematic presentation in the emergency department, both from a diagnostic and a management standpoint. Purpose – The aim of our study is to clarify what happens to patients after leaving the emergency department. Methods – 879 patients were examined at the Semmel­weis University Emergency Department with vertigo and dizziness. We sent a questionnaire to these patients and we had 308 completed papers back (110 male, 198 female patients, mean age 61.8 ± 12.31 SD), which we further analyzed. Results – Based on the emergency department diagnosis we had the following results: central vestibular lesion (n = 71), dizziness or giddiness (n = 64) and BPPV (n = 51) were among the most frequent diagnosis. Clarification of the final post-examination diagnosis took several days (28.8%), and weeks (24.2%). It was also noticed that 24.02% of this population never received a proper diagnosis. Among the population only 80 patients (25.8%) got proper diagnosis of their complaints, which was supported by qualitative statistical analysis (Cohen Kappa test) result (κ = 0.560). Discussion – The correlation between our emergency department diagnosis and final diagnosis given to patients is low, a phenomenon that is also observable in other countries. Therefore, patient follow-up is an important issue, including the importance of neurotology and possibly neurological examination. Conclusion – Emergency diagnosis of vertigo is a great challenge, but despite of difficulties the targeted and quick case history and exact examination can evaluate the central or peripheral cause of the balance disorder. Therefore, to prevent declination of the quality of life the importance of further investigation is high.]

Clinical Neuroscience

Simultaneous subdural, subarachnoideal and intracerebral haemorrhage after rupture of a peripheral middle cerebral artery aneurysm

BÉRES-MOLNÁR Anna Katalin, FOLYOVICH András, SZLOBODA Péter, SZENDREY-KISS Zsolt, BERECZKI Dániel, BAKOS Mária, VÁRALLYAY György, SZABÓ Huba, NYÁRI István

The cause of intracerebral, subarachnoid and subdural haemorrhage is different, and the simultaneous appearance in the same case is extremely rare. We describe the case of a patient with a ruptured aneurysm on the distal segment of the middle cerebral artery, with a concomitant subdural and intracerebral haemorrhage, and a subsequent secondary brainstem (Duret) haemorrhage. The 59-year-old woman had hypertension and diabetes in her medical history. She experienced anomic aphasia and left-sided headache starting one day before admission. She had no trauma. A few minutes after admission she suddenly became comatose, her breathing became superficial. Non-contrast CT revealed left sided fronto-parietal subdural and subarachnoid and intracerebral haemorrhage, and bleeding was also observed in the right pontine region. The patient had leucocytosis and hyperglycemia but normal hemostasis. After the subdural haemorrhage had been evacuated, the patient was transferred to intensive care unit. Sepsis developed. Echocardiography did not detect endocarditis. Neurological status, vigilance gradually improved. The rehabilitation process was interrupted by epileptic status. Control CT and CT angiography proved an aneurysm in the peripheral part of the left middle cerebral artery, which was later clipped. Histolo­gical examination excluded mycotic etiology of the aneu­rysm and “normal aneurysm wall” was described. The brain stem haemorrhage – Duret bleeding – was presumably caused by a sudden increase in intracranial pressure due to the supratentorial space occupying process and consequential trans-tentorial herniation. This case is a rarity, as the patient not only survived, but lives an active life with some residual symptoms.

Clinical Neuroscience

Life threatening rare lymphomas presenting as longitudinally extensive transverse myelitis: a diagnostic challenge

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Background and aims – Description of two cases of rare intravascular large B-cell lymphoma and secondary T-cell lymphoma diagnosed postmortem, that manifested clinically as longitudinally extensive transverse myelitis (LETM). We discuss causes of diagnostic difficulties, deceptive radiological and histological investigations, and outline diagnostic procedures based on our and previously reported cases. Case reports – Our first case, a 48-year-old female was admitted to the neurological department due to paraparesis. MRI suggested LETM, but the treatments were ineffective. She died after four weeks because of pneumonia and untreatable polyserositis. Pathological examination revealed intravascular large B-cell lymphoma (IVL). Our second case, a 61-year-old man presented with headache and paraparesis. MRI showed small bitemporal lesions and lesions suggesting LETM. Diagnostic investigations were unsuccessful, including tests for possible lymphoma (CSF flow cytometry and muscle biopsy for suspected IVL). Chest CT showed focal inflammation in a small area of the lung, and adrenal adenoma. Brain biopsy sample from the affected temporal area suggested T-cell mediated lymphocytic (paraneoplastic or viral) meningoencephalitis and excluded diffuse large B-cell lymphoma. The symptoms worsened, and the patient died in the sixth week of disease. The pathological examination of the presumed adenoma in the adrenal gland, the pancreatic tail and the lung lesions revealed peripheral T-cell lymphoma, as did the brain and spinal cord lesions. Even at histological examination, the T-cell lymphoma had the misleading appearance of inflammatory condition as did the MRI. Conclusion – Lymphoma can manifest as LETM. In cases of etiologically unclear atypical LETM in patients older than 40 years, a random skin biopsy (with subcutaneous adipose tissue) from the thigh and from the abdomen is strongly recommended as soon as possible. This may detect IVL and provide the possibility of prompt chemotherapy. In case of suspicion of lymphoma, parallel examination of the CSF by flow cytometry is also recommended. If skin biopsy is negative but lymphoma suspicion remains high, biopsy from other sites (bone marrow, lymph nodes or adrenal gland lesion) or from a simultaneously existing cerebral lesion is suggested, to exclude or prove diffuse large B-cell lymphoma, IVL, or a rare T-cell lymphoma.

Clinical Neuroscience

Cyanocobalamin and cholecalciferol synergistically improve functional and histopathological nerve healing in experimental rat model

ALBAY Cem, ADANIR Oktay, AKKALP Kahraman Asli, DOGAN Burcu Vasfiye, GULAEC Akif Mehmet, BEYTEMUR Ozan

Introduction - Peripheral nerve injury (PNI) is a frequent problem among young adults. Hopefully, regeneration can occur in PNI unlike central nervous system. If nerve cut is complete, gold standard treatment is surgery, but incomplete cuts have been tried to be treated by medicines. The aim of the study was to evaluate and compare clinical and histopathological outcomes of independent treatment of each of Vitamin B12 (B12) and Vitamin D3 (D3) and their combination on sciatic nerve injury in an experimental rat model. Materials and methods - Experimental animal study was performed after the approval of BEH Ethics Committee No. 2015/10. 32 rats were grouped into four (n=8) according to treatment procedures, such as Group 1 (controls with no treatment), Group 2 (intraperitoneal 1 mg/kg/day B12), Group 3 (oral 3500 IU/kg/week D3), Group 4 (intraperitoneal 1 mg/kg/day B12+ oral 3500 IU/kg/week D3). Sciatic Functional Index (SFI) and histopathological analysis were performed. Results - SFIs of Group 2, 3, 4 were statistically significantly higher than controls. Group 2 and 3 were statistically not different, however Group 4 was statistically significantly higher than others according to SFI. Axonal degeneration (AD) in all treatment groups were statistically significantly lower than in Group 1. AD in Group 4 was significantly lower than in Group 2 and 3; there was no significant difference between Group 2 and 3. There was no significant difference between Group 1,2 and 3 in Axonolysis (A). But A of Group 4 was significantly very much lower than all others. Oedema- inflammation (OE-I) in all treatment groups were significantly lower than in Group 1; there was no significant difference between Group 2 and group 4. OE-I in Group 2 and 4 were significantly lower than in Group 3. There were no significant differences between Group 1, 2 and 3 in damage level scores; score of Group 4 was significantly lower than of Group 1. Conclusions - B12 and D3 were found effective with no statistically significant difference. But combined use of B12 and D3 improve nerve healing synergistically. We recommend combined use of B12 and D3 after PNI as soon as possible.