Hungarian Immunology

[History of immunology in Hungary]

JUNE 20, 2002

Hungarian Immunology - 2002;1(02)

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Hungarian Immunology

[Changes in the signal transduction of T-lymphocytes caused by hyperglycemia]

BOLDIZSÁR Ferenc, BERKI Tímea, MISETA Attila, NÉMETH Péter

[AIMS - Lately the altered calcium balance of different cell types (eg.: erythrocytes, platelets, neutrophil granulocytes) was described in diabetes mellitus. It is also known that patients with diabetes mellitus suffer from various infections more often then healthy individuals because of immunological malfunctions. But the mechanism of these changes is still unclear. In order to investigate the effect of hyperglycemia on the function of immunocompetent cells we established an in vitro diabetes model by culturing human T cells (Jurkat cells) at different glucose concentrations for one week. Then we measured the basal cytosolic calcium level, the calcium signal after ionomycin or anti-CD3 treatment and the tyrosinephosphorylation of signal transducing proteins as well as the fructosamine level of cellular proteins. MATERIALS AND METHOD - Cytosolic free calcium levels were detected by flow cytometry using ion selective fluorescent indicator (Fluo-3 AM). Calcium signals of Jurkat cells were measured after ionomycin or monoclonal anti-CD3 antibody (OKT3) treatment. We also measured the tyrosine-phosphorylation on flow cytometer after anti-CD3 stimulation using indirect immunfluorescent labeling with monoclonal antiphospho- tyrosine antibody. The non-enzymatic glycation of cellular proteins was determined by measuring the fructosamine levels of cell lysates. RESULTS - The higher concentration of extracellular glucose resulted in concentration-dependent elevation of basal cytosolic free calcium level in Jurkat cells. Reduced calcium signal (activation capacity) was measured either after ionomycin or monoclonal anti-CD3 antibody treatments in cells kept at hyperglycemic conditions. In addition, the time kinetics of calcium signal following anti- CD3 activation was found prolonged in the hyperglycemic cells. The tyrosine-phosphorilation of hyperglycemic Jurkat cells also proved to be impaired. High glucose concentrations in tissue culture medium caused increase in the glycation of T-cell proteins. CONCLUSIONS - We propose that increased glycation of proteins involved in calcium transport and/or intracellular signal transduction of T-cells may account for our observations.]

Hungarian Immunology

[CONFERENCE CALENDAR]

Hungarian Immunology

[Autoimmun thyroiditis presence in patient with Hodgkin’s disease in remission]

BÍRÓ Edit, BAKÓ Gyula, SZEGEDI Gyula, ILLÉS Árpád

[INTRODUCTION - It is known that the incidence of hypothyroidism is higher in long term survivor patients with Hodgkin's disease, and it is supposed to be the result of treatment, such as neck radiotherapy. The author believe that other etiologic factors may also play a role in the development of hypothyroidism. PATIENTS AND METHODS - Looking for the possible causes of hypothyroidism, the thyroid function of 151 patients treated for Hodgkin's disease since 1970 were examined. These patients with Hodgkin's disease in complete remission for at least one year and their data on thyroid autoantibody positivity [antithyroid peroxidase antibody (aTPO), antihuman thyroglobulin antibody (aHTG), TSH antireceptor antibody (TRAK)] were analysed. RESULTS - Among the patients with antibody positive 26 received ultrasound scanning and fine needle aspiration cytology of the thyroid, which confirmed autoimmun thyroiditis. There were no significant differences between the mean age, histologic subtypes and stage of the disease between the patients with antibody positive those with antibody negative. A significantly greater number of women in the group of antibody positive patients was found and thyroid dysfunction (two cases of hyper, and 13 cases of hyperthyroidism) was revealed in 53.6% of the patients. Though antibody positivity was more frequent in patients having been treated by neck irradiation, but no significant relationship was found between the form of Hodgkin’s disease treatment and the development of thyroiditis. Thus the authors cannot confirm the assumption according to which the autoantigens released from the thyroid gland damaged by neck irradiation for Hodgkin's disease would provoke the development of thyroiditis. Since - independently of the type of treatment received - the incidence of thyroiditis is higher in patients with Hodgkin's disease, it is probable that immune regulation disorders may also play a role in its development and thus hypothyroidism is the result of a multi-factor process. DISCUSSION - These results underline the importance of a regular control of thyroid hormones and thyroid autoantibodies in follow up Hodgkin’s disease patients. Levothyroxine administered as an isohormone treatment may inhibit the development of hypothyroidism in patients with thyroiditis may improve the quality of their life.]

Hungarian Immunology

[Ocular myositis]

KISS Emese, FACSKÓ Andrea, DÉVÉNYI Katalin, DANKÓ Katalin, ZEHER Margit

[INTRODUCTION - Dermato-/polymyositis is an autoimmune disorder, which belongs to the idiopathic inflammatory myopaties. It involves skeletal muscles in form of weakness and inflammatory infiltrates. Characteristic skin lesions are present in dermatomyositis. Other organs may also be affected mainly in the presence of myositis specific autoantibodies. The inflammation usually involves the proximal muscles of extremities. CASE REPORT - In the present work we report the case of a 52-year-old woman. In the previous history the removal of rectal adenocarcinoma was remarkable in 1994. After that she received chemotherapy. She complied for severe headache and pain in the right eye in 2000 October, therefore a skull CT was performed, indicating thickening of rectus medalis muscle within orbital cavity. There was an enhancement of contrast material in the muscle. Glaucoma was excluded. Neurologist suspected the presence of myositis and indicated 0.5 mg/kg corticosteroid therapy. Soon after the left eye became painful, but due to the corticosteroid treatment both eyes became painless. A control orbital CT was completely negative in 2000 November. Immunology consultancy revealed a mild proximal muscle atrophy in both lower extremities, but CPK and LDH enzyme levels were normal, EMG was characteristic for mild chronic nerve lesion. The biopsy, taken from the involved proximal muscle of lower extremity, did not show inflammatory infiltration. Complete screening for cancer was negative. Thyroid gland disease could be excluded. Immune laboratory data were negative, autoantibodies, including anti-Jo1, could not be detected. Based on the results a rare disease, ocular myositis was diagnosed. Considering the clinical improvement, the withdrawal of corticosteroid therapy was offered. Stringent immunology and oncology follow-up is required. CONCLUSION - In relation to our case report, we discuss clinical symptoms of orbital myositis, diagnostic procedures to identify the disease and also differential diagnostic considerations.]

Hungarian Immunology

[Anti-synthatase syndrome]

PONYI Andrea, CONSTANTIN Tamás, DANKÓ Katalin

[The idiopathic inflammatory myopathies (IIM) are autoimmune diseases, characterized by symmetric proximal muscle weakness. Over the last several decades, many abnormalities of the cellular and humaral immune systems of IIM patients have been described. Some of these are autoantibodies unique to the IIM (the myositis specific autoantibodies MSA). The MSAs are antigen-driven, arise months prior to the onset of myositis, correlate in titre with disease-activity. Studies in the recent years proved that clinically and immuno-geneticaly different disease entities can be defined using myositis specific auto-antibodies. Their use make the serological classification. Myositis specific autoantibodies make it possible to define more homologies subgroups within polymyositis/dermatomyositis that may support the adequate treatment. The most common MSA is the antihistidyl- transfer RNA synthetase (anti-Jo-1), which can be found in 5-30% of patients with myositis. Patients with anti-synthatase antibodies tend to have characteristic clinical presentation of fever, small joint arthritis, intestinal lung disease, Raynaud's phenomenon, mechanic's hands and severe myositis. Sera of 65 PM/DM were tested for anti-Jo- 1 antibody. 15 patients (23%) had anti-Jo-1 antibody (10 PM, 5 DM). The patients with anti-Jo- 1 antibody has a significantly higher incidence of interstitial lung disease, arthritis, fever and Raynaud's phenomenon. These patients needed not only corticosteoid therapy, but other immunosupressive treatment. All 15 patients presented with the onset of weakness between February and July. The determination of myositis-specific autoantibodies has produced more homogenous grouping within the polymyositis/dermatomyositis patients.]

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

MAIHOUB Stefani, MOLNÁR András, CSIKÓS András, KANIZSAI Péter, TAMÁS László, SZIRMAI Ágnes

[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

Autonomic nervous system may be affected after carpal tunnel syndrome surgery: A possible mechanism for persistence of symptoms after surgery

ONDER Burcu, KELES Yavuz Betul

After carpal tunnel surgery, some patients report complaints such as edema, pain, and numbness. Purpose – The aim of this study was to evaluate autonomic nervous system function in patients with a history of carpal tunnel surgery using sympathetic skin response (SSR). Thirty three patients (55 ±10 years old) with a history of unilateral operation for carpal tunnel syndrome were included in the study. The SSR test was performed for both hands. Both upper extremities median and ulnar nerve conduction results were recorded. A reduced amplitude (p=0.006) and delayed latency (p<0.0001) were detected in the SSR test on the operated side compared to contralateral side. There was no correlation between SSR and carpal tunnel syndrome severity. Although complex regional pain syndrome does not develop in patients after carpal tunnel surgery, some of the complaints may be caused by effects on the autonomic nervous system.

Clinical Neuroscience

[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.]

Clinical Neuroscience

[Zonisamide: one of the first-line antiepileptic drugs in focal epilepsy ]

JANSZKY József, HORVÁTH Réka, KOMOLY Sámuel

[Chronic administration of antiepileptic drugs without history of unprovoked epileptic seizures are not recommended for epilepsy prophylaxis. Conversely, if the patient suffered the first unprovoked seizure, then the presence of epileptiform discharges on the EEG, focal neurological signs, and the presence of epileptogenic lesion on the MRI are risk factors for a second seizure (such as for the development of epilepsy). Without these risk factors, the chance of a second seizure is about 25-30%, while the presence of these risk factors (for example signs of previous stroke, neurotrauma, or encephalitis on the MRI) can predict >70% seizure recurrence. Thus the International League Against Epilepsy (ILAE) re-defined the term ’epilepsy’ which can be diagnosed even after the first seizure, if the risk of seizure recurrence is high. According to this definition, we can start antiepileptic drug therapy after a single unprovoked seizure. There are four antiepileptic drugs which has the highest evidence (level „A”) as first-line initial monotherapy for treating newly diagnosed epilepsy. These are: carbamazepine, phenytoin, levetiracetam, and zonisamide (ZNS). The present review focuses on the ZNS. Beacuse ZNS can be administrated once a day, it is an optimal drug for maintaining patient’s compliance and for those patients who have a high risk for developing a non-compliance (for example teenagers and young adults). Due to the low interaction potential, ZNS treatment is safe and effective in treating epilepsy of elderly people. ZNS is an ideal drug in epilepsy accompanied by obesity, because ZNS has a weight loss effect, especially in obese patients.]