Hungarian Immunology

[The use of infliximab in medical therapy]

GESZTES Ákos

MARCH 20, 2007

Hungarian Immunology - 2007;6(03)

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Hungarian Immunology

[Adalimumab treatment in inflammatory joint diseases]

SZÁNTÓ Sándor

[The development of anti-TNF-α agents represents a great advance in the treatment of inflammatory joint diseases. Adalimumab is the first fully human, recombinant IgG1 monoclonal antibody that blocks the interaction of TNF with the p55 and p75 cell surface TNF receptors, thereby neutralising the activity of this cytokine. In well designed, placebocontrolled trials adalimumab significantly reduced symptoms, improved quality of life, and reduced radiologically evident joint damage in patients with rheumatoid athritis, ankylosing spondylitis and psoriatic arhritis. The drug was generally well tolerated, and the follow up studies confirmed, that the incidence of serious adverse events was similar to that generally seen in patients not receiving anti-TNF agents. This review summarises the recent available data related to the efficacy and safety of adalimumab in inflammatory joint diseases.]

Hungarian Immunology

[Adalimumab in the treatment of Crohn’s disease]

LAKATOS Péter László

[Crohn’s disease (CD) is a chronic inflammatory disorder which may involve any part of gastrointestinal tract. The pathogenesis is only partially understood; various environmental and host (e.g. genetic-, epithelial-, immune and non-immune) factors are involved resulting in chronic uncontrolled inflammation, and among pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) seems to play a central role in CD. The last few years have witnessed a significant change in the management of Crohn’s disease. The role of and indications for conventional therapy (aminosalicylates, steroids and immunomodulators) have been reassessed. Over the past decade the increasing knowledge on the pathogenesis of CD led to the development of a number of biological agents targeting specific molecules involved in gut inflammation, first of all TNF-α and its receptors. The aim of this paper is to review the rationale for the use one of the new anti TNF-inhibitors, adalimumab in the treatment of CD.]

Hungarian Immunology

[The importance of etanercept treatment in rheumatology]

POÓR Gyula, GERGELY Péter

[Rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis and psoriatic arthritis are inflammatory rheumatic conditions of unknown origin. Common characteristic features of these disorders include a relatively high prevalence, poorly understood pathogenesis and an unresolved treatment as well as a significant impact on mortality, morbidity and medical expenditures. The recognition of the central role of TNF-α in immune mediated inflammatory conditions, mainly in rheumatoid arthritis has led to the introduction of TNF-α blocking biological therapy into clinical rheumatology revolutionizing the management of these diseases. Etanercept is a human soluble TNF-α receptor attached to human IgG capable of effectively neutralizing TNF-α and lymphotoxin alpha. Since its introduction in 1998 as the first biological agent approved for RA, several clinical trials as well as everyday practice have proven its efficacy and safety. To date approximately 440 thousand patients, mostly with inflammatory rheumatic diseases have been treated with etanercept. In the present paper the pathophysiological role of TNF-α, the results of clinical trials of etanercept and its cost-effectivenes as well as issues regarding the use of etanercept in Hungary are reviewed.]

Hungarian Immunology

[Rituximab in rheumatoid arthritis]

SZEKANECZ Zoltán

[The therapy of rheumatoid arthritis (RA) is not always easy. Classical disease-modifying drugs are ineffective in about 10-15% of the cases. Furthermore, biologic agents, mainly tumor necrosis factor- α (TNF-α) inhibitors, may also be ineffective. Rituximab (RTX) is a B cell-inhibitory monoclonal antibody, which has been registered for the treatment of RA patients refractory to classical immunosuppressive agents including a TNF antagonist. Here we summarize the history of RTX therapy in RA including the presentation of the three major randomized clinical trials. We discuss the efficacy, safety of RTX, the practical points of RTX therapy, as well as some special considerations. The presented data suggest that RTX is a highly effective and safe biological, which can be used upon the inefficacy of any TNF inhibitor. RTX suppresses RA-associated inflammation, symptoms and decreases radiological progression. It may improve the functional capacity and quality of life of RA patients.]

Hungarian Immunology

[First experience with rituximab treatment in rheumatoid artritis: a case report of a multiresistant patient]

SZABÓ Zoltán, SZEKANECZ Zoltán, BESENYEI Tímea, SZŰCS Gabriella, SZÁNTÓ Sándor, SIMKOVICS Enikő, SZENTPÉTERY Ágnes, SZODORAY Péter

[INTRODUCTION - Here we describe the case of the first Hungarian rheumatoid arthritis (RA) patient treated with RTX. CASE REPORT - This multiresistant patient had received numerous immunosuppressive drugs and all three anti-TNF agents had been tried. These biologicals had to be stopped due to inefficacy or side effects. RTX treatment resulted in some subjective clinical improvement, as well as a decrease in rheumatoid factor and anti-CCP production. Clinical activity assessed by DAS28 fell after 18 weeks. B cells disappeared from the circulation, however, the percentage of activated T cells increased. We observed initial B cell recovery after 18 weeks. CONCLUSION - Clinical studies suggest that RTX is more effective right after the failure of the first TNF inhibitor. Efficacy of RTX in this patient suggests that this drug may also be effective in a multiresistant patient, who had tried numerous TNF blockers.]

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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

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

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.

Clinical Neuroscience

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

TAMÁS László, KANIZSAI Péter, MAIHOUB Stefani, MOLNÁR András, CSIKÓS András, 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.]

Lege Artis Medicinae

[A short chronicle of three decades ]

KAPRONCZAY Katalin

[Hungarian professional periodicals started quite late in European context. Their publish­ing, editing and editorial philosophy were equally influenced by specific historical and political situations. Certain breaking points of history resulted in termina­tion of professional journals (War of In­de­pendence 1848-1849, First and Se­cond World Wars), however there were pe­riods, which instigated the progress of sciences and founding of new scientific journals. Both trends were apparent in years after the fall of former Hungarian regime in 1990. The structure of book and journal publishing has changed substantially, some publishers fell “victim” others started successfully as well. The latters include the then-established publishing house Literatura Medica and its own scientific journal, Lege Artis Me­di­cinae (according to its subtitle: New Hun­garian Medical Herald) issued first in 1990. Its appearance enhanced significantly the medical press market. Its scientific publications compete with articles of the well-established domestic medical journals however its philosophy set brand-new trends on the market. Concerning the medical community, it takes on its problems and provides a forum for them. These problems are emerging questions in health care, economy and prevention, in close interrelation with system of public health institutions, infrastructure and situation of those providing individual health services. In all of them, Lege Artis Medicinae follows consequently the ideas of traditional social medicine.]

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.]