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]

GERGELY Péter, POÓR Gyula

[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]

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

[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

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?]

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.]

Lege Artis Medicinae

[Thiazide- or thiazide-like diuretics should be used in the treatment of patients with hypertension? Particularities of the situation in Hungary]

VÁLYI Péter

[Diuretics have remained the cornerstone of the antihypertensive treatment since their widespreading in the 1960s. According to the 2018 ESC/ESH Guidelines for the management of arterial hypertension, in the absence of evidence from direct comparator trials and recognizing that many of the approved single-pill combinations are based on hydrochlorothiazide, this drug and thiazide-like indapamide can be considered suitable antihypertensive agents. In the 2018 Hungarian guidelines indapamide is named as the most efficacious diuretic in the treatment of patients with hypertension. The aim of the publication is redefining thiazide- and thiazide-like diuretic use in the treatment of hypertensive patients, with particular attention to presently available hydrochlorothia­zide and indapamide, and their combination drugs in Hungary.]

Lege Artis Medicinae

[Focus on Lege Artis Medicinae (LAM)]

VASAS Lívia, GEGES József

[Three decades ago, LAM was launched with the goal of providing scientific information about medicine and its frontiers. From the very beginning, LAM has also concerned a special subject area while connecting medicine with the world of art. In the palette of medical articles, it remained a special feature to this day. The analysis of the history of LAM to date was performed using internationally accepted publication guidelines and scientific databases as a pledge of objectivity. We examined the practice of LAM if it meets the main criteria, the professional expectations of our days, when publishing contents of the traditional printed edition and its electronic version. We explored the visibility of articles in the largest bibliographic and scientific metric databases, and reviewed the LAM's place among the Hun­ga­rian professional journals. Our results show that in recent years LAM has gained international reputation des­pite publishing in Hungarian spoken by a few people. This is due to articles with foreign co-authors as well as references to LAM in articles written exclusively by foreign researchers. The journal is of course full readable in the Hungarian bibliographic databases, and its popularity is among the leading ones. The great virtue of the journal is the wide spectrum of the authors' affiliation, with which they cover almost completely the Hungarian health care institutional sys­tem. The special feature of its columns is enhanced by the publication of writings on art, which may increase Hungarian and foreign interest like that of medical articles.]

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.]