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

[The importance of etanercept treatment in rheumatology]

ifj. 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

[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.]

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

[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.]

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Clinical Neuroscience

The etiology and age-related properties of patients with delirium in coronary intensive care unit and its effects on inhospital and follow up prognosis

ALTAY Servet, GÜRDOGAN Muhammet, KAYA Caglar, KARDAS Fatih, ZEYBEY Utku, CAKIR Burcu, EBIK Mustafa, DEMIR Melik

Delirium is a syndrome frequently encountered in intensive care and associated with a poor prognosis. Intensive care delirium is mostly based on general and palliative intensive care data in the literature. In this study, we aimed to investigate the incidence of delirium in coronary intensive care unit (CICU), related factors, its relationship with inhospital and follow up prognosis, incidence of age-related delirium and its effect on outcomes. This study was conducted with patients hospitalized in CICU of a tertiary university hospital between 01 August 2017 and 01 August 2018. Files of all patients were examined in details, and demographic, clinic and laboratory parameters were recorded. Patients confirmed with psychiatry consultation were included in the groups of patients who developed delirium. Patients were divided into groups with and without delirium developed, and baseline features, inhospital and follow up prognoses were investigated. In addition, patients were divided into four groups as <65 years old, 65-75 yo, 75-84 yo and> 85 yo, and the incidence of delirium, related factors and prognoses were compared among these groups. A total of 1108 patients (mean age: 64.4 ± 13.9 years; 66% men) who were followed in the intensive care unit with variable indications were included in the study. Of all patients 11.1% developed delirium in the CICU. Patients who developed delirium were older, comorbidities were more frequent, and these patients showed increased inflammation findings, and significant increase in inhospital mortality compared to those who did not develop delirium (p<0.05). At median 9-month follow up period, rehospitalization, reinfarction, cognitive dysfunction, initiation of psychiatric therapy and mortality were significantly higher in the delirium group (p<0.05). When patients who developed delirium were divided into four groups by age and analyzed, incidence of delirium and mortality rate in delirium group were significantly increased by age (p<0.05). Development of delirium in coronary intensive care unit is associated with increased inhospital and follow up morbidity and mortality. Delirium is more commonly seen in geriatric patients and those with comorbidity, and is associated with a poorer prognosis. High-risk patients should be more carefully monitored for the risk of delirium.

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.]

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.

Clinical Neuroscience

[Interdisciplinary approach of vestibular system impairment]

PONGRÁCZ Endre

[In the first part of this review the definition of vertigo/dizziness was discussed. The major difference between the two signs is the exsistence of the direction, which is specific for vertigo. Dizziness is a frequent complaint in the clinical practice. Its frequency is increasing with advance of age, to intimate the play of declining cognitive process in the pathogenesis of its. The popular health significance of vertigo is in the rowing number of the patients. The onset of the most cases with acute vertigo appears between secundums and minutes so the patients will be provided in circumstances of emergency department. First of all three form schould be take into account: neuronitis vestibularis, benign paroxysmal positional vertigo and Meniere syndrome. Without tipical periferal signs of vertigo, central cause should be searched, principally stroke (lysis possibility). The differential diagnose of the different dizzeness/vertigo forms according to the elapsed time of the onset or congenital and acquired nystagmus was created in tables. The recommendations of the therapy of acute and chronic dizziness/ vertigo syndroms are, lack of results of evidence based trials doubtful. The more often used drugs based on clinical trials are discussed as vinpocetine, betahistine and piracetam. The in vitro and in vivo data suggest that the last molecule is eligible to use both in periferal and central type of vertigo syndroms.]

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.