Search results

Hungarian Immunology

JANUARY 10, 2004

[TNF-α blocking therapy in rheumatoid arthritis]

TAMÁSI László

[The research of pathomechanism of rheumatoid arthritis resulted in remarkable pragmatic results beyond the important theoretical knowledge. These observations led to the development of new effective agents, which were named as biological therapy and introduced in clinical praxis. The key factor of pathomechanism of rheumatoid arthritis is the proinflammatoric citokin TNF-α. It can be found on the top of the inflammation cascade where regulates many other inflammatory mediators and also plays an important role in the defence against infections and tumours. The author describes the TNF-α blocking agents used in clinical practice, their chemical and pharmacological feature, as well as their mode of action and the consequence of inhibition of TNF-α. He reviews the main results of the major clinical tests with infliximab, etanercet, and adalimumab. The results of these clinical studies demonstrate that the TNF-α blocking therapy gives clinical improvement in case of therapy resistant patients, decreases the number of swollen and tender joints, the pain, ESR and CRP, decreases the radiological progression, furthermore improves the quality of life. There are also some data about the favourable impacts observed during the early arthritis treatment. The TNF-α blocking therapy can be used effectively and safely in rheumatoid arthritis. In most cases the infusion reaction and the injection site reaction are not reasons for withdrawal from the study. The sideeffects, however, developed in increasing numbers during widespread applications. Among these the most important ones are the opportunist infection and the tuberculosis. In addition the sporadic occurrence of lupus-like symptoms, demyelinating disease, and aplastic anemia were reported. The fundamental requirements of the safety of the biological therapy are the professional indication and the careful monitoring during the treatment, the principle of which has been already prepared by the Professional College of the Rheumatology and Physiotherapy based on the international experience.]

LAM Extra for General Practicioners

APRIL 21, 2009

[USE OF DRUGS FOR GASTRIC ACID REDUCTION IN GENERAL PRACTICE]

HAJNAL Ferenc

[In order to facilitate (general) practitioner’s therapeutic decisions, this overview reviews advantages and disadvantages of three drug classes used for acid reduction, as to antacids, histamine 2-receptor antagonists (H2RAs), and proton pump inhibitors (PPIs). The possibilities and mechanisms of gastric acid reduction are detailed. This can be achieved either by neutralization of gastric acid by systemic or non-systemic antacids, or by inhibiting acid secretion by H2RAs and PPIs. PPIs are the strongest acid reducing agents indispensable in gastro-esophageal reflux disease (GERD), eradication therapy for Helicobacter pylori ulcers and Zollinger- Ellison syndrome, and they are first choice in non-steroidal anti-inflammatory drug (NSAID) induced gastropathy, epigastric pain syndrome, and functional upper GI dyspepsia. Nonetheless, antacids and H2RAs are faster in relieving pain in the latter pain syndrome and in acute heartburn. Contraindications and adverse effects of these three drug classes are also detailed. The author has concluded that physicians’ up-to-date awareness of these compounds’ pharmacological properties contributes to their ability to tailor acid reduction therapy to patients’ individual needs. Refreshing and expanding this knowledge will finally benefit patients seen in everyday practice.]

Hungarian Immunology

MARCH 20, 2007

[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

JANUARY 30, 2006

[Regional cues and phenotypic responses during the ontogeny and postnatal development of splenic vasculatur]

BALOGH Péter

[Among structured peripheral lymphoid tissues in man and rodents, the spleen demonstrates the most extensive flexibility in functional activities, which is coupled with considerable tissue architecture adjustments during ontogeny and immune reactions. The sequential conversion of a primary lymphohemopoietic tissue into a major peripheral lymphoid organ (while participating in the post-myeloid period of primary B-lymphopoiesis and retaining the potential for myelopoiesis) is accompanied with the ordered segregation involving various non-hemopoietic components of architecture, including the endothelia of blood vessels. In this report we will survey the functional and structural aspects of heterogeneous endothelial cells lining the various splenic vascular beds, comprising the complex circulatory network of the spleen. These features will be correlated with the characteristics of those regulatory mechanisms that have recently been demonstrated to be responsible for the establishment and maintenance of the endothelial divergence during splenic vascular development, including crucial transcription factors, morphogenic regulatory ligands and receptors of the tumor necrosis factor/lymphotoxin (TNF/LT) family and others. The influence of these regulatory elements in mice appears to be highly restricted in terms of regional involvement of the vasculature, with cellular alterations of the marginal sinus representing the most frequently affected region. This complexity highlights the importance of this tissue region in both the formation of splenic vasculature and a possible source for white pulp stromal elements as well as its function as a major gateway for lymphocyte traffic.]

Clinical Neuroscience

AUGUST 20, 2002

[Investigation of the dopamine dysregulation hypothesis of schizophrenia with neuroimaging techniques]

SZEKERES György, PÁVICS László, JANKA Zoltán

[The most elaborated biochemical concept of schizophrenia is the dopamine hypothesis. However, this classical theory is based on indirect observations. It has recently become possible to study this theory directly by means of advanced functional neuroimaging techniques, the development of specific radioligands and study protocols that are eligible to monitor dynamic changes in the neurotransmitter systems. According to the early concept, the essence of schizophrenia is the hyperactivity of the dopamine system. Nevertheless, this idea has gone through many modifications. In accordance with the modified dopamine hypothesis, the cognitive deficit and negative symptoms are related to the hypoactivity of the dorsolateral prefrontal cortex while the acute phasis of the disease associates with hyperactivity of the ventral striatal elements of the dopaminergic system. Between these dysfunctions there is causality via their exuberant connections. Beyond that, the interactions between the prefrontal and striatal anomalies implicate the involvement of other neurotransmitters than dopamine. Observations from model psychosis induced by N-methyl-D-aspartate antagonists and in vivo neuroimaging investigations in humans support primarily the role of glutamatergic system. Our developing knowledge about the neurochemical mechanism of schizophrenia can significantly affect therapeutic strategies as well.]

Lege Artis Medicinae

JULY 14, 2007

[THE USE OF DIRECT VASODILATORS AND DIGITALIS IN CHRONIC HEART FAILURE]

DÉKÁNY Miklós

[For the optimal treatment of heart failure patients with systolic dysfunction, supplementation of the standard diuretics plus neurohormonal antagonists treatment with the direct vasodilator combination dihydralazine+nitrate, as well as with digitalis may be necessary. Addition of hydralazine/dihydralazine+nitrate to the treatment of chronic heart failure is recommended if ACE-inhibitors or angiotensin-receptor blockers cannot be administered. Beta blockers should also be used in these cases. If symptoms persist or worsen, addition of this combination to the standard therapy is reasonable. Supplementation with digitalis, mostly digoxin should be considered in similar conditions. It can be especially beneficial for patients with high-ventricular-rate atrial fibrillation. To achieve maximal survival benefit, the dose of digoxin must not exceed 0.125 mg/day. Low body weight or muscle mass, significantly reduced renal function may make further dose reduction necessary. If renal function is severely limited, digitoxin instead of digoxin may be used.]

Lege Artis Medicinae

MARCH 20, 2011

[New treatment option for oral anticoagulation in the prevention of cardiogenic stroke - Focus on the RE-LY trial]

SZAPÁRY László

[Atrial fibrillation (AF) represents the most common cause of cardioembolic stroke. The prevalence of AF increases with age and affects 10% of elderly people. AF-related stroke is usually severe and has a high mortality. The risk of stroke can be estimated on the basis of risk factors accompanying AF and age. Patients with one of the highest risk are those with AF and previous TIA or stroke. Efficient prevention is achieved by chronic anticoagulation therapy. In clinical practice, the use of vitamin K antagonists (VKA) has been the only option. The use of these agents is limited for a number of reasons, and clinicians are especially reluctant to use them in elderly patients at high risk of stroke. Consequently, of the patients with AF for whom anticoagulant therapy is indicated, only about 50-60% receives such therapy, and only half of the treated patients achieves target INR values. More than 50 years after the introduction of warfarin, data of trials with the new direct thrombin inhibitor dabigatran have been published in the past few years. In this paper, we review the results of the phase III, international RE-LY trial, published in 2009, which evaluated the preventive efficacy dabigatran etexilate in patients with AF compared with warfarin at a therapeutic dose. On the basis of the results, dabigatran used at a dose of 2×110mg daily provides the same protection as warfarin, whereas at a dose of 2×150mg it provides a signiificantly more efficient protection from AF-associated stroke and systemic embolism. In addition to its excellent preventive effect, dabigatran tretament results in a significant decrease in the risk of intracranial haemorrhages, and of other major haemorrhages. On the basis of the results, dabigatran will probably change the current treatment paradigm in the stroke prevention in patients with AF, and its introduction can substantially increase the number of patients treated efficiently and safely.]

Lege Artis Medicinae

DECEMBER 16, 2006

[SEVERE THERAPY RESISTANT BRONCHIAL ASTHMA]

HERJAVECZ Irén, BÁNKÚTI Beáta, CSOMA Zsuzsanna

[While severe asthma associated with high morbidity affects a relatively small proportion of all patients with asthma, it requires special attention and innovative treatment approaches. Although asthma is by definition characterized by reversible airflow obstruction, the obstruction becomes fixed to some extent and refractory to corticosteroids with the progression of the disease. The underlying change in this phenotype is airway wall remodelling. In allergic asthmatic patients who remain symptomatic despite highdose inhaled corticosteroid therapy, blockade of IgE with omalizumab confers appreciable clinical benefit. Chronic severe asthma is also accompanied by a marked increase in TNFproduction that might contribute to corticosteroid resistance. In accordance with this, TNF blockade with entanercept has been shown to improve asthma controll and at the same time to reduce bronchial hyperresponsiveness. Identification of new susceptibility genes, such as ADAM33, will provide further targets for therapy, which in turn can result in the development of treatment tools that modify the natural course of asthma and reverse the changes associated with airway remodelling, rather than simply suppress inflammation and dilate the airways.]

Clinical Neuroscience

DECEMBER 20, 2008

[Changes of the immune functions in patients with eating disorders]

PÁLI Anikó Andrea, PÁSZTHY Bea

[Aims - In this study we investigated whether calorie restriction or redundant food intake influences the function of regulatory T cells (Tregs), and their main regulators (dendritic cells and macrophages), or the targets of Tregs, CD4+ lymphocytes. Patients and methods - We investigated 11 white adolescents (10 girls and 1 boy) with anorexia nervosa, 12 obes adolescents and 10 healthy controlls. With flow cytometry we determined the prevalence of Tregs, myeloid and plasmacytoid dendritic cells. We applied intracellular staining to investigate TNF-alpha and IL-12 production of macrophages, moreover IL-2, IL-4, and IFN-gamma production of CD4+ cells. We also determined calcium flux kinetics upon activation in CD4+ cells. Results - We did not find any difference between obese, anorectic and control individuals in the prevalence of Tregs, dendritic cells, TNF-alpha and IL-12 positive macrophages, IL-4 and IFN-gamma positive CD4+ lymphocytes. We found that the prevalence of IL-2 positive lymphocytes after activation was lower in anorectic than in control subjects [median (range): 11.50 (7.60-15.30) vs. 13.50 (12.00-22.00), p=0.023], and in obese patients, too [12.50 (8.50-15.50) vs. 13.50 (12.00-22.00), p=0.028]. IFN-gamma/IL-4 ratio in CD4+ cells was higher in obese patients compared with control (p=0.046). The calcium flux characteristics of lymphocytes upon activation differed markedly in anorectic and healthy subjects as maximal calcium levels developed later in anorectic patients [86 (45- 232) vs. 215 (59-235) second, p<0.05]. We also tested the association between lymphocyte activation parameters and patients' clinical status, but did not find any association between the variables. Discussion - Our results suggest that the antigen presenting cell - regulatory T cell - CD4+ lymphocyte axis might be affected by calorie and nutritional disturbances, further studies are needed to elucidate the underlying processes.]

Lege Artis Medicinae

JULY 27, 2009

[Combination of leflunomide and biologic agents in the treatment of rheumatoid arthritis]

SZŰCS Gabriella

[Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that leads to progressive joint destruction, functional disability and extra-articular complications. The initial approach to treatment of RA begins with the diagnosis, estimation of patient’s prognosis and the implementation of a therapeutic plan. Most important is early and aggressive treatment with disease-modifying antirheumatic drugs (DMARDs). Among the different protocols, combination therapies including methotrexate and/ or biologics seem to be more effective than monotherapies. Biological therapies introduced in recent years opened a new era in the treatment of RA. Randomized, controlled trials have demonstrated that the addition of methotrexate to biologic agents, such as tumor necrosis factor alpha (TNF-α) inhibitors generally increases their ability to retard structural damage, reduce disease activity and improve function. However, not all patients tolerate or respond to methotrexate. One of the most common used alternative DMARDs is leflunomide. Earlier several smaller retrospective studies, later prospective cohort studies, and finally two new populationbased longitudinal observational studies found that the above-mentioned parameters in RA patients treated with anti-TNF agents and leflunomide were similar to those receiving anti-TNF and methotrexate in combination. In addition, there were no significant differences in the frequency of adverse events between the groups. Taken together, leflunomide should be regarded as an effective and safe alternative in the treatment of rheumatoid arthritis.]