Lege Artis Medicinae

[A rebellion against the father - the chastened Jesus]

MARJAI Kamilla

OCTOBER 20, 2018

Lege Artis Medicinae - 2018;28(10)

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Lege Artis Medicinae

[Juvenile idiopathic arthritis: from diagnosis to treatment]

MOSDÓSI Bernadett

[Juvenile idiopathic arthritis is a heterogeneous group of diseases that is one of the most common chronic diseases of childhood. It begins before 16 years of age, the etiology is unknown, it is persisting for at least 6 weeks and other pathologic conditions could be excluded. Juvenile idiopathic arthritis includes several diseases categories, each of them have distinct methods of presentation, clinical symptoms, pathogenesis and treatment options. Recent advances in the understanding of the immunological pathogenesis of the diseases have led to dramatic improvements in treatment. Although the management is using a multidisciplinary approach, the disease often persist into adulthood and can cause significant long-term morbidity and physical disability. Our article discusses the classification, clinical manifestations, differential diagnosis, treatment and complications of juvenile idiopathic arthritis. ]

Lege Artis Medicinae

[Acetylsalicylic acid (ASA) 75 or 100 mg? ]

KIS János Tibor, ZSIGMOND Kálmán

[The acetylsalicylic acid (ASA) is one of the oldest and most widely used drugs in the world. Currently, it is the most commonly used for the treatment and prophylaxis of cardiovascular diseases. Today, there has been consensus that the risk of ASA’s side effects in primary prevention is greater than the expected benefits. However, it maintains its leading role in the secondary prevention of cardiovascular diseases. There is also a consensus that small doses are recommended for preventive purposes, but there is no agreement whether it should be 75 or 81 or 100 mg. The authors summa­rize the publications published in this topic. ]

Lege Artis Medicinae

[Hormesis: the importance of small doses in the modern medicine]

CSABA György

[The hormesis concept contains that high doses of some substances are harmful (toxic or inhibiting), at the same time small doses of these substances are adventageous and stimulating. The pretreatment with small doses helps to neutralize the later harmful or deleterious effects of large doses and this has therapeutical (clinical) importance in case of numerous diseases and treatments. The review use two examples for demonstrating the importance of hormesis: the effect of radiation and the effect to immunity, in addition general, evolutionary aspects are also highlighted. The importance of evolutionary aspects are discussed. It demonstrates the influence of hormesis to the human evolution and calls attention to the expected changes in human diseases (as inevitable consequences of hormesis in our chemically strongly infected world), which are transmitted to the progenies. Hormesis is a therapeutic possibility as well as a challenge for medicine, this means that it is advisable to use it in the therapy and must prepare ourselves to the challenges. ]

Lege Artis Medicinae

[The Painter’s Revolt against the Father, or Jesus Chastised ]

GEREVICH József

Lege Artis Medicinae

[Gene modified T cells against cancer]

SZÖŐR Árpád

[Chimeric antigen receptor modified (CAR) T cells are hailed as a revolutionary breakthrough in the field of oncology. CAR T cells were first applied, with outstanding success, in the treatment of various leukaemias, yielding unprecedented antitumor activity and long periods of disease free survival. Following the success of CAR T cell therapy in leukaemias, solid tumors should now be targeted. These are more complex targets, therefore CAR T cell therapy needs to be further optimized for this purpose. Also, some unfortunate side effects, including the potentially deadly global inflammation called cytokine storm have to be minimized and possibly even eradicated. The next decade will be an exciting time to define whether this therapy which is yet exclusively used for cancer patients is also successful in the treatment of other diseases. In a recent study, T cells reengineered with CAR derived chimeric autoantibody receptors (CAAR) efficiently prevented disease progression in pre-clinical animal models simulating the serious autoimmune disorder, pemphigus vulgaris. Therapy was based on CAAR constructs which have the unique ability to selectively recognize and eliminate the B-cell clones secreting autoantibodies against a self-protein, thus playing a key role in disease pathogenesis and progression. In this review, we would like to give an overview about the history of the CAR T-cell concept, summarize briefly the currently running clinical trials, and discuss the challenges and future prospects of CAR T-cell therapy.]

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[The role of sleep in the relational memory processes ]

CSÁBI Eszter, ZÁMBÓ Ágnes, PROKECZ Lídia

[A growing body of evidence suggests that sleep plays an essential role in the consolidation of different memory systems, but less is known about the beneficial effect of sleep on relational memory processes and the recognition of emotional facial expressions, however, it is a fundamental cognitive skill in human everyday life. Thus, the study aims to investigate the effect of timing of learning and the role of sleep in relational memory processes. 84 young adults (average age: 22.36 (SD: 3.22), 21 male/63 female) participated in our study, divided into two groups: evening group and morning group indicating the time of learning. We used the face-name task to measure relational memory and facial expression recognition. There were two sessions for both groups: the immediate testing phase and the delayed retesting phase, separated by 24 hours. 84 young adults (average age: 22.36 (SD: 3.22), 21 male/63 female) participated in our study, divided into two groups: evening group and morning group indicating the time of learning. We used the face-name task to measure relational memory and facial expression recognition. There were two sessions for both groups: the immediate testing phase and the delayed retesting phase, separated by 24 hours. Our results suggest that the timing of learning and sleep plays an important role in the stabilizing process of memory representation to resist against forgetting.]

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

[LADA type diabetes, celiac diasease, cerebellar ataxia and stiff person syndrome. A rare association of autoimmune disorders]

SOÓS Zsuzsanna, SALAMON Mónika, ERDEI Katalin, KASZÁS Nóra, FOLYOVICH András, SZŰCS Anna, BARCS Gábor, ARÁNYI Zsuzsanna, SKALICZKI József, VADASDI Károly, WINKLER Gábor

[Celiac disease - in its typical form - is a chronic immunemediated enteropathy with typical clinical symptoms that develops against gliadin content of cereal grains, and is often associated with other autoimmune diseases. In cases of atypical manifestation classic symptoms may be absent or mild, and extra-intestinal symptoms or associated syndromes dominate clinical picture. The authors present a longitudinal follow-up of such a case. A 63-years old woman was diagnosed with epilepsy at the age of 19, and with progressive limb ataxia at the age of 36, which was initially thought to be caused by cerebellar atrophy, later probably by stiff person syndrome. At the age 59, her diabetes mellitus manifested with type 2 diabetic phenotype, but based on GAD positivity later was reclassified as type 1 diabetes. Only the last check-up discovered the celiac disease, retrospectively explaining the entire disease course and neurological symptoms. By presenting this case, the authors would like to draw attention to the fact that one should think of the possibility of celiac disease when cerebellar ataxia, progressive neurological symptoms and diabetes are present at the same time. An early diagnosis may help to delay the progression of disease and help better treatment.]

Lege Artis Medicinae

[CONTROVERSIAL EFFECTS OF NITRIC OXIDE: INTEGRITY AND TOXICITY]

KISS Róbert Gábor, BÉRES Bernát János

[Nitric oxide is a key molecule of the human body. Since its discovery, a library of books and papers have been published on its physiological and pathophysiological role. It is involved in almost all pathological processes. In healthy individuals nitric oxide plays a crucial role in the vascular regulation by protecting against atherosclerosis, myocardial infarction and stroke. In the central nervous system, nitric oxide in its function as a neurotransmitter is responsible for synaptic plasticity, long-term potentiation, memory and a number of neuroendocrine control mechanisms. Furthermore, during inflammation and host defense, macrophages and neutrophils produce nitric oxide that has antibacterial, antiviral, and tumour cell killing activity. In pathologic conditions, however, nitric oxide reacts with superoxide anion to form peroxynitrite that damages the enzymes of the mitochondrial respiratory chain, superoxide-dismutase, reduced glutathion and activates or inactivates signalling molecules. During ischaemia- reperfusion, nitric oxide and peroxynitrite contribute to nitrative/nitrosative stress, DNAfragmentation and consequent polyADP-ribosepolymerase- 1 enzyme activation both in coronary thrombosis and ischaemic stroke.]

Clinical Neuroscience

[Paraneoplastic chronic demyelinating neuropathy and lambert-eaton myasthenic syndrome associated with multiple anti-neural antibodies and small-cell lung cancer]

RÓZSA Csilla, VINCENT Angela, ARÁNYI Zsuzsanna, KOVÁCS G. Gábor, KOMOLY Sámuel, ILLÉS Zsolt

[Lambert-Eaton myasthenic syndrome (LEMS) developed in a patient with presumed chronic inflammatory demyelinating polyneuropathy (CIDP) and negative chest CT. Since antibodies against both Hu and voltage-gated calcium channel (VGCC) were detected, repeated chest CT was performed, which eventually showed a pulmonary mass lesion. Biopsy revealed small cell lung cancer (SCLC) indicating the importance of repeated chest CT in LEMS even when an existing autoimmune-like disease and negative CT may suggest an autoimmune origin. This is the first report of paraneoplastic CIDP and LEMS associated with anti-Hu, anti-VGCC and SCLC.]