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Clinical Oncology

APRIL 10, 2019

[Metals and cancer]

VETLÉNYI Enikő, RÁCZ Gergely

[We often tend to forget about our environment when looking for the origin of a disease. Inhaled air, drinking water and food, substances in contact with the skin all have an effect on the human body. Metals are indispensable parts of our everyday lives, their mining, processing and use cause a continuous exposure to them. Metal exert their effects on the body in various ways. Many of them are essential for maintaining homeostasis, but excessive or harmful metal intake can lead to health damage, including tumour formation through multiple attack points. Metals substitute each other during different transport processes and in the structure of proteins, they cause oxidative stress and bind to DNA, thereby damaging it. Applying them appropriately, the proapoptotic effect of the metal compounds is brought to the fore, thus becoming a therapeutic tool for tumours. Nowadays, platinum(II) compounds are widely used as chemotherapeutic agents and there are many ongoing studies to fi nd metal compounds with an ideal therapeutic and side-effect profi le. The aims of this article were to draw the attention to the dangers of metals in relation to cancer and to highlight their diverse application possibilities in current and future cancer therapy and diagnostics.]

Clinical Neuroscience

MARCH 30, 2016

[The therapeutic use of transcranial magnetic stimulation in major depression]

NÉMETH Viola Luca, CSIFCSÁK Gábor, KINCSES Zsigmond Tamás, JANKA Zoltán, MUST Anita

[The antidepressive effect of repetitive transcranial magnetic stimulation (rTMS) has been investigated for almost 20 years now. Several studies have been published aiming to identify the exact and reliable parameters leading to the desired therapeutic effect. However, the related literature shows great variability. The current overview aims to provide a comprehensive overview of factors associated with the therapeutic effect of rTMS in major depression. High frequency stimulation of the left dorsolateral prefrontal cortex (DLPFC) for 3-6 weeks leads to mood improvement comparable to the effect of antidepressive medications in 35-40% of patients. Pharmacotherapy resistant patients treated with rTMS reach remission for 3 months on average. Low frequency stimulation of the right DLPFC appears to be similarly effective, though much less investigated so far. In addition to the exact delineation of the stimulation area, treatment outcome is also related to stimulation intensity as well as the number of sessions and impulses. Considering the safety and tolerability aspects of rTMS, it might be a significant therapeutic support for therapy resistant patients. Above this, patients diagnosed with major depression might benefit from the additional positive influence of rTMS improving the effect of antidepressive medication. Based on converging research evidence, the Food and Drug Administration (FDA) agency approved the use of rTMS as a treatment option for therapy resistant major depression in 2008. So far, in Hungary rTMS is primarily considered as a promising tool in research settings only. Hopefully, patients suffering from major depression will increasingly benefit from the positive therapeutic effect of this intervention.]

Clinical Neuroscience

MARCH 30, 2016

[The importance of anticoagulant therapy in patients with artial fibrillation in stroke prevention – summary of international data and novel therapeutic modalities]

MIROLOVICS Ágnes, PAPP Csaba, ZSUGA Judit, BERECZKI Dániel

[The most common cardiogenic cause of ischaemic stroke is atrial fibrillation which increases the probability of stroke five-fold and doubles case fatality. Based on international data the incidence of atrial fibrillation is approx. 2% however this rapidly increases with age. The necessity of using oral anticoagulants in the prevention of non-valvular atrial fibrillation related stroke is decided based on estimated stroke risk. The CHADS2 and the more predictive CHA2DS2-VASc scales are used for this purpose while the bleeding risk of patients treated with anticoagulant may be estimated by the HAS-BLED scoring scale. For decades oral anticoagulation meant using vitamin-K antagonists. Based on international data we can see that rate of anticoagulation is unacceptably low, furthermore most of the anticoagulated patients aren’t within the therapeutic range of INR (INR: 2-3). A lot of disadvantages of vitamin-K antagonists are known (e.g. food-drug interaction, need for regular coagulation monitoring, increased risk of bleeding), therefore compounds with new therapeutic target have been developed. The novel oral anticoagulants (NOAC) can be divided in two major subgroups: direct thrombin inhibitors (dabigatran etexilate) and Xa-factor inhibitors (rivaroxaban, apixaban, edoxaban). These products are administered in fix doses, they less frequently interact with other medications or food, and regular coagulation monitoring is not needed when using these drugs. Moreover several studies have shown that they are at least as effective in the prevention of ischaemic stroke than the vitamin-K antagonists, with no more haemorrhagic complications.]

Clinical Neuroscience

JANUARY 30, 2020

[Current questions of multiple sclerosis: the secunder progressive form of the disease]

VÉCSEI László

[Recent data suggest that long-term worsening is common in relapsing-remitting multiple sclerosis patients and is largely independent of relapses or new lesion formation on brain MRI. The current definition of secunder progressive multiple sclerosis is worsening of disability independent of relapses over at least 6-month interval. Early focal inflammatory disease activity and spinal cord lesion are predictors of very-long term disease outcomes in relapse - onset multiple sclerosis. The potential of PET imaging to visualize hidden inflammation in MS brain in vivo is an important contribution for better understanding the progression of the disease. Therefore, PET imaging is a promising tool in detecting the conversion from relapsing remitting multiple sclerosis to secunder progressive form of multiple sclerosis. Furthermore, neuro-axonal damage is the pathological substrate of permanent disability in different neurological disorders including multiple sclerosis. The neurofilament proteins have promise in this context because their levels rise upon neuro-axonal damage not only in the cerebrospinal fluid but also in blood. Patients with increased serum levels of neurofilament at baseline, independent of other clinical and MRI variables, experience significantly more brain and spinal cord volume loss over 2 years and 5 years of follow-up. The kynurenine-pathway abnormalities may be associated with the swich from early-mild stage multiple sclerosis to debilitating progressive forms of the disease. Analysis of these metabolites in serum may have application as multiple sclerosis disease biomarkers. Free radical action has been suggested as a causal factor in the illness. Increased free radical production and consumption of the scavenger molecules were found during the active phase of the disease. Based on the clinical findings (EXPAND Study) and pathomechanism of the disease siponimod is approved by the US Food and Drug Administration for the treatment of relapsing remitting forms of multiple sclerosis, to include secunder progressive multiple sclerosis with active disease, relapsing-remitting multiple sclerosis and clinically isolated syndrome.]

Clinical Neuroscience

NOVEMBER 30, 2019

[Tracing trace elements in mental functions]

JANKA Zoltán

[Trace elements are found in the living organism in small (trace) amounts and are mainly essential for living functions. Essential trace elements are in humans the chromium (Cr), cobalt (Co), copper (Cu), fluorine (F), iodine (I), iron (Fe), manganese (Mn), molybdenum (Mo), selenium (Se), zinc (Zn), and questionably the boron (B) and vanadium (V). According to the biopsychosocial concept, mental functions have biological underpinnings, therefore the impairment of certain neurochemical processes due to shortage of trace elements may have mental consequences. Scientific investigations indicate the putative role of trace element deficiency in psychiatric disorders such in depression (Zn, Cr, Se, Fe, Co, I), premenstrual dysphoria (Cr), schizophrenia (Zn, Se), cognitive deterioration/de­mentia (B, Zn, Fe, Mn, Co, V), mental retardation (I, Mo, Cu), binge-eating (Cr), autism (Zn, Mn, Cu, Co) and attention deficit hyperactivity disorder (Fe). At the same time, the excess quantity (chronic exposure, genetic error) of certain trace elements (Cu, Mn, Co, Cr, Fe, V) can also lead to mental disturbances (depression, anxiety, psychosis, cognitive dysfunction, insomnia). Lithium (Li), being efficacious in the treatment of bipolar mood disorder, is not declared officially as a trace element. Due to nutrition (drinking water, food) the serum Li level is about a thousand times less than that used in therapy. However, Li level in the red cells is lower as the membrane sodium-Li countertransport results in a Li efflux. Nevertheless, the possibility that Li is a trace element has emerged as studies indicate its potential efficacy in such a low concentration, since certain geographic regions show an inverse correlation between the Li level of drinking water and the suicide rate in that area. ]

Lege Artis Medicinae

DECEMBER 10, 2018

[Experimental investigation of the complex energy balance]

GARAMI András

[The complex energy balance includes maintenance of both normal body mass and body temperature. In the homeostasis regulation it is important that the activities of several physiologic processes are balanced with each other, for example, the balance between food intake and energy expenditure is crucial to maintain normal body mass, while the balance between heat production and heat loss is vital in determining body temperature. Obesity and loss of body weight, as well as fever and hypothermia are consequences of the dysregulation in energy balance. In our research, we studied receptorial and neurohumoral mechanisms involved in the maintenance and in the impairment of energy balance. This paper gives an overview of our most important findings, which served as the basis of the application submitted to and awarded with 3rd prize by the Prof. Dr. Laszlo Romics Memorial Foundation. We review the physiologic role of transient receptor potential channels, mostly of vanilloid-1 (formerly: capsaicin receptor) in the regulation of body temperature and body mass. Among the neuropeptides which take part in the maintenance of energy balance, we present the thermoregulatory effects of alpha-melanocyte stimulating hormone and pituitary adenylate cyclase-activating polypeptide. Last, among the molecular mechanisms of systemic inflammation, which is characterized by thermoregulation disorders (e.g., fever, hypothermia), we recap the role of the vanilloid-1 and neurokinin-1 receptor, and bilirubin.]

Lege Artis Medicinae

SEPTEMBER 20, 2018

[Feeding and eating in infancy and early childhood part III. - Development of self-feeding skills in the large-sample of the “For Healthy Offspring” project ]

NÉMETH Tünde, VÁRADY Erzsébet, DANIS Ildikó, SCHEURING Noémi, SZABÓ László

[Feeding and eating in infancy and early childhood part III. - Development of self-feeding skills in the large-sample of the “For Healthy Offspring” project INTRODUCTION - After introducing adequate complementary food to the diet of breastfed/formula-fed babies, the frequency and amount of semisolid/solid food is increasing, the breastmilk/formula intake is decreasing and finally the weaning process is completed. During this process the developing feeding skills of the infant enables them to self-feed. The self-feeding infant and toddler should participate in family meals. SUBJECTS AND METHODS - In the Healthy Offspring project self reported questionnaires were received from 1133 parents of 0-3 year old children. Issues concerning the development of self-feeding skills were analyzed. RESULTS - With advancing age the proportion of infants/toddlers, reported to be able to (partially) self-feed, has increased. The age, at which the majority of toddlers (83.1%) were reported to self-feed, was at 13-15 months. By the age over 2 years 57.2% of the toddlers were fully self-feeding, 39.3% were self-feeding with some assistance, and 3.5% were still completely fed by their mother/caregiver. While self-feeding became more prevalent, the proportion of toddlers with feeding problems and insufficient weight gain has increased. With more prevalent complementary feeding more parents assessed their feeding style rather scheduled than on demand. In the whole sample the proportion of infants/toddlers, who ate with the family, was 43.8%. CONCLUSIONS - In our sample, as previously described in the scientific literature, the developmental readiness to self-feed has developed in the majority of infants by the age of 13-15 months. During progres­sion of weaning an increasing proportion of parents thought, that feeding was rather scheduled than on demand. This finding points at the importance of educating parents about the importance of responsive feeding during and after weaning. For self-feeding toddlers, responsive feeding means, that the mother/caregiver offers a choice of healthy and adequate amount of food, at a proper place, at proper times, responds to the hunger and satiety cues of the child and the toddler decides, whether to eat, what and how much to eat.]

Lege Artis Medicinae

AUGUST 30, 2018

[Feeding and eating in infancy and early childhood part II. - Breastfeeding, complementary feeding and weaning in the Large-sample of the “For Healthy Offspring” project]

NÉMETH Tünde, VÁRADY Erzsébet, DANIS Ildikó, SCHEURING Noémi, SZABÓ László

[INTRODUCTION - Complementary feed-ing is the transitional period from exclusive breastfeeding to family foods, while breastfeeding is continued. It should be started, when breastmilk itself no longer meets the infant’s nutritional requirements, ideally at the age of around 6 months. SUBJECTS AND METHODS - In the Healthy Offspring project self reported questionnaires were received from 1133 parents of 0-3 year old children. Comple­mentary feeding practices and issues of weaning were analyzed. RESULTS - In our sample complementary feeding was started at the age of 5.5±1.8 months. 6% of infants younger than 4 months and about two third of infants at the age between 4 and 6 months were started on complementary feeding. 32% of the 7-12 month old infants were continued on breastfeeding. The proportion of breastfed infants and young children in the 12-24 and 25-36 month age group was 24% and 5.5% respectively. The daily feeding frequency of breastfed infants was 6.7±1.6. The infants and young children, who were breastfed along with complementary feeding were feeding 5.6±1.5 times/day. After completed weaning the range of feeding frequency was limited to 4.9±0.9 occasions/day. 60.4% of mothers regarded their feeding style on demand, while 39.6% on set schedule. 16% of mothers reported that their child had feeding difficulties. CONCLUSIONS - Complementary feeding indicators should be part of infant feeding data collection, such as time of introduction of complementary food, feeding frequency, food consistency, energy density of food and safe preparation. Responsive feeding is part of responsive parenting and should be promoted, along with continuing breastfeeding at least till one year of age, and for as long as mother and infant wish to continue. ]

Lege Artis Medicinae

MAY 02, 2018

[Everyday practice of atrial fibrillation treatment]

KISS István, BENCZÚR Béla

[The clinical importance of atrial fibrillation - the most frequent arrhythmia - is derived from the fact that it means a 5-fold risk of stroke/systemic embolism which contributes to the increased cardiovascular morbidity/mortality. Long-term oral anticoagulant therapy is a cornerstone of stroke prevention in patients with atrial fibrillation. Until recently Vitamin-K antagonists were the only available therapeutic option but its everyday use has several limitations, eg. bleeding risk, narrow therapeutic range, drug and food interactions and the need of monthly INR-control. The advent of NOAC-s may prevent a lot of difficulties regarding VKA-treatment and lead to as efficacious as and safer therapy than VKAs. These benefits can help better adherence of patients to the anticoagulant therapy which is one of the most important element of more effective stroke prevention. NOACs can be used more safely both in real life and in special patient populations (eg. elderly, type 2 diabetes, chronic kidney injury) than VKAs so they can contribute to effective cardiovascular risk reduction.]

Lege Artis Medicinae

JANUARY 20, 2018

[Is the evolvement of schizophrenia preventable?]

SZENDI István

[Considering the developmental nature of the majority of mental disorders, these days prevention has increasingly come into the focus of psychiatry. Schizophrenia - one of the disorders that are most frequently associated with psychosis, one of the most serious psychiatric syndromes - is the leading cause of permanent disability of the young adult generation. A prodrome lasting for several years precedes the onset of the first psychotic episode, which offers an opportunity for preventive interventions. Currently, we have two strategies for the predicition of the outburst of psychotic disorders. The Ultrahigh-risk approach can predict the first psychotic episode regardless of diagnosis, while the Basic symptom strategy predicts the development of schizophrenia specifically. However, there is an inverse relationship between the sensitivity and the specificity of different predictive criteria, which raises clinical and ethical dilemmas for the doctors. The methods of repeated assessments of the help-seeking individuals’ clinical states with designation of syndrome stages, and multivariate analyses of emprirically derived markers have proven promising tools for establishing more balance between the sensitivity and specificity of predictive criteria. Interven­tions of the secondary prevention aim to decrease the morbidity of the underlying pathomechanisms, and to help individuals’ coping with alterations of their experiences. We can consider here the psychosocial interventions as evidence based choices, which we can combine with certain food supplements and well-chosen psychopharmacons de­pending on the clinical state. With our in­terventions, we can influence the process of the individual development with vulnerable basis and steer it toward resilience. ]