Lege Artis Medicinae

[On the new editorial board]

FRENKL Róbert

MARCH 20, 2004

Lege Artis Medicinae - 2004;14(03)

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Lege Artis Medicinae

[INSULIN RESISTANCE: FOCUS ON THE ADIPOSE TISSUE]

URICH Elemér

[Insulin resistance is defined as a state of subnormal biological response to normal quantity of insulin. This phenomenon was first described by Hinsworth and Kerr in 1939, however it has come to the centre of interest only in the last two decades. It is the central pathogenetic factor of type 2 diabetes and the more complex clinical entity of metabolic syndrome, consequently also referred to as insulin resistance syndrome. In the background of insulin resistance alterations of the adipose tissue can be observed which clinically means obesity in most of the cases, however, this issue cannot be simplified to obesity only as increase in adipose tissue growth may be beneficial in certain cases. Current article discusses the explanation of this paradox and the pathophysiologic link between adipose tissue and insulin resistance. It also reviews the therapeutic aspects of insulin resistance emphasizing the role of thiazolidinedione type drugs having recently joined the therapeutic palette.]

Lege Artis Medicinae

[Global alliance against global threat - The anti-tobacco framework of the World Health Organisation]

VADÁSZ Imre

Lege Artis Medicinae

[DASH]

MATOS Lajos

Lege Artis Medicinae

[THE GENOMIC BACKGROUND OF ALLERGY]

SZALAI Csaba

[In this review we summarise the current results of the genomic investigation of allergic diseases. From the genetic point of view allergy is multifactorial, which means that the susceptibility to the disease is determined by the effect of one or more genes or the interactions between multiple genes and involves important nongenetic factors such as the environment for their expression. Among allergic diseases the genomic background of asthma was studied most thoroughly. Until now, using hundreds of DNA markers, located across all of the human chromosomes, 16 genome-wide screens for susceptibility genes for asthma or asthma related intermediate phenotypes in 12 different populations have been published and 20 chromosomal regions have been highlighted for further analysis. In genetic association studies more than 500 genes were identified as candidate genes for asthma. In this review, we selected those results which were consistently reported by several independent studies or appeared particularly important or interesting. According to the results of the human genome programs and association studies we discuss the possible roles of candidate genes found in these loci in the pathomechanism of allergy and atopy.]

Lege Artis Medicinae

[TRIPTAN THERAPY OF MIGRAINE]

UNGUREAN Aurélia, TAJTI János, VÉCSEI László

[Migraine sufferers in Hungary present a major epidemiological challenge with about 12% of the population affected. Authors have reviewed an extensive body of internationally published literature relative to the 5-hydroxi-triptamin receptor agonists such as the triptans. While summarising most relevant data with a view to enable physicians to choose the most effective therapy for an individual, the article also discusses the prevailing questions of efficacy, tolerability and safety. For those patients with differential-diagnostic difficulties referrals should be made to the specialized 'headache centers' of neurological departments.]

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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

Neuroscience highlights: Main cell types underlying memory and spatial navigation

KRABOTH Zoltán, KÁLMÁN Bernadette

Interest in the hippocampal formation and its role in navigation and memory arose in the second part of the 20th century, at least in part due to the curious case of Henry G. Molaison, who underwent brain surgery for intractable epilepsy. The temporal association observed between the removal of his entorhinal cortex along with a significant part of hippocampus and the developing severe memory deficit inspired scientists to focus on these regions. The subsequent discovery of the so-called place cells in the hippocampus launched the description of many other functional cell types and neuronal networks throughout the Papez-circuit that has a key role in memory processes and spatial information coding (speed, head direction, border, grid, object-vector etc). Each of these cell types has its own unique characteristics, and together they form the so-called “Brain GPS”. The aim of this short survey is to highlight for practicing neurologists the types of cells and neuronal networks that represent the anatomical substrates and physiological correlates of pathological entities affecting the limbic system, especially in the temporal lobe. For that purpose, we survey early discoveries along with the most relevant neuroscience observations from the recent literature. By this brief survey, we highlight main cell types in the hippocampal formation, and describe their roles in spatial navigation and memory processes. In recent decades, an array of new and functionally unique neuron types has been recognized in the hippocampal formation, but likely more remain to be discovered. For a better understanding of the heterogeneous presentations of neurological disorders affecting this anatomical region, insights into the constantly evolving neuroscience behind may be helpful. The public health consequences of diseases that affect memory and spatial navigation are high, and grow as the population ages, prompting scientist to focus on further exploring this brain region.

LAM KID

[New findings in the cortical bone biology and its role in bone fractures]

BALOGH Ádám, BHATTOA Harjit Pál

[The authors surveyed the already known factors responsible for the osteoporotic bone fragility. Then the results of using modern imaging techniques (micro-CT, high-resolution peripheral computed quantitative tomograph - HR-pQCT) and advanced computer analytic methods (finite element analysis, FEA) are presented. These data - beyond the already known fracture risk factors (age, risk of falling, bone mineral density - BMD, and fine structure damage of trabecular bone) are stressing the importance of the (micro)damage of cortical bone as a fracture risk factor, which has been still underrated. The cortical thickening and increased porosity - verified on various population samples - are increasing the risk of fractures in certain subgroups of subjects having identical BMD values, even among those, who are considered only osteopenic by the earlier classification based on BMD values. Backed with modern software batteries, the new imaging techniques are expected to enter clinical application in the near future. Pharmacologic agents with stronger cortical effect are already available and research is continuing to find new drugs to use in the management of osteoporotic patients of high fracture risk.]

Clinical Oncology

[Complications of infusion treatment with emphasis on extravasation of cytostatics]

HARISI Revekka

[The extravasation of cytostatics is the most signifi cant complication of infusion therapy in cancer treatment. Extravasation refers to the inadvertent infi ltration of cytostatic drugs into subcutaneous or subdermal tissues surrounding the intravenous or intraarterial administration site. According to literature data incidence estimates between 0,01-7%. Extravasated drugs are classifi ed according to their potential for causing damage as vesicant, irritant and nonvesicant. Knowledge of risk factors, the patientrelated and treatment-related ones is important to minimize the occurrence of extravasation. In order to reduce the risk of extravasation, the staff involved in the tumor infusion therapy must be specially trained to implement several preventive and therapeutical protocols. In 2012, ESMO-EONS has put together a new comprehensive treatment protocol on the topic of cytostatics extravasation. Protocol recommended that every oncological department, who administers chemotherapy have to have extravasation trained team and a standby extravasation kit. According to the new ESMO-EONS guideline subcutaneous corticoids are not recommended, anymore. In case of mechloretamine extravasation the recommendation is immediate subcutaneous injection of sodium thiosulfate. After extravasation of anthracyclines, mitomycin C and platin salts the best treatment opportunity is subcutan dimethyl sulfoxide administration. In case of anthracyclines’ extravasation intravenous dexrazoxane treatment is also effective. Hyaluronidase, injected into or under the skin, facilitates absorption of extravasated drugs because of increases connective tissue permeability, promotes the spreading and reduces the local concentration of the extravasated citostatic agents. Hyaluronidase might be effi cacious in preventing skin necrosis by extravasation due to vinca alkaloids. The treatment of unresolved tissue necrosis or pain lasting more than 10 days is surgical debridement. Because of the medical and juristic importance of the extravasation event, it is necessary to establish uniform guidelines for treatment of extravasation, in all Hungarian Oncological Centers.]

Clinical Neuroscience

[Clinical neurophysiological methods in diagnosis and treatment of cerebrovascular diseases]

NAGY Ildikó, FABÓ Dániel

[Neurophysiological methods are gaining ground in the diagnosis and therapy of cerebrovascular disease. While the role of the EEG (electroencephalography) in the diagnosis of post-stroke epilepsy is constant, quantitative EEG para-meters, as new indicators of early efficiency after thrombolysis or in prognosis of patient’s condition have proved their effectiveness in several clinical studies. In intensive care units, continuous EEG monitoring of critically ill patients became part of neurointenzive care protocols. SSEP (somatosesnsory evoked potencial) and EEG performed during carotid endarterectomy, are early indicative intraoperativ neuromonitoring methods of poor outcome. Neurorehabilitation is a newly discovered area of neurophysiology. Clinical studies have demonstrated the effectiveness of repetitive transcranial magnetic stimulation (rTMS) in the rehabilitation of stroke patients. Brain computer interface mark the onset of modern rehabi-litation, where the function deficit is replaced by robotic tehnology. ]