Hungarian Radiology

[Let’s make it open to the public!]

KIS Zsuzsanna

DECEMBER 20, 2002

Hungarian Radiology - 2002;76(06)

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[EXTENDED BOARD MEETING OF THE SOCIETY OF HUNGARIAN RADIOLOGISTS]

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Neuroscience highlights: Main cell types underlying memory and spatial navigation

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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.

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[The general goal for staging patients with any cancer is to determine the overal extent of disease prior to choice of therapy. It has been well documented that biological behavior of any cancer and, therefore, the prognosis of the patient is strongly linked to the extent of the tumor, the presence or absence of lymphatic dissemination as well as systemic metastases. The staging systems have undergone a number of modifications. Classifications of TNM system identifies the depth of tumor invasion (T), the status of regional lymph nodes (N) and the distant metastases. These three parameters are then incorporated into the final clinical stage. There are further modifications which influence the patient survival, e.g. biological, genetical, hystological factors, tumor grade. All cancer cells show dysregulation of cell cycle controll. As the cancer proliferates and the tumor reaches approximately 1-2 mm in diameter further growth recquires the development of new blood vessels (neo-angiogenesis). Intensity of tumor growth has a prognostic influence to the patient's life and depends on the tumor doubling time, which classifies tumors into slow, intermadiate and rapid growing types. The diagnostic impact of imaging is based on the ability of a technique to detect and evaluate the cancer accurately. The very high accuracy and reproducibility of cross-sectional imaging, paticularly computed tomography (CT) and magnetic resonance imaging (MRI) make these methods extremely important in the detection, staging and in the evaluation of the tumors. The revolutionary advances in detection and treatment of malignant disease have led to an increasing role of the radiologist as a member of the multidisciplinary cancer team.]

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[The cell uses the DNA to keep those information, which are vital to function properly. It is essential to maintain the integrity of the DNA, the stability of the genome. Since DNA damages, caused by external or internal factors, are continuously produced, DNA-repair mechanisms should be ready to identify and eliminate the damages. Either the repair system is successful and the cell can continue its duty, or, if the damages are unrepaired, the programed cell death (apoptosis) is activated according to the rule, that it is prohibited to transfer genomic/epigenomic damages into the daughter cells. It is true that the severness of the damages are not the same. The most important is the identifi cation and repair of those damages which can make genomic instability increasing the risk of cancer development. This may happen when the repair system is insuffi cient, sometimes due to inherited mutations (e.g. BRCA1 mutations can increase the risk of breast cancer, ovarian cancer etc.). Among the damages the DNA double strand breaks are rather common, and also, that the breaks are intended to be repaired in most cases. However, if such repair fails, the cell, here the cancer cell, due to the overhelming damages will dye. This phenomenon is the synthetic lethality. An example: „cooperation” of inherited BRCA1 mutation and PARP-inhibition, can lead to clinical response using PARP inhibitors, as oliparib. New agents and clinical trials intend to take advantage from synthetic lethality.]

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[The widespread application of the LMW heparins promoted the prevention and therapy of the thromboembolic diseases in Hungary. Their propagation is mainly due to their simple clinical application and the active promotion of the producing pharmaceutical companies. However, the recommended “unnecessary” (in the reality the lack of) laboratory control may cause severe complications (bleeding, thromboembolism etc.) sometimes especially at the therapeutic application. For this reason, unfractionated (UF) heparin is advised in case of acute deep vein thrombosis when a patient is in the particular danger of bleeding because of its better controllability and the opportunity to stop anticoagulation immediately. In recent years, the indication of the long-term anticoagulation therapy expanded significantly. The number of patients is ever growing who need continuous anticoagulation because of atrial fibrillation or venous thromboembolic episode taken place earlier. Large randomised multicenter trials proved the efficacy of prolonged coumarin therapy in the prevention of recurrence of thromboembolic episodes in these diseases. Due to its advantageous pharmacological characteristics warfarin is especially suitable for the attainment of continuous anticoagulation. The direct thrombin inhibitor melagatran (and its orally applicable form, ximelagatran) may open a new era in the prophylaxis and therapy of the thromboembolic diseases. Its advantageous pharmacological characteristics and its simple application may make them to the antithrombotics of the future in case of a reasonable price and/or subsidisation.]