LAM KID

[Personal genome - brave new world?]

ÁRVAI Kristóf1, KÓSA János Pál1,2

DECEMBER 23, 2011

LAM KID - 2011;1(03)

AFFILIATIONS

  1. Semmelweis Egyetem, I. Sz. Belgyógyászati Klinika, PentaCore Laboratórium
  2. Semmelweis Egyetem, I. Sz. Belgyógyászati Klinika, Klinikai Kutató és Molekuláris Biológiai Laboratórium

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[Extraskeletal effects of parathyroid hormone]

KISS Zoltán, MUCSI István, TÚRI Sándor, SZABÓ András, KISS István, SZEBENI Andrea, KECSKEMÉTI Valéria, TÓTH Miklós, LAKATOS Péter

[The parathyroid gland and its product, parathyroid hormone (PTH) have been subjects of interests in biomedical research for 150 years. Early studies, understandably, concentrated on the primary function: the regulation of serum calcium level. In the past few decades, however, more and more data have shown that, in contrast with the classical view, PTH receptors are expressed not only on bone and kidney cells, but in almost all organs of the human body. Therefore, the effect of PTH obviously cannot be limited to the regulation of bone and mineral metabolism. Systemic symptoms of hyperparathyroidism also became more understandable and explicable by the results of studies on the extraskeletal effects of PTH. Despite the intensive research, the mechanisms of PTH-mediated effects are not well understood in a number of areas. Therefore, it is of great importance to perform further studies in this field, which will hopefully expand our knowledge soon. In our current work, we aim to summarise the nonclassical, extraskeletal effects of PTH (that is, those not related to the regulation of bone metabolism and kidney function) and the results of related studies.]

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[Treatment of postmenopausal osteoporotic women with strontium ranelate: results at 10 years]

SZEKERES László

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[Vitamin D determination: preanalytical and analytical points of view]

BHATTOA Harjit Pál

LAM KID

[PAGE OF THE HUNGARIAN SOCIETY OF OSTEOPOROSIS AND OSTEOARTHROLOGY]

LAM KID

[The pathogenic and clinical significance of the RANK-RANKL-osteoprotegerin system in rheumatoid arthritis]

SZENTPÉTERY Ágnes, VÁNCSA Andrea, SZABÓ Zoltán, SZEKANECZ Zoltán

[Rheumatoid arthritis (RA) is characterised by increased local and generalised bone resorption, which manifests in the develoment of marginal erosions and generalised osteoporosis, respectively. An increasing number of data suggest that lymphocytes, proinflammatory cytokines and other mediators involved in inflammation contribute to arthritic bone resorption. Therefore, the term ‘osteoimmunology’ has also become widely used. In RA, Receptor Activator of Nuclear Factor kappa B (RANK) and its ligand (RANKL) play a crucial role in bone resorption. These proteins, which belong to the tumor necrosis factor a (TNF-a) receptor and TNF ligand superfamilies, respectively, activate osteoclasts while interacting with T cells, synovial fibroblasts and other cytokines (e.g. IL-1, IL-17), which results in bone resorption. Osteoprotegerin (OPG) is a decoy receptor that also belongs to the TNF receptor family and inhibits RANK-RANKL interactions. There is increased RANKL production and decreased OPG production in RA. The interaction of RANKL with IL-17 is particularly important. Regarding therapy, sulfasalazine, methotrexate and biological agents, especially TNF inhibitors suppress RANKL-mediated bone resorption and thus the development of joint erosions. RANKL-RANK interaction can be directly inhibited by recombinant OPG or anti-RANKL antibody (denosumab). Among these agents, denosumab gave promising results in experiments performed in animal models of arthritis. These were followed by a phase II human RA trial, which proved that denosumab decreased MRI erosion scores in RA.]

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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.

Clinical Neuroscience

[Earlier and more efficiently: the role of deep brain stimulation for parkinson’s disease preserving the working capabilities]

DELI Gabriella, BALÁS István, KOMOLY Sámuel, DÓCZI Tamás, JANSZKY József, ASCHERMANN Zsuzsanna, NAGY Ferenc, BOSNYÁK Edit, KOVÁCS Norbert

[Background – The recently published “EarlyStim” study demonstrated that deep brain stimulation (DBS) for the treatment of Parkinson’s disease (PD) with early fluctuations is superior to the optimal pharmacological treatment in improving the quality of life and motor symptoms, and preserving sociocultural position. Our retrospective investigation aimed to evaluate if DBS therapy was able to preserve the working capabilities of our patients. Methods – We reviewed the data of 39 young (<60 years-old) PD patients who underwent subthalamic DBS implantation at University of Pécs and had at least two years follow-up. Patients were categorized into two groups based on their working capabilities: Patients with active job (“Job+” group, n=15) and retired patients (without active job, “Job-” group, n=24). Severity of motor symptoms (UPDRS part 3), quality of life (EQ-5D) and presence of active job were evaluated one and two years after the operation. Results – As far as the severity of motor symptoms were concerned, similar (approximately 50%) improvement was achieved in both groups. However, the postoperative quality of life was significantly better in the Job+ group. Majority (12/15, 80%) of Job+ group members were able to preserve their job two years after the operation. However, only a minimal portion (1/24, 4.2%) of the Job- group members was able to return to the world of active employees (p<0.01, McNemar test). Conclusion – Although our retrospective study has several limitations, our results fit well with the conclusions of “EarlyStim” study. Both of them suggest that with optimal timing of DBS implantation we may preserve the working capabilities of our patients.]

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[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.]

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[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.]