Lege Artis Medicinae

[TIGECYCLINE, A NEW ANTIBIOTIC]

SZALKA András

JANUARY 20, 2007

Lege Artis Medicinae - 2007;17(01)

[Glycylcyclines are a new class of antimicrobial agents, of which tigecycline is the first to have reached the final stage of clinical trials. It is the 9-t-butylglycylamido derivative of minocycline. The addition of a side-chain into position 9 overcomes the problem of the development of resistance typical to tetracyclines. Tigecycline inhibits translation of bacterial proteins through its effect on the 30S ribosomal subunit. The efficacy of tigecycline is impressive against multiresistant Gram-positive bacteria, including methicillin- resistant Staphylococcus aureus, penicillin- resistant Streptococcus pneumoniae, and vancomycin-resistant enterococci, against most genera of Enterobacteriaceae, including extended- spectrum β-lactamase-producing strains, and against most strains of Bacteroides fragilis, as well as atypical pathogens. Clinical studies showed good results in parenteral treatment for complicated skin, soft tissue and intraabdominal infections. Tigecycline will be most useful as empirical monotherapy in infections with suspected polymicrobial etiology and/or multidrugresistant agents.]

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Lege Artis Medicinae

[PATHOLOGICAL FEATURES OF SYSTEMIC SCLEROSIS]

VARJÚ Cecília, KUMÁNOVICS Gábor, CZIRJÁK László

[Systemic sclerosis is characterized by fibrosis and subsequent atrophy of the skin and several internal organs as well as by generalized obliterative vasculopathy. The ethiology of systemic sclerosis is not quite clear yet, but the role of certain environmental factors, genetic properties and microchimaerism has been proven. Vasculopathy is a key feature that includes both functional changes (Raynaud's phenomenon) and morphological alterations (lesion of the endothel). The triggering event is the activation of endothelial cells. This is followed by an autoimmune inflammatory process causing vascular lesion, which will eventually lead to progressive pathologic fibrosis with increased deposition of collagen and intercellular matrix proteins. Normal tissues of vital internal organs will gradually loose structure, become atrophic and irreversibly damaged. In the treatment of systemic sclerosis the most significant achievements of the past decade have been made in the therapy and prevention of scleroderma renal crisis, pulmonary arterial hypertension and other vascular complications, resulting in higher survival rates and better quality of life. In pulmonary fibrosis the beneficial effect of cyclophosphamide therapy has been proven. Today, research focuses on new therapeutic approaches based on the recently clarified molecular pathological processes, as well as on laboratory and clinical markers that predict the activity of the disease or the efficiency of therapy. The aim of the present paper is to review current knowledge on the pathology of systemic sclerosis and provide help in the diagnosis, therapy and follow-up of the disease.]

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[PREVALENCE OF OSTEOPOROSIS IN PATIENTS WITH COLLES’ FRACTURE]

NAGY József, BÁLINT Géza, TAKÁCS Katalin, WINKLER Valéria, RATKÓ István, BÁLINT Péter

[INTRODUCTION - Studies suggest that Colles’ fracture is the earliest of the osteoporotic fractures, and thus may be the first indication of the disease. PATIENTS AND METHODS - Fifty-seven consecutive patients with Colles’ fracture who presented between 1st of October 2003 and 1st of February 2004 at the traumatology out-patient clinic of Semmelweis Hospital, Kiskunhalas were screened for osteoporosis. RESULTS - Of the 43 postmenopausal women, 41 was found to have osteoporosis by DEXA scan, but only one was aware of her disease and received treatment. Out of these 41 patients 15 had fractures previously, 9 of whom had more than one. None of the four premenopausal women had osteoporotic DEXA measurement values. All of the 10 male patients had osteoporosis, 6 had previous fractures, 5 of them more then once. One patient required surgery, there was a prolonged fracture healing in 10 cases, and reflex sympathetic dystrophy developed in 3 patients. CONCLUSION - Since in this study more than 95% of postmenopausal women with Colles’ fracture had underlying osteoporosis, the authors conclude that DEXA scanning of these patients is recommended. Based on the results, it seems that screening for osteoporosis is indicated for both men and women after radius fracture.]

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[INTRODUCTION - Tigecycline, the first member of the glycylcycline family of antibiotics, is a semisynthetic derivative of minocycline. The modified tetracycline nucleus is protected against the resistance mechanisms that inactivate tetracyclines, thus tigecycline is expected to be effective against tetracycline- resistant strains. The aim of this multicenter survey, performed in 2007 and 2008 by three Hungarian laboratories, was to examine the efficiency of this drug against antianaerobic bacteria in vitro. MATERIALS AND METHODS - The participating laboratories isolated 540 strains of Gram-positive and Gram-negative anaerobic bacteria from various infectious sites. These sites represent the classes of infections for which tigecycline was recently approved as a treatment option (skin and soft tissue and intra-abdominalinfections), or for which it will be licensed in the near future (lower respiratory tract infections). Evaluation of antibiotic susceptibility was performed by Etest, and the efficiencies of six antibiotics were determined using MIC values. RESULTS - The 540 strains belonged to 33 different species. Of the 104 strains of Gram-positive anaerobic cocci, 100% proved to be susceptible to tigecycline. Similarly, 98% of the examined Clostridium strains showed susceptibility to this antibiotic. Two of the 56 Prevotella strains were resistant against tigecycline. MIC50 and MIC90 values in the 280 Bacteroides strains were 0.5 μg/ml and 1 μg/ml, respectively, whereas only 1.8% of the tested strains showed low resistance. CONCLUSION - Similarly to the findings of international surveys, our results show that tigecycline is effective against the great majority (97.4% susceptibility) of relevant anaerobic bacteria that are isolated from skin and soft tissue, intra-abdominal and lower respiratory tract infections. Thus, empiric use of tigecycline is recommended in any infections where anaerobic bacteria alone or a mixed flora of aerobic and anaerobic bacteria are likely to be present.]

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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 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.]

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