Lege Artis Medicinae

[In the focus: gastroenterology]

BANAI János

JUNE 20, 2005

Lege Artis Medicinae - 2005;15(06)

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Lege Artis Medicinae

[Sailing between Scylla and Charybdis - Let us strive to know extensively the medications!]

NEMESÁNSZKY Elemér

Lege Artis Medicinae

[DIAGNOSTIC POSSIBILITIES IN HEAD AND NECK MRI]

GŐDÉNY Mária

[Digital cross-sectional imaging techniques, especially computed tomography (CT) and magnetic resonance imaging (MRI) play an important role in the diagnosis of pathologic conditions affecting the head and neck. MRI, because of its superb soft tissue contrast resolution and multiplanar imaging ability gives the most information regarding the origin and the extent of a laesion, intracranial extension, perineural-, as well as bone marrow involvement and play key role in the management of different diseases. Careful observation of the characteristic radiological features usually leads to correct diagnosis, however, some of the lesions are not typical, looking very similar and can be difficult to differentiate from each other. The purpose of the present article is to provide an overview of the most common pathologic conditions examined with MRI.]

Lege Artis Medicinae

[Report on the Hungarian gastroenterological endoscopic activity from 2004]

NAGY György, JUHÁSZ László

Lege Artis Medicinae

[SUBCONJUNCTIVAL NEMATODE INFECTION]

ACZÉL Klára, DEÁK György, FARKAS Róbert, MAJOROS Gábor

[INTRODUCTION - Nematode infection of the eye occur only sporadically in the continental area. The pathogenic parasite in these cases is usually a Dirofilaria species, mostly D. repens. CASE REPORT - A case of human subconjunctival dirofilariosis is reported, where acquisition from abroad or animal contact in the background of the infection were excluded. The surgical removal of the entire living worm resulted in the complete cure of the patient. CONCLUSION - Knowing the occurrence of Dirofilaria infection of dogs and the increasing spread of the vector mosquitoes during the summer (in towns, too), the increasing occurrence of human dirofilariosis affecting the eye and orbital area in 10-20% of the cases must be taken into account.]

Lege Artis Medicinae

[THE CLINICAL PHARMACOLOGIC BASIS OF THE SAFE USE OF STATIN ANALOGS]

KERPEL-FRONIUS Sándor

[Statins, specific inhibitors of the 3-hydroxy-3-methylglutaryl- coenzyme A (HMG-CoA), decrease significantly pathologically elevated cholesterol levels. The effectiveness and the side effects of the different analogs depend on their inhibitory potency, lipid solubility, active uptake into the liver cells and on the difference in their metabolism. The statins can be divided into three groups on the basis of their clinical effectiveness: the highly effective agents are rosuvastatin and atorvastatin; simvastatin exhibits an intermediate activity, while lovastatin, pravastatin and fluvastatin are the least active drugs. The main metabolic pathways of the statins are oxidation and glucoronidation and finally the spontaneous inactivation by lactone ring formation of the glucoronidated products. Gemfibrozil increases the plasma level of all statin analogs by inhibiting the activity of UGT1A1 and UGT1A3 isoenzymes of the UDPglucoronosyltransferase. Therefore, when a statinfibrate combination is needed, fenofibrate and bezafibrate are recommended, the metabolism of which are linked to other UGT isoenzymes. Similarly elevated plasma levels are produced by inhibiting the specific cytochrome isoforms participating in the oxidation of a particular statin. Severe side effects are rarely observed. The most frequent adverse reaction is the development of myopathy of various severity. Using various statins rhabdomyolysis occurred in 0.0-0.3 cases /100 000 statin prescriptions if the already withdrawn cerivastatin is not considered. The statin+gemfibrozil combination increases the number of rhabdomyolysis approximately tenfold. The long-term benefit of statin therapy far exceeds the risk of the treatment. For achieving very low lipid target values even the most effective statins must be used in high doses. Nevertheless, this goal cannot be reached in about 20% of the cases. High dose statin treatment should be administered with the gradual increase of the dose, tight control of the patients and by meticulously selecting the drugs given simultaneously. Further development can be expected from the application of agents with new mechanisms of action, such as the cholesterol uptake inhibitor ezetimibe.]

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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

The methylation status of NKCC1 and KCC2 in the patients with refractory temporal lobe epilepsy

UNAL Yasemin, KARA Murat, GENC Fatma, OZTURK Aslan Dilek, GÖMCELI Bicer Yasemin, KAYNAR Taner, TOSUN Kursad, KUTLU Gülnihal

Purpose - Methylation is a key epigenetic modification of DNA and regarding its impact on epilepsy, it is argued that “DNA methylation may play an important role in seizure susceptibility and maintenance of the disorder”. DNA methylation status of KCC2 (SCL12A5) and NKCC1 (SCL12A2) associated with refractory temporal lobe epilepsy was investigated in our study. Materials and methods - Thirty-eight patients with temporal lobe epilepsy (TLE) who were diagnosed by video EEG monitoring and 32 healthy control subjects were included in the study. Twenty-three patients in TLE group were men and the remaining 15 were women. Among them, 27 had unilateral temporal focus (9 with right; 18 with left) and 11 patients had bilateral TLE. We analyzed promoter region methylation status of the KCC2 (SCL12A5) and NKCC1 (SCL12A2) genes in the case and control groups. Gene regions of interest were amplified through PCR and sequencing was accomplished with pyro-sequencing. Results - We found a significant relationship between TLE and methylation on the NKCC1. However, there was no association between TLE and methylation on the KCC2 gene. Also, we found no association between right or left and unilateral or bilateral foci of TLE. There was no relationship between TLE and methylation on the NKCC1and KCC2 genes in terms of mesial temporal sclerosis in cranial MRI, head trauma or febrile convulsions. Conclusion - The methylation of NKCC1 can be a mecha­nism of refractory temporal lobe epilepsy. There are limited findings about DNA methylation in TLE. Therefore, further studies with large sample sizes are necessary.

Clinical Neuroscience

[Family planning in multiple sclerosis: conception, pregnancy, breastfeeding]

RÓZSA Csilla

[Family planning is an exceptionally important question in multiple sclerosis, as women of childbearing age are the ones most often affected. Although it is proven that pregnancy does not worsen the long-term prognosis of relapsing-remitting multiple sclerosis, many patients are still doubtful about having children. This question is further complicated by the fact that patients – and often even doctors – are not sufficiently informed about how the ever-increasing number of available disease-modifying treatments affect pregnancies. Breastfeeding is an even less clear topic. Patients usually look to their neurologists first for answers concerning these matters. It falls to the neurologist to rationally evaluate the risks and benefits of contraception, pregnancy, assisted reproduction, childbirth, breastfeeding and disease modifying treatments, to inform patients about these, and then together come to a decision about the best possible therapeutic approach, taking the patients’ individual family plans into consideration. Here we present a review of relevant literature adhering to international guidelines on the topics of conception, pregnancy and breastfeeding, with a special focus on the applicability of approved disease modifying treatments during pregnancy and breastfeeding. The goal of this article is to provide clinicians involved in the care of MS patients with up-to-date information that they can utilize in their day-to-day clinical practice. ]

Hungarian Immunology

[Gene therapy as a treatment for rheumatoid arthritis]

JAMES M. Woods

[A clear understanding of the pathogenic events and/or environmental conditions that lead to the development of rheumatoid arthritis has not been accomplished. In recent years, some of the most capable therapies have targeted individual proteins, such as proinflammatory cytokines, which contribute to persistent inflammation. The success of these therapies in some patients underscores the importance of having a solid pathophysiologic knowledge of the mechanisms at play in the diseased joint. Targeting the joint therapeutically with proteins or other agents has presented many challenges in the treatment of rheumatoid arthritis. To circumvent these obstacles, the idea of providing transgenes to cells of the synovial lining was born. This use of gene therapy, as a delivery vehicle rather than replacement of a genetic deficit, has had many successes in preclinical animal studies. Preliminary results of the first Phase I clinical trial in humans suggests that an ex vivo approach can be safe and enable transgene expression. This review provides a consolidated overview of many of the successful gene therapy strategies undertaken for the treatment of animal models of arthritis. The focus is on: 1. joint targeting strategies, including discussion on the local and systemic approaches as well as the contralateral joint; 2. the applicability of viral vectors, including comparison of adenoviral, retroviral, adeno-associated, and herpes simplex viruses; 3. timing and dosage of treatment; and 4. targets and candidate proteins that have been examined, including targeting proinflammatory cytokines or the use of anti-inflammatory cytokines.]

Lege Artis Medicinae

[The 48. Congress of the Hungarian Society of Gastroenterology - 17-21. June 2006. Szeged]

IZBÉKI Ferenc