Lege Artis Medicinae

[Understanding Pathogenesis Better]

CZAKÓ László

NOVEMBER 19, 2006

Lege Artis Medicinae - 2006;16(11)

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Lege Artis Medicinae

[INSULIN ASPART IN THE CLINICAL PRACTICE]

JERMENDY György

[Insulin aspart (B28 Asp-insulin), which is produced by recombinant DNA technology, is a fast-acting insulin analogue. Due to the aspartate for proline substitution at position 28 of the Bchain, the insulin molecule's tendency for selfassociation is diminished, therefore, insulin aspart rapidly dissociates into dimeric and monomeric forms and absorbs quickly and easily after subcutaneous administration. Compared to human regular insulin, insulin aspart has a faster onset of activity, a higher plasma peak and a shorter duration of action. Overall, the pharmacokinetic profile of insulin aspart better mimics the physiological postprandial insulin secretion. Therefore, insulin aspart can be used for prandial insulin substitution in order to decrease postprandial blood glucose excursion. It should be administered immediately before meals, but some observations suggest that it can also be used after finishing meal. This allows a more flexible lifestyle for patients. Insulin aspart can be used in both type 1 and type 2 diabetes. Compared to regular human insulin, a moderate decrease in the HbA1c values and fewer nocturnal hypoglycaemic events are expected from insulin aspart use. Insulin aspart is appropriate for pump treatment as well. It has recently been approved for use in pregnancy, whereas for children and adolescents the expected benefits should be weighed against the more modest clinical experience available. Similarly to other insulin analogues, results of long-term clinical investigations with insulin aspart with regard to the development of complications are not yet available.]

Lege Artis Medicinae

[Checkmate]

SZIGETI Zoltán

Lege Artis Medicinae

[TREATMENT APPROACHES OF CHRONIC HEPATITIS B IN HUNGARY]

TORNAI István, NEMESÁNSZKY Elemér

[Today, there are less patients with active chronic hepatitis B requiring treatment than patients with chronic hepatitis C. However, the course and outcome of chronic hepatitis B is usually more severe, therefore, the disease has not lost importance. The most dangerous risks are the development of liver cirrhosis and hepatocellular carcinoma. The disease may present in various forms. Symptom-free carriers only need follow-up and hepatologic care. In the active stages with elevated liver enzymes and high level of viral nucleic acid (either HBeAg negative or positive), however, antiviral treatment is strongly indicated. There are two main forms of treatment. Alfa-interferon-based therapy, which is applied for a defined period of time, has a direct antiviral and immunomodulatory effect, but has several adverse effects. Long-term nucleoside analogue treatment represent the other treatment modality. These drugs are administered orally, have minimal side effects, but after some time resistant mutants may develop. Traditional interferon has recently been replaced by pegylated interferon alfa-2a with much better pharmacokinetic properties. Lamivudine has been in use for the longest time of the nucleoside analogues. Its efficacy is high, but after 3 to 4 years of treatment, resistant mutants appear in about 70% of cases. Of the most recent compounds, adefovir dipivoxil has recently become available in Hungary; it is primarily recommended in cases with lamivudine resistant mutants. There are promising new drugs in the stages of clinical trial; of these, entecavir has already been approved in the United States.]

Lege Artis Medicinae

[Val-MARC]

MATOS Lajos

Lege Artis Medicinae

[Autoimmune pancreatitis]

JAKAB Lajos

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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

[Interdisciplinary approach of vestibular system impairment]

PONGRÁCZ Endre

[In the first part of this review the definition of vertigo/dizziness was discussed. The major difference between the two signs is the exsistence of the direction, which is specific for vertigo. Dizziness is a frequent complaint in the clinical practice. Its frequency is increasing with advance of age, to intimate the play of declining cognitive process in the pathogenesis of its. The popular health significance of vertigo is in the rowing number of the patients. The onset of the most cases with acute vertigo appears between secundums and minutes so the patients will be provided in circumstances of emergency department. First of all three form schould be take into account: neuronitis vestibularis, benign paroxysmal positional vertigo and Meniere syndrome. Without tipical periferal signs of vertigo, central cause should be searched, principally stroke (lysis possibility). The differential diagnose of the different dizzeness/vertigo forms according to the elapsed time of the onset or congenital and acquired nystagmus was created in tables. The recommendations of the therapy of acute and chronic dizziness/ vertigo syndroms are, lack of results of evidence based trials doubtful. The more often used drugs based on clinical trials are discussed as vinpocetine, betahistine and piracetam. The in vitro and in vivo data suggest that the last molecule is eligible to use both in periferal and central type of vertigo syndroms.]

Clinical Neuroscience

[LADA type diabetes, celiac diasease, cerebellar ataxia and stiff person syndrome. A rare association of autoimmune disorders]

SOÓS Zsuzsanna, SALAMON Mónika, ERDEI Katalin, KASZÁS Nóra, FOLYOVICH András, SZŰCS Anna, BARCS Gábor, ARÁNYI Zsuzsanna, SKALICZKI József, VADASDI Károly, WINKLER Gábor

[Celiac disease - in its typical form - is a chronic immunemediated enteropathy with typical clinical symptoms that develops against gliadin content of cereal grains, and is often associated with other autoimmune diseases. In cases of atypical manifestation classic symptoms may be absent or mild, and extra-intestinal symptoms or associated syndromes dominate clinical picture. The authors present a longitudinal follow-up of such a case. A 63-years old woman was diagnosed with epilepsy at the age of 19, and with progressive limb ataxia at the age of 36, which was initially thought to be caused by cerebellar atrophy, later probably by stiff person syndrome. At the age 59, her diabetes mellitus manifested with type 2 diabetic phenotype, but based on GAD positivity later was reclassified as type 1 diabetes. Only the last check-up discovered the celiac disease, retrospectively explaining the entire disease course and neurological symptoms. By presenting this case, the authors would like to draw attention to the fact that one should think of the possibility of celiac disease when cerebellar ataxia, progressive neurological symptoms and diabetes are present at the same time. An early diagnosis may help to delay the progression of disease and help better treatment.]

Clinical Neuroscience

[Vinpocetin in neurological diseases]

SZAPÁRY László, KÉSMÁRKY Gábor, TÓTH Kálmán, MISNYOVSZKY Melinda, TÓTH Tímea, BALOGH Ágnes, NAGY Krisztián, NÉMETH György, FEHÉR Gergely

[Introduction - Stroke is the third leading cause of death worldwide (following cardiovascular and cancer mortality) and associated with serious disability for the vast majority of patients. There is no salvage therapy for irreversibly damaged brain areas, improving the circulation of the surrounding hypoperfused territories may be associated with benefitial clinical states. Cerebral hypoperfusion may play a role in the pathogenesis of other kind of neurological diseases, improvement of global circulation may have a preventive effect on these conditions. Aims - The aim of our study was to review the experimental and clinical articles focusing on the role of vinpocetin in different neurological conditions. Results - Vinpocetin appears to have several different mechanisms of action that allow for its antiinflammatory, antioxidant, vasodilating, antiepileptic and neuroprotective activities in experimental conditions. On the other hand, several meta-analysis of the existing studies in acute stroke examining short and long term fatality rates with vinpocetin was unable to assess efficacy. In chronic cerebrovascular patients, vinpocetin improves impaired hemorheological variables, has significant vasodilating properties, improves endothelial dysfunction, neuroimaging studies showed selective increase in cerebral blood flow and cerebral metabolic rate, all of which are potentially beneficial in cerebrovascular disease and may improve cognitive functions. Summary - Based on the above mentioned results vinpocetin plays an important role both in basic research and in clinical management of different neurological diseases.]

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.]