Lege Artis Medicinae

[Genomic background of asthma]

SZALAI Csaba

DECEMBER 20, 2010

Lege Artis Medicinae - 2010;20(12)

[From a genomic point of view asthma is a multifactorial disease. It means that the susceptibility to the disease results from interaction of several (possibly several hundred) genes; in addition, the development of the disease requires environmental factors, as well. In the last years the hypothesis-free methods became widespread in the field of genomics investigating the genomic background of diseases. These methods do not need previous knowledge about the pathomechanism of the diseases and make it possible to discover new metabolic pathways. In this review all of the new asthma genes will be presented detected in the last few years by two such methods, by positional cloning and genome wide association study. The careful design of the studies, the large populations, the robust genomic and bioinformatic methods make it likely that these genes are really asthma genes playing important roles in the pathomechanism of the disease and are potential new therapeutic targets.]

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[Lecturis Salutem! Greetings to the Reader!]

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[Members of the editorial and advisory board and the redaction of the LAM, 1990-2010]

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[Farewell to rosiglitazone: where to go?]

TAMÁS GYULA, KERÉNYI ZSUZSA

[The European Medicines Agency concluded that the marketing authorisation for all rosiglitazonecontaining medicines (Avandia, Avandamet, Avaglim) should be suspended across the European Union. The National Health Insurance Fund Administration in Hungary in a circular letter called the attention of GP’s to the necessity in getting the medical proposal (of an internist, endocrinologist or diabetologist) for substituting rosiglitazone to arrange a smooth modification of their treatment regimen. The review taking into account updated recommendations of the ADA-EASD and the Hungarian Diabetes Association summarises the potential drugs. The first line therapy of choice has to be starting with insulin. Pioglitazone might also be administered, with all known side effects of the glitazone family, e.g. congestive heart failure and bone fractures. Further alternatives are choosing the newer drugs of the incretin principle: the incretin mimetics (exenatid, liraglutid) and the incretin enhancers (sitagliptin, vildagliptin, saxagliptin). Beside their favourable profile of effect they do not have longterm follow up outcome studies and evidences for cardiovascular safety.]

Lege Artis Medicinae

[On rivaroxaban’s mechanism of effect]

BODA Zoltán

[A new era of anticoagulant therapy is approaching. No new oral anticoagulants have been introduced for seventy years. However, two large groups of anticoagulants (molecules with anti-FXa and anti-FIIa acitivity) are currently at advanced stages of clinical trials. This publication summarises the most important information on the mechanism of effect of the anti-FXa drug rivaroxaban. The possible advantages of the “direct” effect and the anti-FXa effect are emphasized. The most significant drug interactions of the new anticoagulant are also presented.]

Lege Artis Medicinae

[Pancreatology in practice: acute pancreatitis]

TAKÁCS Tamás

[Acute pancreatitis requires various diagnostic and treatment procedures. The clinical picture of acute pancreatitis is diverse, ranging from mild abdominal pain or dyspepsia to severe, lifethreatening multiorgan failure or sepsis. Most cases of pancreatitis result in a mild/edematous inflammation of the pancreas, whereas the remaining 15-20 percent results in severe necrotising pancreatitis with a mortality rate as high as 10-30 percent, although imaging diagnostics, operative endoscopy and intensive internal and surgical therapy have improved significantly in the past few years. Quick and accurate diagnosis of the disease is required for early therapeutic intervention. For example, we know that in cases of biliary acute pancreatitis an early (within 24-48 hours following the onset of symptoms) endoscopic sphincterotomy and stone extraction significantly improve the prognosis of the disaese. It is also important to introduce an adequate perfusion/rehydration therapy and a simultaneous enteral feeding introduced as soon as possible to avoid the superinfection of the pancreatic necrosis. Therefore, when reviewing the epidemiological characteristics, pathophysiology, up-to-date diagnostic and therapeutic approaches of the disease, we emphasise early interventions. We also highlight the importance of patient care and follow-up checks after an incident of acute pancreatitis.]

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[Depression is a multifactorial disease with both genes and environmental factors as well as complex relationships between these factors playing a role in its background. However, in spite of several decades of research no genetic variants playing a straightforward and robust role in the background of depression have been identified. One reason behind this is the genetic and biological heterogeneity of depression, while another is that in the majority of studies environmental effects interacting with genetic variants have not been considered which may mask important genetic effects. Furthermore, relative contribution of genetic and environmental factors may vary in case of different manifestations and subtypes of depression which has not only etiopathological relevance but may also influence choice and efficiency of treatment. Consideration of heterogeneity of depressive syndromes, as well as environmental effects in case of both candidate gene and whole genome association studies, and qualitative analysis of environmental effects in depression and antidepressant research may extend our existing knowledge concerning the pathophysiology of depression and may also aid identification of new antidepressive therapeutic targets. ]

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[The well-known gap bet­ween stroke mortality of Eastern and Western Euro­pean countries may reflect the effect of socioeconomic diffe­rences. Such a gap may be present between neighborhoods of different wealth within one city. We set forth to compare age distribution, incidence, case fatality, mortality, and risk factor profile of stroke patients of the poorest (District 8) and wealthiest (District 12) districts of Budapest. We synthesize the results of our former comparative epidemiological investigations focusing on the association of socioeconomic background and features of stroke in two districts of the capital city of Hungary. The “Budapest District 8–12 project” pointed out the younger age of stroke patients of the poorer district, and established that the prevalence of smoking, alcohol-consumption, and untreated hypertension is also higher in District 8. The “Six Years in Two Districts” project involving 4779 patients with a 10-year follow-up revealed higher incidence, case fatality and mortality of stroke in the less wealthy district. The younger patients of the poorer region show higher risk-factor prevalence, die younger and their fatality grows faster during long-term follow-up. The higher prevalence of risk factors and the higher fatality of the younger age groups in the socioeconomically deprived district reflect the higher vulnerability of the population in District 8. The missing link between poverty and stroke outcome seems to be lifestyle risk-factors and lack of adherence to primary preventive efforts. Public health campaigns on stroke prevention should focus on the young generation of socioeconomi­cally deprived neighborhoods. ]

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[Affective temperaments (cyclothymic, hypertymic, depressive, anxious, irritable) are stable parts of personality and after adolescent only their minor changes are detectable. Their connections with psychopathology is well-described; depressive temperament plays role in major depression, cyclothymic temperament in bipolar II disorder, while hyperthymic temperament in bipolar I disorder. Moreover, scientific data of the last decade suggest, that affective temperaments are also associated with somatic diseases. Cyclothymic temperament is supposed to have the closest connection with hypertension. The prevalence of hypertension is higher parallel with the presence of dominant cyclothymic affective temperament and in this condition the frequency of cardiovascular complications in hypertensive patients was also described to be higher. In chronic hypertensive patients cyclothymic temperament score is positively associated with systolic blood pressure and in women with the earlier development of hypertension. The background of these associations is probably based on the more prevalent presence of common risk factors (smoking, obesity, alcoholism) with more pronounced cyclothymic temperament. The scientific importance of the research of the associations of personality traits including affective temperaments with somatic disorders can help in the identification of higher risk patient subgroups.]

Clinical Neuroscience

Life threatening rare lymphomas presenting as longitudinally extensive transverse myelitis: a diagnostic challenge

TOLVAJ Balázs, HAHN Katalin, NAGY Zsuzsanna, VADVÁRI Árpád, CSOMOR Judit, GELPI Ellen, ILLÉS Zsolt, GARZULY Ferenc

Background and aims – Description of two cases of rare intravascular large B-cell lymphoma and secondary T-cell lymphoma diagnosed postmortem, that manifested clinically as longitudinally extensive transverse myelitis (LETM). We discuss causes of diagnostic difficulties, deceptive radiological and histological investigations, and outline diagnostic procedures based on our and previously reported cases. Case reports – Our first case, a 48-year-old female was admitted to the neurological department due to paraparesis. MRI suggested LETM, but the treatments were ineffective. She died after four weeks because of pneumonia and untreatable polyserositis. Pathological examination revealed intravascular large B-cell lymphoma (IVL). Our second case, a 61-year-old man presented with headache and paraparesis. MRI showed small bitemporal lesions and lesions suggesting LETM. Diagnostic investigations were unsuccessful, including tests for possible lymphoma (CSF flow cytometry and muscle biopsy for suspected IVL). Chest CT showed focal inflammation in a small area of the lung, and adrenal adenoma. Brain biopsy sample from the affected temporal area suggested T-cell mediated lymphocytic (paraneoplastic or viral) meningoencephalitis and excluded diffuse large B-cell lymphoma. The symptoms worsened, and the patient died in the sixth week of disease. The pathological examination of the presumed adenoma in the adrenal gland, the pancreatic tail and the lung lesions revealed peripheral T-cell lymphoma, as did the brain and spinal cord lesions. Even at histological examination, the T-cell lymphoma had the misleading appearance of inflammatory condition as did the MRI. Conclusion – Lymphoma can manifest as LETM. In cases of etiologically unclear atypical LETM in patients older than 40 years, a random skin biopsy (with subcutaneous adipose tissue) from the thigh and from the abdomen is strongly recommended as soon as possible. This may detect IVL and provide the possibility of prompt chemotherapy. In case of suspicion of lymphoma, parallel examination of the CSF by flow cytometry is also recommended. If skin biopsy is negative but lymphoma suspicion remains high, biopsy from other sites (bone marrow, lymph nodes or adrenal gland lesion) or from a simultaneously existing cerebral lesion is suggested, to exclude or prove diffuse large B-cell lymphoma, IVL, or a rare T-cell lymphoma.