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Lege Artis Medicinae

MARCH 20, 2019

[The modern therapy of lipid disorders in the daily practice ]

REIBER István

[Elevated LDL-C and/or triglycerides and decreased HDL-C levels contribute to development of vascular lesions. In the absence of detectable vascular disease the lipid values of providing vascular protection preferably with a healthy diet, regular physical activity and by trying to get out of harmful passions. If the healthy lifestyle is not effective enough, lipid-lowering medication may also be necessary in primary prevention. In the cases of inherited lipid disorders and in patients with high or very high cardiovascular risk it is necessary to take lipid lowering medications in effective dose. The Hun­ga­rian and the international guidelines have been formulated the targets of lipid values for vascular protection. The paper is trying to help for everyday medical practice, how to treat the dyslipidemic patients with the application of widely available lipid parameters and lipid lowering medications effectively. ]

Hypertension and nephrology

FEBRUARY 20, 2019

[The importance of statin therapy in hypertension]

PARAGH György, PÁLL Dénes

[Hypertension and hypercholesterolaemia often co-occur and promote early cardiovascular disease. Previous studies have shown that antihypertensive treatment may be more effective if LDL cholesterol is also reduced. This may be due to the increased expression of angiotensin-1 receptor in hypercholesterolaemia, which increases peripheral vascular resistance through angiotensin-2, and adversely affects endothelial and smooth muscle cells. Other authors indicate that high cholesterol levels increase the production of angiotensin-2 through the activation of the chymase system. High cholesterol levels increase the amount of circulating oxidized LDL which binds to the transmembrane oxidized LDL receptor (LOX- 1) also activates the angiotensin-1 receptor. In addition, angiotensin-2 has an effect on intracellular cholesterol synthesis by enhancing the key enzyme of the synthesis of intracellular cholesterol, HMG-CoA reductase. The authors present the studies that support cholesterol lowering can contribute to lowering blood pressure and other major meta-analyses in which the beneficial effects of cholesterol lowering and lipid lowering on blood pressure reductions were not proven. In the background, it may well be that these studies are not designed to evaluate the effect of cholesterol-lowering drugs on hypertension in patients with hypercholesterolaemia, and non-statin-treated patients are not randomized.]

Lege Artis Medicinae

JANUARY 20, 2019

[Pharmacotherapy of dementia ]

PÁKÁSKI Magdolna, KÁLMÁN János

[The goal of treatment of dementia-related disorders is to reserve cognitive and functional ability, minimize behavioral and psychological disturbances, and slow disease progression, since currently available therapies can not reverse the pathologic processes. Among them, the most common is Alzheimer’s disease and vascular dementia. The authors review the therapeutic guidelines of these dementia types adapted to Hungarian conditions. Cho­li­nesterase inhibitors represent first-line therapy for patients with mild to moderate Alzheimer’s disease, whereas a glutamate N-metil-D-aspartate antagonist is used in the treatment of moderate to severe Alzheimer’s disease. In milder stages, phar­macotherapy may be supplemented by the use of nootropics. The progression slowing drugs have not only impact on cognitive symptoms but also affect behavioral and psychological symptoms. De­pen­ding on the severity of dementia and the existence of behavioral and psychological symptoms, these medicines may be re­commended as monotherapy or in combination. To further alleviate behavioral and psychological symptoms a variety non-pharmacological methods are known, at present their effectiveness has not been proven. Antipsychotics may be used to reduce agitation and aggression. Taking into account the side effects profile of antipsychotics, tiapride or risperidon ad­mi­nistration can be considered. In the case of their ineffectiveness, haloperidol may be used. ]

Hypertension and nephrology

DECEMBER 10, 2018

Hypertension and nephrology

AUGUST 20, 2018

[Results of the CONADPER-HU program: blood pressure reduction, achieving target blood pressure, factors affecting the target, characteristics of medication]

KISS István, KÉKES Ede, PAKSY András, SZEGEDI János

[The authors analysed in detail the data of 4071 “active” and 2654 “nonactive” groups of patients. In the 18-64 age group, systolic and diastolic blood pressure was significantly reduced during the first three months of the baseline, and maintained for a further year. The largest systolic pressure drop was achieved by members of the active group using the Medigen application. The blood pressure target rate (< of 140/90 mmHg) in the active and non-active group was significantly higher than the baseline at all visit times (above 70%) and this decrease could be maintained throughout the observation period. Here the most favorable results were also found in Medigen software applications. Over the age of 65, reaching the target blood pressure increased significantly in the first three months as well, but due to the significantly uneven number of the two groups, the data received was only considered as approximate value. Main factors of non-achievement of target blood pressure: obesity, alcohol consumption, diabetes mellitus and peripheral vascular disorder, and the fact that the individual is male. Increases the access probabilities of Medigen users by 21% compared to non-users of the active group. Compared to the inactive group, this chance increase is 31%. The difference in target blood pressure reach between the active and non-active group was even more pronounced in diabetic hypertensive patients. The analysis demonstrates that drug treatment in domestic and ESH guidelines is fully consistent with and reflects well on domestic clinical practice.]

Lege Artis Medicinae

JUNE 20, 2018

[Treatment of EGFR mutant lung adenocarcinoma after progression]

BOGOS Krisztina

[Precision medicine proposes the personalization of health services in order to make the best individual decisions about the interventions and treatments for the patient. Molecular genetic diagnostic tests help to select the appropriate therapy, so-called targeted therapy. In the case of extensive lung cancer with EGFR mutation, EGFR tyrosine kinase inhibitors are immediately applicable; they are very effective and can reach long-term remission of the disease. However, resistance mutation can develop during the treatment, which causes the progression of the disease; therefore change of therapy is needed. In our case, we show the possibility of targeted treatment beyond the progression, emphasizing the importance of detecting resistance mutation. ]

Clinical Oncology

FEBRUARY 10, 2018

[EMT (Epithelial-Mesenchymal transition) – CSC (Cancer Stem Cells)]

KOPPER László

[The effi cacy of the antitumor therapy is usually limited due to the resistance against the chemotherapy. One of the most important reason of the secunder resistance is the intratumoral heterogeneity, which is the consequence of the variety tumor phenotypes in the same tumor. Such clonal heterogeneity develops during the tumor growth or tumor therapy. The cancer stem cells (CSC), according to the concept, can determine the progression of the tumor, including metastatization, which probably the major enemy for clinical oncology. This activity of CSC, in tumors with epithelial origin, is supported by a change from epithelial to mesenchymal phenotype (epithelial-mesenchymal transition); but not entirely. The CSC phenotype is very similar to characteristic of the normal stem cells, as resistance, self-renewal etc. The mechanisms of these concepts is known only partially, but the technical advances contribute to the identifi cation of key genetic and epigenetic regulatory pathways. If such improvement becomes real, we can be much ahead both with markers and therapeutic targets.]

Hypertension and nephrology

APRIL 20, 2018

[Role of β-blockers, especially carvedilol in the treatment of hypertension]

PÁLL Dénes, MARODA László, ZRÍNYI Miklós

[Changes in hypertension guidelines in the past years have affected the clinical thinking about β-blockers. Authors reviewed the development of β-blockers emphasizing the differences across various active pharmaceutical agents. Different hemodynamic and metabolic effects are being discussed in details for the third ge - neration vasodilatator carvedilol. Carvedilol has no effect on cardiac output but decreases peripheral vascular resistance which results in lower blood pressure values. However, carvedilol, opposite to unfavorable effects of traditional β-blockers, has a neutral impact on both carbohydrate and lipid metabolisms. Its more advanced cardiac effects include decreased left ventricular hypertrophy and increased coronary flow reserve. Vasodilatator type β-blockers (carvedilol, nebivolol) are indicated in the combi - nation treatment of hypertension, especially when the patient has heart failure, coronary disease or suffered from a previous heart attack.]

Hypertension and nephrology

MARCH 20, 2018

[Nebivolol’s unique molecule structure and its effect onthe quality of life]

KERKOVITS Gábor

[The β receptor blockers have very different effects depending on their receptor selectivity, ISA effect, which gives a wide opportunity of beneficial therapeutic choice. Resulting from its unique molecule structure nebivolol has its unique effects. It consists two isomers in 1:1 ratio. D-nebivolol is a highly β1 receptor blocker, while l-nebivolol causes NO release resulting vasodilatation. As a result of this dual effect, nebivolol more strongly reduces the blood pressure. The pressure reducing effect of nebivolol is stronger than 25 mg of atenolol, and is equal with the effect of 100 mg of atenolol. Nebivolol has a significantly higher responders’ rate than bisoprolol, and significantly fewer adverse effect. Comparing to losartan nebivolol produces significantly higher reduction in systolic and in diastolic blood pressure as well. Nebivolol has beneficial haemodynamic effects. It raises the stroke volume by 20.6 percent, the cardias output by 7.1 per cent, the ejection fraction by 7.8 per cent while reduces the peripheral resistance by 13.2 per cent. Both at rest and during exercise nebivolol cases significantly higher reduction in pulmonary wedge pressure than atenolol. Nebivolol has a better profile of adverse effects. The following adverse effects were observed: fatigue in 1.3 per cent, cold extremities in 0.8 per cent, impotence in 0.08 per cent and dyspnea in 0.05 per cent. It has also a beneficial effect on erectile dysfunction. It cases a significant elevation in erectile dysfunction score from 17.22 to 22.09. The number of sexual activity also raised from 3.41 to 6.38 during nebivolol treatment. The prevalence of erectile dysfunction is also significantly lower as compared to any β receptor blocker. Nebivolol has a synergic effect on PDE5 blockers, raises the cGMP concentration in the erectile tissue. There is also a significant difference among the β receptor blockers in the reduction of exercise tolerance. The nonselective β receptor blocker cause 40 per cent, carvedilol 35 per cent, the β1 selective receptor blocker 25 per cent while nebivolol 6 per cent reduction in the duration time.]

Clinical Neuroscience

MARCH 30, 2018

[Perinatal stroke - from symptoms to follow-up]

VOJCEK Eszter, CSÉCSEI Márta, FLACH Edina, RUDAS Gábor, GRÁF Rózsa, PRINCZKEL Erzsébet

[Background and purpose - We aimed to analyze patient characteristics of term neonates with the diagnosis of stroke between 2006 and 2017 at the 3rd level Neonatal Intensive Care Unit of the Szent János Hospital. Method - We conducted a retrospective and prospective analysis including 18 newborns with stroke. Presentation, imaging methods, etiology and clinical context were discussed. All patients had a follow-up at 2 years of age or later. Subject of the study - In the past 10 years 17 term born and one premature neonate born at 36 weeks of age were diagnosed with stroke in our unit. All patients were born at good condition generally with high Apgar scores (9±1). Cesarean section was performed in 4 cases. Results - With an estimated incidence of one in 1600-4000 births, the incidence of perinatal stroke in our unit was found to be the same as mentioned in the international databeses. Regarding imaging method, cranial ultrasound scan do not visualise arterial ischaemic stroke therefore head MRI is recommended. Neurological symptoms of the patients presented in the first two days of life. Etiology included thrombophilia (4/18), infection (4/18), vascular malformation (2/18), moderate asphyxia (2/18) and pre-eclampsia (2/18). Middle cerebral artery was involved in 50% while the anterior cerebral artery was affected in 33%. The stroke occured in the left hemisphaerium in 44%, in the right side in 39% and was bilateral in 17%. In two cases the stroke was diagnosed in utero. Early childhood developmental support resulted in average or above average gross and fine motor development and cognitive outcome. Conclusion - Presenting neurological symptoms tipically occur in the first few days after birth when perinatal stroke need to be considered among the broad spectrum of neonatal illnesses. Normal developmental outcome can be achieved even in cases of extensive brain damage with early childhood developmental support. Severely impaired development was observed in the cases of in utero stroke. Inherited prothrombotic disorders may have implications for subsequent pregnancies of the mother. ]