[Measurement of natriuretic peptides in heart failure: the good laboratory and clinical practice]. / Natriureticus peptidek mérése szívelégtelen betegekben: a helyes laboratóriumi és klinikai gyakorlat.

Cardiac natriuretic peptides (BNP, NT-proBNP) play a pivotal role in cardiovascular homeostasis, mainly due to their roles in vasodilatation, natriuresis, diuresis and due to their antiproliferative properties. Proper measurement of the natriuretic peptide levels may help differentiate between respiratory and cardiac forms of dyspnea, diagnose early forms of heart failure, evaluate severity of heart failure (prognosis) and monitor the efficacy of therapy. In many countries natriuretic peptide levels are being used as one of the earliest diagnostics tools to evaluate the involvement of the heart. Current theoretical and clinical data confirm the importance of natriuretic peptides in routine healthcare. These roles are clearly described in international recommendations and guidelines. In the current review the authors discuss the problems of the measurement of natriuretic peptides in Hungary, including several aspects related to laboratory medicine, cardiology and health economy.

[Personalized medicine and healthcare: where are we now, where should we go?] / Személyre szabott orvoslás és egészségügy: hol tartunk, merre menjünk?

The authors of this manuscript are representatives of different subdisciplines of medicine, all of them are experienced researchers. As of their origin, they are practicing doctors from the primary care and from the clinical/hospital setting, diagnostics experts, researchers from healthcare management, health economics, representatives of patients' rights and patient organizations. They are all devoted to the implementation of personalized medicine and personalized healthcare in Hungary. The current manuscript - also meant to be a keynote message provoking further discussion in the medical community - is devoted to correcting for two false ideas. One is that personalized medicine is not yet ready for practical applications, it is merely a research area of futurologists. The other false idea is that only (or mainly) the lack of financial resources hinders the introduction of personalized healthcare in Hungary. Orv Hetil. 2023; 164(6): 202-209.

[Vitamin D supply among healthy blood donors in Vas County, Hungary]. / D-vitamin-ellátottság felmérése Vas megye egészséges véradói körében.

INTRODUCTION: There is growing evidence showing the importance of adequate vitamin D supply for preserving health. AIM: The aim of the study was to evaluate the vitamin D supply among healthy blood donors and healthy elderly subjects in County Vas, Hungary. METHODS: Serum 25-hydroxyvitamin D, intact parathyroid hormone, calcium and albumin (Cobas, Modular, Roche), as well as serum alfa-2-globulin concentrations (Gelelfo, Interlab) were determined in 178 serum samples (68 men, 110 women, 41 were taking oral contraceptives). The results were analysed according to sex and age (younger and older than 43 years), and the impact of oral contraceptive use was also taken into consideration. RESULTS: Deficiency and insufficiency in vitamin D levels were detected in 9.6% and 32% of the studied subjects, respectively, whereas sufficient vitamin D levels were present in 58.4% of the subjects. 63% of the older and 41.2% of the younger group had suboptimal vitamin-D supply (p < 0.01). In women taking oral contraceptives serum 25-hydroxyvitamin D and alfa-2-globulin levels were significantly higher, whereas serum albumin and calcium levels were lower than in the control group. There was no difference in serum intact parathyroid hormone concentration between oral contraceptive users and non-users. CONCLUSIONS: The occurrence of suboptimal vitamin D supply is significant, although less frequent than that in literature reports. In women taking oral contraceptives, serum 25-hydroxyvitamin D levels were higher, but serum intact parathyroid hormone concentrations were not decreased suggesting that the increased 25-hydroxyvitamin D levels may be the consequence of oestrogen-induced alterations of serum protein fractions.

Investigations of follicular fluid biomarkers in patients undergoing / A tüszofolyadék biomarkereinek vizsgálata in vitro fertilizációs kezelésben részesült betegekben.

Összefoglaló. A szerzok ismertetik vizsgálataik eredményeit, melyeket a közelmúltban az in vitro fertilizációs kezelésben részesülo betegeikben a tüszofolyadék biomarkereinek analízisével értek el. A vizsgálatok célja annak feltárása volt, hogy az in vitro fertilizációs eljárás során a petesejtek aspirációjakor nyert tüszofolyadék-biomarkerek lokális/ovarialis vagy szisztémás eredetuek, és milyen összefüggést mutatnak az in vitro fertilizáció eredményességét jelzo paraméterekkel. Megerosítettük, hogy az autokrin/parakrin szerotoninrendszer már a fejlodés legkorábbi idoszakában is muködoképes, és mind az anyai szérum, mind a tüszofolyadék szerotoninszintje szignifikáns pozitív összefüggést mutatott az érett petesejtek számával és a klinikai terhességgel (ß = 0,447, p = 0,015, illetve ß = 0,443, p = 0,016). Az agyi eredetu neurotrofikus faktor (BDNF) esetében ilyen kapcsolat nem volt igazolható, de a tüszofolyadék BDNF- és szerotoninszintjei közötti pozitív korreláció (r = 0,377, p = 0,040) azt mutatja, hogy a két neurohormon 'feed-forward' (elorecsatoló ) szabályozása ovarialis szinten is muködik. A hypothalamicus kisspeptin esetében csupán a posztstimulációs anyai szérumhormonszint befolyásolta az érett petesejtek számát (ß = 0,398, p = 0,029). A triptofán-kinurenin-szerotonin rendszer elemzése azt mutatta, hogy kedvezobb in vitro fertilizációs kimenetel várható, ha a szerotonin-kinurenin egyensúly a szerotonin javára tolódik el. Az oxidatívstressz-markerek közül vizsgálták a DNS-károsodás biomarkerét, a 8-hidroxi-2'-deoxiguanozin és a totális antioxidáns-kapacitás szérum- és tüszofolyadékszintjeit, és megállapították, hogy mindkét marker kedvezotlenül befolyásolja az életképes embriók számát (r = 0,302, p = 0,027 és r = 0,268, p = 0,039). A protektív hatású szirtuinok - nikotinamid-adenin-dinukleotid-függo hiszton-deacetiláz fehérjék - közül a vizsgált szirtuin-1 és szirtuin-6 a szérumszintektol függetlenül kimutatható a tüszofolyadékban. Szignifikáns pozitív korreláció van a tüszofolyadék-szirtuin-6 és az érettpetesejt-szám (F = 6,609, p = 0,016), valamint a szérum-szirtuin-1 (F = 10,008, p = 0,005) és a szérum-szirtuin-6 (F = 5,268, p = 0,031) és a klinikai terhesség gyakorisága között. Eredményeink alapján megállapítható, hogy a tüszofolyadék biomarkereinek vizsgálata javíthatja az in vitro fertilizáció kimenetelének megítélését. Orv Hetil. 2021; 162(14): 523-529. Summary. This article outlines the result of recent studies on several follicular fluid biomarkers in patients undergoing in vitro fertilization. The aim of these studies was to investigate whether 1) the follicular fluid biomarkers in question are produced locally by the ovaries or they originate from the circulating plasma, 2) and to establish their association with parameters of in vitro fertilization outcome. It was confirmed that the autocrine/paracrine serotonin system is functional already at the earliest stage of development and both maternal serum and follicular fluid serotonin levels were positively related to the number of mature oocytes (ß = 0.447, p = 0.015 and ß = 0.443, p = 0.016, respectively) and clinical pregnancy (ß = 1.028, p = 0.047). Such associations for brain-derived neurotrophic factor (BDNF) could not be found, but BDNF and serotonin in the follicular fluid were closely related (r = 0.377, p<0.040) suggesting that the feed-forward regulation of these neurohormones is activated at ovarian level. The hypothalamic kisspeptin in the post-stimulation maternal serum also increased the number of mature oocytes (ß = 0.398, p = 0.029). Analysis of the tryptophan-kynurenine-serotonin system showed a more favourable in vitro fertilization outcome when the serotonin-kynurenine balance was shifted and serotonin predominated over kynurenine. The oxidative stress markers, 8-hydroxy-2'-deoxyguanosine, an indicator of DNA damage and the total antioxidant capacity in follicular fluid and maternal serum had negative impact on the number of viable embryos (r = 0.302, p = 0.027 and r = 0.268, p = 0.039), respectively. The protective sirtuins - the nicotinamide adenine dinucleotide-dependent histone deacetylase proteins - could be detected in follicular fluid irrespective of their maternal serum levels. Significant positive relationship was demonstrated between follicular fluid sirtuin 6 and mature oocytes (F = 6.609, p = 0.016) as well as between serum sirtuin 1 (F = 10.008, p = 0.005) and serum sirtuin 6 (F = 5.268, p = 0.031) and the rate of clinical pregnancy, respectively. On the basis of these results, it can be concluded that measuring several follicular fluid biomarkers may improve the prediction of the outcome of in vitro fertilization. Orv Hetil. 2021; 162(14): 523-529.

[Health policy experiences of publicly financed laboratory services in Hungary with health insurance data analysis]. / A közfinanszírozott laboratóriumi szolgáltatások egészségpolitikai tapasztalatai Magyarországon egészségbiztosítási adatok elemzésével.

Introduction: In order to provide appropriate prevention, diagnosztics, decision on therapy and monitoring the results of medical treatment, there is an increasing need for laboratory examinations. Aim: The aim of our study is the health-ecnomics analysis of laboratory budget of the Hungarian Health Insurance Fund. Data and method: Data were derived from the financial database of the National Health Insurance Fund Administration. The analysis covered the period of 2002-2018. We analysed the annual budget for laboratory examinations, the number of patients and examinations, the market share of laboratory services providers according to their owner structure from the health insurance curative-preventive budget. Results: The budget available for financing the laboratory examinations (21-22 billion Hungarian forint (Ft)/év) did not change significantly between 2005 and 2015. There was a significant decrease in the number of both patients and examinations between 2006 and 2008. In the latest years, there were 14-15 million cases per year and 180 million examinations per year. The market share of for-profit companies decreased from 29.0% in 2010 to 10.6% in 2018, while the market share of governmental institutions increased from 27.1% in 2010 to 78.7% in 2018. Conclusion: The activity of laboratories was stabilized in the latest years. After the necessary correction of professional regulations and code maintenance, the laboratory budget can be increased towards the mainly public laboratory services providers. Orv Hetil. 2020; 161(12): 468-473.

[Investigation of adolescents' bone metabolism in the western part of Transdanubia]. / Serdülôk csontanyagcsere-markereinek vizsgálata a nyugat-dunántúli régióban.

UNLABELLED: Childhood reference range based on the age is not available in Hungary, therefore the diagnosis and therapy of bone metabolic diseases of childhood are subject to difficulties. The aim of this work is to provide information about the adolescents' results of bone mineral density and bone biomarkers. SUBJECTS AND METHODS: Measurements were performed in 169 healthy adolescents (98 girls, 71 boys, age: 17.0+/-1.2 years). Bone mineral content (BMC) and bone mineral density (BMD) of the lumbar spine were measured using Double X-ray Absorptiometry (DXA, LUNAR, GE Health Care, USA) and Z-score values were analyzed using different reference population. In the serum, bone biomarkers osteocalcin (OC) and beta-crosslaps (beta-Cl) were measured by a fully automated, electrochemiluminescence immunoassay method (Elecsys-2010, Roche). Data were analyzed according to gender and the Tanner stage and grade system. Associations between body mass index (BMI), calcium intake, consumption of soft drinks and coke, and physical exercise were investigated. RESULTS: BMC values for both age groups were significantly elevated in boys of the Tanner stage V. (15-16 years: 62.9+/-14.3 g; 17-19 years: 69.8+/-9.3g) than in girls (58.1+/-10.4; 61.6+/-8.5 g) (p<0.001). BMD values were higher in girls, than in boys (1.17+/-0.12 g/cm 2 vs. 1.13+/-0.11 g/cm 2) (p<0.05). OC and beta-Cl levels showed negative correlation with age in both gender (p<0.01), while OC and beta-Cl levels were higher in boys, than in girls (p<0.001). Elevation of BMC and BMD values were associated with increase of BMI in both gender (p<0.05), but the biomarkers in thin girls were higher, than in overweight girls (p<0.05). Authors obtained excellent correlations between the BMD-Z-score values compared to the German standard and to their own population (girls: r=0.97, boys: 0.88), but the absolute values significantly differed from one another. 80% of adolescents are on a diet with insufficient calcium intake, while 38% of them do not play sport regularly. Excessive intake of soft drinks was determined in 60% of adolescents. In the case of insufficient calcium intake (4.7%, 6/127), low bone mass was measured using the Z-score of the German reference values. Among children with adequate calcium intake, BMD assessed by DXA was normal. CONCLUSION: These data help to determine normal reference values among healthy high school students. Further studies are needed in wider range of young population for the establishment of Hungarian reference values of bone markers.

[Multidrug resistance: diagnostic approaches and difficulties]. / Többszörös gyógyszer-rezisztencia: diagnosztikai megközelítések es nehézségek.

During the mid sixties scientists recognized that tumour cells can be resistant to a variety of chemotherapeutical drugs of different chemical structure simultaneously. They named this phenomenon multidrug resistance (MDR). Following this observation, number of in vitro and in vivo experiments proved that transmembrane proteins of the cell membrane are responsible for the mechanism. Many details of the underlying biochemical mechanisms were explored during the past decade. Nowadays the importance of MDR is well appreciated in different walks of medical science. MDR is an important problem during the treatment of many haematological conditions and solid organ tumors. Also, MDR is an important factor during immunosuppressant therapy of the transplanted patients. In spite of extensive research there are many uncertainties around MDR. This brief review describes the present options in the investigation of MDR. Based upon the MDR genotyping and expression level the likelihood of drug resistance may be predicted with reasonable accuracy. Additional information may be obtained by measuring the P-glycoprotein expression on the cell surface and the outward transport of test molecules from the cells. Although the tests described above provide significant help in predicting MDR or in the confirmation of existing MDR there is no consensus about the laboratory diagnosis.

[Macroprolactinemia in the differential diagnosis of hyperprolactinemia]. / A macroprolactinaemia és a hyperprolactinaemia differenciáldiagnosztikája.

INTRODUCTION: Biologically active prolactin and the inactive fraction of macroprolactin can be present in hyperprolactinaemic sera. The reaction of routinely used prolactin assays with macroprolactin is variable. AIMS: The present study was undertaken to analyse the leading clinical signs of hyperprolactinemia in macroprolactinemia and true hyperprolactinemia and to assess the prevalence of macroprolactinemia in hyperprolactinemic females. METHODS: 1571 consecutive female patients were investigated for hyperprolactinemia. Prolactin was measured before and after precipitation of macroprolactin by polyethylene glycol in 285 hyperprolactinemic (> 520 mlU/l) patients. Since not a single case of macroprolactinemia (recovery < 40%) was found in the range of 520-700 mlU/l, only in women with prolactin > 700 mlU/l (N = 254) entered the study. RESULTS: In 59 patients (23%) macroprolactinemia was found. In women, the occurrence of macroprolactinemia increased with advancing age (p < 0.05). "A priori" clinical signs indicating hyperprolactinemia occurred less frequently in patients with macroprolactinemia than in those with true hyperprolactinemia. Pituitary microadenoma was found in 9.8% of macroprolactinemia vs. 31.6% in true hyperprolactinemia (p < 0.01); galactorrhea: 4% in macroprolactinemia vs. 19% in true hyperprolactinemia, (p < 0.05); infertility: 17% in macroprolactinemia vs. 44% in true hyperprolactinemia (p < 0.05). In 8 out of 59 women with macroprolactinemia, true hyperprolactinemia appeared simultaneously (15.3%). Occurrence of polycystic ovaries syndrome was more frequent in the true hyperprolactinemia (12%) that in macroprolactinemia (4.5%). CONCLUSIONS: It has been shown that macroprolactin does not occur in mild hyperprolactinemia. In women, the occurrence of macroprolactinemia increases with age. "A priori" clinical signs indicating hyperprolactinemia and pituitary abnormality are less frequent in macroprolactinemia than in true hyperprolactinemia. The diagnosis of macroprolactinemia should be used only, when the PRL levels fall to the normal range after precipitation. To avoid diagnostic and therapeutic pitfalls the screening for macroprolactin of all patients with prolactin > 700 mlU/L is recommended.