52 research outputs found
Treatment of Hypertension: Favourable Effect of the Twice-Daily Compared to the Once-Daily (Evening) Administration of Perindopril and Losartan
Background/Aims: Little is known about the effect of twice daily administration of same dose of ACE inhibitor and ARB on the diurnal/nocturnal blood pressure (BP) ratio. We aimed to assess the effect of two widely used long-acting drugs: perindopril and losartan in the treatment of hypertension comparing the once-daily (evening) vs. twice-daily (morning and evening) administration with the same daily doses. Methods: Untreated primary hypertensive patients without complaints (a total of 164: 65 men, 99 women, 55.7±13.7 years of age, 41-41 patients per treated groups) were selected with non-dipper phenomenon, estimated by diurnal index (DI) Results: The mean BP, the percent time elevation index, and the hyperbaric impact decreased in both drug groups. Significant difference was observed in the DI in the case of twice-daily administration vs once-daily evening dosing. Conclusions: The twice-daily administration with the same daily dose of perindopril or losartan seems to be more effective compared to the once daily evening administration in eliminating the non-dipper phenomenon. According to some authors the non-dipping phenomenon increases cardiovascular risk, while others are of the opinion that the association of non-dipping with cardiovascular events does not necessarily mean that selective treatment of non-dipping improves cardiovascular outcomes
A herediter haemorrhagiás teleangiectasia (Osler–Weber–Rendu-kór) genetikai diagnosztikája = Genetic diagnostics of hereditary hemorrhagic telangiectasia (Osler–Weber–Rendu disease)
Absztrakt:
Bevezetés: A herediter haemorrhagiás teleangiectasia (HHT) egy
1 : 5000 – 1 : 10 000 prevalenciájú, autoszomális domináns módon öröklődő
többszervi vascularis anomália. Diagnózisa a klinikai Curacao-kritériumokra
épül. Az esetek körülbelül 85%-ában az ENG- vagy az
ACVRL1-génben igazolhatók családspecifikus mutációk
heterozigóta formában. Célkitűzés: Jelen tanulmányunkban 23
hazai HHT-család klinikai és genetikai vizsgálatát, családszűrését és az alapító
hatások vizsgálatát tűztük ki célul. Módszer: A probandokat
részben az intézményünk ellátási területének stratifikált populációs szűrésével,
részben a genetikai vizsgálat igényével hozzánk forduló egyének között
azonosítottuk. A diagnózis a karakterisztikus teleangiectasia lokalizációkkal
kiegészített fül-orr-gégészeti fizikális vizsgálatból, a belszervi
arteriovenosus malformatiók képalkotó vizsgálataiból, továbbá az
ENG- és az ACVRL1-gén
szekvenciaanalíziséből állt. A családszűrés része a családfa-analízis, az
elsőfokú rokonok fizikális vizsgálata és családspecifikus mutációra történő
genetikai szűrése, valamint a definitív/valószínű HHT-betegek és/vagy a
mutációhordozó egyének esetében az arteriovenosus malformatiók képalkotó
vizsgálata. Eredmények: Huszonkét családban 63 mutációhordozó
egyént találtunk, közülük 48-an definitív, 12-en valószínű HHT-betegek. Hét
ENG- és ugyanennyi ACVRL1-mutációt
észleltünk, többségük patogén. Három esetben alapító hatás igazolódott. Egy
definitív HHT-ban szenvedő proband valamennyi vizsgált HHT-specifikus locuson a
vad típusú allélt hordozta. Következtetések: A genetikai teszt
jelentős szereppel bír a HHT megerősítésében vagy kizárásában a patogén
mutációval rendelkező családok fiatal tünetmentes tagjaiban. Az
ENG- és az ACVRL-mutáció által okozott
betegség tünettana átfedi egymást, így a genetikai leletnek prognosztikai
jelentősége nincs. Az alapító mutációk azonosítása az illető régióból származó
új HHT-betegek genetikai diagnosztikáját jelentősen egyszerűsítheti. Orv Hetil.
2019, 160(18): 710–719.
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Abstract:
Introduction: Hereditary hemorrhagic telangiectasia (HHT) is an
autosomal dominant multisystemic vascular disease with a worldwide prevalence of
1 : 5000 – 1 : 10 000. Diagnosis is based on clinical Curacao criteria.
Approximately 85% of HHT cases have heterozygous family-specific mutations in
the ENG or ACVRL1 genes. Aim:
We investigated 23 Hungarian HHT families, established the genetic diagnosis,
executed family-screening and confirmed founder effects.
Method: Probands were identified by the stratified
population screening of the primary attendance area of our institution and from
individuals contacting our study group voluntarily. Diagnosis is based on the
otorhinolaryngological physical examination completed with characteristic
telangiectasis sites, a visceral arteriovenous malformation screening and the
sequence analysis of ENG and ACVRL1 genes. The
family screening consists of physical examination and genetic screening for the
family-specific mutation, followed by the arteriovenous malformation screening
in patients with definite/suspected HHT and/or in individuals with the mutation.
Results: Sixty-three individuals with family-specific
mutations were identified in 22 families, 48 of them with definite and 12 with
suspected HHT. Seven ENG and ACVRL1 mutations
were detected, respectively; most of these are pathogenic. Three founder
mutations were observed. One proband with definite HHT had wild-type alleles in
all tested HHT-specific loci. Conclusions: The significance of
genetic testing is confirming or excluding HHT in young asymptomatic individuals
in families with pathogenic mutations. As ENG and
ACVRL1 mutations result in overlapping fenotypes, the
genetic testing lacks any prognostic value. The identification of founder
effects might simplify the genetic diagnosis of new HHT patients from a given
region. Orv Hetil. 2019; 160(18): 710–719
Subjective expectations regarding ageing: a cross‑sectional online population survey in Hungary
Background We aimed to investigate individuals’ subjective expectations regarding health and happiness alongside their
provisions on life circumstances for older ages.
Methods A cross-sectional online survey was performed involving a representative sample (N=1000; mean age 50.9,
SD=15.4; female 54.5%) in Hungary. Subjective expectations on health status (EQ-5D-3L/-5L, GALI, WHO-5), happiness
(0–10 VAS), employment status, care time, and forms of care for ages 60, 70, 80, and 90 were surveyed.
Results Current mean EQ-5D-5L was 0.869 (SD =0.164) and happiness was 6.7 (SD =2.4). Subjective life expectancy
was 80.9 (SD =11.1), and median expected retirement age was 65. Mean expected EQ-5D-5L for ages 60/70/80/90 was
0.761/0.684/0.554/0.402, and no activity limitations (GALI) were expected by 64%/40%/18%/14%, respectively. Expected
happiness score was 6.8/6.7/6.2/5.7, and a decrease in mental well-being (WHO-5) was provisioned. A substantial increase in
drug expenses and care time was anticipated, but only 52% thought to have extra income besides pension. The great majority
expected to be helped by the family (77%/72%/53%/40%) if needed. Educational level, GALI, and longevity expectations
were signifcant predictors of EQ-5D-5L expectations using a standard 5% signifcance level of decision. Current happiness
was major determinant of expected future happiness.
Conclusions Individuals expect a signifcant deterioration of health with age but only a moderate decrease in happiness.
Overestimation of future activity limitations suggests a gap between statistical and subjective healthy life expectancy. The
majority expects to rely on informal care in the elderly. Raise in retirement age is underestimated. Our results can be used
as inputs for economic modelling of labor force participation and ageing
The potential impact of new generation transgenic methods on creating rabbit models of cardiac diseases
Since the creation of the first transgenic rabbit thirty years ago, pronuclear microinjection remained the single applied method and resulted in numerous important rabbit models of human diseases, including cardiac deficiencies, albeit with low efficiency. For additive transgenesis a novel transposon mediated method, e.g., the Sleeping Beauty transgenesis, increased the efficiency, and its application to create cardiac disease models is expected in the near future. The targeted genome engineering nuclease family, e.g., the zink finger nuclease (ZFN), the transcription activator-like effector nuclease (TALEN) and the newest, clustered regularly interspaced short palindromic repeats (CRISPR) with the CRISPR associated effector protein (CAS), revolutionized the non-mouse transgenesis. The latest gene-targeting technology, the CRISPR/CAS system, was proven to be efficient in rabbit to create multi-gene knockout models. In the future, the number of tailor-made rabbit models produced with one of the above mentioned methods is expected to exponentially increase and to provide adequate models of heart diseases
„A mosoly is gyógyít?” Beteg gyermekek immunválasza is változhat a Mosolygó Kórház Alapítvány művészeinek látogatásakor = “Does happiness help healing?” Immune response of hospitalized children may change during visits of the Smiling Hospital Foundation’s Artists
A pozitív élményekkel kapcsolatos pszicho-neuro-immunológiai vizsgálatok száma kevés, klinikai alkalmazhatósága korlátozott. Célkitűzés: A Mosolygó Kórház Alapítvány művészeinek beteg gyermekekre gyakorolt hatását vizsgálták a szerzők. Módszer: Branülön keresztül, fájdalommentesen vérmintákat vettek infektológiai osztályon mesélő, bábos és kézműves művészek látogatása előtt 30 perccel és utána egy órával. Huszonnégy gyermeket meglátogattak a művészek, a kontrollcsoportban kilenc gyermek volt. Vizsgálták a vérben a lymphocytaszámot és a Th1/Th2 citokinszinteket. A művészek a látogatást követően hatásukat szubjektív skálán értékelték. Eredmények: A meglátogatott csoportban a lymphocytaszám-emelkedés 8,43%-kal kifejezettebb, a csökkenés 12,45%-kal mérsékeltebb volt. A meglátogatott csoportban a lymphocytaszám-emelkedést mutató gyermekek aránya nagyobb volt. A változások a művészek szerint sikeresebb látogatásoknál voltak kifejezettebbek. A meglátogatott csoportban páros t-próbával nem szignifikáns, de nagy szórás mellett is mérhető változást találtunk az interferon-γ-szintben (p < 0,055) és a Th1/Th2 citokin mérlegben (q-érték = 0,076 permutációs teszttel). Következtetések: Ez az első gyermekeken végzett klinikai pszicho-neuro-immunológiai felmérés, amely azt jelzi, hogy a gyermekekre fordított kitüntetett figyelem esetén gyors immunváltozásokkal is számolhatunk. Orv. Hetil., 2011, 152, 1739–1744.
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Psychoneuroimmunologic studies on positive emotions are few, and their clinical relevance is limited. Aims: This “SHoRT” (Smiling Hospital Research Team) study evaluates the effects that Smiling Hospital artists have on hospitalized children. Methods: Blood samples were taken in a non-painful way through branules in an accredited Infectology Ward, 30 minutes before and 1 hour after a visit of tale tellers, puppeteers and handicraft artists. 24 children were visited and 9 were included in the control group. Blood lymphocyte counts and Th1/Th2 cytokine levels were determined. Artists evaluated their effect on a subjective scale. Results: In the visited group, the increase of lymphocytes was 8.43% higher, the decrease was 12.45% lower, and the proportion of children showing increased lymphocyte counts was more increased. Changes were more marked after more successful visits. Authors found non-significant, still considerable changes in interferon-γ level (p < 0.055) and in Th1/Th2 cytokine ratios. Conclusions: This pediatric study suggests that immunological changes may develop when more attention is given to hospitalized children. Orv. Hetil., 2011, 152, 1739–1744
Transgenic LQT2, LQT5, and LQT2-5 rabbit models with decreased repolarisation reserve for prediction of drug-induced ventricular arrhythmias
Background and Purpose
Reliable prediction of pro‐arrhythmic side effects of novel drug candidates is still a major challenge. Although drug‐induced pro‐arrhythmia occurs primarily in patients with pre‐existing repolarisation disturbances, healthy animals are employed for pro‐arrhythmia testing. To improve current safety screening, transgenic long QT (LQTS) rabbit models with impaired repolarisation reserve were generated by overexpressing loss‐of‐function mutations of human HERG (HERG‐G628S , loss of IKr; LQT2), KCNE1 (KCNE1‐G52R , decreased IKs; LQT5), or both transgenes (LQT2‐5) in the heart.
Experimental Approach
Effects of K+ channel blockers on cardiac repolarisation and arrhythmia susceptibility were assessed in healthy wild‐type (WT) and LQTS rabbits using in vivo ECG and ex vivo monophasic action potential and ECG recordings in Langendorff‐perfused hearts.
Key Results
LQTS models reflect patients with clinically “silent” (LQT5) or “manifest” (LQT2 and LQT2‐5) impairment in cardiac repolarisation reserve: they were more sensitive in detecting IKr‐blocking (LQT5) or IK1/IKs‐blocking (LQT2 and LQT2‐5) properties of drugs compared to healthy WT animals. Impaired QT‐shortening capacity at fast heart rates was observed due to disturbed IKs function in LQT5 and LQT2‐5. Importantly, LQTS models exhibited higher incidence, longer duration, and more malignant types of ex vivo arrhythmias than WT.
Conclusion and Implications
LQTS models represent patients with reduced repolarisation reserve due to different pathomechanisms. As they demonstrate increased sensitivity to different specific ion channel blockers (IKr blockade in LQT5 and IK1 and IKs blockade in LQT2 and LQT2‐5), their combined use could provide more reliable and more thorough prediction of (multichannel‐based) pro‐arrhythmic potential of novel drug candidates
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