35 research outputs found
A danazolkezelés hatåsa C1-inhibitor-hiåny okozta hereditaer angiooedemås gyermekek növekedésére
Absztrakt:
Bevezetés: Az attenuålt androgéneket gyakran alkalmazzåk
C1-inhibitor-hiĂĄnyos hereditaer angiooedema akut epizĂłdjainak megelĆzĂ©sĂ©re.
Praepubertason tĂșli alkalmazĂĄsuk az epifĂzisfugĂĄk korai zĂĄrĂłdĂĄsĂĄhoz, ezĂĄltal
növekedés-visszamaradåshoz vezethet. CélkitƱzés: A danazol
hereditaer angiooedemås gyermekek hossznövekedésére kifejtett hatåsånak
felmĂ©rĂ©se. MĂłdszer: RetrospektĂv tanulmĂĄnyunk negyvenkettĆ, 21
Ă©vesnĂ©l idĆsebb hereditaer angiooedemĂĄs beteg adatait elemezte. A betegek
esetében meghatåroztuk a vårható testmagassågtól való eltérést, majd azt a
betegek neme, valamint a 21 Ă©ves kor elĆtt vĂ©gzett danazolkezelĂ©s összdĂłzisa Ă©s
idĆtartama fĂŒggvĂ©nyĂ©ben elemeztĂŒk. Danazollal 16 Ă©ves kora elĆtt kezelt betegek
esetĂ©ben összefĂŒggĂ©st kerestĂŒnk a vĂĄrhatĂł testmagassĂĄgtĂłl valĂł eltĂ©rĂ©s, valamint
a kezelĂ©s idĆtartama, illetve kumulatĂv dĂłzisa között.
EredmĂ©nyek: Nem talĂĄltunk szignifikĂĄns kĂŒlönbsĂ©get a
vĂĄrhatĂł testmagassĂĄgtĂłl valĂł eltĂ©rĂ©sben danazolt szedĆ/nem szedĆ, illetve fiĂș Ă©s
leĂĄny betegek között. Ezt a kĂŒlönbsĂ©get a danazol dĂłzisa Ă©s alkalmazĂĄsĂĄnak
idĆtartama 16 vagy 21 Ă©vesnĂ©l fiatalabb korban vĂ©gzett kezelĂ©s esetĂ©n sem
befolyåsolta. Következtetések: A danazol a minimålis hatékony
dózisban alkalmazva nem befolyåsolta a növekedést. Orv Hetil. 2017; 158(32):
1269â1276.
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Abstract:
Introduction: Attenuated androgens are used for the prevention
of angioedema attacks of hereditary angioedema with C1-inhibitor deficiency.
After prepuberty, their use can lead to growth retardation.
Aim: We assessed the effect of danazol on the growth of
pediatric patients with hereditary angioedema. Method: In the
retrospective study on 42 patients diagnosed with hereditary angioedema, we
calculated the deviation from the mid-parental target height, and analyzed it
against the gender, the dose and duration of danazol treatment administered
before the age of 21 years and before the age of 16 years.
Results: Regarding the deviation from the mid-parental
target height, we did not find any significant difference between patients
taking vs. not taking danazol, males vs.
females taking danazol. The dose and the duration of danazol treatment did not
influence that value neither before 21, nor before 16 years of age.
Conclusions: Our findings suggest that treatment with the
lowest effective doses of danazol does not influence growth. Orv Hetil. 2017;
158(32): 1269â1276
Methylation Status of CYP27B1 and IGF2 Correlate to BMI SDS in Children with Obesity
OBJECTIVE: Worldwide increasing childhood obesity is due to interactions between environmental and genetic factors, linked together by epigenetic mechanisms such as DNA methylation. METHODS: 82 obese children (>95th BMI percentile , age: 3-18 years) were included. Anthropometric data, metabolic parameters, 25-OH vitamin D (25OHD), and pubertal status were recorded, 24-hour blood pressure monitoring was performed. BMI standard deviation score (SDS) was calculated. Using candidate gene approach, obesity- (insulin-like growth factor 2 (IGF2), proopiomelanocortin (POMC)) and vitamin D metabolism-related genes (1-alfa-hydroxylase (CYP27B1), VDR) regulated by DNA methylation were selected. After isolating DNA from peripheral blood, bisulfite conversion, bisulfite specific polymerase chain reaction (BS-PCR), and pyrosequencing were carried out. RESULTS: No significant correlation between 25-OHD and metabolic parameters and DNA methylation status, but a tendency of positive correlation between VDR methylation status and 25-OHD (r = 0.2053,p = 0.066) were observed. Significant positive correlations between BMI SDS and CYP27B1 hypermethylation (r = 0.2371,p = 0.0342) and a significant negative correlation between IGF2 hypomethylation and BMI SDS (r = -0.305,p = 0.0059) were found. Conclusions Rate of obesity shows correlation with DNA methylation. Hypomethylation of IGF2 and hypermethylation of CYP27B1 genes might positively influence the rate of BMI observed in obese children
LaktĂĄtszintvĂĄltozĂĄsok diabeteses ketoacidosisban Ă©s frissen diagnosztizĂĄlt 1-es tĂpusĂș diabetes mellitusban
Absztrakt:
Bevezetés: A klinikumban ismert a diabeteses ketoacidosisban
(DKA) kialakuló hyperlactataemia, azonban a håttérben ålló mechanizmusok és a
vĂĄltozĂĄsok kinetikĂĄja tisztĂĄzatlan. Az emberi szervezetben fiziolĂłgiĂĄsan fĆleg a
laktĂĄt L-izomere van jelen. HyperglykaemiĂĄs ĂĄllapotokban azonban fokozott lehet
a D- Ă©s L-laktĂĄt-termelĂ©s is, Ăgy a szöveti hypoperfusio mellett ez a tĂ©nyezĆ is
szerepet jåtszhat a laktåtvåltozåsokban. CélkitƱzés:
Vizsgålatunk célja a ketoacidosisban és a frissen diagnosztizålt diabetesben
jelentkezĆ laktĂĄtvĂĄltozĂĄsok kinetikĂĄjĂĄnak Ă©s mechanizmusĂĄnak feltĂ©rkĂ©pezĂ©se
volt. MĂłdszer: Ketoacidosis (DKA-csoport, n = 13) Ă©s frissen
diagnosztizĂĄlt 1-es tĂpusĂș diabetes mellitus (T1DM-csoport, n = 6) miatt felvett
5â18 Ă©ves gyermekek prospektĂv vizsgĂĄlata törtĂ©nt. A felvĂ©telt követĆen
0â12â24â48 ĂłrĂĄval vĂ©rgĂĄzvizsgĂĄlatot vĂ©geztĂŒnk, mely az L-laktĂĄt-koncentrĂĄciĂł
meghatĂĄrozĂĄsĂĄra is alkalmas. Minden idĆpontban meghatĂĄroztuk az összlaktĂĄtot (L
+ D) is gåzkromatogråfiås tömegspektrometriåval. Eredmények:
Felvételkor minden ketoacidoticus betegnél kórosan magas L-laktåt-koncentråciót
mĂ©rtĂŒnk, ami magasabb volt, mint a T1DM-csoportban (p<0,05). 12 Ăłra
elteltével az L-laktåt-szint ketoacidosisban csökkent, majd ismét megemelkedett
24 és 48 óra utån (p<0,01). A T1DM-csoportban csak a 48 órås érték emelkedett
szignifikĂĄnsan (p<0,05 versus 12 Ăłra). 0â12 Ăłra között az
összlaktĂĄt-koncentrĂĄciĂł jelentĆsen meghaladta az L-laktĂĄt-szintet, ez a
D-laktĂĄtot tĂŒkrözĆ kĂŒlönbsĂ©g fokozatosan csökkenve 48 Ăłra utĂĄn megszƱnt.
KövetkeztetĂ©s: A ketoacidosisban Ă©szlelt kĂ©t laktĂĄtcsĂșcs
közĂŒl az elsĆ 12 ĂłrĂĄban a hyperlactataemia kialakulĂĄsĂĄban az anaerob
glikolĂzisnek van szerepe. A mĂĄsodik, inzulinkezelĂ©s Ă©s rendezett
folyadĂ©khĂĄztartĂĄs mellett kialakulĂł csĂșcs hĂĄtterĂ©ben fokozott aerob glikolĂzis
ĂĄllhat. Az L-laktĂĄt- Ă©s összlaktĂĄtszintek közötti kezdeti kĂŒlönbsĂ©g D-laktĂĄt
kĂ©pzĆdĂ©sĂ©re utal, amely a ketoacidosis kezdeti fĂĄzisĂĄban az L-laktĂĄttal azonos
nagysĂĄgrendben termelĆdik. Orv Hetil. 2019; 160(45): 1784â1790.
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Abstract:
Introduction: It is known that lactate concentration is
increased in diabetic ketoacidosis (DKA), however, the pathophysiology and
kinetics of lactate changes are still unclear. Normally, L-lactate is the major
form in the human body. According to previous data, also D- and L-lactate might
be increased in hyperglycaemic disorders. Aim: We aimed to
describe the kinetics and mechanisms of lactate concentration changes in
ketoacidosis and newly diagnosed diabetes. Method: We performed
a prospective study, including 5â18-year-old children with ketoacidosis (DKA, n
= 13) and with newly diagnosed type 1 diabetes without ketoacidosis (T1DM, n =
6). We performed routine blood gas analysis 0â12â24â48 hours after admission,
which also measured L-lactate levels. We also determined total venous serum
lactate level by gas chromatographyâmass spectrometry. Results:
Initial plasma lactate concentration was increased in ketoacidosis as compared
to the newly diagnosed diabetes group (p<0.05). After 12 h of rehydration,
lactate levels were greatly reduced in ketoacidotic patients but after 24â48 h
it was repeatedly increased (all p<0.01). In the 0â12 h phase, total serum
lactate level was higher than L-lactate level, referring to D-lactate
production. Conclusion: We described two L-lactate peaks in
ketoacidosis. In the first 12 hours anaerobic glycolysis seems to have major
role in hyperlactataemia. We assume that stimulated aerobic glycolysis leads to
the second lactate peak. However, D-lactate is not routinely measured, it may
contribute to the initial hyperlactataemia in both groups and is comparable to
L-lactate production in ketoacidosis. Orv Hetil. 2019; 160(45): 1784â1790
A SHOX gĂ©ndeletio elĆfordulĂĄsa idiopathiĂĄs alacsonynövĂ©sben
INTRODUCTION: The isolated haploinsufficiency of the SHOX gene is one of the most common cause of short stature determined by monogenic mutations. The heterozygous deviation of the gene can be detected in 2-15% of patients with idiopathic short stature (ISS), in 50-90% of patients with Leri-Weill dyschondrosteosis syndrome (LWS), and in almost 100% of patients with Turner syndrome. AIM: The aim of our study was to evaluate the frequency of SHOX gene haploinsufficiency in children with ISS, LWS and in patients having Turner syndrome phenotype (TF), but normal karyotype, and to identify the dysmorphic signs characteristic for SHOX gene deficiency. METHOD: A total of 144 patients were included in the study. Multiplex Ligation-dependent Probe Amplification (MLPA) method was used to identify the SHOX gene haploinsufficiency. The relationships between clinical data (axiological parameters, skeletal disorders, dysmorphic signs) and genotype were analyzed by statistical methods. RESULTS: 11 (7.6%) of the 144 patients showed SHOX gene deficiency with female dominance (8/11, 81% female). The SHOX positive patients had a significantly higher BMI (in 5/11 vs. 20/133 cases, p<0.02) and presented more frequent dysmorphic signs (9/11vs 62/133, p = 0.02). Madelung deformity of the upper limbs was also significantly more frequent among the SHOX positive patients (4/11, i.e. 36%, vs. 14/133, i.e. 10%, p = 0.0066). There were no statistically significant differences between the mean age, mean height and auxological measurements (sitting height/height, arm span/height) between the two groups of patients. CONCLUSIONS: The occurrence of SHOX gene haploinsufficiency observed in our population corresponds to the literature data. In SHOX positive patients, in addition to short stature, the dysmorphic signs have a positive predictive value for SHOX gene alterations. However, the SHOX deletion detected in a patient with idiopathic short stature without dysmorphic signs suggest that SHOX deletion analysis can be recommended in patients with ISS. Orv Hetil. 2017; 158(34): 1351-1356
ElsĆdleges genetikai vizsgĂĄlat PraderâWilli-szindrĂłma igazolĂĄsĂĄra
INTRODUCTION: According to the international literature, DNA methylation analysis of the promoter region of SNRPN locus is the most efficient way to start genetic investigation in patients with suspected Prader-Willi syndrome. AIM: Our aim was to develop a simple, reliable first-tier diagnosis to confirm Prader-Willi syndrome, therefore to compare our self-designed simple, cost-efficient high-resolution melting analysis and the most commonly used methylation-specific multiplex ligation-dependent probe amplification to confirm Prader-Willi syndrome. METHOD: We studied 17 clinically suspected Prader-Willi syndrome children and their DNA samples. With self-designed primers, bisulfite-sensitive polymerase chain reaction, high-resolution melting analysis and, as a control, methylation-specific multiplex ligation-dependent probe amplification were performed. RESULTS: Prader-Willi syndrome was genetically confirmed in 6 out of 17 clinically suspected Prader-Willi syndrome patients. The results of high-resolution melting analysis and methylation-specific multiplex ligation-dependent probe amplification were equivalent in each case. CONCLUSION: Using our self-designed primers and altered bisulfite-specific PCR conditions, high-resolution melting analysis appears to be a simple, fast, reliable and effective method for primarily proving or excluding clinically suspected Prade-Willi syndrome cases. Orv Hetil. 2018; 159(2): 64-69
Szteroid-21-hidroxilĂĄz-deficientia, a congenitalis adrenalis hyperplasia leggyakoribb oka
Abstract: Congenital adrenal hyperplasia is a group of genetic diseases due to the disablement of 7 genes; one of them is steroid 21-hydroxylase deficiency. The genes of congenital adrenal hyperplasia encode enzymes taking part in the steroidogenesis of adrenal gland. Steroid 21-hydroxylase deficiency is an autosomal recessive disorder caused by mutations of the steroid 21-hydroxylase gene. The mutations of steroid 21-hydroxylase gene cause 95% of the congenital adrenal hyperplasia cases. Although the non-classic steroid 21-hydroxylase deficiency with mild symptoms is seldom diagnosed, the classic steroid 21-hydroxylase deficiency may lead to life-threatening salt-wasting and adrenal crises due to the insufficient aldosterone and cortisol serum levels. The classic type requires life-long steroid replacement which may result in cushingoid side effects, and typical comorbidities may be also developed. The patients? quality of life is decreased, and their mortality is much higher than that of the population without steroid 21-hydroxylase deficiency. The diagnosis, consequences and the patients? life-long clinical care require a multidisciplinary approach: the specialists in pediatrics, internal medicine, endocrinology, laboratory medicine, genetic diagnostics, surgery, obstetrics-gynecology and psychology need to work together. Orv Hetil. 2018; 159(7): 269?277
Preliminary Evidence for Cell Membrane Amelioration in Children with Cystic Fibrosis by 5-MTHF and Vitamin B12 Supplementation: A Single Arm Trial
Cystic fibrosis (CF) is one of the most common fatal autosomal recessive disorders in the Caucasian population caused by mutations of gene for the cystic fibrosis transmembrane conductance regulator (CFTR). New experimental therapeutic strategies for CF propose a diet supplementation to affect the plasma membrane fluidity and to modulate amplified inflammatory response. The objective of this study was to evaluate the efficacy of 5-methyltetrahydrofolate (5-MTHF) and vitamin B12 supplementation for ameliorating cell plasma membrane features in pediatric patients with cystic fibrosis.A single arm trial was conducted from April 2004 to March 2006 in an Italian CF care centre. 31 children with CF aged from 3 to 8 years old were enrolled. Exclusion criteria were diabetes, chronic infections of the airways and regular antibiotics intake. Children with CF were supplemented for 24 weeks with 5-methyltetrahydrofolate (5-MTHF, 7.5 mg /day) and vitamin B12 (0.5 mg/day). Red blood cells (RBCs) were used to investigate plasma membrane, since RBCs share lipid, protein composition and organization with other cell types. We evaluated RBCs membrane lipid composition, membrane protein oxidative damage, cation content, cation transport pathways, plasma and RBCs folate levels and plasma homocysteine levels at baseline and after 24 weeks of 5-MTHF and vitamin B12 supplementation. In CF children, 5-MTHF and vitamin B12 supplementation (i) increased plasma and RBC folate levels; (ii) decreased plasma homocysteine levels; (iii) modified RBC membrane phospholipid fatty acid composition; (iv) increased RBC K(+) content; (v) reduced RBC membrane oxidative damage and HSP70 membrane association.5-MTHF and vitamin B12 supplementation might ameliorate RBC membrane features of children with CF.ClinicalTrials.gov NCT00730509