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1.
Pediatr Nephrol ; 39(8): 2475-2481, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38536515

RESUMO

BACKGROUND: Neonatal hypertension is common in preterm infants with bronchopulmonary dysplasia (BPD). Our study aimed to examine blood pressure variation in the first three months of life in preterm BPD patients. METHODS: We conducted a retrospective, single-centre study at the Neonatal Intensive Care Unit of the University of Szeged, Hungary. We collected blood pressure data from 26 preterm infants (born at < 30 weeks gestation) with moderate or severe BPD over three years (2019-2021). We calculated the BPD group's daily average blood pressure values and used previously defined normal blood pressure values from a preterm patient group born at < 30 weeks gestation as a reference. We used 19,481 systolic, diastolic and mean blood pressure measurement data separately to calculate daily average blood pressures. RESULTS: We found a statistically significant correlation between the blood pressure values of the BPD patient group and the reference data. The difference between the blood pressure curve of the group with BPD and that of the reference group was also statistically significant. We also analysed individual patients' daily average blood pressure values and found that 11 patients (42%) had hypertensive blood pressure values for three or more days within the first 90 days of life. Within this group, our statistical analysis showed a 25% chance of acute kidney injury. CONCLUSION: The blood pressure of the BPD group not only correlated with but also significantly differed from the reference data. Hypertension lasting three or more days occurred more frequently in patients with acute kidney injury accompanied by BPD.


Assuntos
Pressão Sanguínea , Displasia Broncopulmonar , Recém-Nascido Prematuro , Humanos , Displasia Broncopulmonar/fisiopatologia , Displasia Broncopulmonar/complicações , Displasia Broncopulmonar/diagnóstico , Estudos Retrospectivos , Recém-Nascido , Feminino , Masculino , Pressão Sanguínea/fisiologia , Lactente , Hungria/epidemiologia , Hipertensão/fisiopatologia , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Idade Gestacional , Determinação da Pressão Arterial/métodos
2.
Int J Mol Sci ; 25(2)2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38256038

RESUMO

Dent disease type 1 is characterized by pathogenic CLCN5 gene variants and impaired receptor-mediated endocytosis in proximal tubules. However, mutation-related abnormalities in proximal tubules have not yet been described. Here, we present three patients with CLCN5 alterations and distinct morphological changes of the apical endocytic-lysosomal apparatus. The proximal tubular ultrastructure was investigated in kidney biopsy samples of three boys genotyped for non-nephrotic proteinuria. Controls: seven patients with nephrotic-range glomerular proteinuria. The genotyping findings revealed an already-known missense mutation in one patient and hitherto undescribed frameshift variants in two patients. Low-molecular-weight proteinuria, focal global glomerulosclerosis, proximal tubular changes, and tubular calcium deposits characterized each case. Three subsets of proximal tubular cells were observed: those without any abnormality, those with aplasia of apical endocytic-lysosomal apparatus and shrinkage of cells, and those with hypoplasia of apical endocytic apparatus, accumulation of proteinaceous substance in dysmorphic lysosomes, and dysmorphic mitochondria. The distribution of subsets varied from patient to patient. In one patient with a frameshift variant, an oxidative stress-like injury of proximal tubular cells and podocytes accompanied the above-mentioned alterations. Focal aplasia/hypoplasia of apical endocytic apparatus and subsequent changes in cytoplasmic organelles characterized proximal tubules in the CLCN5 pathogenic variants.


Assuntos
Glomerulosclerose Segmentar e Focal , Lisossomos , Masculino , Humanos , Mutação , Mutação da Fase de Leitura , Mutação de Sentido Incorreto , Proteinúria
3.
Pediatr Nephrol ; 38(10): 3369-3378, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37145184

RESUMO

BACKGROUND: We aimed to provide data on the normal blood pressure of haemodynamically stable neonates. Our study uses retrospective, real-life oscillometric blood pressure measurement values to determine the expected blood pressure in different gestational age, chronological age and birth weight groups. We also investigated the effect of antenatal steroid on neonatal blood pressure. METHODS: Our retrospective study (2019-2021) was carried out in the Neonatal Intensive Care Unit of the University of Szeged, Hungary. We involved 629 haemodynamically stable patients and analysed 134,938 blood pressure values. Data were collected from electronic hospital records of IntelliSpace Critical Care Anesthesia by Phillips. We used the PDAnalyser program for data handling and the IBM SPSS program for statistical analysis. RESULTS: We found a significant difference between the blood pressure of each gestational age group in the first 14 days of life. The systolic, diastolic and mean blood pressure rise are steeper in the preterm group than in the term group in the first 3 days of life. No significant blood pressure differences were found between the group with a complete antenatal steroid course and those who received incomplete steroid prophylaxis or did not receive antenatal steroids. CONCLUSION: We determined the average blood pressure of stable neonates and obtained normative data by percentiles. Our study provides additional data on how blood pressure varies with gestational age and birth weight. A higher resolution version of the Graphical abstract is available as Supplementary information.


Assuntos
Pressão Arterial , Determinação da Pressão Arterial , Recém-Nascido , Humanos , Feminino , Gravidez , Peso ao Nascer/fisiologia , Estudos Retrospectivos , Pressão Sanguínea/fisiologia , Idade Gestacional
4.
BMC Pediatr ; 23(1): 301, 2023 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-37328771

RESUMO

BACKGROUND: The incidence of tonsillopharyngitis is especially prevalent in children. Despite the fact that viruses cause the majority of infections, antibiotics are frequently used as a treatment, contrary to international guidelines. This is not only an inappropriate method of treatment for viral infections, but it also significantly contributes to the emergence of antibiotic-resistant strains. In this study, EBV and CMV-related tonsillopharyngitis were distinguished from other pathogens by using machine learning techniques to construct a classification tree based on clinical characteristics. MATERIALS AND METHODS: In 2016 and 2017, we assessed information regarding 242 children with tonsillopharyngitis. Patients were categorized according to whether acute cytomegalovirus or Epstein-Barr virus infections were confirmed (n = 91) or not (n = 151). Based on symptoms and blood test parameters, we constructed decision trees to discriminate the two groups. The classification efficiency of the model was characterized by its sensitivity, specificity, positive predictive value, and negative predictive value. Fisher's exact and Welch's tests were used to perform univariable statistical analyses. RESULTS: The best decision tree distinguished EBV/CMV infection from non-EBV/CMV group with 83.33% positive predictive value, 88.90% sensitivity and 90.30% specificity. GPT (U/l) was found to be the most discriminatory variable (p < 0.0001). Using the model, unnecessary antibiotic treatment could be reduced by 66.66% (p = 0.0002). DISCUSSION: Our classification model can be used as a diagnostic decision support tool to distinguish EBC/CMV infection from non EBV/CMV tonsillopharyngitis, thereby significantly reducing the overuse of antibiotics. It is hoped that the model may become a tool worth considering in routine clinical practice and may be developed to differentiate between viral and bacterial infections.


Assuntos
Infecções por Citomegalovirus , Infecções por Vírus Epstein-Barr , Faringite , Humanos , Criança , Infecções por Vírus Epstein-Barr/diagnóstico , Antibacterianos/uso terapêutico , Herpesvirus Humano 4 , Faringite/diagnóstico , Faringite/tratamento farmacológico , Árvores de Decisões
5.
Eur J Neurol ; 29(2): 382-389, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34741372

RESUMO

BACKGROUND AND PURPOSE: Antiseizure medications (ASMs) should be tailored to individual characteristics, including seizure type, age, sex, comorbidities, comedications, drug allergies, and childbearing potential. We previously developed a web-based algorithm for patient-tailored ASM selection to assist health care professionals in prescribing medication using a decision support application (https://epipick.org). In this validation study, we used an independent dataset to assess whether ASMs recommended by the algorithm are associated with better outcomes than ASMs considered less desirable by the algorithm. METHODS: Four hundred twenty-five consecutive patients with newly diagnosed epilepsy were followed for at least 1 year after starting an ASM chosen by their physician. Patient characteristics were fed into the algorithm, blinded to the physician's ASM choices and outcome. The algorithm recommended ASMs, ranked in hierarchical groups, with Group 1 ASMs labeled as the best option for that patient. We evaluated retention rates, seizure freedom rates, and adverse effects leading to treatment discontinuation. Survival analysis contrasted outcomes between patients who received favored drugs and those who received lower ranked drugs. Propensity score matching corrected for possible imbalances between the groups. RESULTS: Antiseizure medications classified by the algorithm as best options had a higher retention rate (79.4% vs. 67.2%, p = 0.005), higher seizure freedom rate (76.0% vs. 61.6%, p = 0.002), and lower rate of discontinuation due to adverse effects (12.0% vs. 29.2%, p < 0.001) than ASMs ranked as less desirable by the algorithm. CONCLUSIONS: Use of the freely available decision support system is associated with improved outcomes. This drug selection application can provide valuable assistance to health care professionals prescribing medication for individuals with epilepsy.


Assuntos
Anticonvulsivantes , Epilepsia , Adolescente , Adulto , Algoritmos , Anticonvulsivantes/uso terapêutico , Epilepsia/induzido quimicamente , Epilepsia/tratamento farmacológico , Humanos , Internet , Convulsões/tratamento farmacológico
6.
Metab Brain Dis ; 36(7): 2131-2139, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34287746

RESUMO

Cerebral calcification may be caused by several potentially treatable conditions, however, in most cases it does not receive special attention in clinical practice. From the point of view of etiology, the diseases associated with cerebral calcification can be divided into two main groups: idiopathic (mostly incurable) and secondary (potentially treatable). The first group includes mainly the hereditary diseases identified before 2021 (primary familial brain calcification subtypes, previously known as Fahr's disease or Fahr's syndrome). In contrast, the second group includes diseases with cerebral calcification that develop generally as a consequence of metabolic/endocrine/autoimmune abnormalities. The aim of our research was to present hereditary and non-hereditary etiologies associated with extensive brain calcification. We compare the detailed clinical, radiological and laboratory results of 6 patients with prominent cerebral calcification identified in our clinic in the last 3 years (idiopathic and secondary etiologies as well). Our research draws attention to the complexity of the etiologies in the context of cerebral calcification. We recommend, beside NGS-based sequence analyses, the application of array comparative genomic hybridization as well, to identify potential genetic etiologies associated with brain calcification.


Assuntos
Doenças dos Gânglios da Base , Calcinose , Doenças Neurodegenerativas , Encéfalo/diagnóstico por imagem , Calcinose/complicações , Calcinose/diagnóstico por imagem , Calcinose/genética , Hibridização Genômica Comparativa , Humanos
7.
J Hum Genet ; 63(11): 1189-1193, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30181650

RESUMO

Heterozygous disruptions in FOXP1 are responsible for developmental delay, intellectual disability and speech deficit. Heterozygous germline PTCH1 disease-causing variants cause Gorlin syndrome. We describe a girl with extreme megalencephaly, developmental delay and severe intellectual disability. Dysmorphic features included prominent forehead, frontal hair upsweep, flat, wide nasal bridge, low-set, abnormally modelled ears and post-axial cutaneous appendages on the hands. Brain MRI showed partial agenesis of the corpus callosum and widely separated leaves of the septum pellucidum. Exome sequencing of a gene set representing a total of 4813 genes with known relationships to human diseases revealed an already known heterozygous de novo nonsense disease-causing variant in FOXP1 (c.1573C>T, p.Arg525Ter) and a heterozygous novel de novo frameshift nonsense variant in PTCH1 (c.2834delGinsAGATGTTGTGGACCC, p.Arg945GlnfsTer22). The composite phenotype of the patient seems to be the result of two monogenic diseases, although more severe than described in conditions due to disease-causing variants in either gene.


Assuntos
Agenesia do Corpo Caloso/genética , Fatores de Transcrição Forkhead/genética , Deficiência Intelectual/genética , Megalencefalia/genética , Mutação , Receptor Patched-1/genética , Proteínas Repressoras/genética , Agenesia do Corpo Caloso/patologia , Criança , Feminino , Humanos , Deficiência Intelectual/patologia , Megalencefalia/patologia
8.
Pediatr Blood Cancer ; 65(2)2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28843050

RESUMO

Pseudomyogenic hemangioendothelioma (PMH) is a rare, mostly indolent vascular tumor. Extensive cases are treated with amputation as chemotherapy seems to be ineffective. Recently, promising results were published using mammalian target of rapamycin (mTOR) inhibitors in tumors of vascular origin. Here, we present a case of a child with advanced PMH relapsing after surgery and chemotherapy. Sirolimus achieved significant clinical improvement and stabilization of the lesions without any remarkable toxicity. This case contributes to the growing evidence regarding the efficacy of mTOR inhibitors, such as sirolimus, in multifocal PMH.


Assuntos
Hemangioendotelioma/terapia , Sirolimo/administração & dosagem , Neoplasias Vasculares/terapia , Criança , Hemangioendotelioma/diagnóstico por imagem , Humanos , Masculino , Serina-Treonina Quinases TOR/antagonistas & inibidores , Neoplasias Vasculares/diagnóstico por imagem
9.
Pediatr Nephrol ; 33(3): 439-446, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29032433

RESUMO

BACKGROUND: A 7-month-old male infant was admitted because he was suffering from nephrotic syndrome, along with encephalomyopathy, hypertrophic cardiomyopathy, clinically suspected deafness and retinitis pigmentosa, and an elevated serum lactate level. METHODS: Coenzyme Q10 supplementation was started because of the clinical suspicion of primary CoQ10 deficiency. Despite intensive efforts, he passed away 4 weeks after admission. RESULTS: The results of genetic tests, available postmortem, explored two hitherto undescribed mutations in the PDSS2 gene. Both were located within the polyprenyl synthetase domain. Clinical exome sequencing revealed a heterozygous missense mutation in exon 3, and our in-house joint-analysis algorithm detected a heterozygous large 2923-bp deletion that affected the 5 prime end of exon 8. Other causative defects in the CoQ10 and infantile nephrosis-related genes examined were not found. A postmortem histological, immunohistochemical, and electron microscopic evaluation of the glomeruli revealed collapsing-sclerosing lesions consistent with diffuse mesangial sclerosis. The extrarenal alterations included hypertrophic cardiomyopathy and diffuse alveolar damage. A histological evaluation of the central nervous system and skeletal muscles did not demonstrate any obvious abnormality. CONCLUSIONS: Until now, the clinical features and the mutational status of 6 patients with a PDSS2 gene defect have been reported in the English literature. Here, we describe for the first time detailed kidney morphology features in a patient with nephrotic syndrome carrying mutations in the PDSS2 gene.


Assuntos
Alquil e Aril Transferases/genética , Ataxia/genética , Rim/patologia , Doenças Mitocondriais/genética , Debilidade Muscular/genética , Síndrome Nefrótica/genética , Esclerose/genética , Ubiquinona/deficiência , Ataxia/complicações , Autopsia , Evolução Fatal , Testes Genéticos/métodos , Humanos , Lactente , Masculino , Doenças Mitocondriais/complicações , Debilidade Muscular/complicações , Mutação , Síndrome Nefrótica/complicações , Síndrome Nefrótica/etiologia , Esclerose/complicações , Ubiquinona/análogos & derivados , Ubiquinona/genética , Ubiquinona/uso terapêutico
10.
Pediatr Nephrol ; 33(10): 1713-1721, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29956005

RESUMO

BACKGROUND: Autosomal recessive polycystic kidney disease (ARPKD) is genetically one of the least heterogeneous ciliopathies, resulting primarily from mutations of PKHD1. Nevertheless, 13-20% of patients diagnosed with ARPKD are found not to carry PKHD1 mutations by sequencing. Here, we assess whether PKHD1 copy number variations or second locus mutations explain these cases. METHODS: Thirty-six unrelated patients with the clinical diagnosis of ARPKD were screened for PKHD1 point mutations and copy number variations. Patients without biallelic mutations were re-evaluated and screened for second locus mutations targeted by the phenotype, followed, if negative, by clinical exome sequencing. RESULTS: Twenty-eight patients (78%) carried PKHD1 point mutations, three of whom on only one allele. Two of the three patients harbored in trans either a duplication of exons 33-35 or a large deletion involving exons 1-55. All eight patients without PKHD1 mutations (22%) harbored mutations in other genes (PKD1 (n = 2), HNF1B (n = 3), NPHP1, TMEM67, PKD1/TSC2). Perinatal respiratory failure, a kidney length > +4SD and early-onset hypertension increase the likelihood of PKHD1-associated ARPKD. A patient compound heterozygous for a second and a last exon truncating PKHD1 mutation (p.Gly4013Alafs*25) presented with a moderate phenotype, indicating that fibrocystin is partially functional in the absence of its C-terminal 62 amino acids. CONCLUSIONS: We found all ARPKD cases without PKHD1 point mutations to be phenocopies, and none to be explained by biallelic PKHD1 copy number variations. Screening for copy number variations is recommended in patients with a heterozygous point mutation.


Assuntos
Variações do Número de Cópias de DNA , Heterozigoto , Fenótipo , Rim Policístico Autossômico Recessivo/genética , Receptores de Superfície Celular/genética , Adolescente , Alelos , Criança , Pré-Escolar , Análise Mutacional de DNA , Éxons/genética , Feminino , Testes Genéticos , Humanos , Lactente , Recém-Nascido , Masculino , Mutação Puntual , Rim Policístico Autossômico Recessivo/diagnóstico , Índice de Gravidade de Doença
11.
Ann Nutr Metab ; 72(4): 259-264, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29597205

RESUMO

BACKGROUND/AIMS: The prevalence of overweight and obesity in children and adolescents is increasing worldwide, and this condition is a risk factor for cardiovascular mortality. The aim of this study was to assess the prevalence of overweight and obesity among the 3-18-year-old population in Szolnok City and the surrounding areas. METHODS: Anthropometric data from healthy, white individuals recruited from nursery, elementary, and secondary schools were used to assess the prevalence of obesity and overweight in Szolnok City and the surrounding area, Jász-Nagykun-Szolnok county, Hungary. Healthy subjects numbering 6,824 (54% boys) were included; overweight and obesity were defined according to the relevant guidelines. RESULTS: Overweight individuals constituted 13.4% of the population and 6.6% were obese. The total prevalence was higher in boys (21.6%) than in girls (18.1%). The peak of the prevalence was observed at age 10 in both sexes (boys 33%, girls 27%) followed by a gradual decrease, which was more significant in the case of girls. CONCLUSIONS: On the basis of the recent Hungarian data, we have not detected any changes in overweight and obesity in the age group 3-9 years and we have found a significant decrease in the age group 7-14 years. Prevention of overweight and obesity in early childhood is essential.


Assuntos
Sobrepeso/epidemiologia , Obesidade Infantil/epidemiologia , Adolescente , Índice de Massa Corporal , Criança , Pré-Escolar , Feminino , Humanos , Hungria/epidemiologia , Masculino , Prevalência
12.
Pediatr Dermatol ; 35(5): e272-e275, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29962053

RESUMO

Neonatal blue-light phototherapy induced a blistering reaction followed by eruption of melanocytic nevi on the exposed skin surface of a child with transient neonatal porphyrinemia. New nevi are still developing 4 years after the triggering event. The role of phototoxicity-induced epidermal injury, that of porphyrins and the influence of neonatal blue-light therapy, in this unique phenomenon are discussed.


Assuntos
Dermatite Fototóxica/etiologia , Nevo Pigmentado/etiologia , Fototerapia/efeitos adversos , Porfirinas/sangue , Neoplasias Cutâneas/etiologia , Vesícula/etiologia , Humanos , Lactente , Recém-Nascido , Masculino , Nevo Pigmentado/patologia , Pele/patologia , Neoplasias Cutâneas/patologia
13.
J Am Soc Nephrol ; 28(10): 3066-3075, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28526779

RESUMO

The recent discovery of mutations in the gene encoding diacylglycerol kinase ε (DGKE) identified a novel pathophysiologic mechanism leading to HUS and/or MPGN. We report ten new patients from eight unrelated kindreds with DGKE nephropathy. We combined these cases with all previously published cases to characterize the phenotypic spectrum and outcomes of this new disease entity. Most patients presented with HUS accompanied by proteinuria, whereas a subset of patients exhibited clinical and histologic patterns of MPGN without TMA. We also report the first two patients with clinical and histologic HUS/MPGN overlap. DGKE-HUS typically manifested in the first year of life but was not exclusively limited to infancy, and viral triggers frequently preceded HUS episodes. We observed signs of complement activation in some patients with DGKE-HUS, but the role of complement activation remains unclear. Most patients developed a slowly progressive proteinuric nephropathy: 80% of patients did not have ESRD within 10 years of diagnosis. Many patients experienced HUS remission without specific treatment, and a few patients experienced HUS recurrence despite complete suppression of the complement pathway. Five patients received renal allografts, with no post-transplant recurrence reported. In conclusion, we did not observe a clear genotype-phenotype correlation in patients with DGKE nephropathy, suggesting additional factors mediating phenotypic heterogeneity. Furthermore, the benefits of anti-complement therapy are questionable but renal transplant may be a feasible option in the treatment of patients with this condition.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/genética , Diacilglicerol Quinase/genética , Glomerulonefrite Membranoproliferativa/genética , Síndrome Hemolítico-Urêmica Atípica/epidemiologia , Síndrome Hemolítico-Urêmica Atípica/terapia , Pré-Escolar , Análise Mutacional de DNA , Feminino , Glomerulonefrite Membranoproliferativa/epidemiologia , Glomerulonefrite Membranoproliferativa/terapia , Humanos , Incidência , Lactente , Lituânia/epidemiologia , Masculino , Fenótipo
15.
Orv Hetil ; 158(48): 1909-1918, 2017 Dec.
Artigo em Húngaro | MEDLINE | ID: mdl-29172662

RESUMO

INTRODUCTION: Infant vitamin B12 deficiency can manifest as a severe neurodegenerative disorder and is usually caused by maternal deficiency due to vegetarian diet or pernicious anaemia. Its early recognition and treatment can prevent potentially serious and irreversible neurologic damage. Biochemically, vitamin B12 deficiency leads to an accumulation of methylmalonic acid, homocysteine, and propionylcarnitine. Expanded newborn screening using tandem mass spectrometry may identify neonatal and maternal vitamin B12 deficiency by measurement of propionylcarnitine and other metabolites in the dried blood spot sample of newborns. AIM: To summarize our experiences gained by screening for vitamin B12 deficiency. METHOD: Clinical and laboratory data of vitamin B12-deficient infants diagnosed in Szeged Screening Centre were retrospectively analysed. RESULTS: In Hungary, expanded newborn screening was introduced in 2007. Since then approximately 395 000 newborns were screened in our centre and among them, we identified four newborns with vitamin B12 deficiency based on their screening results. In three cases an elevated propionylcarnitine level and in the fourth one a low methionine level were indicative of vitamin B12 deficiency. We also detected an additional vitamin B12-deficient infant with neurological symptoms at 4 months of age, after a normal newborn screening, because of elevated urinary methylmalonic acid concentration. Vitamin B12 deficiency was secondary to maternal autoimmune pernicious anaemia in all the five infants. As a result of the recognized cases the incidence of infant vitamin B12 deficiency in the East-Hungarian region was 1.26/100 000 births, but the real frequency may be higher. Conslusions: Optimizing the cut off values of current screening parameters and measuring of methylmalonic acid and/or homocysteine in the dried blood spot, as a second tier test, can improve recognition rate of vitamin B12 deficiency. Orv Hetil. 2017; 158(48): 1909-1918.


Assuntos
Triagem Neonatal/métodos , Complicações na Gravidez/diagnóstico , Deficiência de Vitamina B 12/diagnóstico , Anemia Perniciosa/imunologia , Feminino , Humanos , Hungria , Incidência , Recém-Nascido , Fenômenos Fisiológicos da Nutrição Materna , Gravidez , Estudos Retrospectivos , Espectrometria de Massas em Tandem , Deficiência de Vitamina B 12/sangue , Deficiência de Vitamina B 12/etiologia , Deficiência de Vitamina B 12/urina
16.
Pediatr Blood Cancer ; 62(4): 622-8, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25557962

RESUMO

BACKGROUND: Cytarabine (cytosine arabinoside, ara-C) is a chemotherapeutical agent used in the treatment of pediatric acute lymphoblastic leukemia (ALL). Adverse drug reactions, such as interpatient variability in sensitivity to ara-C, are considerable and may cause difficulties during chemotherapy. Single nucleotide polymorphisms (SNPs) can play a significant role in modifying nucleoside-drug pharmacokinetics and pharmacodynamics and thus the development of adverse effects. Our aim was to determine whether polymorphisms in genes encoding transporters and enzymes responsible for the metabolism of ara-C are associated with toxicity and clinical outcome in a patient population with childhood ALL. PROCEDURE: We studied 8 SNPs in the CDA, DCK, DCTD, SLC28A3, and SLC29A1 genes in 144 patients with childhood acute lymphoblastic leukemia treated according to ALLIC BFM 1990, 1995 and 2002 protocols. RESULTS: DCK rs12648166 and DCK rs4694362 SNPs were associated with hematologic toxicity (OR = 2.63, CI 95% = 1.37-5.04, P = 0.0036 and OR = 2.53, CI 95% = 1.34-4.80, P = 0.0044, respectively). CONCLUSIONS: Our results indicate that DCK polymorphisms might be important genetic risk factors for hematologic toxicity during ALL treatment with ara-C. Individualized chemotherapy based on genetic profiling may help to optimize ara-C dosing, leading to improvements in clinical outcome and reduced toxicity.


Assuntos
Citarabina/efeitos adversos , Desoxicitidina Quinase/genética , Genes Neoplásicos , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Criança , Pré-Escolar , Citarabina/administração & dosagem , Citarabina/farmacocinética , Desoxicitidina Quinase/metabolismo , Feminino , Humanos , Lactente , Masculino , Proteínas de Neoplasias/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Estudos Retrospectivos , Fatores de Risco
17.
Blood Press Monit ; 29(4): 198-202, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38465742

RESUMO

OBJECTIVE: Ambulatory blood pressure monitoring (ABPM) devices play a crucial role in diagnosing hypertension, not only in adults but also in pediatric patients. ABPM-06, the latest oscillometric device from Meditech Ltd. (Budapest, Hungary), is the focus of this study. The objective was to validate the ABPM-06 device using the International Organization for Standardization (ISO) 81060-2 : 2018 standard. METHODS: A total of 86 healthy patients, consisting of 34 males and 52 females, aged between 3 and 17 years, were enrolled in this study. During the ambulatory phase, a total of 50 patients were enrolled, with 35 patients falling within the 3- to 12-year-old age range and 15 patients aged between 12 and 17 years. Additionally, for the dynamic test, 36 patients were selected, comprising of 10 individuals aged 3-12 years and 26 patients aged 12-17 years. These patients were recruited from the outpatient clinics of the Department of Pediatrics at Albert Szent-Györgyi University in Szeged, Hungary. The validation process involved utilizing the same-arm sequence protocol, both in resting positions and during stress testing. RESULTS: The ABPM-06 performed well in both clinical and ambulatory validations. In terms of validation criterion 1, the mean ± SD of the differences between the test device and reference blood pressure readings was -1.3 ±â€…3.5  mmHg for systolic and -0.1  ±â€…2.3 mmHg for diastolic, in children under the age of 12 years. For those over the age of 12 years, the mean ± SD of the differences was -2.8 ± 4.6 mmHg for systolic and -0.5 ± 2.7 mmHg for diastolic. Regarding the ambulatory validation, for children under 12 years old, the mean ± SD of the differences was -1.3  ±â€…3.5  mmHg for systolic and -0.1  ±â€…2.3  mmHg for diastolic. In the age group above 12 years, the mean ± SD of the differences was -2.8 ± 4.6 mmHg for systolic and -0.5 ± 2.7 mmHg for diastolic. Both tests successfully met the established criteria regarding the mean and SD values of the differences between the device readings and the observed SBP and DBP measurements. CONCLUSION: The ABPM-06 oscillometric device fully adheres to the ISO 81060-2 : 2018 standard requirements for ABPM determination in the pediatric population (ages 3-17 years). Consequently, this ABPM device proves to be suitable for effectively managing hypertension in children and adolescents.


Assuntos
Monitorização Ambulatorial da Pressão Arterial , Humanos , Criança , Masculino , Feminino , Adolescente , Monitorização Ambulatorial da Pressão Arterial/instrumentação , Monitorização Ambulatorial da Pressão Arterial/normas , Pré-Escolar , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Pressão Sanguínea
18.
Nephrol Dial Transplant ; 28(9): 2237-45, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23787556

RESUMO

BACKGROUND: Atypical forms of haemolytic uraemic syndrome (aHUS) include HUS caused by defects in the regulation of alternative complement pathway and HUS linked to neuraminidase-producing pathogens, such as Streptococcus pneumoniae. Increasing data support a pathogenic role of neuraminidase in the development of S. pneumoniae-associated haemolytic uraemic syndrome (SP-HUS), but the role of complement has never been clarified in detail. Therefore, we aimed to investigate whether the pathologic complement profile and genetic risk factors of aHUS are present in patients with SP-HUS. METHODS: Enrolling five patients with SP-HUS classical and alternative pathway activity, besides C3, C4, factors H, B, I and anti-factor H autoantibody levels were determined. The coding regions of CFH, CFI, CD46 (MCP), THBD, C3 and CFB genes were sequenced and the copy number of CFI, CD46, CFH and related genes were also analyzed. RESULTS: We found that in the acute phase samples of SP-HUS patients, complement components C4, C3 and activity of the classical and alternative pathways were decreased, indicating severe activation and complement consumption, but most of these alterations normalized later in remission. Three of the patients carried mutations and risk haplotypes in complement-mediated aHUS associated genes. The identified mutations include a previously published CFI variant (P50A) and two novel ones in CFH (R1149X) and THBD (T44I) genes. CONCLUSIONS: Our results suggest that severe complement dysregulation and consumption accompany the progress of invasive pneumococcal disease (IPD)-associated SP-HUS and genetic variations of complement genes may contribute to the development of this complication in a proportion of the affected patients.


Assuntos
Proteínas do Sistema Complemento/genética , Síndrome Hemolítico-Urêmica/etiologia , Infecções Pneumocócicas/imunologia , Streptococcus pneumoniae/imunologia , Proteínas ADAM/metabolismo , Proteína ADAMTS13 , Pré-Escolar , Proteínas do Sistema Complemento/imunologia , Feminino , Síndrome Hemolítico-Urêmica/metabolismo , Humanos , Lactente , Mutação/genética , Neuraminidase/metabolismo , Infecções Pneumocócicas/complicações , Infecções Pneumocócicas/microbiologia , Reação em Cadeia da Polimerase , Estudos Prospectivos , Streptococcus pneumoniae/genética
19.
Clin Exp Nephrol ; 17(4): 569-74, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23224027

RESUMO

BACKGROUND: The development of erythropoiesis-stimulating agents (ESAs) with extended serum half-lives has allowed marked prolongation of the administration intervals. The level of oxidative stress is increased in chronic kidney disease, and is reportedly decreased after long-term ESA treatment. However, the effect of different dosing regimens of ESAs on oxidative stress has not been elucidated. METHODS: Five-sixths nephrectomized (NX) rats received either 0.4 µg/kg darbepoetin alfa (DA) weekly or 0.8 µg/kg DA fortnightly between weeks 4 and 10. NX animals receiving saline and a sham-operated (SHAM) group served as controls. The levels of oxidized and reduced glutathione (GSSG, GSH) were followed from blood samples drawn fortnightly. RESULTS: During the follow-up, the ratios GSSG/GSH showed similar trends in both DA groups, levels being significantly lower than those in the SHAM group at weeks 8 and 10. GSSG levels were lower than the baseline throughout the study in all groups except for NX controls. The GSH levels were increased in all three NX groups (weeks 6-10) compared with both the baseline and the SHAM group CONCLUSION: Our results suggest that the extent of oxidative stress is similar in response to different dosing regimens of DA in 5/6 NX rats when comparable hemoglobin levels are maintained. These findings remain to be confirmed in chronic kidney disease patients.


Assuntos
Eritropoetina/análogos & derivados , Dissulfeto de Glutationa/sangue , Glutationa/sangue , Hematínicos/administração & dosagem , Animais , Darbepoetina alfa , Esquema de Medicação , Eritropoetina/administração & dosagem , Masculino , Nefrectomia , Estresse Oxidativo , Ratos
20.
Orv Hetil ; 164(31): 1222-1230, 2023 Aug 06.
Artigo em Húngaro | MEDLINE | ID: mdl-37543974

RESUMO

INTRODUCTION: Previously, all admitted neonates to our tertiary Neonatal Unit, University of Szeged, had a cranial and abdominal ultrasound performed as part of their care. OBJECTIVE: To analyze the findings and to evaluate the effectiveness of the universal ultrasound screening. METHOD: Results of cranial and abdominal ultrasound imaging performed in our Unit between 1st January 2014 and 31st December 2015 were analyzed retrospectively. Abnormalities found during the screening scans were studied further and assessed until discharge and during the first 2 years. All imagings were performed by a radiologist. RESULTS: During the examined 2 years, 579 neonates were admitted (gestational age mean 34.2 weeks [23-41, SD ± 4.04]), abdominal ultrasound was performed in 562 (97%) and cranial ultrasound in 560 (97%) babies, on the 3.6th day of life at an average (0-18, SD ± 2.24). Of all abdominal ultrasound scans, 87% (n = 488) was carried out as screening, and the found abnormalities in 140 (29%) of the cases: renal pelvic dilatation (n = 67 [47.9%]), free abdominal fluid (n = 17 [12.1%]), echogenic kidneys (n = 13 [9.3%]), congenital abnormalities of the kidney and urinary tract (n = 9 [6.4%]), abnormalities of the liver, bile system, adrenal gland [n = 14 [10%]). The screening identified 4 (0.8%) neonates with renal abnormilaties requiring surgical correction. In regards of renal abnormalities, we observed male (p = 0.18) and left sided (p = 0.54) predominance. Screening cranial ultrasound was performed in 65% (n = 362) of all neonates, discovering 51 (14%) anomalies: plexus chorioideus cyst (n = 21 [41%]), plexus chorioideus hemorrhage (n = 9 [17.6%]), mild ventricular asymmetry (n = 8 [15.7%]), subependymal hemorrhage (n = 5 [9.8%]), abnormalities of the periventricular area (n = 4 [7.8%]), colpocephaly, hydrocephalus externus, echogenic meninx and thalamic nodule [n = 1-1 (1.9-1.9%)]. CONCLUSION: Abdominal ultrasound screening discovered renal abnormalities and umbilical line complications as clinically relevant findings. However, a small number of renal abnormalities identified by screening required surgical intervention. Further studies are needed to identify possible risk groups to develop more efficient screening strategy to decrease the number of screened babies for 1 relevant finding (number to screen). Cranial ultrasound screening did not identify any abnormalities that needed intervention. We can not recommend universal cranial ultrasound screening based on our results. Orv Hetil. 2023; 164(31): 1222-1230.


Assuntos
Encefalopatias , Unidades de Terapia Intensiva Neonatal , Recém-Nascido , Humanos , Masculino , Lactente , Estudos Retrospectivos , Ecoencefalografia/métodos , Ultrassonografia
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