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G Fekete

Publications and source records attributed to G Fekete.

At least 19 recordsLinked to original sources
PubMed2006

National registry of patients with juvenile idiopathic inflammatory myopathies in Hungary--clinical characteristics and disease course of 44 patients with juvenile dermatomyositis.

Idiopathic inflammatory myopathies (IIMs) are systemic autoimmune diseases characterized by chronic muscle inflammation resulting in progressive weakness and frequent involvement of internal organs, mainly the pulmonary, gastrointestinal and cardiac systems which considerably contribute to the morbidity and mortality of the IIMs. Aim of this study was to present clinical characteristics, disease course, frequency of relapses and survival in patients with juvenile dermatomyositis (DM). A national registry of patients with juvenile IIMs was elaborated by the authors in Hungary. We have summarized data of the register according to signs and symptoms, disease course, frequency of relapses and survival of patients with juvenile IIM. Analysis was performed using data of 44 patients with juvenile DM diagnosed between 1976 and 2004 according to Bohan and Peter's criteria. Survival probability was calculated by Kaplan-Meier method. Data of patients with juvenile DM were compared with data of 66 patients with adult DM. The most frequent cutaneous features were facial erythema and heliotrope rash. Extramuscular and extraskeletal manifestations of the disease were more frequent in adult patients. The most common extramuscular feature was arthralgia in both groups of patients with juvenile or adult DM. Cardiac manifestation of the disease was not observed in juvenile patients. Respiratory muscle involvement and interstitial lung disease (ILD) were more frequent among adult DM patients than cardiac manifestation of the myositis. In view of the disease course, the authors found that frequency of polycyclic and monophasic subtypes of the disease were mainly similar. The hazard of relapse was found higher during the first year after the remission. None of the juvenile patients died. Among adult patients four disease-specific deaths occurred. There was no correlation between relapse free survival and initial therapeutic regimen. Many of our patients had polycyclic or chronic disease. As relapses can occur after a prolonged disease-free interval, patients should be followed up for at least 2 years. Although we found favourable survival probability, further investigations are needed to assess functional outcome.

Adolescent↗
PubMed2005

Mutational spectrum of steroid 21-hydroxylase and the genotype-phenotype association in Middle European patients with congenital adrenal hyperplasia.

OBJECTIVE: To analyze the mutational spectrum of steroid 21-hydroxylase (CYP21) and the genotype- phenotype correlation in patients with congenital adrenal hyperplasia (CAH) registered in the Middle European Society for Pediatric Endocrinology CAH database, and to design a reliable and rational approach for CYP21 mutation detection in Middle European populations. DESIGN AND METHODS: Molecular analysis of the CYP21 gene was performed in 432 CAH patients and 298 family members. Low-resolution genotyping was performed to detect the eight most common point mutations. High-resolution genotyping, including Southern blotting and sequencing was performed to detect CYP21 gene deletions, conversions, point mutations or other sequence changes. RESULTS: CYP21 gene deletion and In2 and Ile172Asn mutation accounted for 72.7% of the affected alleles in the whole study group. A good genotype-phenotype correlation was observed, with the exception of Ile172Asn and Pro30Leu mutations. In 37% of patients low resolution genotyping could not identify the causative mutation or distinguish homozygosity from hemizygosity. Using high-resolution genotyping, the causative mutations could be identified in 341 out of 348 analyzed patients. A novel mutation Gln315Stop was found in one simple virilising CAH (SV-CAH) patient from Austria. In the remaining seven patients polymorphisms were identified as the leading sequence alteration. The presence of elevated basal and ACTH-stimulated 17-hydroxyprogesterone, premature pubarche, advanced bone age and clitoral hypertrophy directly implicated Asn493Ser polymorphism in the manifestation of nonclassical- (NC) and even SV-CAH. CONCLUSIONS: By genotyping for the most common point mutations, CYP21 gene deletion/conversion and the 8 bp deletion in exon 3, it should be possible to identify the mutation in 94-99% of the diseased alleles in any investigated Middle European population. In patients with a mild form of the disease and no detectable mutation CYP21 gene polymorphisms should be considered as a plausible disease-causing mutation.

Adrenal Hyperplasia, Congenital↗
PubMed2003

Limited value of serum steroid measurements in identification of mild form of 21-hydroxylase deficiency.

BACKGROUND: ACTH stimulation test is widely used as a basic diagnostic method for non-classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD). However, the interpretation of this test has not been definitely established. To determine the cut-off values of basal and post-ACTH serum 17-OHP concentrations, data of patients with suspected 21-OHD has been analysed. PATIENTS AND METHODS: Two hundred and eighty-seven patients with postnatal/peripubertal virilization were investigated. Serum steroid concentrations were measured by RIA, urinary steroid profile was determined by capillary gas chromatography and mutation analysis of CYP21 gene was performed by allele specific PCR. 21-OHD was diagnosed by elevated serum 17-OHP concentrations, high level of the urinary 17-OHP metabolites and/or homozygosity for CYP21 mutations. RESULTS: Twenty-one patients of the total of 287 subjects (7.3 %) were identified as having 21-OHD. The numbers of 21-OHD patients compared to total numbers of patients with different ranges of serum 17-OHP were as follows: basal values below 3.5 ng/ml (mean + 1 SD) 0/225; between 3.5 - 6.6 ng/ml 3/41; above 6.6 ng/ml (mean + 2 SD) 18/21. Post-ACTH values below 6.4 ng/ml (mean + 1 SD) 0/226, between 6.4 - 10.3 ng/ml 0/35, above 10.3 ng/ml (mean + 2 SD) 21/26. CONCLUSION: There are patients with inappropriate peripubertal virilization who have slightly elevated 17-OHP concentrations. In this subgroup of patients more sensitive and specific methods are needed to establish the diagnosis of 21-OHD. Therefore we suggest performing an ACTH stimulation test in patients with a morning 17-OHP level above 3.5 ng/ml. Furthermore, urinary steroid profile and/or CYP21 gene analysis are needed in patients with a stimulated 17-OHP value between 10 and 30 ng/ml. These tests will distinguish between patients with non-classical 21-OHD and patients with other disorders.

Adolescent↗
PubMed2002

Terbinafine (Lamisil) treatment of toenail onychomycosis in patients with insulin-dependent and non-insulin-dependent diabetes mellitus: a multicentre trial.

BACKGROUND: Diabetes mellitus (DM) affects an estimated 175 million people world-wide. Approximately one-third of patients with DM have toenail onychomycosis. OBJECTIVES: To determine the efficacy and safety of terbinafine treatment of toenail onychomycosis in patients with DM receiving insulin and/or oral antidiabetic agents. Special interest was focused on potential drug interactions with oral hypoglycaemic substances. METHODS: In a multicentre trial, patients suffering from insulin-dependent DM (IDDM) or non- insulin-dependent DM (NIDDM) with toenail onychomycosis were treated for 12 weeks with oral terbinafine 250 mg daily and followed up to 48 weeks. In addition to clinical, mycological and laboratory investigations, blood glucose levels were monitored. RESULTS: At the end of the trial (week 48), a mycological cure rate of 73% was achieved. The rates of clinical cure and complete cure (mycological cure plus clinical cure) were 57% and 48%, respectively. There was no statistically significant difference between the NIDDM and IDDM groups with respect to the cure rates (P > 0.05). No hypoglycaemic episode was reported and none of the patients had hypoglycaemia during the treatment phase. CONCLUSIONS: With excellent cure rates and a good tolerability profile, terbinafine should continue to be a drug of choice for the treatment of toenail onychomycosis in the rising number of NIDDM patients receiving multiple medication.

Adolescent↗
PubMed2001

[Androgen insensitivity syndrome. Clinical features and molecular genetics].

Androgen insensitivity syndrome (AIS) is an X-linked hereditary disorder caused by the mutation of the androgen receptor gene leading to variable phenotypes according to the depth of the hormonal resistance. There is a lack of knowledge regarding the criteria used to decide the management of infants with partial AIS, particularly with respect to sex of rearing. Therefore a national survey of patients with AIS in Hungary has been decided to compose a database for analyzing current practice. Preliminary results of the analysis for the mutations in the androgen receptor gene of Hungarian patients with AIS has been presented. The authors suggest that guidelines for clinicians on appropriate diagnostic and management strategies for AIS patients, particularly in the case of suspected partial AIS, would be helpful.

Androgen-Insensitivity Syndrome↗
PubMed2001

Differences by sex in cardiovascular disease in Williams syndrome.

OBJECTIVE: To analyze the incidence and severity of cardiovascular disease in patients with Williams syndrome (WS) and to identify factors contributing to its variable expression. METHODS: Clinical data on patients with WS were collected from several WS centers. Elastin gene deletions were confirmed in all patients. Age at diagnosis, growth data, and cardiovascular diagnoses were recorded retrospectively. Cardiac diagnoses were made on the basis of echocardiographic data. The severity of supravalvular aortic stenosis was recorded by using a 4-step scale (none, mild, moderate, severe). RESULTS: Statistical analysis of the data revealed that the severity of both supravalvular aortic stenosis and total cardiovascular disease was significantly greater in male patients than female patients (P <.002 and P <.002, respectively; Kruskal-Wallis rank-sum test). This difference was not accounted for by differences in height, weight, body mass index, or head circumference. The clinical diagnosis of WS was made at a significantly younger age in male patients (P <.01, Student t test). Earlier diagnosis was partly because of increased incidence and severity of cardiovascular disease. Another determinant of early diagnosis was low body mass index. CONCLUSION: Penetrance and severity of the elastin arteriopathy in patients with WS is affected by sex. We hypothesize that differences by sex in arterial stenoses may be related to prenatal hormonal effects. Future epidemiologic and in vitro studies may provide additional insight into the pathogenetic mechanisms of these observed differences.

Adolescent↗
PubMed2000

[Life expectancy in Down syndrome infants and children with congenital heart defects, 1974-1997].

Authors analysed 359 cases with Down's syndrome and congenital heart defects registered between 1974-1997 in Hungary. The total death rate was 19.9% (70 cases). Mortality in the operated group (85 cases) was 10.5% (9 patients), in the non-operated group (274 cases) 22.2% (61 patients). The death rate was lower in the group with early primary reconstruction (2.3%) than in the group with palliation + reconstruction (15.3%), or in the group with only palliative procedure (20%). These results indicate that the life expectancy of infants and children with Down's syndrome and congenital heart disease after early primary reconstructive procedure is the same as in Down syndrome patients without cardiac defects. The prognosis depends on the patient's social circumstances. The results after correct surgical procedure in patients with the same cardiac defect are similar to that of the patients with or without Down's syndrome.

Cardiac Surgical Procedures↗
PubMed2000

[Aberrations of chromosome 18 and their significance in genetic counseling].

In order to get information on the origin of chromosome 18 aberrations trisomy 18 cases were analysed as well as different chromosome 18 rearrangements. In total, their study population consisted of 100 trisomy 18 patients and their parents, 67 out of which have already been published. Additionally, seven families were analysed with structural aberrations of chromosome 18 including four patients with tetrasomy 18p. Determination of parent and cell stage of origin was performed by short tandem repeat typing (STR, microsatellites). These investigations revealed that the additional chromosomal material in the majority of the chromosomal 18 aberrations was maternal in origin (97/107). In most of the cases the nondisjunction occurred during maternal meiosis II. This was in agreement with findings of other groups. Thus, independently from the type of aberration, there was a predisposition of chromosome 18 for nondisjunction in maternal meiosis II. In this respect, chromosome 18 seemed to be unique among human autosomes. Furthermore, these results showed that molecular genetic analyses of chromosomal aberrations and their formation mechanisms were meaningful tools in genetic counselling situations: in 5 cases where cytogenetic investigations could not performed, the clinical diagnosis of Edwards syndrome could be confirmed by molecular findings. Thus, in these cases other genetic diseases with differing types of inheritance could be excluded from being the cause of the observed malformations. In a further structural rearrangement of chromosome 18, the origin could be determined as being mitotic, therefore a recurrence risk could be excluded for this couple.

Chromosome Aberrations↗
PubMed2000

Acid sphingomyelinase deficiency in Beckwith Wiedemann syndrome.

We report the association of Beckwith-Wiedemann syndrome (BWS) and a residual acid sphingomyelinase (ASM) activity of about 35% in a 23 months old Hungarian boy. Besides the classical triad of exomphalos, macroglossia and gigantism some other BWS-related features: polyhydramnios (known from the praenatal history), hemihypertrophy, craniofacial dysmorphy, a mild mental retardation, bilaterally undescended testes, cardiac anomalies and a terminally developed, fatal embryonal rhabdomyosarcoma were present in the patient. The decreased activity of the ASM was measured in the patient s skin fibroblasts. This result, with hepatomegaly, mental retardation, feeding problems, a failure to thrive and muscle-hypotony, partially resembled the ASM-deficient forms of Niemann-Pick disease (NPD). Morphological analysis of the bone-marrow cells gave normal results. There was no chromosomal alteration found by conventional karyotyping of the patient s lymphocytes.BWS-associated genes as well as the human ASM gene (SMPD1) are all located at 11p15. DNA-studies by region specific markers as well as mutational analysis for the most common NPD-mutations are planned in the future. This is the first report on the simultaneous occurrence of BWS and ASM-deficiency.

Beckwith-Wiedemann Syndrome↗
PubMed1999

Screening for mutations of 21-hydroxylase gene in Hungarian patients with congenital adrenal hyperplasia.

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders, causing impaired secretion of cortisol and aldosterone from the adrenal cortex, with subsequent overproduction of adrenal androgens. The most common enzyme defect causing CAH is steroid 21-hydroxylase deficiency. To determine the mutational spectrum in the Hungarian CAH population, the CYP21 active gene was analyzed using PCR. A total of 297 Hungarian patients with 21-hydroxylase deficiency are registered in the 2nd Department of Pediatrics, Budapest, Hungary, and their clinical status was evaluated. Blood samples for CYP21 genotype determination could be obtained from 167 patients (representing 306 unrelated chromosomes and 56.2% of the total group of patients). Eight of the most common mutations were screened [In2 (intron 2 splice mutation), I172N, Del (Del: apparents large gene conversion), Q318X, R356W, 1761Tins, ClusterE6, V281L] using allele-specific amplification. The most frequent mutation in the Hungarian CAH population was found to be In2. Our results have shown a good genotype/phenotype correlation in case of most mutations; the In2 mutation is associated mostly with the severe form of the disease, whereas I172N was expressed in a wide spectrum of phenotypes. 1999)

Adrenal Hyperplasia, Congenital↗
PubMed1998

Transthyretin mutation (serine 84) associated with familial amyloid polyneuropathy in a Hungarian family.

A Hungarian family with familial amyloid polyneuropathy (FAP) was studied. The disease presented in two individuals with carpal tunnel syndrome in the fourth and fifth decades of life. The proband subsequently developed vitreous opacities requiring vitrectomy and now has evidence of cardiomyopathy. Single strand conformation polymorphism analysis and direct DNA sequencing revealed a variant AGC (serine) codon at amino acid position 84 of the amyloid precursor protein, transthyretin (TTR). The same single amino acid substitution in TTR was detected in an Indiana kindred with Swiss/German origin. Six individuals of the 11 tested being at risk for FAP proved to have the mutation in the present Hungarian kindred. This is the first description of this TTR gene mutation in Europe. Despite TTR gene haplotype analysis which suggests that the Hungarian and Indiana kindreds may have a common origin, no genealogical link has been identified between the families living in Indiana and Hungary.

Amyloid↗
PubMed1998

A new route, jet injection for anesthetic induction in children. IV. Midazolam plasma levels.

The jet injector route for midazolam was used in 40 children 1 - 6 years of age undergoing various short duration surgical procedures. A randomly selected dose of 100, 150, and 200 microg/kg was given by a jet injector and compared to 80 microg/kg by conventional i.m. injection with syringe and needle to induce sedation/anesthesia. Because of clinical limitations, plasma midazolam levels were measured for only up to 32 min post-injection. Peak levels were 70.4, 105.8, 157.3, and 135.5 ng/ml in the corresponding groups. Plasma levels reached their peak faster after 200 microg/kg jet injection than after 80microg/kg i.m. midazolam. Furthermore, midazolam plasma levels were sustained longer after 200 microg/kg by jet injection. Larger doses of midazolam are required by jet injection than by i.m. injection. Individual subjects showed considerable variability in plasma levels of midazolam by both methods of administration, although jet injection was more convenient and less traumatic.

Adjuvants, Anesthesia↗
PubMed1997

[Genetic diagnosis of Williams syndrome].

Williams syndrome is a complex developmental disorder. The major cardiovascular component of Williams syndrome is supravalvular aortic stenosis, a progressive disease that may need surgical repair. Williams syndrome is associated with heterozygous microdeletion in the chromosomal region 7q11.23 encompassing the elastin gene. We have identified a new, highly informative tetranucleotide repeat polymorphism within the human elastin gene. This marker together with other, previously described elastin gene markers was used to show deletion of the elastin gene in nine sporadic Williams syndrome patients from Hungary. Application of polymorphisms within and flanking the elastin gene on chromosome 7 provides a fast, polymerase chain reaction based method for mutational analysis of Williams syndrome patients.

Aortic Valve Stenosis↗
PubMed1997

[Chronic granulomatous disease (CGD): dysfunction of the neutrophil granulocyte NADPH-oxidase enzyme system].

Dysfunction of NADPH oxidase results in chronic granulomatous disease (CGD), a syndrome characterized by severe bacterial and fungal infections. Phagocytes of the patients are unable to kill ingested microorganisms which leads to the formation of granulomas and abscesses. Predominant pathogens are the catalase-positive bacteriae (Staphylococcus aureus) and some fungi (Aspergillus species). Infections of these patients should be treated by antimicrobial agents, which penetrate cells and kill pathogens inside. The aim of this study was to give a short description of the structure and function of the NADPH oxidase enzyme and to summarize the results obtained during the diagnostic of 10 patients with chronic granulomatous disease. Characterization of the disease was confirmed by mutation analyses.

Common Variable Immunodeficiency↗
PubMed1997

[Clinical application of analysis of microsatellite markers in the prenatal diagnosis of cystic fibrosis].

Cystic Fibrosis (CF) is an autosomal recessive hereditary disease, caused by the defect of a membrane transport protein. The defect is due to the mutation of the gene coding this protein. To date, these mutations have been analysed by direct mutational analyses in prenatal diagnosis. During gene sequencing, intragenic polymorphic markers (microsatellites) were identified, enabling the indirect analysis of the mutant allele. The markers characterize the given allele, so that the inheritance according to the Mendelian rules could be followed. We introduced a DNA-diagnostic method based on the amplification of three intragenic microsatellites. This new and efficient prenatal diagnostic tool would provide more reliable test results for previously screened CF families, in which direct mutation analysis was not informative.

Cystic Fibrosis↗
PubMed1997

A new route, jet injection for anesthetic induction in children--III. Ketamine pharmacokinetic studies.

The jet injector route for ketamine was used on 30 children 1-6 years of age undergoing various surgical procedures. A randomly selected dose of 2.5, 3.5, or 6.0 mg/kg of ketamine was given to induce anesthesia. Peak plasma ketamine levels did not follow a simple arithmetic increment related to dose. Dosage based on mg/m2 body surface area or mg/kg body weight provided similar blood levels of ketamine. The beta-phase t1/2 of ketamine in these children was shorter than that found in adults. Considerable individual variability was observed in both the plasma levels to a given dose of jet-injected ketamine and in the beta-phase t1/2. The ketamine beta-t1/2s were not dose related.

Aging↗