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Biomedical subjects

A Gürgey

Publications and source records attributed to A Gürgey.

At least 19 recordsLinked to original sources
PubMed2003

Benefit of high-dose methylprednisolone in comparison with conventional-dose prednisolone during remission induction therapy in childhood acute lymphoblastic leukemia for long-term follow-up.

Eight-year event-free survival (EFS) was evaluated in 205 patients with acute lymphoblastic leukemia (ALL), to consider the efficacy of high-dose methylprednisolone (HDMP) given during remission induction chemotherapy between 1 and 29 days. The St Jude Total XI Study protocol was used after some minor modifications in this trial. Patients were randomized into two groups. Group A (n = 108) received conventional dose (60 mg/m(2)/day orally) prednisolone and group B (n = 97) received HDMP (Prednol-L, 900-600 mg/m(2) orally) during remission induction chemotherapy. Complete remission was obtained in 95% of the 205 patients who were followed-up for 11 years; median follow-up was 72 months (range 60-129) and 8-year EFS rate was 60% overall (53% in group A, 66% in group B). The EFS rate of group B was significantly higher than of group A (P = 0.05). The 8-year EFS rate of groups A and B in the high-risk groups was 39% vs 63% (P = 0.002). When we compared 8-year EFS rate in groups A and B in the high-risk subgroup for both ages together </=2 or >/=10 years, it was 44% vs 74%, respectively. Among patients in the high-risk subgroup with a WBC count >/=50 x 10(9)/l, the 8-year EFS was 38% in group A vs58% in group B. During the 11-year follow-up period, a total of 64 relapses occurred in 205 patients. In group A relapses were higher (39%) than in group B (23%) (P = 0.05). These results suggest that HDMP during remission-induction chemotherapy improves the EFS rate significantly for high-risk patients in terms of the chances of cure.

Adolescent↗
PubMed2002

Importance of RDW value in differential diagnosis of hypochrome anemias.

Red cell distribution width (RDW) was studied in adults carrying delta-beta thalassemia traits (deltabeta-TT) who were 20-40 years of age (n = 29), beta thalassemia traits (beta-TT) with an age range of 18-60 years (n = 49), iron deficiency anemia (IDA) in individuals aged 1-18 years (n = 27), and in controls with an age range of 20-40 years (n = 20). Although red blood cell count, MCV, and MCH values showed no statistically significant differences between deltabeta-TT and beta-TT, the mean RDW value was significantly higher in deltabeta-TT (20.14 +/- 1.21) compared to beta-TT (14.88 +/- 1.77) (P < 0.001). No difference was observed between the means of RDW in deltabeta-TT and IDA (18.00 +/- 1.94) (P > 0.05). A significant rise in RDW in IDA 5-7 days after initiation of iron therapy (P = 0.00) which was continued to rise up to the 4(th) week of therapy was suggested as an important tool in differentiation of IDA from deltabeta-TT. These observations could be kept in mind in the differential diagnosis of deltabeta-TT from beta-TT and IDA by determining the red blood cell count, red cell indices, and RDW only.

Adolescent↗
PubMed2001

Spectrum of perforin gene mutations in familial hemophagocytic lymphohistiocytosis.

Familial hemophagocytic lymphohistiocytosis (FHL) is an autosomal recessive disease of early childhood characterized by nonmalignant accumulation and multivisceral infiltration of activated T lymphocytes and histiocytes (macrophages). Cytotoxic T and natural killer (NK) cell activity is markedly reduced or absent in these patients, and mutations in a lytic granule constituent, perforin, were recently identified in a number of FHL individuals. Here, we report a comprehensive survey of 34 additional patients with FHL for mutations in the coding region of the perforin gene and the relative frequency of perforin mutations in FHL. Perforin mutations were identified in 7 of the 34 families investigated. Six children were homozygous for the mutations, and one patient was a compound heterozygote. Four novel mutations were detected: one nonsense, two missense, and one deletion of one amino acid. In four families, a previously reported mutation at codon 374, causing a premature stop codon, was identified, and, therefore, this is the most common perforin mutation identified so far in FHL patients. We found perforin mutations in 20% of all FHL patients investigated (7/34), with a somewhat higher prevalence, approximately 30% (6/20), in children whose parents originated from Turkey. No other correlation between the type of mutation and the phenotype of the patients was evident from the present study. Our combined results from mutational analysis of 34 families and linkage analysis of a subset of consanguineous families indicate that perforin mutations account for 20%-40% of the FHL cases and the FHL 1 locus on chromosome 9 for approximately 10%, whereas the major part of the FHL cases are caused by mutations in not-yet-identified genes.

Amino Acid Substitution↗
PubMed2001

Factor V Leiden mutation in Turkish patients with homozygous cystathionine beta-synthase deficiency.

Venous and arterial thromboembolism can occur in patients with homocystinuria. Resistance to activated protein C, which is caused by a single point mutation in the gene for factor V, renders an individual at risk for thrombosis. It has been suggested that coexistence of hereditary homocystinuria and factor V Leiden mutation might jointly play a role in the development of thrombosis. We analysed six patients with homocystinuria due to cystathionine beta-synthase deficiency for factor V Leiden and prothrombin G20210A mutations. Only one patient was found to have the factor V Leiden mutation in homozygous form and this patient had suffered from severe thrombosis. One patient was found to be heterozygous with no documented thrombosis. None of the patients had prothrombin G20210A mutation. We stress the necessity for screening for known thrombophilic risk factors in patients with cystathonine beta-synthase deficiency. The coexistence of the factor V Leiden mutation can cause severe thrombotic events in patients with homocystinuria.

Adolescent↗
PubMed2001

beta-Thalassaemia intermedia in a Turkish girl: homozygosity for G-->A substitution at +22 relative to the beta-globin cap site.

We provide the first description of a homozygote patient for the G-->A substitution in the 5' UTR of the beta-globin gene. The proband was a 17-year-old girl with beta-thalassaemia intermedia who had never received a blood transfusion. The physical examination revealed a well-developed women with no facial or bony abnormalities. There was mild paleness and mild splenomegaly which was 2 cm below the costal margin. The haemoglobin (Hb) was 7.6 g/dl, Hb A(2) 5.4% and Hb F 14.6% of the total Hb. The Hb A(2) of both parents was 3.5%. The Hb F level in the mother and father were 0.9, 1.2% and the mean cell volume (MCV) value was 70 and 72 fl respectively. DNA analysis of the beta-gene region of the propositus revealed homozygosity for a G-->A substitution at nucleotide +22 relative to the beta-gene cap site, within a functional downstream region that was referred to as the DCE (downstream core element). In addition to the data obtained previously from in vitro transcription assays, clinical findings and in vivo expression studies gave some valuable clues about the effect of +22 G-->A mutation on the expression of beta-gene. Phenotypic expression of this homozygous patient is highly suggestive that G-->A substitution at nt +22 confers a relatively mild (silent) beta(+)-thalassaemia phenotype.

5' Untranslated Regions↗
PubMed2001

Molecular pathology of haemophilia A in Turkish patients: identification of 36 independent mutations.

Haemophilia A is an X-linked recessive bleeding disorder caused by heterogeneous mutations in the factor VIII gene. In an attempt to reveal the molecular pathology of Turkish haemophilia A patients, the coding sequence of the gene, excluding a large portion of exon 14, was amplified from genomic DNA and subjected to denaturing gradient gel electrophoresis prior to DNA sequencing. Fifty-nine haemophilia A patients were included in the study with severe, moderate and mild phenotypes observed in 24, 15 and 16 patients, respectively. Factor VIII activity and clinical phenotypes were not available for four patients. A total of 36 independent mutations were found, with a mutation detection efficacy of 61%. The mutations that were reported for the first time include 20 point mutations, one 8-bp insertion (TCAAGATA) in exon 4 and one large deletion greater than 2.8 kb involving exon 14. The novel point mutations were composed of three nonsense (Ser681Ter, Cys2021Ter and Gln2113Ter), one splicing error (IVS-1G-->A), 15 missense mutations (Lys48Asn; Leu-98Phe; Thr118Ala; Cys248Tyr; Glu456Lys; Asp560Ala; Tyr664Cys; Phe679Leu; Gly691Trp; Asp1769His; Val1857Leu; Gly2026Gln; Arg2163Pro; Asp2288Ala; and Arg2304Leu) and a T deletion in exon 25 that caused a frameshift followed by a stop codon. All missense mutations except Val1857Leu, which maintained a conserved nonpolar R group, occurred at amino acids conserved among four species and were most probably pathogenic. In addition, two sequence changes (IVS3-9C-->T) and (Leu2230Leu) were also detected in patients carrying Val1857Leu and Phe679Leu missense mutations, respectively. Identification of mutation origins in eight sporadic cases revealed an equal sex ratio of mutations.

DNA Mutational Analysis↗
PubMed2001

Low serum carnitine concentrations in healthy children with iron deficiency anemia.

Carnitine is not only obtained from animal-derived foods but also synthesized in the body. It plays an important role in the energy metabolism of many tissues, including heart and skeletal muscles. Iron is known to be essential for the biosynthesis of carnitine. Although many conditions are well known to cause secondary carnitine deficiency, iron deficiency, which is a very common condition in children, is not well studied as a cause of secondary carnitine deficiency in humans. This study demonstrates the coexistence of iron deficiency and low carnitine levels in otherwise healthy children. The mean carnitine concentration of 18 otherwise healthy children with iron deficiency anemia was significantly lower compared to the mean carnitine concentration of healthy children without iron deficiency anemia. Based on the evidence about the effect of low iron on carnitine stores in experimental animals, we proposed that low serum carnitine levels in these children may be secondary to iron deficiency. However, further studies need to be done to further clarify this relationship.

Anemia, Iron-Deficiency↗
PubMed2001

Lethal hydrops fetalis due to congenital dyserythropoietic anemia in a newborn: association of a new skeletal abnormality.

Congenital dyserythropoietic anemias (CDAs) are a group of hereditary refractory anemias characterized by ineffective erythropoiesis, typical morphological abnormalities of erythroblasts, a low or no reticulocyte response, hyperbilirubinemia, and splenomegaly. A massive hydropic newborn born with a very severe anemia (Hb 4.8 g/dL), diffuse edema, hepatosplenomegaly, ascites, pulmonary edema and respiratory distress, and shortness and hallux varus deformity of the great toe of the right foot was diagnosed to have congenital dyserythropoietic anemia on the basis of the hematological (macrocytosis, anisopoikilocytosis, fragmented red cells and erythroblastosis in the peripheral blood, and erythroid hyperplasia with erythroblastosis and erythroblasts with double nuclei and thin chromatin bridges connecting these nuclei in the bone marrow) and serological (negative acidified serum lysis test and no agglutination with anti-i antibodies) findings. In this article the seventh case of neonatal congenital dyserythropoietic anemia presenting with a very severe (lethal) form of hydrops fetalis and a new (hallux varus) deformity of the great toe of the right foot is presented. Congenital dyserythropoietic anemia should be considered in the differential diagnosis of hydrops fetalis presenting with a very severe anemia and a skeletal abnormality of the great toe.

Anemia, Dyserythropoietic, Congenital↗
PubMed2001

Homozygosity for Hb E-Saskatoon [beta22(B4)Glu-->Lys] in a Turkish patient.

A 30-year-old female who is homozygous for a Hb E-like abnormal hemoglobin and her immediate relatives were studied. Clinical examination of the proband revealed no abnormality. Routine hematological analysis showed that her hemoglobin level was 12 g/dL, MCV 82 fL, MCH 28 pg, RDW 15%. DNA sequence analysis indicated the presence of a G-->A substitution at codon 22 corresponding to an abnormal hemoglobin, namely Hb E-Saskatoon [beta22(B4)Glu-->Lys (GAA-->AAA)]. Absence of any abnormalities in clinical and routine hematological investigations of the homozygous patient indicated that the phenotypical expression of the Hb E-Saskatoon is very mild. Using a reverse transcription-polymerase chain reaction technique, the alpha/beta and betaX/betaA-mRNA (X = Hb E-Saskatoon) ratios were determined. Normal alpha/beta and betaX/betaA-mRNA ratios were found in the homozygous patient and in all heterozygotes, indicating that the respective mutation did not alter the stability of the mRNA. FokI restriction enzyme analysis of the polymerase chain reaction products obtained from the genomic DNA and/or beta-globin mRNA made it possible for rapid diagnosis of Hb E-Saskatoon, and for its differentiation from Hb E [beta26(B8)Glu-->Lys (GAG-->AAG)]. Analysis of the restriction fragment length polymorphism (RFLP) in the beta-globin gene complex of the index patient and of another unrelated family with a compound heterozygosity for Hb E-Saskatoon and beta-thalassemia revealed that the Hb E-Saskatoon mutation shared a common allele.

Adult↗
PubMed2001

Evaluation of coagulation in pediatric bone marrow transplantation patients.

A hypercoagulable state is frequently described in adult patients undergoing bone marrow transplantation (BMT). In this study, the coagulation profile of 29 children was prospectively investigated in the pre- and post-transplant period. A significant rise in the activated partial thromboplastin time (aPTT) values was detected on days 7 and 14 after transplantation. Moreover, an increase in the d-dimer level was also notable, regardless of the clinical condition of the patients. The other coagulation parameters investigated (i.e. protein S, protein C, anti-thrombin III, factor VIII, von Willebrand factor, and prothrombin time) remained essentially unchanged. However, hyper-fibrinogenemia was observed in all patients with chronic myeloid leukemia (CML) (n=5) before and after transplantation. In summary, in the present study pediatric bone marrow transplantation patients did not show a hyper-coagulable state after marrow infusion. However, a significant rise in PTT and d-dimer values were noted.

Adolescent↗
PubMed2000

CD34/CD117 co-expression in childhood acute leukemia.

CD117 protein is expressed by the primitive CD34 positive haemopoietic stem cells and also demonstrated on the blasts of 30-100% of AML cases, but rarely on lymphoblasts. Therefore several investigators have used CD117 expression to exclude lymphoblastic origin of blasts. However, conflicting results exist in the literature. We investigated CD34 and CD117 status at initial presentation of 232 children with acute leukemia. CD34 was commonly expressed in all types of acute leukemias, whereas CD117 molecule seemed to be a more specific marker for leukemia of myeloid origin being demonstrated on > 5% of blasts in 60 out of 73 cases of AML patients, but rarely detected in ALL (9/140 patients). Moreover, co-expression of CD34/CD117 was extremely rare on lymphoblasts with only 3/140 ALL patients demonstrating > 5% co-expression of CD34 and CD117, and therefore we suggest that it should be used in the exclusion of ALL.

Adolescent↗
PubMed2000

The factor V Leiden mutation: a possible contributor to the hepatic artery thrombosis encountered after liver transplantation in a child.

A 10-year-old girl has experienced 3 recurrences of hepatic artery thrombosis (HAT) after a liver transplantation. She responded to intraarterial administrations of urokinase after the first 2 attacks. However, the restoration of the arterial flow was not possible after the third attack. The child and her father were both heterozygous for factor V Leiden mutation. In addition to the technical factors, the factor V Leiden mutation should be considered as a factor that plays a role in HAT.

Child↗
PubMed2000

The role of natural anticoagulant deficiencies and factor V Leiden in the development of idiopathic portal vein thrombosis.

One of the causes of portal hypertension is portal vein thrombosis (PVT). The aim of this study was to determine whether natural anticoagulant deficiencies, activated protein C resistance (APCR), and factor V Leiden play a role in the development of PVT, leading to cavernous transformation of the portal vein (CTPV). Twenty-three patients with idiopathic CTPV (group 1) seen at Hacettepe University Hospital during the past 12 years were identified and prospectively studied. These 23 patients underwent a detailed hematological evaluation including measurement of protein S, protein C, antithrombin III, activated protein C resistance (APCR), and factor V Leiden gene mutation. Additionally, all patients were tested for anticardiolipin antibodies (ACA), IgG, IgM, and lupus anticoagulant (LA). Natural anticoagulants and APCR were measured using available commercial kits, and factor V Leiden mutation (R506Q) was detected by Mnl I digestion of an amplified factor V DNA fragment. All parameters were measured at least 6 months after the diagnosis of CTPV was established. No patient was on anticoagulant or antiaggregant treatment while tested. The findings in these 23 patients were compared with those in 20 healthy control subjects (group 2), in whom all tests mentioned above were also performed. In 23 patients (group 1), who had no recognizable factor for portal vein thrombosis, considerably natural anticoagulant deficiencies and factor V Leiden mutation positivity were found when we compare them to those healthy controls (group 2). The protein C levels of six patients (26%), the protein S levels of 10 patients (43.5%), and the antithrombin III levels of five patients (26%) were lower than in control subjects. Two patients were found to have combined protein S and antithrombin III deficiency, and one had combined protein S and C deficiency and APCR. APCR was detected in seven of the 23 patients, and six of these seven patients were found to have R506Q factor V Leiden mutations. In group 1, ACA IgG levels were higher in four patients (17%) and ACA IgM level was higher in one (4%) compared with the control group. LA was positive in only one patient in group 1. Natural anticoagulant deficiencies and factor V Leiden mutation are strongly associated with PVT. The natural anticoagulant deficiencies and APCR (almost totally caused by R506Q mutation) produce a favorable medium for thrombus generation. PVT seems to be related to the natural anticoagulant deficiencies and factor V Leiden R506Q mutation. A combination of these defects increases the incidence of PVT and these factors should be evaluated carefully in patients with idiopathic CTPV.

Activated Protein C Resistance↗
PubMed2000

Molecular analysis of turkish beta-thalassemia heterozygotes with normal Hb A2 levels.

Four parents of three unrelated families who are obligatory beta-thalassemia heterozygotes and two parents with Hb Knossos are presented. In these subjects, although the red blood cell counts and red cell indices were compatible with beta-thalassemia trait, the Hb A2 values were between 1.9-2.9% of the total hemoglobin. Examination of the delta-globin gene by Southern blot, restriction endonuclease analysis, and by direct sequencing of amplified DNA revealed the presence of the (delta0) -7.2 kb Corfu type deletion, the (delta+) codon 27 (G-->T) and (delta0) IVS-I-2 (T-->C) mutations in trans or in cis with a severe beta-thalassemia allele, and the (delta0) codon 59 (-A) deletion in cis with the betaKnossos allele.

Adult↗
PubMed2000

Beta-thalassemia intermedia associated with homozygosity for the -87 (C-->T) mutation in a Turkish family.

We report on two siblings with beta+-thalassemia intermedia. Molecular studies of the beta-globin gene indicated that the patients are homozygous for the -87 (C-->T) mutation. This genotype has not been previously described. Homozygosity for the -87 (C-->T) mutation produces a mild form of beta+-thalassemia associated with moderate Hb F elevation (26-38%) and highly elevated Hb A2 (10-8.6%) levels, respectively. Hematological parameters of homozygous -87 (C-->G) and -87 (C-->A) mutations, and compound heterozygous patients with either C-->T, C-->G, or C-->A at -87 and one of the severe beta+- or beta0-thalassemia mutations, are given for comparison.

Adult↗