H. Pergantou - Academia.edu (original) (raw)

Papers by H. Pergantou

Research paper thumbnail of Two de novo factor VIII gene mutations in the family of an isolated severe haemophilia A patient

Research paper thumbnail of Comparative study of validity of clinical, X-ray and magnetic resonance imaging scores in evaluation and management of haemophilic arthropathy in children

Haemophilia, 2006

To evaluate joints alterations, we performed clinical examination, X-rays and magnetic resonance ... more To evaluate joints alterations, we performed clinical examination, X-rays and magnetic resonance imaging (MRI) (Denver score) in 165 joints of 40 children with severe (n, 32) or moderate (n, 8) haemophilia A or B. All investigated joints had a history of more than three bleeds. At evaluation, 25 of 40 haemophilic patients were on prophylaxis for the last 1-8 years (mean: 3.5 years). MRI revealed chronic synovitis in 55.4% and 50% of joints, which were diagnosed, as normal by the clinical scale and plain radiography respectively. Moreover, MRI unmasked more profound alterations than those observed by plain radiography in 70% of cases. Statistical analysis showed that the clinical and Pettersson scores in contrast to the Denver score provide an underestimation of arthritic changes.

Research paper thumbnail of Immune tolerance induction with high von Willebrand factor/factor VIII content ratio concentrate in children with haemophilia A and high-responding inhibitor

Research paper thumbnail of Osteoid osteoma in a child with severe von Willebrand disease

Haemophilia, 2009

VWD suggest that these patients are at a very high risk of bleeding complications, intraoperative... more VWD suggest that these patients are at a very high risk of bleeding complications, intraoperative and postoperative bleeding, physical and emotional negative impact with hysterectomy [5]. So, long-term prophylaxis with Haemate-P thought to be ideal treatment for our VWD patient, and during the 6 months, the clinical response was rated as excellent/good. Hospitalizations, outpatient visits, requirements for other drugs were reduced, and the patientÕs work activities and quality of life were also significantly improved thereafter.

Research paper thumbnail of Impact of HLA alleles and cytokine polymorphisms on inhibitors development in children with severe haemophilia A

Haemophilia, 2013

Human Leucocyte Antigen (HLA) alleles, cytokine polymorphisms and the type of factor VIII (FVIII)... more Human Leucocyte Antigen (HLA) alleles, cytokine polymorphisms and the type of factor VIII (FVIII) gene mutation are among predisposing factors for inhibitors (inh) development in children with severe haemophilia A (HA). The aim was to investigate the correlations among (i) FVIII gene intron-22 inversion, (ii) HLA alleles and haplotypes and (iii) certain cytokine polymorphisms, with the risk for FVIII inhibitors development in 52 Greek severe HA children, exclusively treated with recombinant concentrates. We performed Long-Range PCR for detection of intron-22 inversion and PCR-SSP, PCR-SSO for genotyping of HLA-A, B, C, DRB1, DQB1 alleles and also for cytokine polymorphisms of TNF-α, TGF-β1, IL-10, IL-6 and IFN-γ. Chi-squared test and Fischer's exact test were used for statistical analysis. A total of 28 children had developed inhibitors (Group I), 71.4% high responding, while 24 had not (Group II). No statistically increased intron-22 inversion prevalence was found in Group I compared with Group II (P = 0.5). Comparison of HLA allele frequencies between the two groups showed statistically significant differences in the following genotypes (i) promoting inhibitors development: DRB1*01(P = 0.014), DRB1*01:01(P = 0.011) and DQB1*05:01 (P = 0.005) and (ii) possibly protecting from inhibitors development: DRB1*11 (P = 0.011), DRB1*11:01 (P = 0.031), DQB1*03 (P = 0.004) and DQB1*03:01 (P = 0.014). Analysis of cytokines revealed a higher incidence of inhibitor detection only in homozygotes of the haplotypes ACC and ATA for IL-10 polymorphisms (P = 0.05). There is evidence that HLA alleles and cytokine polymorphisms play an important role in FVIII inh development. On the contrary, no statistically significant results were obtained for intron-22 inversion and its impact on FVIII inhibitors formation.

Research paper thumbnail of Mutations and Polymorphisms in Genes Affecting Hemostasis Proteins and Homocysteine Metabolism in Children with Arterial Ischemic Stroke

Cerebrovascular Diseases, 2006

The pathogenesis of thrombosis in childhood seems to be multifactorial implicating genetic and en... more The pathogenesis of thrombosis in childhood seems to be multifactorial implicating genetic and environmental factors. To compare the distributions of mutations/polymorphisms in genes affecting hemostasis (factor V Leiden - FVL, FV H1298R-FVR2, FII 20210A, b-Fib 455G>A, FXIII V34L, PAI-1 4G, HPA-1b) or homocysteine metabolism (MTHFR C677T, MTHFR A1298C) among 90 children with arterial ischemic stroke (AIS) and 103 controls, and to associate the carriage of these mutations/polymorphisms with their corresponding proteins in children with AIS. AIS was more frequent in boys (p < 0.01). No studied mutation/polymorphism was found to be a risk factor for AIS, except for FVL [odds ratio 4.2 (95% CI 1.5-12.1)], the presence of which was even higher in 31 children with congenital AIS [odds ratio 6.82 (95% CI 2.0-22.8)]. FVL carriers had an odds ratio of 5.76 (95% CI 1.6-6.4) when FVR2 was absent. In thrombosed children, activated protein C resistance, prothrombin and fibrinogen levels were higher in the presence of FVL, FII20210A or b-Fib 455G-->A, respectively. Double heterozygotes in both MTHFR C677T and A1298T or homozygotes in one had significantly elevated homocysteine levels. Except for FVL, no definite conclusion could be reached regarding the involvement of the studied mutations/polymorphisms in childhood AIS.

Research paper thumbnail of Assessment of the progression of haemophilic arthropathy in children

Haemophilia, 2010

Arthropathy is considered as an irreversible and progressive complication in patients with haemop... more Arthropathy is considered as an irreversible and progressive complication in patients with haemophilia, even in children on prophylaxis. To estimate the progression of haemophilic arthropathy, 85 joints of 24 boys with severe (n = 18) and moderate (n = 6) haemophilia (A: 22, B: 2) were investigated with clinical examination, X-rays and magnetic resonance imaging (MRI) at two time periods (time 0 and 1). Patients' age at time 0 was 10.5 ± 3.6 years and time elapsed to time 1 was 3.8 ± 1.4 years. At time 0: all investigated joints had more than three bleeds. Sixteen boys were on secondary prophylaxis for 5.4 ± 2.8 years. Clinical score (a modification of World Federation of Haemophilia's scale): 2.0 ± 3.6, X-ray score (Pettersson): 2.1 ± 2.8, MRI score (Denver): 4.5 ± 3.8. After the first evaluation, prophylaxis was intensified in 11 children and initiated in four. At time 1: clinical score: 1.5 ± 3.1, X-ray: 1.7 ± 2.7, MRI score: 5.1 ± 4.1. On average, the clinical and X-ray scores showed a significant improvement (26% and 40% of the joints respectively, P < 0.01) and the number of haemarthroses evidenced a threefold reduction from time 0 to 1 (P < 0.01), findings that could be associated with the modification of prophylaxis after time 0. MRI findings showed deterioration in 34% of the joints. Conversely, 14 joints (16.5%) with mild or moderate synovitis without cartilage degradation at time 0 showed an improvement at time 1. The information carried by the three scales could be divided into information shared by the three scores and information specific to each score, thus giving a more complete picture of joint damage caused by bleedings.

Research paper thumbnail of Two de novo factor VIII gene mutations in the family of an isolated severe haemophilia A patient

Research paper thumbnail of Comparative study of validity of clinical, X-ray and magnetic resonance imaging scores in evaluation and management of haemophilic arthropathy in children

Haemophilia, 2006

To evaluate joints alterations, we performed clinical examination, X-rays and magnetic resonance ... more To evaluate joints alterations, we performed clinical examination, X-rays and magnetic resonance imaging (MRI) (Denver score) in 165 joints of 40 children with severe (n, 32) or moderate (n, 8) haemophilia A or B. All investigated joints had a history of more than three bleeds. At evaluation, 25 of 40 haemophilic patients were on prophylaxis for the last 1-8 years (mean: 3.5 years). MRI revealed chronic synovitis in 55.4% and 50% of joints, which were diagnosed, as normal by the clinical scale and plain radiography respectively. Moreover, MRI unmasked more profound alterations than those observed by plain radiography in 70% of cases. Statistical analysis showed that the clinical and Pettersson scores in contrast to the Denver score provide an underestimation of arthritic changes.

Research paper thumbnail of Immune tolerance induction with high von Willebrand factor/factor VIII content ratio concentrate in children with haemophilia A and high-responding inhibitor

Research paper thumbnail of Osteoid osteoma in a child with severe von Willebrand disease

Haemophilia, 2009

VWD suggest that these patients are at a very high risk of bleeding complications, intraoperative... more VWD suggest that these patients are at a very high risk of bleeding complications, intraoperative and postoperative bleeding, physical and emotional negative impact with hysterectomy [5]. So, long-term prophylaxis with Haemate-P thought to be ideal treatment for our VWD patient, and during the 6 months, the clinical response was rated as excellent/good. Hospitalizations, outpatient visits, requirements for other drugs were reduced, and the patientÕs work activities and quality of life were also significantly improved thereafter.

Research paper thumbnail of Impact of HLA alleles and cytokine polymorphisms on inhibitors development in children with severe haemophilia A

Haemophilia, 2013

Human Leucocyte Antigen (HLA) alleles, cytokine polymorphisms and the type of factor VIII (FVIII)... more Human Leucocyte Antigen (HLA) alleles, cytokine polymorphisms and the type of factor VIII (FVIII) gene mutation are among predisposing factors for inhibitors (inh) development in children with severe haemophilia A (HA). The aim was to investigate the correlations among (i) FVIII gene intron-22 inversion, (ii) HLA alleles and haplotypes and (iii) certain cytokine polymorphisms, with the risk for FVIII inhibitors development in 52 Greek severe HA children, exclusively treated with recombinant concentrates. We performed Long-Range PCR for detection of intron-22 inversion and PCR-SSP, PCR-SSO for genotyping of HLA-A, B, C, DRB1, DQB1 alleles and also for cytokine polymorphisms of TNF-α, TGF-β1, IL-10, IL-6 and IFN-γ. Chi-squared test and Fischer&#39;s exact test were used for statistical analysis. A total of 28 children had developed inhibitors (Group I), 71.4% high responding, while 24 had not (Group II). No statistically increased intron-22 inversion prevalence was found in Group I compared with Group II (P = 0.5). Comparison of HLA allele frequencies between the two groups showed statistically significant differences in the following genotypes (i) promoting inhibitors development: DRB1*01(P = 0.014), DRB1*01:01(P = 0.011) and DQB1*05:01 (P = 0.005) and (ii) possibly protecting from inhibitors development: DRB1*11 (P = 0.011), DRB1*11:01 (P = 0.031), DQB1*03 (P = 0.004) and DQB1*03:01 (P = 0.014). Analysis of cytokines revealed a higher incidence of inhibitor detection only in homozygotes of the haplotypes ACC and ATA for IL-10 polymorphisms (P = 0.05). There is evidence that HLA alleles and cytokine polymorphisms play an important role in FVIII inh development. On the contrary, no statistically significant results were obtained for intron-22 inversion and its impact on FVIII inhibitors formation.

Research paper thumbnail of Mutations and Polymorphisms in Genes Affecting Hemostasis Proteins and Homocysteine Metabolism in Children with Arterial Ischemic Stroke

Cerebrovascular Diseases, 2006

The pathogenesis of thrombosis in childhood seems to be multifactorial implicating genetic and en... more The pathogenesis of thrombosis in childhood seems to be multifactorial implicating genetic and environmental factors. To compare the distributions of mutations/polymorphisms in genes affecting hemostasis (factor V Leiden - FVL, FV H1298R-FVR2, FII 20210A, b-Fib 455G&gt;A, FXIII V34L, PAI-1 4G, HPA-1b) or homocysteine metabolism (MTHFR C677T, MTHFR A1298C) among 90 children with arterial ischemic stroke (AIS) and 103 controls, and to associate the carriage of these mutations/polymorphisms with their corresponding proteins in children with AIS. AIS was more frequent in boys (p &lt; 0.01). No studied mutation/polymorphism was found to be a risk factor for AIS, except for FVL [odds ratio 4.2 (95% CI 1.5-12.1)], the presence of which was even higher in 31 children with congenital AIS [odds ratio 6.82 (95% CI 2.0-22.8)]. FVL carriers had an odds ratio of 5.76 (95% CI 1.6-6.4) when FVR2 was absent. In thrombosed children, activated protein C resistance, prothrombin and fibrinogen levels were higher in the presence of FVL, FII20210A or b-Fib 455G--&gt;A, respectively. Double heterozygotes in both MTHFR C677T and A1298T or homozygotes in one had significantly elevated homocysteine levels. Except for FVL, no definite conclusion could be reached regarding the involvement of the studied mutations/polymorphisms in childhood AIS.

Research paper thumbnail of Assessment of the progression of haemophilic arthropathy in children

Haemophilia, 2010

Arthropathy is considered as an irreversible and progressive complication in patients with haemop... more Arthropathy is considered as an irreversible and progressive complication in patients with haemophilia, even in children on prophylaxis. To estimate the progression of haemophilic arthropathy, 85 joints of 24 boys with severe (n = 18) and moderate (n = 6) haemophilia (A: 22, B: 2) were investigated with clinical examination, X-rays and magnetic resonance imaging (MRI) at two time periods (time 0 and 1). Patients' age at time 0 was 10.5 ± 3.6 years and time elapsed to time 1 was 3.8 ± 1.4 years. At time 0: all investigated joints had more than three bleeds. Sixteen boys were on secondary prophylaxis for 5.4 ± 2.8 years. Clinical score (a modification of World Federation of Haemophilia's scale): 2.0 ± 3.6, X-ray score (Pettersson): 2.1 ± 2.8, MRI score (Denver): 4.5 ± 3.8. After the first evaluation, prophylaxis was intensified in 11 children and initiated in four. At time 1: clinical score: 1.5 ± 3.1, X-ray: 1.7 ± 2.7, MRI score: 5.1 ± 4.1. On average, the clinical and X-ray scores showed a significant improvement (26% and 40% of the joints respectively, P < 0.01) and the number of haemarthroses evidenced a threefold reduction from time 0 to 1 (P < 0.01), findings that could be associated with the modification of prophylaxis after time 0. MRI findings showed deterioration in 34% of the joints. Conversely, 14 joints (16.5%) with mild or moderate synovitis without cartilage degradation at time 0 showed an improvement at time 1. The information carried by the three scales could be divided into information shared by the three scores and information specific to each score, thus giving a more complete picture of joint damage caused by bleedings.