Fanni Athanassiadou

Adenosine Deaminase Activity and its Isoenzyme Pattern in Patients with Juvenile Rheumatoid Arthritis and Systemic Lupus Erythematosus

Abstract: Adenosine deaminase (ADA) is involved in purine metabolism and plays a significant role in the mechanisms of the immune system. The aim of this study was to investigate the activity of total ADA (tADA) and its isoenzymes ADA1 and ADA2 in serum and peripheral blood lymphocytes (PBLs) of children with juvenile rheumatoid arthritis (JRA) and systemic lupus erythematosus (SLE) in different phases of the diseases. The study comprised 34 patients with rheumatic disease, 24 with JRA and 10 with SLE, and 64 healthy controls. The tADA activity and its isoenzymes were measured in serum and PBLs of all patients by the method of Giusti and by the presence or absence of EHNA (erythro-9-(2-hydroxy-3-nonyl)adenine) during the active phase of the disease (before treatment), as well as during remission and relapse. Our data show that increased tADA activity in the serum and PBLs of patients with JRA and SLE is correlated mainly to increased levels of ADA2 activity in serum and ADA1 activity in PBLs. It also closely correlates with clinical disease activity and relapse. The cause of this increased tADA/ADA2 activity in serum and tADA/ADA1 activity in PBLs in JRA and SLE remains to be elucidated. Nevertheless, it may be noted that the measurement of tADA activity, together with ADA2 activity in serum and tADA with ADA1 activity in PBLs, could offer a biochemical approach to the assessment of the pathophysiology of JRA and SLE. Also, tADA and its isoenzymes could be used as alternative parameters representing disease activity.

Serum adenosine deaminase and procalcitonin concentrations in neutropenic febrile children with acute lymphoblastic leukaemia

Abstract Neutropenia as a state of immunosuppression is probably the major problem in patients suffering from acute lymphoblastic leukaemia undergoing intensive chemotherapy. Fever is frequent in neutropenic patients and often related to infection. Clinically, the presence of infection in patients with neutropenia may be difficult to establish, because there are usually few signs of infection. The aim of this work was to study sensitive markers for early diagnosis of microbial infection in neutropenic children undergoing intensive chemotherapy as a treatment for acute lymphoblastic leukaemia. The study included three groups (A, B and C) of children with acute lymphoblastic leukaemia and neutropenia. Group A consisted of 29 children with febrile neutropenia and microbial infection, aged 1–14 years (5.8±2.9), 11 boys and 18 girls; Group B of 38 children with febrile neutropenia without microbial infection, aged 2–14 years (6.8±3.1), 14 boys and 24 girls; and Group C of 53 children with neutropenia without fever and without infection, aged 1–14 years (5.9±2.1), 21 boys and 32 girls. Blood samples were collected upon admission and before the start of any antimicrobial treatment. The samples were used for blood culture, serological tests, leukocyte count and analysis of levels of C–reactive protein, procalcitonin, total adenosine deaminase (ADA) activity and its isoenzymes, ADA–1 and ADA–2. According to our results the procalcitonin levels and total ADA activity discriminated best between neutropenic febrile (Groups A and B) and neutropenic afebrile episodes (Group C). In conclusion, this study suggests procalcitonin and total ADA activity as two easily measurable and cost effective markers for the assessment of immune response in febrile neutropenic patients with acute lymphoblastic leukaemia.

Circulating soluble adhesion molecule levels in children with acute lymphoblastic leukaemia

AbstractThe aim of this study was to evaluate levels of serum soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble E-selectin (sE-selectin) as parameters of disease activity and to monitor the response to treatment in children with acute lymphoblastic leukaemia (ALL). The above soluble adhesion molecules were determined in the serum of 35 children with ALL and 30 healthy children (control group) of the same age range. The samples were obtained before treatment, 6 months after the beginning of the treatment (remission of the disease), 6 months after the end of the treatment and during relapse of the disease. The mean levels of sICAM-1, sVCAM-1 and sE-selectin at the onset of the disease were 646.6 ± 80.9 ng/ml, 1786 ± 151.8 ng/ml and 140.5 ± 17.3 ng/ml, respectively. These values were significantly higher (P < 0.001) than those of the control group, which were, 245.8 ± 25.7 ng/ml, 798.6 ± 78.9 ng/ml and 44.7 ± 18.2 ng/ml respectively. During remission, the mean levels did not differ significantly from those of the control group. After the end of the treatment the mean levels again did not show any significant differences compared to the control group. During relapse the soluble adhesion molecule mean levels (923.9 ± 110.1 ng/ml, 2945.7 ± 349.9 ng/ml and 258.2 ± 5.1 ng/ml) were significantly higher (P < 0.001) than those of the control group and also than those obtained during remission and after the end of the treatment (P < 0.001). Pearsons correlation coefficient r was computed in order to detect possible linear correlations between: (1) sICAM-1 and sVCAM-1 (r = 0.632); (2) sICAM-1 and sE-selectin (r = 0.788) and (3) sVCAM-1 and sE-selectin (r = 0.752). All three cases correspond to P < 0.001, thus indicating strong linear correlations. Conclusion The levels of soluble circulating adhesion molecule levels can be utilized for monitoring disease activity of ALL and its response to treatment, as well as for early detection of relapse. Strong linear correlations between the three soluble adhesion molecules tested suggest that each of them may be sufficient as an indicator.

Tumour necrosis factor gene polymorphisms and migraine in Greek children.

Introduction Migraine is considered to be a multifactorial, complex disease. Various genetic and environmental factors contribute to the manifestation of this disease. The aim of this study was to determine whether polymorphisms in the tumour necrosis factor (TNF) region are associated with the risk of migraine. We examined the association between 6 single nucleotide polymorphisms in the coding regions of TNF-α and TNF-β genes and migraine. Material and methods The study included two groups of children (group A and group B). Group A consisted of 103 unrelated children with typical migraine without aura 5–14 years of age. Group B (control group) consisted of 178 unrelated healthy children. The diagnosis of migraine was, in all patients, made according to the International Classification of Headache Disorders (ICHD II). Results According to our results positive family history was present in 62.2% of patients of group A. No significant differences were found in the frequencies of genotypes or alleles between patients and controls. The non-parametric analyses of variance showed no significant differences in the age at onset between genotype groups of the TNF-α and TNF-β gene polymorphisms. Comparison of genotype frequencies between boys and girls in affected patients and control individuals were not significantly different (p = 0.089, p =0.073 respectively). The distribution of TNF polymorphisms was not associated with the presence of family history of migraine in patients. Conclusions Our data indicate that TNF-α and TNF-β gene polymorphisms are not a significant risk factor for migraine without aura in Greek children.

Giant-cell tumor of the rib in a 12-year-old girl: a case report.

(2003). Giant-Cell Tumor of the Rib in a 12-Year-Old Girl: A Case Report. Pediatric Hematology and Oncology: Vol. 20, No. 4, pp. 351-355.

HEMANGIOPERICYTOMA IN AN ADOLESCENT GIRL: A Case Report

Hemangiopericytoma (HPC) is a rare soft tissue tumor. The few published reports account for the little information available on its clinical management. Here the authors report the successful treatment of an adolescent girl with rare HPC of the tongue. After incomplete surgical excision of the tumor she was admitted to the Hematology–Oncology Department and was treated with a 3-drug combination regimen (ifosfamide, actinomycin D, vincristine) for 8 weeks. She achieved partial remission in week 9 based on the magnetic resonance imaging (MRI) findings. Conventional radiation therapy was initiated at week 9 and continued until week 16. At week 20, according to the MRI findings, she achieved complete remission and continuation therapy was initiated. The young girl has been alive without evidence of the disease for the last 3 years of follow-up. In conclusion, the current report indicates that in cases of incomplete surgical excision of the tumor, chemotherapy and radiotherapy seem to be effective.

Prognostic significance of adenosine deaminase in children with malignancies

In 33 children, 23 with acute lymphoblastic leukemia (ALL) and 10 with solid tumors, the phenotype of the enzyme adenosine deaminase (ADA) was detected in the erythrocytes by electrophoresis in cellulose acetate. In all children the ADA enzyme activity was also determined in the plasma by spectrophotometry at the onset of the disease, during remission, at the end of the therapy, and during relapse. The phenotype in all children was ADA1-1. There was a difference in enzyme activity between the mean values of children with ALI and those with solid tumors. There were also differences among the subtypes of ALL and also among the stages of ALL and the stages of solid tumors. In 23 children with ALL the mean value (MV) and the corresponding standard error (SEM) of enzyme activity at the onset of the disease were MV +/- SEM = 60.2 +/- 6.2 IU/L. This was higher than that of the control group (control group: MV +/- SEM = 27.8 +/- 3.3 IU/L). During remission the enzyme activity was lower than that of the control group (MV +/- SEM = 19.6 +/- 1.7 IU/L); at the end of the therapy it was MV +/- SEM = 24.0 +/- 1.3 IU/L, which is close to that of the control group; and during relapse it was much higher compared with the control group (MV +/- SEM = 73.1 +/- 4.6 IU/L). These values are discussed in connection to the leukaemic subtypes. In 10 children with solid tumors the mean value of enzyme activity at the onset of the disease was MV +/- SEM = 48.8 +/- 2.4 IU/L. During therapy it was MV +/- SEM = 32.4 +/- 1.9 IU/L and at the end of therapy MV +/- SEM = 22.1 +/- 2.5 IU/L. The aim of this work is to study the qualitative isoenzyme abnormalities to better understand the biological nature of the malignancies, to distinguish main groups and subsets of ALL and solid tumors on an enzymatic basis, and to identify possible sensitive key enzymes as targets for chemotherapy.