Selma Unal

Additive effects of dexamethasone in nebulized salbutamol or L-epinephrine treated infants with acute bronchiolitis.

Abstract Background : Although it is the most common lower respiratory infection of infancy, the optimal treatment for acute bronchiolitis is still controversial. The aim of this study was to compare the early and late effects of nebulized l‐epinephrine (EPI) and intramuscular dexamethasone (DEX) combination therapy with nebulized salbutamol (SAL) and dexamethasone combination and bronchodilators alone in outpatients with acute bronchiolitis.

Children with acute myeloblastic leukemia presenting with extramedullary infiltration: the effects of high-dose steroid treatment

To evaluate whether children with acute myeloblastic leukemia (AML) presenting with extramedullary infiltration (EMI) have different clinical, morphologic features and prognosis from children without EMI, a 127 consecutive previously untreated children with AML were entered in this study. Fifty-one children (40%) had EMI at diagnosis and 27% of these showed multiple site involvement. Twenty-seven of 127 children (21%) presented myeloid tumors. No age related differences in the incidence of EMI was noted. However, analysis of clinical and biological features at diagnosis showed that WBC count > or =50 x 10(9) l(-1), hepatosplenomegaly >5 cm, FAB AML-M4 and AML-M5 subtypes and CD13, CD14 expression of bone marrow (BM) leukemic cells (>20%) were more frequent in children with EMI. Two consecutive treatment protocols were used. In both protocols remission was achieved with combined high-dose methylprednisolone (HDMP) as a differentiating and apoptosis inducing agent with mild cytotoxic chemotherapy (low-dose cytosine arabinoside (LD Ara-C), weekly mitoxantrone and Ara-C or 6-thioguanine). Administration of short-course (4-7 days) HDMP (20-30 mg/kg per day) alone resulted in a remarkable decrease in peripheral blood, BM blasts and in the size of EMI in responding patients. In both protocols, remission rate in patients with EMI was 71 and 80%, which was lower than that of the patients without EMI (87 and 89%). This may be attributed to the higher frequency of unfavorable features in children with EMI. However, in patients who presented with myeloblastoma and treated with a more intensive post-remission therapy (AML-94), the 4-year disease-free survival (DFS) and event-free survival (EFS) rates were not found to be significantly different from children who had no EMI (P>0.05). Whereas, the outcome of children who presented with gingival infiltration did not improve. In further studies, the prognostic significance of different localisation of EMI and the effect of addition of HDMP to cytotoxic chemotherapy should be explored in larger series.

Evaluation of thrombotic children with malignancy

The purpose of this study was to evaluate inherited and acquired prothrombotic risk factors among children with malignancies who have thrombosis and emphasize the importance of inherited prothrombotic risk factors. Thirty-seven consecutive children with thrombosis and malignancy were included in this study. The patients were evaluated separately for time of development of thrombosis, insertion of a central venous line (CVL), history of l-asparaginase usage, and recent infections. Prothrombotic risk factors such as factor V G1691A and prothrombin G20210A mutation, protein C, protein S, antithrombin III deficiencies, factor VIII and lipoprotein(a) elevation, and antiphospholipid antibodies were analyzed for all patients. Of 387 children with thrombosis, 37 (9.5%) had a malignancy. Thrombosis was detected in 9 patients at the time of diagnosis, during maintenance therapy in 25 patients, and after the discontinuation of treatment in 3 patients. One or two additional prothrombotic risk factors other than l-asparaginase therapy and insertion of central venous lines were present in 20 of these patients (54%). It was found that eight patients had the factor V G1691A mutation in the heterozygote state. One of them had the factor V G1691A mutation associated with a history of infection and one patient had the factor V G1691A mutation associated with factor VIII elevation. One had the the prothrombin G20210A mutation in the heterozygote state, four had lipoprotein(a) elevation, two had factor VIII elevation, one had a decreased protein S level, one had a decreased protein C level, one had antiphospholipid positivity, and two had histories of infection. Malignancy is an important risk factor for the development of childhood thrombosis. However, the risk of thrombosis increases when accompanied by additional prothrombotic risk factors. For this reason, especially children with malignancy and at high risk for the development of thrombosis, such as those who have received l-asparaginase or a replaced CVL during their therapy, might be screened for additional prothrombotic risk factors and appropriate measures might be taken to prevent the development of thrombosis.

Evaluation of the Psychological Problems in Children with Sickle Cell Anemia and Their Families

Sickle cell anemia (SCA) is a chronic disease and it would be expected that the children with SCA are at high risk of developing psychosocial problems. In this study the authors intended to evaluate both the psychiatric problems among SCA patients and their families and put forward the relation between the clinical findings and psychiatric problems. Forty children were included in the study. The patients were classified according to their histories of painful crises in the past 1 year. The children who have had a history of painful crisis 1–4, 5–10, and over 10 times were classified as group 1, group 2, and group 3, respectively. The depression levels of the children in group 3 were higher than group 1 (P = .018). The state of the anxiety level of the children and Beck Anxiety Inventory of the mothers were higher in group 3 than in group 1 (P = .004). In addition, anxiety levels of the mothers who had children with social limitations and painful episodes were higher than the anxiety levels of the mothers who had children without social limitations and painful episodes (P = .006 and P = .004, respectively). We found a relationship between the anxiety and depression levels in children and the anxiety, depression, and marital adjustment levels in mothers. In conclusion, the frequency of psychological disorders appears to increase in patients with SCA, as with many chronic diseases. Especially, the patients who had higher frequencies of painful crises and their mothers had increased depression and state anxiety levels. Thus, the patients with SCA and their families should be evaluated regularly in terms of psychological disorders.

Plasma protein oxidation is correlated positively with plasma iron levels and negatively with hemolysate zinc levels in sickle-cell anemia patients

Introduction:  Sickle‐cell anemia (SCA) is a disease of high oxidative stress. The oxidative medium of SCA was evaluated by protein oxidation parameters and their correlation with lipids and ions were investigated both in the plasma and in the erythrocyte.

Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α) Levels and IL-6, TNF-Polymorphisms in Children With Thrombosis

Infection has an important role in the pathogenesis of thrombosis and it becomes more prominent in childhood cases, in whom the infection frequency is higher. It has been suggested that patients with high tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels might be at increased risk of developing thrombotic complications owing to the effects of these cytokines on the coagulation pathway. Functional polymorphisms in the promoter regions of the genes coding for TNF-α and IL-6 are associated with increased plasma levels of these cytokines. The aims of this study were to evaluate the serum levels of acute phase reactants, such as C-reactive protein, and of cytokines (TNF-α and IL-6) and to investigate the association between the TNF-α-308 G/A and IL-6-174 G/C polymorphisms in Turkish pediatric patients with thrombosis. Fifty-eight children with thrombosis (group 1) and 89 controls (group 2) were included in the study. Patients who had a history of infection within the 15 days before thrombosis were classified as group 1a and those who had no infection history before thrombosis were classified as group 1b. Serum TNF-α did not differ significantly between the groups. However, the IL-6 level was higher in group 1a than in group 1b (P<0.05). The genotype distribution and allele frequencies of TNF-α G/A polymorphism were significantly higher in the thrombotic children without infection and in the control group than in the thrombotic children with an infection history (P<0.05). The IL-6-174 C/C genotype was significantly higher in thrombotic children with an infection history (P<0.05); there were no differences between the groups in mean allele frequency (Table 2). On the basis of our results, patients with a history of infection seem to have higher C-reactive protein and IL-6 levels and IL-6-174 C/C genotype. Furthermore, venous thrombosis is more frequent in this group than arterial thrombosis (P<0.05).

Prothrombin G20210A mutation in Turkish children with thrombosis and the frequency of prothrombin C20209T.

The prothrombin G20210A mutation has been described as the second most common genetic risk factor in thrombotic patients. Recently a new prothrombin gene variant namely prothrombin C20209T has also been found to be associated with thrombosis. In the present study the frequency of these two thrombin variants have been searched in two different groups. Group 1: A total of 377 children with thrombosis were analyzed during 7 years between January 1997 and 2004 and screened for prothrombin G20210A mutation. Twenty-four of 387 children (6.3%) with thrombosis were diagnosed as having PT G20210A mutation. The mean age of the patients was 6.1 years (median: 6 years, range: 4 months to 17 years, 15 male, 9 female). Six of 24 children were below 2 years of age (25%). Fifteen of 24 children (62.5%) had arterial thrombosis, most of whom (93.3%) had cerebral infarct. Group 2: The prothrombin C20209T variant has been analyzed in 200 thrombotic patients and in 200 healthy subjects. None of the thrombotic patients and healthy individuals carried the prothrombin C20209T variant. In conclusion, arterial thrombosis as the cerebral infarct is the most prominent type of thrombosis in children with prothrombin G20210A mutation. It seems that the prothrombin C20209T variant is not an important risk factor for the population studied.

Procalcitonin is more useful than C-reactive protein in differentiation of fever in patients with sickle cell disease.

This study aimed at evaluating the value of C-reactive protein (CRP) and procalcitonin (PCT) levels in the differential diagnosis of fever in patients with sickle cell disease (SCD). The study included 86 children with SCD (group 1) and 49 controls (group 2). During the study, the patients had 114 acute episodes or routine visits to the units. They were classified as having vasoocclusive crisis with fever (group 1A), vasoocclusive crisis without fever (group 1B), and no crisis or fever (steady state, group 1C). Only patients with crises were admitted to the hospital. Patients admitted to the hospital with various clinical signs and symptoms each and every time were included in groups 1A, 1B, and 1C. Thus, a total of 114 clinical episodes were analyzed. The mean CRP levels in the 3 patient groups were significantly higher than that in the group 2, and among the patient groups, the mean CRP was significantly higher in group 1A than the other groups. The mean CRP level in group 1A and group 1B was significantly higher than that in group 1C. There were no significant differences among the 3 SCD groups in terms of the median serum PCT level; however, the median PCT level in group 1A, group 1B, and group 1C patients was significantly higher than that in group 2 patients. These data indicate that vasoocclusive disease with or without fever apparently does not significantly increase PCT levels in relation to the baseline status of children with SCD, which in turn are clearly more elevated than PCT levels of control children.

Assessment of clinical and laboratory presentations of familial hemophagocytic lymphohistiocytosis patients with homozygous W374X mutation

Homozygous W374X mutation was identified in unrelated 13 patients (6M/7F) from consanguineous families, 62% of which had history of deceased sibling. Haplotype analysis provided evidence for the probable existence of a founder effect. Age at disease onset ranged from 1 day to 5.5 months (median 2 months). Hepatic dysfunction was observed in 69%, ascite 62%, hypertriglyceridemia 77%, each hyperferritinemia and hypofibrinogenemia 85%, CNS involvement 46% of patients while birth weights were in normal range. Those with very high ferritin (>20,000ng/ml) had extremely low fibrinogen levels. Two-thirds of patients receiving HLH protocol died within 20 days of therapy.

Frequency and risk factors of endocrine complications in Turkish children and adolescents with sickle cell anemia.

Objective: To define frequency and risk factors of abnormalities in growth, puberty, thyroid function, and bone and carbohydrate metabolisms in children and adolescents with sickle cell disease (SCD). Materials and Methods: Endocrine problems including short stature, puberty and thyroid disorders, and carbohydrate and bone metabolisms in 50 Turkish children and adolescents with SCD were evaluated. Relationships among sex, disease type, blood transfusions, exchange and exacerbation frequency, ferritin levels, and endocrine pathologies were investigated. Results: The mean age of the study group was 13.1±2.9 years. Weights and heights of 12 participants (24%) were below -2 standard deviations and 4 participants (8%) had malnutrition. Mean difference (±standard deviation) between bone and chronological age of patients was -1.73±1.86 years. Fifty percent of patients had at least one endocrine abnormality other than vitamin D deficiency and insufficiency. Hypergonadotropic hypogonadism in 3 patients (6%), hypogonadotropic hypogonadism in 1 female patient (2%), and small testicular volume in respect to age in 3 male patients (8.5%) were seen. Growth hormone deficiency was detected in 1 (2%) female patient, and hypothyroidism was diagnosed in 3 patients (6%; 1 central case, 2 cases of primary hypothyroidism). At vertebral level, 5 patients (11.1%) had osteopenia and 1 patient (2.2%) had osteoporosis, while 5 patients (11.1%) had osteopenia at femur neck level. The most common endocrine abnormality was vitamin D deficiency. 25-Hydroxyvitamin D was deficient in 63.2% and insufficient in 18.4% of patients. Sex, disease type, blood transfusion frequency, exacerbation frequency, and ferritin levels were not related to endocrine pathologies. As the age was increased, standard deviation scores of femur neck bone mineral density was decreased (r =-0.56; p<0.05). Vitamin D was lower in patients whose weights and/or heights were below -2 standard deviations from the mean (p<0.05). Conclusion: Endocrine organ dysfunctions are commonly detected in children and adolescents with SCD, and vitamin D deficiency is the most commonly encountered endocrine disorder. Regular follow- ups of patients for endocrine complications, starting from early ages of patients, and initiation of appropriate treatments will elongate expectancy and quality of life. Conflict of interest:None declared.