Endothelial nitric oxide synthase Glu298Asp gene polymorphism in the cases of idiopathic thrombocytopenic purpura.

Background: Nitric oxide (NO) can induce apoptosis in megakaryocytes. Stimulatory function of NO on platelet production may be important in the pathophysiology of idiopathic thrombocytopenic purpura (ITP). NO is produced by three isoforms of NO synthase (NOS). The endothelial nitric oxide synthase (eNOS) isoform has been detected in platelets. Polymorphism of the eNOS gene, which supplies NO synthesis, changes the functions of this enzyme. In this study, the role of eNOS Glu298Asp gene polymorphism in etiopathogenesis, its course, and treatment of ITP was investigated. Methods: Sixty-six patients [51 newly diagnosed ITP (ND-ITP), 15 chronic ITP (CH-ITP), and 60 healthy controls (HC)] were enrolled in this study. Results: In all patients, the frequency of the GT genotype was 48.5%. The frequency of the GG genotype was determined to be 40.9% and the TT genotype was 10.6%. The most common allele in all patients was the G allele. eNOS Glu298Asp gene polymorphism might be a risk factor in the etiopathogenesis of ITP. Patients with the GG genotype were thought to have a high intention for CH-ITP. Patients with the GG genotype responded effectively to medical treatment using IVIG therapy. The presence of the G allele was observed to have a positive effect on the medical treatment of patients with CH-ITP, whereas the T allele exhibited a negative effect. Conclusion: In the present study, a significant correlation was found between ITP and eNOS Glu298Asp gene polymorphism. This correlation suggested that eNOS Glu298Asp gene polymorphism might be a risk factor in the ethiopathogenesis of ITP.

The Effect of Iron Deficiency Anemia and Different Treatment Methods on DNA Damage: 8-hydroxy-2-deoxyguanosine Level.

Ionic iron causes damages at the cellular level by forming free radicals. Reactive oxygen species lead to the formation of oxidative base damages in DNA. Among these forms the most common one and the one which has the best known mutagenity is 8-hydroxy-2'-deoxyguanosine (8-OHdG). We aimed to determine iron deficiency anemia (IDA) and its different forms of treatments; probable oxidative damage on DNA by looking at the level of 8-OHdG. The patients were divided into 4 subgroups: Oral treatment (p.o.) group; Intramuscular treatment (i.m.) group; Intravenous treatment (i.v.) group; Healthy control group. Blood and urine samples were taken from all patients totally 4 times. 8-OHdG levels detected in blood and urine samples were compared with the control group. IDA and the treatment of it affect the level of 8-OHdG. p.o. therapy should be the top priority on children.

Can we differentiate malignant peripheral nerve sheath tumor from benign neurofibroma without invasive sampling.

One of the most important benign tumors in neurofibromatosis type 1 (NF1) is plexiform neurofibroma, and there is a risk of developing malignant peripheral nerve sheath tumor (MPNST) throughout life approximately 10%. However lesion characterization by anatomical imaging methods are not possible. Because of that most of cases goes to biopsy. Using of fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) for lesion characterization can be helpful in NF1 patients. We aimed to present an example of the efficacy of FDG-PET/CT in distinguishing benign neurofibroma from MPNST. A 6-year-old male patient who had NF1 admitted to emergency service due to high fever. Acute upper respiratory tract infection was diagnosed; antipyretic and abundant fluid intake was suggested. When high fever continued, the patient referred to our hospital on detection of axillary lymphadenopathy. Leukocytosis was detected in patient's blood count. Sedimentation was 54 mm/h, C-reactive protein 166 g/L, and lactate dehydrogenase 276U/L. Blood and throat cultures did not show pathogenic bacteria. In serological tests, VZV-IgG, EBV-VCA-IgG, and CMV-IgG were avidite positive; Hepatitis B Ag, Anti-HIV, Anti-HAV IgG and IgM, Anti-HCV, EBV-VCA IgM, and VZV-IgM were negative. Based on these results, cervical and thoracic contrast-enhanced computed tomography was performed on preliminary diagnosis of MPNST. Solid lesions with rounded margins, large one being 49 mm in size, that extend from superior mediastinum to posterior mediastinum, left axillary region, and left part of neck were detected, and they were surrounding the vascular structures. Since neurofibroma, MPNST, and lymphoma could not be distinguished, patient referred to FDG-PET/CT scanning. In FDG-PET/CT, highest lesion maximum standardized uptake value (SUVmax) was 1.5; SUVmax lesion/SUVmax liver 1.0, and SUVmax/ SUV mean liver 1.5. Biopsy from mediastinal and axillary region did not have LN structure and was positive for S-100 immunostaining, and patient was diagnosed as benign neurofibroma. We believe that there is no need for biopsy in lesions considered benign based on FDG-PET/CT parameters.

Insufficiency of bone scintigraphy in vertebral lesions of langerhans cell histiocytosis compared to f-18 fluorodeoxyglucose positron emission tomography/computed tomography and diagnostic computed tomography.

Langerhans cell histiocytosis (LCH) is a benign disorder related to the histiocytes which can infiltrate bone tissue. The most effective method for demonstrating severity of this disease is PET/CT and bone scintigraphy might show bone lesions. We present a seventeen year old male patient with disseminated LCH presented with exophtalmos and having multiple vertebral lesions which were identified by F-18 FDG PET/CT scan and diagnostic CT but not in the bone scintigraphy.

The levels of calcium and magnesium, and of selected trace elements, in whole blood and scalp hair of children with growth retardation.

OBJECTIVE: Metals such as copper (Cu), zinc (Zn), iron (Fe) are essential for human beings. Chronic metabolic disturbances may result from an excess or deficiency of these metals. Ca and Mg are also nutrient elements and play an important role in biological systems. Thus, it is very important to check regularly trace elements concentration in the body. The purpose of this study was to measure the content of Fe, Cu, Zn, Ca and Mg in whole blood and hair of children with growth retardation compared to that of controls. METHODS: A quantitative elemental analysis of whole blood and scalp hair of children with constitutional growth retardation (n = 27) and matched controls (n = 21) was used to find out correlation and possible changes, between growth retardation and healthy controls. Atomic absorption spectrophotometric (AAS) analysis of quantitative method was used to determine iron, zinc, copper, calcium and magnesium levels of whole blood and scalp hair. FINDINGS: The whole blood levels of Fe and Zn were significantly lower in children with growth retardation (P<0.05), but there were no differences in Cu, Ca and Mg concentrations in whole blood between children with growth retardation and healthy controls. The hair levels of Fe, Zn, Ca and Mg were significantly lower in children with growth retardation when compared to that of controls (P<0.05). The Cu concentrations in the hair of children with growth retardation and healthy controls showed no significant differences (P>0.05). CONCLUSION: The usefulness and significance of these elements in growth retardation should be discussed more detailed in the light of the most recent data.

The role of positron emission tomography/CT in hypoxic ischaemic encephalopathy in children.

The role of positron emission tomography/CT (PET/CT) in diagnosis and follow-up of newborns with hypoxic ischaemic encephalopathy has been documented before; however, this is the first presentation of elder children with both diagnostic and follow-up PET/CT results as far as we know.

Iron deficiency anemia and levels of oxidative stress induced by treatment modality.

BACKGROUND: The effects of iron deficiency anemia (IDA) and its treatment on plasma total antioxidant capacity (TAOC) were investigated. METHODS: Sixty patients with IDA and 20 healthy controls were divided into four subgroups: an oral (per os: PO) group (n = 20); an intramuscular (IM) group (n = 20); an intravenous (IV) group (n = 20); and the control group (n = 20). Blood samples were obtained from all patients before treatment, and at 24 h, 7 days, 6 and 13 weeks after initiation of IDA therapy. RESULTS: TAOC in the IDA group was low when compared with the control group (P < 0.001). Although TAOC at 24 h in the PO group was not different from the control group, the TAOC in the IM and IV groups was relatively lower (P < 0.001). The TAOC in the PO group at 7 days, and at 6 and 13 weeks was closest to the control group level. The mean TAOC in the IV group at 13 weeks was clearly lower relative to the PO and IM groups. CONCLUSIONS: Oxidative stress was minimally induced with oral therapy, while IM and IV therapies induced higher levels of oxidative stress, in increasing order of intensity.

PET/CT images of a patient with haemophagocytic lymphohistiocytosis.

Haemophagocytic lymphohistiocytosis (HLH) is a rare immune disorder that predominantly affects macrophages and T lymphocytes and leads to multiple organ disease and death. The characteristic pathological finding in the bone marrow and the other affected tissues is haemophagocytosis of macrophages (macrophages digesting erythrocyte). Primary (hereditary) and secondary (acquired) forms of the disease are present. A patient with documented HLH disease revealed by positron emission tomography/CT is reported in this paper.

Use of phototherapy for neonatal hyperbilirubinemia affects cytokine production and lymphocyte subsets.

BACKGROUND: Most studies regarding the influence of ultraviolet radiation on levels of inflammatory cytokines were conducted mainly in cultures of human keratinocytes or in laboratory animals. Few studies were also performed in human subjects. OBJECTIVES: To investigate the influence of the use of phototherapy on the levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, IL-8 such as cytokines expressed from keratinocytes and on the expression of some lymphocyte subsets in the prevention or treatment of neonatal hyperbilirubinemia. METHODS: The study group included 21 term newborns with hyperbilirubinemia and the control group included 16 healthy term newborns. Blood samples were obtained from hyperbilirubinemic newborns before and at 72 h of exposure to phototherapy and from controls at the examination time. The levels of TNF-alpha, IL-1beta, IL-6, IL-8 and lymphocyte subsets were measured in the samples using appropriate methods. RESULTS: Serum TNF-alpha, IL-1beta, IL-6, and IL-8 levels are similar in study and control groups. At 72 h of exposure to phototherapy serum TNF-alpha, IL-1beta and IL-8 levels are significantly increased, while the serum IL-6 level at the same time is not significantly changed. Lymphocytes, lymphocyte subsets and white blood cell levels are similar in the study and control groups. Only, the percentage of CD3+ lymphocyte subset is significantly lower in newborns at 72 h of exposure to phototherapy. All other lymphocyte subsets are decreased by the exposure to phototherapy, and this change was not statistically significant. CONCLUSIONS: The results demonstrate that in addition to the well-known positive effect of phototherapy on the neonatal serum bilirubin level, this treatment can affect the function of the immune system in newborns via alterations in cytokine production.

Neonates with culture proven sepsis have lower amounts and percentage of CD45RA+ T cells.

To evaluate the expression of lymphocyte subsets in newborns diagnosed as culture proven or culture negative sepsis and to investigate the differentiation. The aim of this study is to explore neonatal immunology in newborns diagnosed as culture proven or culture negative neonatal sepsis and to identify their place in the diagnosis. This prospective study was performed in newborns who were diagnosed as neonatal sepsis and hospitalized in a tertiary care hospital and who were classified as culture proven sepsis (n=12), as culture negative sepsis (n=21) and healthy (n=17). Lymphocyte subsets were obtained at time of diagnosis. Culture proven sepsis had statistically significant increase of WBC compared to culture negative sepsis and control groups (p<0.05). Significant decreases were observed of percentage of lymphocyte, when compared to culture negative sepsis and control group (p<0.05). Percentage of CD4(+) was lower in culture proven sepsis and absolute count of CD4(+) was lower in culture negative sepsis (p<0.05). Percentage and absolute count of CD45RA(+) were lower in culture negative sepsis than control and percentage of CD45RA(+) was lower in culture proven sepsis than control (p<0.05). Percentage of CD45RO(+) was higher in culture proven sepsis than control group (p<0.05). It is clear that during neonatal sepsis lymphocyte subsets are different from healthy controls. Whether the described abnormalities represent the absence of a normal maturation process, rather, pathological events is still not clear.

Cord blood prolidase activity correlates with gestational age and birth weight.

BACKGROUND: Prolidase, a specific iminopeptidase involved in collagen turnover, is especially active in growing tissues. OBJECTIVES: To investigate the relationship between cord blood prolidase activity and both birth weight and gestational age. METHODS: Cord blood was collected consecutively from 50 healthy newborns (35 term, 15 preterm). Prolidase activity was measured in the samples using standard methods. RESULTS: Themean +/- SD cord blood prolidase activity was 41.4 +/- 6.9 U/l in term infants and 35.2 +/- 8.0 U/l in preterm infants and these were significantly different (p < 0.01). There were positive correlations between cord blood prolidase and both birth weight (r = 0.533, p < 0.01) and gestational age (r = 0.806, p < 0.01). CONCLUSION: Cord blood prolidase activity may be a good indicator of fetal maturation and gestational age.

Plasma ghrelin levels in various stages of development of iron deficiency anemia.

OBJECTIVES: Ghrelin stimulates food intake and induces metabolic changes leading to an increase in body weight and body fat mass. Iron-deficiency anemia (IDA) is the most frequently seen cause of nutritional anemia, that is a type of starvation. There is no available study related to levels of ghrelin in IDA. The aim of this study is to show an association with ghrelin levels and iron deficiency and to demonstrate whether changes seen in iron deficiency (ID) are explained by ghrelin, as opposed to whether ghrelin levels correlate with ID. MATERIALS AND METHODS: The study group was consisted of children who were admitted in the outpatient clinic of pediatrics. Control group (C) was defined as cases with normal hemoglobin (Hb), serum iron (SI), transferrin saturation (TS), and ferritin (F) (>12 ng/mL) values; group hypoferritinemia (IDec) Hb: N, SI: N, TS: N, F<12 ng/mL; group iron deficiency (IDef), Hb: N, SI: decreased, TS

Effects of febrile and afebrile seizures on oxidant state in children.

No comparative studies have addressed the oxidant and antioxidant states of blood and cerebrospinal fluid. To reveal this differential state, the study was designed to identify the seizure type with the worse prognosis by determining erythrocyte arginase and erythrocyte catalase, plasma and cerebrospinal fluid malondialdehyde, and plasma and cerebrospinal fluid nitric oxide levels. Study groups were classified as febrile (group 1, n = 21), afebrile (group 2, n = 21), and control (group 3, n = 41, subdivided as 3a, febris positive, convulsion negative, and 3b, febris negative, convulsion negative). Levels of erythrocyte arginase, erythrocyte catalase, plasma malondialdehyde, cerebrospinal fluid malondialdehyde, plasma nitric oxide, and cerebrospinal fluid nitric oxide levels were determined for all groups. A difference was detected between the control and febrile seizure groups with respect to erythrocyte catalase and plasma and cerebrospinal fluid levels of nitric oxide (P < 0.05). Both febrile states and convulsions influence oxidative mechanism. Oxidative stress-generating potential differs for febrile and afebrile seizures. In afebrile seizures, greater levels of oxidative stress might affect prognosis adversely. This phenomenon can be interpreted in terms of fever as a protective factor against possible neurological damage during convulsive seizures.

Rickets with Dorfman-Chanarin syndrome.

BACKGROUND: Dorfman-Chanarin syndrome is a rare, autosomal recessive, inherited, lipid storage disease. It is characterized by nonbullous congenital ichthyosiform erythroderma, leukocyte vacuoles and variable involvement of the liver, muscles and central nervous system, due to errors of triacylglycerol metabolism. To date only 32 cases of this syndrome have been described worldwide. AIMS: To report the case of a boy with Dorfman-Chanarin syndrome with rickets. CASE REPORT: A boy of Turkish origin was born of a nonconsanguineous marriage after an uncomplicated perinatal period. On examination the patient had failure to thrive, diffuse erythroderma and ichthyosis and clinical features suggesting rickets. A light-microscopic examination of peripheral smear revealed vacuolated leukocytes typical of Jordans' anomaly. Lipid analysis showed an increase in triacylglycerol and very low density lipoprotein. A radiographic study of the wrist revealed rickets. CONCLUSION: The clinical progression in these patients ranges from mild to fatal. We believe that patients with ichthyosis should be evaluated bearing in mind the possibility of Dorfman-Chanarin syndrome. This may increase the number of reported Dorfman-Chanarin syndrome cases, and the pathogenesis and progression of the disease will become clearer.

The levels of Ghrelin, TNF-alpha, and IL-6 in children with cyanotic and acyanotic congenital heart disease.

BACKGROUND/AIM: Ghrelin has effects on nutrient intake and growth. The cause of growth retardation in congenital heart disease is multifactorial. The aim of the present study is to investigate the ghrelin in congenital heart disease and the association of ghrelin with TNF-alpha and IL-6. Materials and methods. We measured serum ghrelin, TNF-alpha, and IL-6 levels using specific immunoassay in 68 patients (47 acyanotic, 21 cyanotic with congenital heart disease) and in 25 control subjects. Results. In comparison to controls, serum ghrelin, TNF-alpha levels were significantly higher in acyanotic patients and cyanotic patients with congenital heart disease (P<.0001). In acyanotic and cyanotic patients with congenital heart disease, there was a positive correlation between ghrelin and TNF-alpha (r=.485, P<.05 and r=.573, P<.01, resp.). CONCLUSION: Serum ghrelin levels is elevated in acyanotic and cyanotic patients with congenital heart disease. Increased ghrelin levels represents malnutrition and growth retardation in these patients. The relation of ghrelin with cytokines may be explained by the possible effect of chronic congestive heart failure and chronic shunt hypoxemia.

Seroprevalence of mumps, varicella and rubella antibodies in children 1-16 years of age in eastern Turkey.

In this study, seroprevalence of mumps, varicella and rubella was investigated in 803 unvaccinated children in eastern Turkey whose ages ranged between 1 and 16 years. Mumps IgG, varicella IgG and rubella IgG antibody levels in all children were studied by enzyme-linked immunosorbent assay (ELISA) method. Information regarding socioeconomic characteristics, number of siblings and disease history was gathered for each participant. No significant difference in seropositivity was detected between girls and boys. Seroprevalence of mumps increased with age, with a seropositivity rate of 29.9% in children aged 1-4 years and of 88.8% in those aged 13-16 years. Seroprevalence of varicella increased with age, with a seropositivity rate of 26.8% in children aged 1-4 years and of 90.3% in those aged 13-16 years. Seroprevalence of rubella also increased with age, with a seropositivity rate of 47.3% in the children aged 1-4 years and of 89.2% in those aged 13-16 years. There was a statistically significant increase in the rate of seropositivity with advancing age through the group of 13-16 years old (p < 0.05). In conclusion, in order to avoid mumps, varicella and rubella diseases and their possible complications, children should be vaccinated against these three diseases before the age of two, since seroprevalence increases with age.

Frequency of hypoferritinemia, iron deficiency and iron deficiency anemia in outpatients.

The prevalence rates of hypoferritinemia (IDec/one abnormal indicator), iron deficiency (IDef/two abnormal indicators) and iron deficiency anemia (IDA) in children who were referred to the outpatient clinics of the Department of Pediatrics for the first time within 1 month were investigated. Exclusion criteria were iron therapy before and during the study period and a history of chronic illness. Acute-phase reactants, such as erythrocyte sedimentation rate and C-reactive protein levels, were measured in all cases indicative of infectious diseases. Blood samples were obtained from each study patient admitted to the outpatient clinics during the study period. The hospital charts were later further evaluated, and samples of patients with any current illness known to interact with the iron status of the patient were discarded, and patients were contacted to supply new samples about 1 month after treatment of the infection. Thus, in patients with indications of an infection, samples obtained 1 month after treatment were assessed. The children (n = 557) were divided into four age groups: those aged 4 months to 2 years (group I), 2-6 years (group II), 7-12 years (group III) and 12-18 years (group IV). Children with a decrease in serum ferritin levels without anemia (IDec), and those with lower ferritin, transferrin saturation (TS) and serum iron (SI) concentration (IDef) were evaluated. IDA was diagnosed if hemoglobin (Hb) concentrations were lower than those adjusted for age, ferritin <12 ng/ml and TS

Treatment of iron deficiency anemia with intravenous iron preparations.

OBJECTIVE: We aimed to determine the effects of intravenous iron therapy on blood parameters in pediatric patients who do not tolerate oral iron therapy for any reason. PATIENTS AND METHODS: The patient group consisted of candidates for elective operations requiring blood transfusions in order to raise hemoglobin (Hb) concentrations rapidly and for whom oral iron administration is useless and compliance with long-term treatment is definitely impossible due to sociocultural factors. Sixty-two children were included in the study. Venous blood samples were taken at diagnosis, and after 1 week and 1, 2 and 3 months. Hb, hematocrit, erythrocyte indices (mean erythrocyte volume, mean erythrocyte Hb and mean erythrocyte Hb concentration), serum iron (SI) levels, iron binding capacity, transferrin receptor (CD71) and serum ferritin levels were measured. Iron sucrose was used as an intravenous iron preparation. RESULTS: All children showed improvements in iron deficiency anemia. A statistically significant elevation occurred between the time of diagnosis and week 1 (p<0.05) in nearly all parameters. SI was raised until at least 1 month of therapy. There was no significant difference between transferrin receptors measured before and after the intravenous iron therapy. Ferritin did not exceed the values achieved in the 1st month. Mild side effects were encountered in only 8 (12.9%) patients. Treatment was not discontinued because of side effects in any case. The patients in the control group were given an oral form containing ferroglycine sulfate. CONCLUSION: Intravenous iron therapy can replace oral therapy in patients whose blood parameters must be raised rapidly and in situations where oral iron administration would not be appropriate for any reason. However, reinforcement with oral iron therapy or additional intravenous doses would be appropriate.

Serum IL-1beta, IL-2, and IL-6 in insulin-dependent diabetic children.

Insulin-dependent diabetes mellitus (IDDM) is a chronic disease characterized by T-cell-dependent autoimmune destruction of the insulin-producing beta cells in the pancreatic islets of Langerhans, resulting in an absolute lack of insulin. T cells are activated in response to islet-dominant autoantigens, the result being the development of IDDM. Insulin is one of the islet autoantigens responsible for the activation of T-lymphocyte functions, inflammatory cytokine production, and development of IDDM. The aim of this study was to investigate serum concentrations of interleukin (IL)-1beta, IL-2, IL-6, and tumor necrosis factor (TNF)-alpha in children IDDM. The study population consisted of 27 children with IDDM and 25 healthy controls. Children with IDDM were divided into three subgroups: (1) previously diagnosed patients (long standing IDDM) (n : 15), (2) newly diagnosed patients with diabetic ketoacidosis (before treatment) (n : 12), and (3) newly diagnosed patients with diabetic ketoacidosis (after treatment for two weeks) (n : 12). In all stages of diabetes higher levels of IL-1beta and TNF-alpha and lower levels of IL-2 and IL-6 were detected. Our data about elevated serum IL-1beta, TNF-alpha and decreased IL-2, IL-6 levels in newly diagnosed IDDM patients in comparison with longer standing cases supports an activation of systemic inflammatory process during early phases of IDDM which may be indicative of an ongoing beta-cell destruction. Persistence of significant difference between the cases with IDDM monitored for a long time and controls in terms of IL-1beta, IL-2, IL-6, and TNF-alpha supports continuous activation during the late stages of diabetes.

Mucopolysaccharidosis IIIB, cerebral vasculopathy and recurrent subdural hematoma.

Mucopolysaccharidoses are characterized by involvement of multiple organs, including blood vessels. We present a case of mucopolysaccharidosis IIIB admitted with recurrent subdural hematoma; further evaluation and dural biopsy revealed an association with cerebral vasculopathy.