The effect of early and long-term propranolol therapy on learning and memory in mice.

Propranolol is the treatment of choice for infantile hemangioma. We investigated the effects of long-term propranolol use in early infancy on learning and memory later in life in mice. At three weeks of age, mice were randomly divided into six experimental groups. Groups 1 and 2 (controls) received only saline for 21 days. Groups 3 and 4 received propranolol (2.5 mg/kg) for 21 days. Groups 5 and 6 received propranolol (5 mg/kg) for 21 days. Groups 1, 3 and 5 were tested at the end of 21 days of treatment (week 6). However, groups 2, 4 and 6 received a 2-week break and then (week 8) exposed to tests. In the Morris water maze test, propranolol (2.5 and 5 mg/kg) dose-dependently increased the time spent in the target quadrant in mice at weeks 6 and 8. However, propranolol did not affect the swimming speed in both time periods. There were no significant effects of propranolol on the number of errors evaluated during the radial arm maze tests. In conclusion, long-term use of propranolol in early infancy did not disrupt the learning and memory of mice.

Intravenous Iron Therapy for Children With Iron Deficiency Anemia.

Iron deficiency anemia in children is a public health problem. Although oral iron treatment is the first choice, common side effects and compliance problems can cause the treatment to be interrupted. This study retrospectively evaluated children treated with intravenous (IV) iron sucrose or ferric carboxymaltose (FCM) and compared the treatment processes and efficacy. The demographic characteristics and treatment details of the 44 children with iron deficiency anemia were retrospectively evaluated. Iron sucrose was administered to 25 patients and FCM was administered to 19 patients. The IV iron infusion was applied to 64% of the patients because of unresponsiveness to oral treatment, 25% of the patients because of compliance problems, and 11% of the patients because of severe anemia. IV iron therapy increased hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin, red-cell distribution width, and serum ferritin levels and decreased platelet count. The mean number of infusions per patient in the FCM group was lower, and the total treatment time was shorter. In conclusion, IV iron sucrose or FCM can be used in children with nonadherence to oral therapy and severe anemia in addition to specific indications.

Acquired Thrombotic Thrombocytopenic Purpura in a 5-Year-old Child With Wiskott-Aldrich Syndrome.

Thrombocytopenia is often seen as a laboratory finding during childhood. A supposed idiopathic thrombocytopenic purpura patient who was later diagnosed as Wiskott-Aldrich syndrome (WAS) and developed acquired thrombotic thrombocytopenic purpura (aTTP). Although autoimmune manifestations in WAS described, aTTP was reported just once. Five-year-old-boy was initially brought with cough, bloody stool (diarrhea), oral mucosal bleeding at 12th months of age. Following diagnosed with idiopathic thrombocytopenic purpura and receiving intravenous immunoglobulin, platelet count raised from 20,000 to 50,000/µL. One year after WAS diagnosis by mutation analysis, he presented with complaints of resistant fever, epistaxis, and melena. Hemoglobin decreased from 10 to 5.9 g/dL. Schistocytes in peripheral blood smear and high anti-ADAMTS-13 antibody level indicated development of aTTP.

Refugee children with beta-thalassemia in Turkey: Overview of demographic, socioeconomic, and medical characteristics.

AIM: Since the beginning of the Syrian civil war, more than 3.5 million Syrians have been under temporary protection status in Turkey. Because beta-thalassemia (BT) is a prevalent disorder in the Mediterranean countries, we decided to estimate the prevalence of and make an overview of the demographic, socioeconomic, medical characteristics, and healthcare problems of refugee children with BT. PATIENTS: Eighteen Turkish Pediatric Hematology Oncology Centers (PHOC) with 318 refugee children from 235 families participated in the study. The mean age of the patients was 8.1 ± 4.8 years (0.5-21 years). The mean time after immigration to Turkey was 2.5 ± 1.5 years (range, 0.1-7 years). Seventy-two (22.6%) of them were born and diagnosed with BT in Turkey. On physical examination, 82 patients (26%) were underweight and 121 patients (38%) were stunted. The appearance of a thalassemic face was reported for 207 patients (65.1%). Hepatomegaly and splenomegaly were reported in 217 (68.2%) and 168 (52.8%) patients, respectively. The median ferritin level was 2508 ng/mL (range, 17-21 000 ng/mL) at the first admission, and 2841 ng/mL (range, 26-12 981 ng/mL) at the last visit after two years of follow-up in a PHOC (P > 0.05). The most frequently encountered mutation was IVSI-110 (G>A) (31%). Before immigration, only 177 patients (55.6%) reported the use of chelators; after immigration it increased to 268 (84.3%). CONCLUSION: Difficulties in communication, finding a competent translator capable in medical terminology, nonregular use of medications, and insensitivity to prenatal diagnosis were preliminary problems. The current extent of migration poses emerging socioeconomic and humanitarian challenges for refugee patients with BT.

Salusin-α levels are negatively correlated with diastolic blood pressure in children with obesity.

Salusins have emerged as a new biomarker that reflects an increased inflammatory state, which is associated with cardiovascular risk. We investigated the predictive value and usefulness of salusins as an inflammatory biomarker in obese children. This prospective cohort study included 75 obese children and 101 healthy children (as a control group). Salusin-α, Salusin-ß, and various cardiovascular parameters were assessed in both groups. Correlation analyses of Salusin-α and Salusin-ß with body mass index standard deviation scores and inflammatory and cardiovascular markers were performed. The mean patient age was 11.9±2.4 years for the obese group and 12.5±2.1 years for the control group. The obese children had a significantly higher heart rate, systolic blood pressure, diastolic blood pressure, epicardial adipose tissue thickness, and left ventricular mass than did the children in the control group. There was no significant correlation between Salusin-α and Salusin-ß and body mass index; however, there was a negative correlation between Salusin- α and diastolic blood pressure (r = 0.277, p = 0.004). Overall, there was no significant difference in the Salusin-α and Salusin-ß levels between obese and healthy children. However, a negative correlation was found between Salusin-α and diastolic blood pressure. Although this result suggests that Salusin-α might be an early marker of cardiovascular involvement in obese children, further studies are needed to demonstrate the predictive value of salusins.

Assessment of Humoral Immunity to Hepatitis B, Measles, Rubella, and Mumps in Children After Chemotherapy.

BACKGROUND: Cancer survival rates and longevity of patients after therapy have significantly improved during the last few decades. Therefore, lasting protection against infections should be provided. PROCEDURE: A total of 162 children diagnosed with acute lymphoblastic leukemia, acute myelogenous leukemia, solid tumors, non-Hodgkin lymphoma, and Hodgkin lymphoma were enrolled in the study. Antibody levels against hepatitis B virus was assessed both at the time of diagnosis and within 6 months after completion of chemotherapy. However, measles, mumps, and rubella (MMR) antibodies levels were measured just within 6 months after completion of chemotherapy. RESULTS: Anti-HBs antibody titers had decreased below the protective level after treatment in 25 of 96 patients having protective antibody levels for hepatitis B virus before therapy. In 66 patients without pretreatment protective levels of antibody, in spite of the immunization during chemotherapy, only 6 of them were found to be anti-HBS positive after treatment. In 153 patients previously vaccinated with MMR, 19 had protective antibody titers after treatment. MMR seropositivities were negatively correlated to age as expected. CONCLUSIONS: Our data demonstrate that a significant number of children lose preexisting humoral immunity against MMR and hepatitis B after completion of chemotherapy.

Seven Patients With Transcobalamin Deficiency Diagnosed Between 2010 and 2014: A Single-Center Experience.

Transcobalamin deficiency (OMIM 275350) is a rare autosomal recessive disease presenting with nonspecific clinical features in early infancy. We report the clinical and laboratory manifestations of 7 children diagnosed with transcobalamin deficiency. All patients were admitted between 2 and 4 months of age with anemia, thrombocytopenia, and hyperhomocysteinemia. The most common complaints at admission were pallor, weakness, and poor feeding. Genetic analysis was performed in 5 patients and it revealed the same homozygous mutation. We initially treated all patients with intramuscular injections of a maximum of 1 mg cyanocobalamin (CN-Cbl) daily and with a final dose of 1 mg per week. Hemoglobin and platelet counts significantly decreased upon decrease or cessation of CN-Cbl therapy. The patients were reevaluated between 2 and 4 years of age and all had delay in speech and walking. In conclusion, 1 mg of intramuscular CN-Cbl every week suffices for hematological improvement but not for normal neurological development in patients who all had relapse due to decrease or cessation of treatment.

Positive correlation between insulin resistance and iron overload-induced oxidative stress in patients with fanconi anemia (FA)- and non-FA-related bone marrow failure: The results of a multicenter study.

This study investigated the relationship between DNA, protein, and lipid oxidations and insulin resistance in patients with Fanconi anemia (FA)- and non-FA-related bone marrow failure. Sixteen patients with FA, 7 non-FA-related aplastic anemia, and 10 controls were included in the study. Fasting blood glucose, simultaneous insulin, hepcidin, ferritin, 8-hydroxy deoxyguanosine (8-OHdG), protein carbonyls, malondialdehyde (MDA), and homeostatic model assessment-insulin resistance (HOMA-IR) were investigated in the patients and controls. Diepoxybutane test-positive (DEB+) patients were diagnosed with FA, whereas DEB-patients were diagnosed as non-FA. 8-OHdG levels in both FA and non-FA patients were significantly higher than those in the controls (P = .001 and P = .005, respectively). Serum ferritin levels were also higher in FA and non-FA patients than in the controls (P = .0001 and P = .005, respectively). Insulin resistance (IR) was significantly higher in FA patients than in non-FA patients and controls (P = .005 and P = .015, respectively). Significant differences were observed between 8-OHdG, ferritin, and MDA levels in patients with or without IR (P = .009, P = .001, and P = .013, respectively). Moderate and strong relations of 44% and 85% were determined between IR and ferritin levels in patients with FA or non-FA (P = .08 and P = .014, respectively). FA and non-FA patients exhibited a tendency to IR. IR was related to ferritin levels, and ferritin levels were also correlated with oxidative stress. These findings suggest that the increased rate of IR in patients with FA and non-FA may derive from increased oxidative stress, which may in turn be due to elevated serum ferritin levels.

Effects of massage therapy on pain and anxiety arising from intrathecal therapy or bone marrow aspiration in children with cancer.

Cancer and its treatment are stressful and reduce the quality of life in children. The aim of this study was to investigate the effect of massage therapy on pain and anxiety arising from intrathecal therapy or bone marrow aspiration in children with cancer. We conducted a controlled pretest/posttest quasi-experimental study at a paediatric oncology unit in Turkey. Twenty-five children were enrolled in this study. Their pain and anxiety were determined using a visual analogue scale. When the pretest and posttest pain and anxiety levels of the groups were compared, no statistically significant difference was found (P > 0.05). It was determined that pain and anxiety levels in the experimental group decreased significantly. This study provides preliminary evidence for the effectiveness in children of massage in reducing pain and anxiety arising from intrathecal therapy or bone marrow aspiration.

Parenteral glutamine supplementation has no effect on chemotherapy-induced toxicity in children with non-Hodgkin lymphoma.

PURPOSE: Protecting patients from the acute and/or chronic toxicity of antineoplastic therapy has become a major concern of oncology centers around the world. Glutamine has been used as a multisystemic protective agent to minimize the side effects arising from the treatment of childhood cancers. In this study, the effect of intravenous glutamine supplementation was investigated in children receiving chemotherapy for non-Hodgkin lymphoma. METHODS: Twelve children, of 48 to 120 months of age, and who had non-Hodgkin lymphoma were enrolled in the study. Thirty chemotherapy courses were given in combination with glutamine, and 31 chemotherapy courses were given without glutamine. Glutamine was given intravenously for 7 days, at a dose of 0.4 g/kg/d. Patients were evaluated in each course with regard to gastrointestinal, mucosal, and hematological toxicities. RESULTS: There were no significant differences in the hematological parameters between the 2 groups. The requirements for red blood cells and platelets during the chemotherapy courses were similar in both groups (P=0.64 and 0.40, respectively). Patients supplemented with glutamine developed mucositis in 21 of 30 courses (70%) and patients without glutamine supplements developed mucositis in 23 of 31 courses (74%). The mean duration of mucositis and the mean mucositis score in each course were similar between the 2 groups. In addition, gastrointestinal system and hepatic toxicity did not differ between groups. The mean duration of febrile neutropenia and the length of hospitalization were also similar in both groups (P=0.09 and 0.13, respectively). CONCLUSIONS: Parenteral glutamine supplementation has no effect on mucositis, fever and febrile neutropenia, length of hospitalization, red blood cell, and platelet requirements, and hematological, gastrointestinal, and hepatic toxicities in children receiving severe chemotherapy.

Papillon-Lefèvre syndrome: report of three cases in the same family.

Papillon-Lefèvre syndrome is a rare autosomal recessive disorder caused by cathepsin C gene mutation leading to the deficiency of cathepsin C enzymatic activity. The disease is characterized by palmoplantar hyperkeratosis, periodontopathy and precocious loss of dentition, and increased susceptibility to infections. Pyogenic liver abscess is an increasingly recognized complication. Three cases of Papillon-Lefevre syndrome in the same family are presented here. Two of the three siblings presented with characteristic manifestations of the syndrome. The third case had died previously due to liver abscess prior to a diagnosis of Papillon-Lefèvre syndrome.

Silibinin Effect on Methotrexate-Induced Hepatotoxicity in Rats.

OBJECTIVE: Hepatotoxicity is one of the major side effects of methotrexate and limits its use. In this study, we investigated the hepatoprotective effect of silibinin and the role of oxidative stress markers and cytokines on high-dose methotrexate-induced hepatotoxicity in rats. MATERIALS AND METHODS: In this study, rats were randomly divided into 5 groups (n=7). Methotrexate (20 mg/kg, intraperitoneally) was administered on the first day in all groups except control. Silibinin was injected for 5 days to methotrexate-silibinin25, methotrexate-silibinin50, and methotrexate-silibinin100 groups at a dose of 25, 50, and 100 mg/kg/day, respectively. On the sixth day, blood and liver samples were obtained and rats were sacrificed. Serum total antioxidant capacity, total oxidant status, total thiol, native thiol, alanine aminotransferase, aspartate transaminase, bilirubin, albumin, tumor necrosis factor-alpha, and interleukin-10 levels were measured. In addition, a histopathological evaluation of liver tissues was performed. RESULTS: Methotrexate reduced total antioxidant capacity and increased disulfide/total thiol ratio. Histopathologic examination revealed that methotrexate increased hepatic damage and 50 mg/kg/dose of silibinin prevented inflammatory cell infiltration in particular. CONCLUSION: Our results suggest that silibinin (50 mg/kg/day) may reduce the hepatic damage in methotrexate-induced hepatotoxicity in rats by increasing antioxidant capacity.

Resolution of pulmonary hypertension with low-molecular-weight heparin, steroid, and prostacyclin analogue therapy: could it be early-phase pulmonary veno-occlusive disease?

Pulmonary veno-occlusive disease (PVOD) is a rare cause of pulmonary hypertension. The authors present a case of neuroblastoma with progressive dyspnea, hypoxemia, and pulmonary hypertension. A computed tomography scan of the chest revealed septal thickening and diffuse micronodules. The patient was diagnosed as PVOD and was successfully treated with low-molecular-weight heparin (LMWH) and corticosteroid.

Epidural blockade for alternative management of priapism: A case report of child with T-cell acute lymphoblastic leukemia.

Priapism is a clinical condition that rarely presents with leukemia in childhood. Management of priapism treatment can become more complex and difficult when accompanied by acute leukemia. We presented a 16 years old child with t-cell acute lymphoblastic leukemia (ALL) who developed priapism. Due to the failure of conservative methods and intracavernosal drainage, we performed epidural blockade which has limited data reported with successful results in the literature before shunt surgery.

Comparison of safety and effectiveness of two different transfusion rates in children with severe anemia.

We compared the safety and efficacy of 2 transfusion regimens in children with severe anemia (hemoglobin <5 g/dL) and without overt signs of congestive heart failure requiring transfusion of packed red blood cells (PRBCs). Forty-three patients were randomly divided into 2 groups: group A and group B. The transfusion regimens consisted of continuous infusion of PRBC at a rate of 1 mL/kg/h for group A and 3 mL/kg/h for group B. The patients were closely monitored for any clinical signs of heart failure throughout transfusion. Heart and respiratory rate, and arterial blood pressure were measured hourly for 6 hours during transfusion. None of the patients developed any signs of cardiac failure during or after the transfusion. The mean heart rate, respiratory rate, diastolic and systolic blood pressure were similar in both groups throughout transfusion. Group A needed significantly more PRBC units than group B to attain the same hemoglobin increase. Transfusion of PRBC at a rate of 3 mL/kg/h, and at a rate of 1 mL/kg/h, is a safe regimen for children with severe anemia of gradual onset requiring transfusion therapy.

The Comparison of The Efficacy and Safety of Original and Biosimilar Filgrastim in Prevention of Chemotherapy-Induced Neutropenia in Children with Cancer.

OBJECTIVE: In adults and children, the duration of chemotherapy-induced neutropenia and associated complications has decreased because of the prophylactic use of granulocyte colony-stimulating factors (G-CSFs). Biosimilar G-CSFs can play an important role in reducing treatment costs in daily practice. However, some concerns regarding the efficacy and safety of new biosimilar products exist among clinicians. This study compared the efficacy and safety of original and biosimilar filgrastims for the prophylaxis of chemotherapy-induced neutropenia in children. MATERIALS AND METHODS: Thirty children receiving myelosuppressive chemotherapy were enrolled in this study. Filgrastims (5 µg/kg/day) were subcutaneously administered in Group A (biosimilar, Leucostim®; Dem Ilaç) and Group B (original drug, Neupogen®; Roche). Hemoglobin, white blood cell (WBC) count, platelet count, transfusion requirements, duration of hospitalization, and frequency and duration of adverse events including fever, neutropenia, and mucositis were evaluated following 25 treatment cycles in both groups. RESULTS: The hemoglobin value, WBC count, and platelet count on days 1, 5, and 10, and the red blood cell and platelet transfusion requirements, frequency, duration, and severity of mucositis, and durations of fever, febrile neutropenia, and hospitalization were similar in both groups. Although the mean WBC counts on days 1 and 5 were lower in Group A, the difference was statistically insignificant. CONCLUSION: The biosimilar filgrastim, Leucostim, is as effective and safe as the original drug for prophylaxis of chemotherapy-induced neutropenia in children.

Late side effects of high-dose steroid therapy on skeletal system in children with idiopathic thrombocytopenic purpura.

Corticosteroids have been widely used in the treatment of idiopathic thrombocytopenic purpura (ITP). We evaluated the late side effects of high-dose methylprednisolone (HDMP) therapy on bone metabolism in children with ITP. Twenty-eight children with acute ITP treated with HDMP (30 mg/kg/d for 3 d then 20 mg/kg/d for 4 d) and 28 controls were enrolled in the study. Bone mineral density (BMD), urinary calcium creatinine ratio, urinary levels of deoxypyridinoline, serum levels of calcium, phosphate, parathyroid hormone, total alkaline phosphatase, and bone-specific alkaline phosphatase were measured in both groups. Magnetic resonance imaging of the femoral head was performed only in study group. The mean levels of serum phosphate, parathyroid hormone, urinary deoxypyridinoline, and calcium creatinine ratio were significantly increased in the study group. There was no significant difference between the 2 groups in terms of serum calcium, total alkaline phosphatase, bone-specific alkaline phosphatase, and BMD values. There was a statistically significant negative correlation between cumulative steroid dose and BMD values in study group (r = -0.379). Osteonecrosis was observed in 3 of 25 patients by magnetic resonance imaging. In conclusion, HDMP therapy, especially in high cumulative doses, increases the bone resorption and may cause osteonecrosis in children with ITP.

Vacuolated cells in bone marrow aspirate of children with neuroblastoma.

Cytoplasmic vacuoles that have been seen in FAB L3-type lymphoblasts are not usual in neuroblastoma. The authors report three children with neuroblastoma having vacuolated cells mimicking L3-type lymphoblasts on bone marrow aspiration smears.