Publications by authors named "Salih Gozmen"

34 Publications

Metabolic syndrome and risk factors after hematopoietic stem cell transplantation in children and adolescents.

J Pediatr Endocrinol Metab 2021 Apr 25;34(4):485-493. Epub 2021 Feb 25.

Department of Pediatric Hematology & Oncology and Bone Marrow Transplantation, Medical School of Ege University, Izmir, Turkey.

Objectives: The early and late complications after hematopoietic stem cell transplantation (HSCT) determine the patients' prognosis and life quality. We aim to determine the metabolic syndrome development frequency after HSCT in children to find out the risk factors and compare them with healthy adolescents.

Methods: Thirty-six children who underwent HSCT at least two years ago were analyzed prospectively and cross-sectionally. Our study included 18 healthy children between the ages of 11 and 17 as a control group. All of the cases were assessed in terms of metabolic syndrome (MS) through the use of Modified WHO Criteria.

Results: The patients' median age was 10.6 (5.1-17) years, the median time of follow-up after HCST was 4.1 (2-13.5) years and 70% were male. Two cases were diagnosed with MS (5.6%). When considered in terms of the sub-components of MS, 2 cases (5.6%) were found to have obesity, 17 cases (47%) abnormal glucose tolerance, 11 cases (30.7%) dyslipidemia, and 3 cases (8.6%) hypertension. The MS rate was not different when compared with the 11-17 year-old healthy control group (0 vs. 11%, p=0.48). Myeloablative conditioning regimen (65 vs. 20%) and the increased age at which HSCT was performed were considered to be risk factors in terms of insulin resistance (p=0.025 and 0.002).

Conclusions: Age and conditioning regimens were found to be the risk factors for insulin resistance development. The long-term follow-up of the cases who had undergone HSCT in childhood in terms of MS and its sub-components is important in order to increase life quality.
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http://dx.doi.org/10.1515/jpem-2020-0584DOI Listing
April 2021

Effect of pyridoxine plus pyridostigmine treatment on vincristine-induced peripheral neuropathy in pediatric patients with acute lymphoblastic leukemia: a single-center experience.

Neurol Sci 2021 Jan 13. Epub 2021 Jan 13.

Department of Pediatric Hematology and Oncology, Dr. Behçet Uz Children's Hospital, Izmir, Turkey.

Background: Vincristine (VCR), which is a key component of chemotherapy, is important for survival. VCR is associated with a well-known side effect, including neurotoxicity.

Aims: The aim of this study was to evaluate the features of vincristine-induced peripheral neuropathy (VIPN) and the effectiveness of pyridoxine plus pyridostigmine therapy in children with acute lymphoblastic leukemia.

Methods: The WHO and NCI CTCAE neurotoxicity scorings were used to evaluate VIPN at diagnosis, in the first month, and after the third month of the treatment. The clinical features of 23 patients having acute lymphoblastic leukemia with VIPN during the period of July 2013-February 2016 were prospectively evaluated.

Results: The mean age was 72.8 ± 51.6 months, and 26.1%, 56.5%, and 17.4% were in standard, moderate, and high-risk groups, respectively. Neuropathy frequently occurred at induction (82.6%) and reinduction (17.4%) of the protocol. Drop foot (82.6%), leg pain (82.6%), and difficulty in walking (82.6%) were observed. The mean total cumulative dose of neuropathy occurrence was 5.6 ± 2.03 mg/m. Our study showed that both the WHO and NCI CTCAE scorings were significantly improved via pyridoxine plus pyridostigmine therapy.

Conclusion: The WHO and NCI CTCAE scorings may be used for evaluating neuropathy at diagnosis and follow-up of neurotoxicity with treatment. Pyridoxine plus pyridostigmine therapy may be an effective option in the treatment of VIPN.
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http://dx.doi.org/10.1007/s10072-020-04970-wDOI Listing
January 2021

Children with chronic-refractory autoimmune cytopenias: a single center experience.

Turk J Pediatr 2020 ;62(4):525-532

Departments of Pediatric Hematology-Oncology, Dr. Behçet Uz Children Research and Training Hospital, İzmir, Turkey.

Background And Objectives: Autoimmune cytopenias are a group of heterogeneous disorders characterized by immune-mediated destruction of one or more hematopoietic lineage cells. The differential diagnosis of children with autoimmune cytopenias requires much time and laboratory investigations. The aim of the present study was to evaluate the clinical course and significance of autoimmune cytopenias due to immunodeficiency or autoimmune diseases in children at a single children`s hospital.

Method: Between February 1997 and September 2015, chronic/refractory autoimmune cytopenias patient data were evaluated retrospectively. Twenty-three patients were assessed in this study.

Results: The median duration of following was 2.6 years (4 months-18.5 years). The median age of diagnosis was 3.1 years (6 months-16 years). A total of 13 patients (56.5%) had single-lineage and 10 (46.5%) had multilineage cytopenias. The most frequent single-lineage cytopenia was thrombocytopenia, followed by anemia. In 22 of the patients, cytopenias was detected before the primary diseases. All of the patients were treated with corticosteroids or intravenous immune globulin as first-line treatment. Ten patients (43.5%) needed second or further-line immunosuppressive therapies that patients diagnosed as systemic lupus erythematosus, hypogammaglobulinemia, or common variable immunodeficiency. A total of 8 patients (34.7%) recovered from autoimmune cytopenias after the treatment of primer disease. Cytopenias were continued in 14 patients.

Conclusion: Cytopenia may be the first finding of an immunodeficiency or autoimmune disease and primary disease may be diagnosed in the clinical course. Taking the new targeted treatment options into consideration; early diagnosis is likely to become more important in the near-future in order to begin the treatment for the underlying disease as early as possible.
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http://dx.doi.org/10.24953/turkjped.2020.04.001DOI Listing
January 2020

Evaluation of Liver Iron Content by Magnetic Resonance Imaging in Children with Acute Lymphoblastic Leukemia after Cessation of Treatment

Turk J Haematol 2020 11 20;37(4):263-270. Epub 2020 Feb 20.

Dr. Behcet Uz Child Disease and Pediatric Surgery Training and Research Hospital, Division of Pediatric Hematology and Oncology, İzmir, Turkey

Objective: There are a limited number of studies evaluating iron overload in childhood leukemia by magnetic resonance imaging (MRI). The aim of this study was to determine liver iron content (LIC) by MRI in children with acute lymphoblastic leukemia (ALL) who had completed treatment and to compare those values with serum iron parameters.

Materials And Methods: A total of 30 patients between the ages of 7 and 18 who had completed ALL treatment were included in the study. Serum iron parameters (serum iron, serum ferritin [SF], and total iron-binding capacity) and liver function tests were studied. R2 MRI was performed for determining LIC.

Results: Normal LIC was detected in 22 (63.4%) of the cases. Seven (23.3%) had mild and 1 (3.3%) had moderate liver iron deposition. In contrast, severe iron overload was not detected in any of the cases. LIC levels were correlated with the numbers of packed red blood cell (pRBC) transfusions (r=0.637, p<0.001), pRBC transfusion volume (r=0.449, p<0.013), SF levels (r=0.561, p=0.001), and transferrin saturation (r=0.353, p=0.044). In addition, a positive correlation was found between the number of pRBC transfusions and SF levels (r=0.595, p<0.001).

Conclusion: We showed that the frequency of liver iron deposition was low and clinically less significant after the end of treatment in childhood ALL patients. LIC was demonstrated to be related to SF and transfusion history. These findings support that SF and transfusion history may be used as references for monitoring iron accumulation or identifying cases for further examinations such as MRI.
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http://dx.doi.org/10.4274/tjh.galenos.2020.2019.0364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7702656PMC
November 2020

Assessment of Self-Image With the Offer Self-Image Questionnaire in Adolescents With Hemophilia: A Single-Center Experience.

J Pediatr Hematol Oncol 2020 04;42(3):e159-e163

Departments of Pediatric Haematology.

Background: Hemophilia, which is a chronic illness associated with recurrent bleeding, may occur with psychosocial and behavioral problems.

Aim: The aim of this study was to evaluate the clinical characteristics and demographic features and changes in the self-image of adolescents with hemophilia.

Materials And Methods: Data about hemophilia type, the severity of hemophilia, secondary prophylaxis received, and annual bleeding rate (ABR) were recorded from patient files. Hemophilia Joint Health Score (HJHS) and the Offer Self-Image Questionnaire (OSIQ) (as a measure of self-esteem) were applied to hemophilia patients and a healthy control group.

Results: Thirty-two hemophilia patients (mean age=16.2±3.06 y) and 35 healthy male individuals (mean age=16.02±1.4 y) were enrolled in the study. Hemophilia patients had lower total OSIQ score than their peers (P=0.007). There was no difference between patients who received and who did not receive secondary prophylaxis (P=0.408) in terms of total OSIQ score. The median total OSIQ score of patients with pathologic HJHS (>0 points) was lower than that of patients with normal HJHS (0 points) (P=0.010). The median of ABR was 6 (range: 0 to 20) in the whole hemophilia group. There were no differences between hemophilia patients with ABR≤4 and >4 (P=0.084). All of the subscale parameters of the OSIQ were lower for hemophilia patients compared with their peers, besides one. The subscale of sexuality attitudes was better for hemophilia patients than for the healthy control group (P=0.028).

Conclusions: Low self-esteem in hemophilia patients indicates the importance of lifelong psychosocial support. Patients with pathologic HJHS are at risk of low-esteem. Using OSIQ with HJHS during follow-up of hemophilia patients may be useful for management.
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http://dx.doi.org/10.1097/MPH.0000000000001664DOI Listing
April 2020

Assessment of Serum Galactomannan Test Results of Pediatric Patients With Hematologic Malignancies According to Consecutive Positivity and Threshold Level in Terms of Invasive Aspergillosis Diagnosis: Cross-Sectional Research in a Tertiary Care Hospital.

J Pediatr Hematol Oncol 2020 07;42(5):e271-e276

Departments of Pediatric Infectious Diseases.

The aim of this study was to evaluate the diagnostic utility of serum galactomannan (GM) positivity for invasive aspergillosis (IA) in children. Positive GM results between January 2015 and August 2017 were reviewed retrospectively in children with hematologic malignancies. Single and consecutive positive GM results were evaluated according to the different galactomannan index (GMI) (>0.5, >0.7, >1.0 and >1.5) values. There were 104 positive GM results of 70 patients. IA was identified in 29 patients (41.4%) (2 proven and 27 probable). For a single positive GMI of >0.5, >0.7, >1.0, and >1.5, the numbers were 104, 76, 57, and 32 and the positive predictive values (PPVs) were 39.4%, 43.2%, 47.2%, and 50.0%, respectively. The single GM positivity at different thresholds showed no difference between the IA and non-IA group (P>0.05). For 2 consecutive positive GMI values of >0.5, >0.7, >1.0, and >1.5, the numbers were 34, 20, 13, and 4, and the PPVs were 58.8%, 65.0%, 84.6%, and 100.0%, respectively. In the IA group, positivity was higher at all thresholds (P<0.05). According to our findings, consecutive GM positivity has higher PPVs independently from the cutoff value chosen. In pediatric patients with high risk, consecutive sampling should be preferred.
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http://dx.doi.org/10.1097/MPH.0000000000001653DOI Listing
July 2020

A New Homozygous Mutation (c.393-394del TA/c.393-394del TA) in the NT5C3 Gene Associated With Pyrimidine-5'-Nucleotidase Deficiency: A Case Report.

J Pediatr Hematol Oncol 2019 Nov;41(8):e484-e486

Division of Pediatric Hematology, Dr. Behçet Uz Children's Hospital, Izmir, Turkey.

Pyrimidine-5-nucleotidase (P5'N-1) deficiency is a rare nonspherocytic hemolytic anemia due to pyrimidine nucleotide deposition within erythrocytes. This rare erythrocyte disorder shows autosomal recessive inheritance with mutation of the pyrimidine-5'-nucleotidase gene, which is localized on 7p15-p14. Consanguinity of parents increases the probability of disease with novel mutations. Here, we report a 12-year-old boy with a delayed diagnosis of P5'N deficiency whose parents were consanguineous. He had a hemoglobin level of 7.5 g/dL, mean corpuscular volume of 93 fL, 7% reticulocyte, and lactate dehydrogenase of 678 IU/L. A peripheral blood smear showed polychromasia, marked anisopoikilocytosis with schistocytes, elliptocytes, stomatocytes, spherocytes, dacryocyte, and basophilic stippling in red blood. Decreased purine/pyrimidine ratio was 1.07 (normal range=1.4 to 2.98). Molecular analysis with direct DNA sequencing of the NT5C3 gene, codifying for P5'N-1, revealed the presence of a novel homozygous mutation, c393-394delTA, in the gene coding P5'N enzyme in the patient. To our knowledge, this is a newly defined mutation in P5'N deficiency.
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http://dx.doi.org/10.1097/MPH.0000000000001482DOI Listing
November 2019

A 3-Year Retrospective Study of the Epidemiology of Acute Respiratory Viral Infections in Pediatric Patients With Cancer Undergoing Chemotherapy.

J Pediatr Hematol Oncol 2019 May;41(4):e242-e246

Pediatric Infection.

Background: Acute viral respiratory infections are common causes of febrile episodes in children. There are still limited data about distribution of acute viral respiratory infections in children with cancer.

Objective: The first aim of this study was to evaluate the viral etiology and seasonality of acute viral respiratory infection in pediatric patients with cancer in a 3-year study. Our second aim was to evaluate the impact of viral infections on delaying the patients' chemotherapy or radiotherapy.

Materials And Methods: This cross-sectional study was conducted from January 2014 to July 2017. Nasopharyngeal aspirates were analyzed in patients younger than 21 years with acute respiratory infections. Patients were treated in the Pediatric Hematology and Oncology Department of Dr. Behçet Uz Children's Hospital with real-time multiplex polymerase chain reaction. Data were analyzed to determine the frequency and seasonality of infections. The χ or the Fisher exact tests were used.

Results: A total of 219 samples of nasopharyngeal aspirates and blood were analyzed. The mean patient age was 76.8±59.3 months, with 46.3% female and 53.7% male children in a total of 108 patients. Of this total, 55% (60/108 cases) had multiple acute respiratory infections. Acute lymphoblastic leukemia (48.1%) was the most prevalent disease. The 3 most prevalent viruses were human rhinovirus (HRV) (33.1%), parainfluenza (PI) (18.7%), and coronavirus (CoV) (14.8%). In terms of the seasonal distribution of viruses, PI was most common in winter 2014, HRV in spring 2014, HRV in fall 2014, PI in winter 2015 and summer 2015, CoV in spring 2015, HRV in fall 2015, both influenza and HRV in winter 2016, both human metapneumovirus and bocavirus in spring 2016, HRV in summer 2016, both HRV and PI in fall 2016, both respiratory syncytial virus and influenza in winter 2017, HRV in spring 2017, and both HRV and adenovirus in summer 2017. The mean duration of neutropenia for patients with viral respiratory infection was 17.1±13.8 (range: 2 to 90) days. The mean duration of symptoms of viral respiratory infection was 6.8±4.2 (range: 2 to 31) days. A delay in chemotherapy treatment owing to viral respiratory infection was detected in 73 (33.3%) patients. The mean duration of delay in chemotherapy treatment was 9.6±5.4 (range: 3 to 31) days.

Conclusions: In conclusion, we report our 3-year experience about the frequency and seasonality of respiratory viruses in children with cancer.
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http://dx.doi.org/10.1097/MPH.0000000000001418DOI Listing
May 2019

Quality of Life and Depression in Turkish Patients with β-Thalassemia Major: A Cross-Sectional Study.

Hemoglobin 2018 Sep - Nov;42(5-6):326-329. Epub 2019 Jan 23.

b Clinic of Pediatric Hematology-Oncology, Sağhk Bakanlığı Üniveristesi, İzmir Dr. Behçet Uz Çocuk Sağlığı ve Cerrahisi Eğitim Araştırma Hastanesi , İzmir , Turkey.

Thalassemias are the most common monogenic disorders worldwide. Thalassemia patients experience difficulties in their schooling, finding jobs and/or marriage because of functional and physical limitations caused by this disease. It is expected that the quality of life (QoL) of patients with thalassemia will be lower than those without this disease. The aim of this study was to benefit worldwide thalassemia patients in terms of QoL and mental health. This cross-sectional study was performed in Turkey. The study population consisted of of 57 β-thalassemia major (β-TM) patients and the control group. The short form-36 (SF-36) questionnaire and Beck depression inventory (BDI) were used. The mean age of the patients was 21.6 ± 6.6 (age range 15-39) and the male-to-female ratio was 0.7. The mean SF-36 scores of the patient and the control groups were 59.2 ± 12.4 and 75.7 ± 11.8, and the mean BDI scores of the patients and controls were 13.5 ± 6.4 and 6.1 ± 3.7, respectively. There was a statistically significant difference between the total SF-36 and BDI scores of patients and controls. We aimed to investigate the effects of the decrease in morbidity and mortality of β-thalassemia (β-thal) due to regular transfusions and chelation therapy on the QoL and mental health of patients. The β-TM patients have a comparatively worse QoL score than the normal population. Improving QoL should be the target of clinicians who are monitoring adolescent or young adult β-TM patients.
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http://dx.doi.org/10.1080/03630269.2018.1551231DOI Listing
May 2019

A New Variant of PKLR Gene Associated With Mild Hemolysis may be Responsible for the Misdiagnosis in Pyruvate Kinase Deficiency.

J Pediatr Hematol Oncol 2019 01;41(1):e1-e2

Division of Pediatric Hematology, Dr. Behçet Uz Children's Hospital, Izmir, Turkey.

Pyruvate kinase deficiency (PKD) is the most common glycolytic defect leading to hemolytic anemia. PKD is caused by the mutations in the PKLR gene; however, the detection of a decreased PK activity should be first measured for rapid diagnosis. We report here the case of a 1-year-old girl with mild hemolysis and PKD. At the time of the study, the patient showed a hemoglobin level of 9.5 g/dL, mean corpuscular volume of 93 fL, reticulocyte of 6.7%, and lactate dehydrogenase of 218 IU/L. Peripheral blood smear showed polychromasia, anisocytosis, tear drop cells, fragmented eyrtrocytes, and target cells. When a biochemical analysis was performed in our patient and her parents who had consanguinity, a decreased PK activity was detected in the patient and her father. After the molecular study of PKLR gene, a new homozygote variant, c.1708G>T (pVal570Leu), was found in our patient and her father. Her father had a misdiagnosis of Gilbert syndrome because he had unconjugated hyperbilirubinemia and not anemia. Her mother was also a carrier of the mutation in heterozygous state. Patients presenting with hemolytic anemia, either severe or mild hemolytic anemia, should be screened for PKD in the first year of life. Patients with mild hemolytic findings can be followed-up with misdiagnoses.
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http://dx.doi.org/10.1097/MPH.0000000000001254DOI Listing
January 2019

Identification of a Novel Mutation in the SEC23B Gene Associated With Congenital Dyserythropoietic Anemia Type II Through the Use of Next-generation Sequencing Panel in an Undiagnosed Case of Nonimmune Hereditary Hemolytic Anemia.

J Pediatr Hematol Oncol 2018 10;40(7):e421-e423

Division of Pediatric Hematology, Dr. Behçet Uz Children's Hospital, Izmir, Turkey.

Congenital dyserythropoietic anemias (CDAs) are rare hereditary blood disorders characterized by ineffective erythropoiesis, hemolysis, and erythroblast morphologic abnormalities in the bone marrow. The 3 main types of CDA, I to III, and variant types of CDA, IV-VIII, have been described. The causative genes have been identified as CDAN1, C15ORF41, SEC23B, KIF23, KLF1, and GATA1. CDA type II is the most frequent form. Typical symptoms are jaundice, hepatosplenomegaly, mild-to-severe normocytic anemia, and inadequate reticulocyte response. We report an 18-year-old boy who had chronic mild congenital anemia, jaundice, and splenomegaly mimicking nonautoimmune hemolytic anemia since 18 months of age. Compound heterozygous mutations in SEC23B gene were detected by the use of a gene-targeted next-generation sequencing panel: the already reported missense mutation c.40C>T (p.Arg14Trp), and a new frameshift deletion (c.489_489delG, p.Val164Trpfs*3), confirming the diagnosis of CDA type II. The study underlines the molecular heterogeneity of CDA II and the importance of a precise diagnosis in rare congenital diseases such as CDA II. In consequence, it can be difficult to diagnose because of limited resources, financial constraint, and rarity of disease in the developing country. Advanced laboratories and new molecular approaches may help in diagnosing rare anemias.
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http://dx.doi.org/10.1097/MPH.0000000000001207DOI Listing
October 2018

Risk factors for bacteremia with extended-spectrum β-lactamase production in positive Escherichia coli bacteremia in a pediatric setting.

Am J Infect Control 2017 12;45(12):1414-1415

Department of Pediatric Infectious Diseases, Dr. Behçet Uz Children's Hospital, İzmir, Turkey.

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http://dx.doi.org/10.1016/j.ajic.2017.08.023DOI Listing
December 2017

Evaluation of the Clinical and Laboratory Characteristics of Previously Followed-up Thalassemia Intermedia Patients to Provide Them Better Care in the Future.

J Pediatr Hematol Oncol 2017 08;39(6):440-444

*Department of Pediatric Hematology, Dokuz Eylül University Hospital †Department of Pediatric Hematology-Oncology, Tepecik Research Hospital, İzmir, Turkey.

The increased awareness about the severity of complications in thalassemia intermedia patients led authorities to develop strategies for better management and follow-up of these patients. In this study, we aimed to define the clinical and laboratory characteristics in previously followed-up β-thalassemia intermedia patients and wanted to gain an insight about the follow-up of this patient population in a developing country to provide them better care in the future. The mean age at diagnosis was 4 years, and the mean hemoglobin was 7.13 g/dL. The mean age at the beginning of regular transfusion was 4.8 years. An overall 74% of patients were on a regular transfusion program. The mean ferritin values at diagnosis and the last follow-up were 487 and 1225 ng/mL, respectively. The most common mutations detected in patients were IVS-I-110, IVS-I-6, IVS-II-1, and FCS 8/9 in order of frequency. Complications were seen in 48% of patients. The most common complications were osteopenia/osteoporosis (34%), growth retardation (24%), hypogonadism (18%), and cardiomyopathy (13%). In conclusion, the relatively higher complication rate in our patients who were previously treated highlights once again the need for an increased effort for optimal management and follow-up of this specific group of patients.
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http://dx.doi.org/10.1097/MPH.0000000000000914DOI Listing
August 2017

Idiopathic Pulmonary Hemosiderosis Mimicking Iron Deficiency Anemia: A Delayed Diagnosis?

Hematol Rep 2017 Jun 15;9(2):7048. Epub 2017 Jun 15.

Division of Pediatric Hematology, Dr. Behçet Uz Children's Hospital, İzmir, Turkey.

Idiopathic pulmonary hemosiderosis (IPH) is an uncommon chronic disorder in children. It is characterized by recurrent pulmonary hemorrhage and may result in hemoptysis and pulmonary insufficiency. The most common hematologic manifestation of IPH is iron deficiency anemia. The etiology of IPH is not known and its diagnosis may be difficult due to the variable clinical courses. The most helpful signs for identifying IPH are iron deficiency anemia and recurrent or chronic cough, hemoptysis, dyspnea, wheezing. We report here 5 pediatric cases of IPH presenting with iron deficiency anemia and without pulmonary symptoms. Mean corpuscular volume was low in all patients; iron was low in 4 out of 5 cases; total iron binding capacity was high in all of them; ferritin was low in 3 patients. At follow up, none of them had responded successfully to the iron therapy. Although they didn't present with pulmonary symptoms, chest radiographs incidentally revealed diffuse reticulonoduler shadows in all of them. Computed tomography revealed diffuse ground-glass opacities, consolidation, increased density. The diagnosis was confirmed by the detection of hemosiderin-laden macrophages in bronchoalveolar lavage fluid and gastric aspirate. If patients with iron deficiency anemia don't respond to iron therapy, they should be examined for IPH. Chest radiographs should be taken even in absence of pulmonary symptoms. Early diagnosis is important for a timely management of IPH.
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http://dx.doi.org/10.4081/hr.2017.7048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5477471PMC
June 2017

Clinical accuracy of non-contact infrared thermometer from umbilical region in children: A new side.

Turk J Pediatr 2016 ;58(2):180-186

Pediatric Infectious Diseases, Dr. Behcet Uz Children's Training and Research Hospital, İzmir, Turkey.

Measurement from axillary site with digital thermometer has been accepted as the most accurate method. But this method is time consuming. Tympanic and forehead measurements are often used but don't always seem to be more appropriate. Another site, umbilical region, could be an alternative site. This study aims to compare the measurements with axillary digital thermometer and non-contact infrared thermometers at sites from umbilicus and forehead to determine whether umbilical site could be used accurately in children. For each method, 2,048 measurements in total were performed. Using axillary method as gold standard, with a cut-off temperature of 38oC, the sensitivities and specificities, positive and negative predictive values of umbilical and forehead temperatures and area under the ROC curve were determined in non obese children. There was a significant positive correlation between axillary and umbilical temperatures with a correlation coefficient of 0.78. The average difference between the mean of both axillary and umbilical temperatures was -0.47 ± 0.65°C. The Bland-Altman plot showed good accuracy with only 2.5 % of the readings falling outside the 95% level of confidence. Umbilical measurements showed sensitivity of 71.7% and specificity of 95.8%. The area under the ROC curve was 0.93. The easy application may lead noncontact measurements from umbilicus site to be the preferable method for health care providers, but agreement limits mentioned in this study should be considered.
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http://dx.doi.org/10.24953/turkjped.2016.02.009DOI Listing
May 2017

Early Diagnosis and Hematopoietic Stem Cell Transplantation for IL10R Deficiency Leading to Very Early-Onset Inflammatory Bowel Disease Are Essential in Familial Cases.

Case Reports Immunol 2016 6;2016:5459029. Epub 2016 Sep 6.

Faculty of Medicine, Department of Pediatric Immunology, Ege University, Izmir, Turkey.

Alterations of immune homeostasis in the gut may result in development of inflammatory bowel disease. A five-month-old girl was referred for recurrent respiratory and genitourinary tract infections, sepsis in neonatal period, chronic diarrhea, perianal abscess, rectovaginal fistula, and hyperemic skin lesions. She was born to second-degree consanguineous, healthy parents. Her elder siblings were lost at 4 months of age due to sepsis and 1 year of age due to inflammatory bowel disease, respectively. Absolute neutrophil and lymphocyte counts, immunoglobulin levels, and lymphocyte subsets were normal ruling out severe congenital neutropenia and classic severe combined immunodeficiencies. Quantitative determination of oxidative burst was normal, excluding chronic granulomatous disease. Colonoscopy revealed granulation, ulceration, and pseudopolyps, compatible with colitis. Very early-onset colitis and perianal disease leading to fistula formation suggested probability of inherited deficiencies of IL-10 or IL-10 receptor. A mutation at position c.G477A in exon of the gene, resulting in a stop codon at position p.W159X, was identified. The patient underwent myeloablative hematopoietic stem cell transplantation from full matched father at 11 months of age. Perianal lesions, chronic diarrhea, and recurrent infections resolved after transplantation. IL-10/IL-10R deficiencies must be considered in patients with early-onset enterocolitis.
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http://dx.doi.org/10.1155/2016/5459029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5028855PMC
September 2016

Comparison of the BD GeneOhm VanR assay and a chromogenic agar-based culture method in screening for vancomycin-resistant enterococci in rectal specimens of pediatric hematology-oncology patients.

Turk J Pediatr 2015 Mar-Apr;57(2):161-6

Department of Pediatrics, Dr. Behçet Uz Children's Hospital, İzmir, Turkey.

VRE species are an increasingly important and universal problem in intensive care units and hematology-oncology departments due to the spread of glycopeptide resistance. Rapid and accurate identification of VRE is therefore crucial. The intent of this study was to compare the diagnostic performance of a real-time PCR test, the BD GeneOhm VanR assay (GeneXpert vanA/ vanB, Cepheid, USA), with conventional cultures for screening hospitalized immunocompromised hematology-oncology patients for VRE. Three hundred and six duplicate rectal swab specimens were obtained from 120 pediatric hematology-oncology patients. PCR and conventional culture-based studies were performed. One hundred and twenty patients, 46 female and 74 male, participated in the study. The mean age of the patients was 7.5±4.7 years. A total of 51 specimens from 306 samples were found to be positive for vanA or vanB. Mean turnaround time for PCR was 0.5±0.2 days. Compared to the culture method, the RT-PCR assay had an overall sensitivity of 91.8% (34/37) and a specificity of 93.6%. The positive predictive value and negative predictive value were 66.6% and 98.8%, respectively. This study demonstrates that RT-PCR is a suitable alternative to culture-based procedures for rapid and accurate identification of VRE in hematology-oncology patients, as the overall performance of PCR is comparable to that of a chromogenic agar-based culture method for VRE screening, especially for detection of VRE-negative patients.
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August 2016

Secondary hemophagocytic lymphohistiocytosis in children with brucellosis: report of three cases.

J Infect Dev Ctries 2015 Oct 29;9(10):1172-6. Epub 2015 Oct 29.

Sütçü Imam University Medical School, Kahramanmaraş, Turkey.

Brucellosis is a systemic zoonotic infectious disease that may cause fever, fatigue, sweating, arthritis, hepatosplenomegaly, cytopenia, and lymphadenopathy. It continues to be an important health problem worldwide. Hemophagocytic lymphohistiocytosis (HLH) is characterized by fever, hepatosplenomegaly, cytopenias, high serum levels of ferritin and triglycerides, low serum fibrinogen levels, and hemophagocytosis in bone marrow, lymph nodes, spleen, or liver. Hemophagocytic lymphohistiocytosis associated with brucellosis is a very rare condition in the pediatric age group. Here, three pediatric cases of secondary HLH associated with brucellosis are reported. Hemophagocytic lymphohistiocytosis should be considered in patients with brucellosis having cytopenias. Hemophagocytosis in brucellosis seems to be cured with appropriate antibiotics and intravenous immunoglobulin.
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http://dx.doi.org/10.3855/jidc.6090DOI Listing
October 2015

Management of Two Juvenile Myelomonocytic Leukemia Patients According to Clinical and Genetic Features.

Turk J Haematol 2015 Jun;32(2):175-9

Dokuz Eylül University Faculty of Medicine, Department of Pediatric Hematology, İzmir, Turkey Phone: +90 232 412 61 41 E-mail:

Juvenile myelomonocytic leukemia (JMML) is a rare clonal myeloproliferative disorder of childhood. Major progress has been achieved in diagnosis and the understanding of the pathogenesis of JMML by identifying the genetic pathologies that occur in patients. Mutations of RAS, NF1, PTPN11, and CBL are found in approximately 80% of JMML patients. Distinct clinical features have been reported to be associated with specific gene mutations. The advent of genomic studies and recent identification of novel genetic mutations in JMML are important not only in diagnosis but also in the management and prognosis of the disease. Herein, we present 2 patients with JMML harboring different mutations, NRAS and c-CBL, respectively, with distinct clinical features and different therapeutic approaches.
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http://dx.doi.org/10.4274/tjh.2014.0034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451488PMC
June 2015

B-cell-activating factor, a proliferation inducing ligand and co-stimulatory molecules in the pathogenesis of immune thrombocytopenia in childhood.

Blood Coagul Fibrinolysis 2016 Jul;27(5):494-9

aDepartment of Pediatric Hematology, Dokuz Eylül University Faculty of Medicine bDepartment of Pediatric Hematology and Oncology, Dr Behçet Uz Children's Hospital cDokuz Eylül University Faculty of Medicine, Laboratory of Hematology, Izmir, Turkey.

The aim of this study was to measure the levels of B-cell-activating factor (BAFF), a proliferation-inducing ligand (APRIL), and co-stimulatory molecules in immune thrombocytopenia (ITP) of childhood to investigate the interaction between T and B lymphocytes and the impact of proliferation of B lymphocytes in the pathogenesis. Twenty newly diagnosed ITPs, 20 chronic ITPs, and 20 healthy controls between 2 and 18 years were enrolled in this study. Hemogram, BAFF, APRIL, interleukin-4, and interferon (IFN)-γ levels in sera and expressions of CD19, CD 3, CD21, CD40, and CD 154 on leukocytes were measured by ELISA and flow cytometry. Mean BAFF level in newly diagnosed ITP group was higher than the mean BAFF level in other groups. BAFF levels were significantly decreased after the treatment in newly diagnosed ITP group. APRIL, interleukin-4, and IFN-γ in newly diagnosed ITP group and BAFF, APRIL, interleukin-4, and IFN-γ in chronic ITP group were similar before and after treatment. There was no statistical difference for expressions of CD 19 and CD3 on lymphocytes, CD40 on leukocytes, CD154 on T cells, and for percentages of CD21/CD40, CD21/CD40, CD21/CD40 B cells, and CD19/CD3 lymphocytes for pretreatment and posttreatment levels in both ITP groups. In conclusion, our study strongly demonstrated that BAFF has an important role in the pathogenesis of newly diagnosed childhood ITP. It may be important in the follow-up and in novel therapy modalities of these patients.
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http://dx.doi.org/10.1097/MBC.0000000000000144DOI Listing
July 2016

The long-term results of childhood acute lymphoblastic leukemia at two centers from Turkey: 15 years of experience with the ALL-BFM 95 protocol.

Ann Hematol 2014 Oct 27;93(10):1677-84. Epub 2014 May 27.

Department of Pediatric Hematology, Faculty of Medicine, Uludağ University, Bursa, Turkey.

Dramatic progress in the treatment of childhood acute lymphoblastic leukemia (ALL) has been achieved during the last two decades in Western countries, where the 5-year event-free survival (EFS) rate has risen from 30 to 85 %. However, similarly high cure rates have not always been achieved in all centers in developing countries due to limited sources. We evaluated the treatment results of the ALL-Berlin-Frankfurt-Münster (BFM) 95 protocol as used between 1995 and 2009 in the pediatric hematology departments of two university hospitals. A retrospective analysis of 343 children newly diagnosed with ALL (M/F 200/143, median age 6.8 years) was performed. The overall survival (OS) and EFS according to age, initial leukocyte count, immunophenotype, chemotherapy responses (on days 8, 15, and 33), and risk groups were analyzed by Kaplan-Meier survival analysis. Median follow-up time was 6.4 years. Complete remission was achieved in 97 % of children. Five-year EFS and OS were found to be 78.4 and 79.9 %, respectively. Children younger than 6 years old had significantly better EFS and OS (83.7 and 85.2 %) than children aged ≥6 years (71.4 and 72.8 %). Adolescents achieved 63 % EFS and 65 % OS. Patients who had initial leukocyte counts of <20 × 10(9)/L had better EFS and OS (82.2 and 84.6 %) than children with higher initial leukocyte counts (72.6 and 72.6 %). EFS for B-cell precursor and T-cell ALL was 81.5 and 66.7 %, respectively. Children with a good response to prednisolone on day 8 (87 %) achieved significantly better EFS and OS (81.2 and 81.9 % vs. 55.3 and 60.5 %). Children whose bone marrow on day 15 was in complete remission had higher EFS and OS (83.7 and 86.6.1 % vs. 56.4 and 61.5 %). Children in the standard-risk and medium-risk groups obtained statistically significantly higher EFS (95.5 and 82.7 %) and OS (97.7 and 82.3 %) compared to the high-risk group (EFS 56.3 %, OS 63.4 %). The relapse rate was 14.8 %. The median relapse time from diagnosis was 23.2 months. Death occurred in 69 of 343 patients (20.1 %). The major causes of death were infection and relapse. None of the patients died of drug-related toxicity. The ALL-BFM 95 protocol was applied successfully in these two centers. In developing countries in which minimal residual disease cannot be monitored, this protocol can still be used with high survival rates.
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http://dx.doi.org/10.1007/s00277-014-2106-0DOI Listing
October 2014

Secondary bacteremia in rotavirus gastroenteritis.

Pediatr Infect Dis J 2014 Jul;33(7):775-7

From the *Department of Pediatrics; †Department of Pediatric Infectious Diseases; ‡Department of Microbiology and Clinical Microbiology; and §Nurse, Infection Control Committee, Dr. Behçet Uz Children's Training and Research Hospital, İzmir, Turkey.

The aim of the study was to determine the frequency of secondary bacteremia in children with rotavirus gastroenteritis and persistence or reemergence of fever. We identified 376 children with a mean of age of 14.2 ± 10.1 months. A significant pathogen was isolated from blood cultures in 5 patients [Enterococcus faecium (n = 1), Klebsiella spp (n = 1), Staphylococcus aureus (n = 1), Raoultella planticola (n = 1), Candida albicans (n = 1); 1.3%]. The frequency of secondary bacteremia in children with rotavirus gastroenteritis is low, but it should be considered when there is fever lasting >48 hours or reemergence of fever.
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http://dx.doi.org/10.1097/INF.0000000000000324DOI Listing
July 2014

A single center's experience with Candida parapsilosis related long-term central venous access device infections: the port removal decision and its outcomes.

Pediatr Hematol Oncol 2014 Aug 2;31(5):435-41. Epub 2014 Jan 2.

1Division of Pediatric Infectious Disease, Dr. Behçet Uz Children's Hospital, İzmir, Turkey.

Pediatric cancer patients have an increased risk of potentially life-threatening fungal infections such as Candida parapsilosis, associated with long-term CVADs. The Infectious Diseases Society of America (IDSA) guidelines on Candida catheter-related bloodstream infections recommend systemic antifungal therapy and catheter removal. In this study, we focused on our experience with antifungal failure due to totally implanted catheter-associated C. parapsilosis bloodstream infections. We investigated cases leading to port removal in pediatric malignancy patients and the associated patient outcomes. In the first phase of the study, a retrospective chart review was performed to collect patient information, including primary disease; time from hospitalization to port-related candidemia; antifungal drug choice; and the time at which port removal occurred. During the second phase, antifungal susceptibility tests for C. parapsilosis were performed in our microbiology laboratory. All patients had fevers and were neutropenic at the time of candidemia diagnosis. The mean duration between the first isolation of Candida parapsilosis from the port samples to the port removal was 9.75 ± 5.29 days for 11 patients. Patient fevers lasted for a mean time of 16.22 ± 6.51 days. The median recovery duration from fever after CVC removal was four days (range 2-12 days). The median duration for achieving negative blood cultures, following antifungal treatment was 18 days (range 10-27 days). Our data favored the removal of catheters in the presence of ongoing fever, as suggested by the guidelines, independent of the chosen antifungal treatment. Future studies with large samples are needed to evaluate the effects of catheter removal on mortality rates and patient outcomes.
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http://dx.doi.org/10.3109/08880018.2013.862587DOI Listing
August 2014

Clinical accuracy of tympanic thermometer and noncontact infrared skin thermometer in pediatric practice: an alternative for axillary digital thermometer.

Pediatr Emerg Care 2013 Sep;29(9):992-7

From the *Department of Pediatric Infectious Diseases, Behçet Uz Children's Hospital; †Department of Pediatric Hematology, Dokuz Eylül University Hospital; and Departments of ‡Pediatrics and §Pediatric Intensive Care, Behçet Uz Children's Hospital, İzmir, Turkey.

Introduction: The aim of this study was to compare the body temperature measurements of infrared tympanic and forehead noncontact thermometers with the axillary digital thermometer.

Methods: Randomly selected 50 pediatric patients who were hospitalized in Dr Behcet Uz Children's Training and Research Hospital, Pediatric Infectious Disease Unit, between March 2012 and September 2012 were included in the study. Body temperature measurements were performed using an axillary thermometer (Microlife MT 3001), a tympanic thermometer (Microlife Ear Thermometer IR 100), and a noncontact thermometer (ThermoFlash LX-26).

Results: Fifty patients participated in this study. We performed 1639 temperature readings for every method. The average difference between the mean (SD) of both axillary and tympanic temperatures was -0.20°C (0.61°C) (95% confidence interval, -1.41°C to 1.00°C). The average difference between the mean (SD) of both axillary and forehead temperatures was -0.38 (0.55°C) (95% confidence interval, -1.47°C to 0.70°C). The Bland-Altman plot showed that most of the data points were tightly clustered around the zero line of the difference between the 2 temperature readings. With the use of the axillary method as the criterion standard, positive likelihood ratios were 17.9 and 16.5 and negative likelihood ratios were 0.2 and 0.4 for tympanic and forehead measurements, respectively.

Discussion: The results demonstrated that the infrared tympanic thermometer could be a good option in the measurement of fever in the pediatric population. The noncontact infrared thermometer is very useful for the screening of fever in the pediatric population, but it must be used with caution because it has a high value of bias.
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http://dx.doi.org/10.1097/PEC.0b013e3182a2d419DOI Listing
September 2013

Multicentric plasma cell type of castleman disease in a child: difficulty in diagnosis and treatment.

J Pediatr Hematol Oncol 2013 Oct;35(7):e306-8

Department of Pediatric Hematology, Dokuz Eylül University Faculty of Medicine, Izmir, Turkey.

Multicentric plasma cell variant of Castleman disease (CD) has rarely been reported and the optimal therapeutic approach is unknown, especially in childhood. In this case report, we discuss the case of a 7-year-old boy with multicentric plasma cell variant of CD, who presented with cervical lymphadenopathies, autoimmune hemolytic anemia, bone marrow insufficiency, pulmonary, renal, hepatic, and gastrointestinal involvement, emphasizing the difficulty in diagnosis and treatment approach.
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http://dx.doi.org/10.1097/MPH.0b013e31829cdd2aDOI Listing
October 2013

The evaluation of protein Z levels of children with acute lymphoblastic leukaemia during induction therapy.

Blood Coagul Fibrinolysis 2013 Jun;24(4):375-80

Department of Pediatrics, Dokuz Eylül University Faculty of Medicine, Izmir, Turkey.

The objective of this study was to evaluate the protein Z levels of children with acute lymphoblastic leukaemia (ALL) during induction therapy. Although several studies investigated the association between steroid and L-asparaginase (L-ASP) administration and levels of coagulation proteins such as protein C, protein S and antithrombin in children with ALL, protein Z levels have not been examined in any study yet. Peripheral blood was drawn from the study group before chemotherapy (PZ0) at diagnosis, at 12th day (PZ1), 15th day (PZ2), 18th day (PZ3) and 21st day (PZ4) of treatment wherein L-ASP treatment is given along with steroid administration according to ALL BFM-1995 chemotherapy protocol. Plasma protein Z levels were measured by enzyme immunoassay method. Mean protein Z level at PZ0 was 1.628 ± 0.485 μg/ml in the study group and 1.672 ± 0.662 μg/ml in the control group. No statistical difference was observed. In the study group, there was a slight increase in protein Z levels between the PZ0 and PZ1 periods in which only steroid therapy was administered. Statistically significant decrease was observed between protein Z levels in PZ0-PZ4, PZ1-PZ2, PZ1-PZ3, PZ1-PZ4 and PZ3-PZ4 periods. During the induction treatment, symptomatic haemorrhage or thrombosis was not followed up in any patients. We demonstrated that children with ALL have similar protein Z values to those of the control group at diagnosis. A significant decrease occurs at the end of the induction treatment with steroid and L-ASP administration. However, this deficiency does not result in development of symptomatic thrombosis or bleeding in these patients.
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http://dx.doi.org/10.1097/MBC.0b013e32835d06f1DOI Listing
June 2013

A case with unexplained bleeding from multiple sites: munchausen syndrome by proxy.

Pediatr Hematol Oncol 2011 Aug;28(5):439-43

Department of Pediatric Hematology, Dokuz Eylul University Faculty of Medicine, Izmir, Turkey.

Munchausen syndrome by proxy (MBP) is an extreme form of child abuse where children were unnecessarily treated or investigated for medical conditions that were falsified by their caregivers. Here the authors report a 16-year-old female with the complaints of bleeding from multiple and unusual sites, including hemoptysis, hematuria, bloody tears, and bloody nipple discharge, all of which are only witnessed by her mother. Extensive investigation revealed no organic etiologies for bleeding. The diagnosis of MBP was put by a multidisciplinary team. The diagnosis of MBP must be kept in mind in conditions where there is no underlying organic pathology in a bleeding patient.
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http://dx.doi.org/10.3109/08880018.2011.565493DOI Listing
August 2011

A rare complication of intrathecal methotrexate in a child with acute lymphoblastic leukemia.

Pediatr Hematol Oncol 2011 Sep 24;28(6):517-22. Epub 2011 Jun 24.

Department of Pediatric Hematology, Dokuz Eylul University, Izmir, Turkey.

Methotrexate (MTX) is an essential component of chemotherapy for childhood acute lymphoblastic leukemia (ALL). Both intravenous and most commonly intrathecal routes of MTX have been implicated in acute, subacute, and chronic neurotoxicity syndromes. Subacute MTX neurotoxicity occurs within days to weeks after the intravenous or intrathecal therapy and characterized by a distinct presentation with remarkable clinical resemblance to stroke, including hemiparesis, hemisensory deficits, aphasia, dysarthria, dysphagia, and diplopia. Herein the authors describe the clinical and typical neuroimaging features of a female patient with ALL who presented with subacute MTX neurotoxicity that rapidly progressed to a severe clinical condition in a few hours but eventually resolved completely with dexamethasone and folinic acid. Subacute MTX neurotoxicity is a transient neurological dysfunction that should be considered in patients presenting with stroke-like and various neurological symptoms 10 to 14 days after intrathecal therapy and diffusion-weighted magnetic resonance imaging should be undertaken for the correct diagnosis and exclusion of possible ischemic infarct. Discontinuation of subsequent intrathecal MTX therapies should be considered in severe cases and treatment with dexamethasone and folinic acid may help to resolve the symptoms.
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http://dx.doi.org/10.3109/08880018.2011.563773DOI Listing
September 2011

Vitamin A status of healthy children in Manisa, Turkey.

Nutr J 2010 Sep 1;9:34. Epub 2010 Sep 1.

Celal Bayar University, Faculty of Medicine, Department of Pediatrics, Manisa, Turkey.

Background: Vitamin A deficiency is a major public health nutrition problem in the developing world. Even subclinical Vitamin A deficiency is associated with increased childhood mortality. Severe maternal vitamin A deficiency may cause increased mortality in the first months of life. There have been a limited number of studies regarding vitamin A status in Turkey. The aim of this study was to assess vitamin A status of healthy children in Manisa, Turkey.

Methods: Vitamin A status of 100 healthy children aged 36-48 months is evaluated. The children were seen during routine examination. Serum retinol concentrations were measured by high-performance liquid chromatography. Duration of breast feeding, age solid foods introduced, use of supplementary vitamins, weight and height, and intake of specific groups of nutrients on a daily, weekly and monthly basis were collected from a questionnaire completed by the mothers. Height and weight z-scores were calculated according to national standards. Mothers of 20 of the 100 children were known to have normal serum and breast milk retinol concentrations. Children with normal serum retinol concentration were compared with the children with VAD. Student's t-test and Mann-Whitney test were used to compare independent variables. The Pearson correlation analysis test was used to test relation between numeric variables.

Results: Mean retinol concentration was 0.98 ± 0.32 μmol/L in the whole study group. Serum retinol concentrations were normal (>0.70 μmol/L) in 89% of the children. When children with normal serum retinol concentrations were compared with those with retinol concentrations lower than 0.70 μmol/L, there was no difference in terms of age, gender, weight and height at the time of study, z-scores, birth weight, birth length, duration of breast feeding, time to begin solid food, rate of supplementary vitamin use, and rate of infections (P > 0.05). There was not any relation between vitamin A concentrations and weight and height at the time of study, z-scores, birth weight, birth length, duration of breast feeding, time to begin solid food, vitamin use, and frequency of intake of specific groups of nutrients (P > 0.05).

Conclusions: This study showed that VAD is a moderate health problem in Manisa.
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http://dx.doi.org/10.1186/1475-2891-9-34DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2940924PMC
September 2010