Deniz Tekin

Arg753Gln polymorphism of the human Toll-like receptor 2 gene from infection to disease in pediatric tuberculosis

The aim of this study is to examine the occurrence of the Arg753Gln polymorphism of the Toll-like receptor 2 (TLR2) gene in Turkish children with pulmonary and/or extrapulmonary tuberculosis (TB) disease compared with that in healthy children with latent TB infection (LTBI) and to assess the risk of progression from LTBI to active TB disease in children. The Arg753Gln polymorphism of the TLR2 gene was studied in 198 TB patients compared with 200 ethnically and age-matched children with LTBI. The culture confirmed TB patients were more frequently Arg753Gln heterozygous [odds ratio (OR) 5.05, 95% confidence interval (95% CI) 2.61-9.76, p = 0.00], and Gln allele frequency was significantly higher in the patient group (13.86% vs 3.5%, OR 4.40, 95% CI 2.34-8.30, p = 0.00). We also showed that the frequencies of the heterozygous Arg753Gln genotype and the Gln allele were significantly higher in patients with pulmonary TB alone and in patients with definitive pulmonary plus extrapulmonary TB than in children with LTBI. Our data suggest that the Arg753Gln polymorphism of the TLR-2 gene influences the speed of progression from infection to TB disease in children. Further investigations are needed to clarify whether this polymorphism has a strong impact on susceptibility to TB in children.

Relationship between Toll-Like Receptor 8 Gene Polymorphisms and Pediatric Pulmonary Tuberculosis

Objectives: Genetic variants in Toll-like receptors (TLRs) are considered a potential indicator for host susceptibility to and outcome of several infectious diseases including tuberculosis. The aim of this study was to determine whether −129 C/G and Met1Val polymorphisms of TLR8 were associated with pediatric pulmonary tuberculosis in Turkish population. Methods: The −129 C/G and Met1Val polymorphisms were studied in 124 children with pulmonary tuberculosis compared to 150 age-matched healthy control subjects. Results: We did not identify any statistically significant differences between the patients with TB and control groups with regard to the frequency of genotypes GG or G/(−), CG, and CC or C/(−); and alleles G and C at rs3764879 (p > 0.05). We found a strong association with genotype A/(−) at rs3764880 with susceptibility to pulmonary TB in males (OR 2.87, 95%CI 1.38–5.98, p = 0.007). Conclusions: Our results provide evidence, for the first time, of a role for the TLR8 gene in susceptibility to pulmonary TB in male children. Additional research to verify our results are necessary. Tuberculosis in children presents particularly difficult challenges, but research priorities and advances in pediatric tuberculosis could provide wider insights and opportunities for tuberculosis control.

The effects of metallothionein 2A polymorphism on placental cadmium accumulation: Is metallothionein a modifiying factor in transfer of micronutrients to the fetus?

Metallothionein affects the metabolism, transport and storage of micronutrients such as zinc, copper and iron, and the detoxification of heavy metals, especially cadmium. Cd is a common, highly toxic environmental pollutant that accumulates in human placenta, elevated concentrations of which are associated with impaired zinc transfer to the fetus. This prospective study investigated the effects of metallothionein 2A (MT2A) −5 A/G single nucleotide polymorphism on the accumulation of Cd in human placenta and micronutrient transfer to the fetus in 95 pregnant women and their newborns. Venous blood from the mother was collected to investigate Cd, Zn, Cu, Fe levels and MT2A polymorphism. Cord blood from the neonate and placenta was collected for metal levels. MT2A polymorphism was determined by the standard PCR‐restriction fragment length polymorphism technique. Metal levels were analyzed by Atomic Absorption Spectrometry (AAS). Maternal blood Cd levels were statistically higher for mothers with a heterozygote genotype compared with a homozygote genotype (P < 0.05). In contrast, placental Cd levels were significantly higher in mothers with a homozygote rather than a heterozygote genotype (P < 0.05). No difference existed in cord blood Cd, Zn and Cu levels. However, cord blood Fe levels of newborns with heterozygote genotype mothers were higher than in others. Placental Cd levels of heterozygote genotype mothers were negatively associated with Zn in cord blood. Cd exposure at environmental levels may be associated with alteration of the umbilical cord micronutrient levels for newborns with mothers of a heterozygote genotype. Copyright

Polymorphism in the p2x7 gene increases susceptibility to extrapulmonary tuberculosis in Turkish children.

The P2X7 gene polymorphisms have been linked to increased risk for pulmonary and extrapulmonary tuberculosis in some populations. In this study, the genotype and allelic frequencies 1513A→C variant within the P2X7 gene was significantly higher than in the healthy controls (P = 0.035, P = 0.041). This is the first study demonstrating that the 1513A→C polymorphism is associated with extrapulmonary tuberculosis in children.

Establishment of interdisciplinary child protection teams in Turkey 2002–2006: Identifying the strongest link can make a difference!

OBJECTIVES The University of Iowa Child Protection Program collaborated with Turkish professionals to develop a training program on child abuse and neglect during 2002-2006 with the goals of increasing professional awareness and number of multidisciplinary teams (MDT), regional collaborations, and assessed cases. This paper summarizes the 5-year outcome. METHODS A team of instructors evaluated needs and held training activities in Turkey annually, and provided consultation when needed. Descriptive analysis was done via Excel and SPSS software. RESULTS Eighteen training activities were held with 3,570 attendees. Over the study period, the number of MDTs increased from 4 to 14. The MDTs got involved in organizing training activities in their institutions and communities. The number of medical curriculum lectures taught by MDTs to medical students/residents, conferences organized by the MDTs, and lectures to non-medical professional audiences increased significantly (R(2)=91.4%, 83.8%, and 69.2%, respectively). The number of abuse cases assessed by the MDTs increased by five times compared to pre-training period. CONCLUSIONS A culturally competent training program had a positive impact on professional attitudes and behaviors toward recognition and management of child abuse and neglect in Turkey. The need to partner with policy makers to revise current law in favor of a greater human services orientation became clear. PRACTICE IMPLICATIONS Pioneers in developing countries may benefit from collaborating with culturally competent instructors from countries with more developed child protection systems to develop training programs so that professional development can improve recognition and management of child abuse and neglect.

Importance of NOD2/CARD15 gene variants for susceptibility to and outcome of sepsis in Turkish children

Objective: Severe sepsis remains a leading cause of morbidity and mortality in children. Given the link to pathogenesis, polymorphisms in genes involved in infection and inflammation may influence the outcomes in patients with sepsis and septic shock. The role of mutations within the innate immunity receptor NOD2/CARD15 has recently been demonstrated as a risk factor for bacteremia and mortality in adult patients with sepsis. The aim of this study was to evaluate the role of mutations of the NOD2/CARD15 gene in pediatric patients with sepsis. Design: Prospective cohort study. Setting: A tertiary care, ten-bed, pediatric intensive care unit. Patients: One hundred twenty-eight patients with sepsis admitted to the pediatric intensive care unit and healthy control group were included. Interventions: Venous blood from the children with sepsis and healthy controls was collected to investigate common polymorphisms (Arg702Trp, Gly908Arg, Leu1007fsincC) within the NOD2/CARD15 gene. Standard polymerase chain reaction restriction fragment length polymorphism technique was used to determine NOD2/CARD15 gene polymorphism. Measurement and Main Results: R702W, G908R, and Leu1007fsinsC variants in the NOD2/CARD15 gene were determined as significant risk factors associated with susceptibility to sepsis (p = .025, p = .031, p = .014, respectively). Sepsis-related mortality was increased in children carrying the Leu1007fsinsC variant (p = .041). Conclusions: The present article is the first report of clinical implications of NOD2/CARD15 gene variants in children with sepsis. Our findings suggest that common polymorphisms in the NOD2/CARD15 gene may play a major role in susceptibility to sepsis and the outcome of sepsis in children.

Effects of the interleukin-6 (IL-6) polymorphism on toxic metal and trace element levels in placental tissues

The placenta is a crucial organ of fetal origin that functions in providing nutrients to the fetus from the mother. During pregnancy, the need for essential micronutrients, such as Fe and Zn, increases due to the requirements of the growing fetus. Maternal Fe deficiency induces an increase in Cu levels and can also affect cytokine levels in the placenta. On the other hand, Cu deficiency, although not as common, can also have destructive effects on the fetus. Interleukin-6 (IL-6) is a pleiotropic cytokine with a wide range of biological activities, including such as immune responses, acute-phase reactions, and inflammation. The placenta produces a significant amount of IL-6 during pregnancy. The effects of the IL-6 -174 G/C single nucleotide polymorphism (SNP) on IL-6 gene transcription and on plasma cytokine levels were assessed in the present study. We investigated the association between the IL-6 -174 G/C polymorphism and trace element/toxic metal levels in placental tissues. For the purposes of this study, 95 healthy volunteers were evaluated. Presence of the IL-6 polymorphism was determined using the standard polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) technique, and metal levels were analyzed by atomic absorption spectrometry (AAS). Based on our data, there were no significant associations between the IL-6 -174 G/C polymorphism and Pb, Cd, Fe, or Zn levels in the placental tissues (p>0.05), but a statistically significant association was detected between the polymorphism and Cu levels (p=0.016). We determined that the mean Cu levels in the placental tissues from individuals with GG, GC and CC genotypes were 5.62±1.98, 6.22±3.22 and 8.00±1.32 ppm, respectively, whereas the overall mean Cu level from the placental tissues was 5.98±2.51 ppm.

New challenges of the pediatric emergency department: synthetic cannabinoids

To the Editor, In recent years, the frequency of use of synthetic cannabinoid (SC) has increased in the adolescent age group (1). While it is known as “K2”, “Spice”, “Aroma”, ”Mr.Smiley”, “Zohai”, “Eclipse”, “Black Mamba”, “Red X Dawn”, “Blaze”, the name “Bonzai” has come to the forefront in our country (2). Synthetic cannabinoids are sprayed on plants, are sold in packages with warnings including “natural plant mixture”, “incense”, ‘’not for human use” and is consumed like cigarette (3). It is important to recognize poisonings due to this kind of substances the content and dosage of which are unclear and to perform appropriate interventions. In this article, it was aimed to present a 17-year old male patient who presented to the pediatric emergency department after usage of SC after obtaining verbal consent and to draw attention of physicians working in pediatric emergency departments to this issue. A 17-year old male patient was brought to the pediatric emergency department by 112 ambulence because of headache, muscle aches, nervousness, restlessness and drowsiness following use of SC. The Glascow coma scale was found to be 15 and systemic examination and vital findings were found to be normal. It was learned that he was using depakin because of epilepsy and had no additional illness. In his history, it was learned that he started to use SC approximately 6 months ago, obtained the substance from street vendors and used SC like cigarette. He was not using any other illegal substance or alcohol. He did not attend the school and was working as an errand-boy in industry. Complete blood count, blood biochemistry and electrocardiography were found to be normal. It was thought that his complaints arised from SC. Nervousness and restlessness improved after 5 mg oral diazepam. No additional problem developed during the 6-hour follow-up period. He was discharged to be referred to the Alcohol and Substance Addicts Research and Treatment Center. A significant increase has occured in substance abuse and related mortality in recent years. In our country, 12 deaths related with substance abuse were reported in 2000, whereas this figure reached 147 in 2007 (4). The frequency is increasing in the adolescence because of low price and easy accessibility. The issue is in the news in visual and printed media almost everyday and a growing number of cases present to emergency departments. Adolescents may abuse substance because of many different reasons. Individual risk factors include antisocial personality, agressiveness, hyperacitivity and chronic diseases. Environmental risk factors include intra-familial violence, parents who abuse illegal substances, weak family bonds and exposure to abuse. Social risk factors include easy accessibility of illegal subtances, poverty, unemployment and a high rate of crime in the area of residence (5). In our case, presence of underlying epilepsy and working as an employee in industry instead of attending the school were thought to be risk factors. In the diagnosis, the most important clue is a history of usage of SC. In patients with cognitive, behavioral and mood disorders, usage of SC should be suspected, if sympatomimetic findings are present additionally. The signs and symptoms reported after use of synthetic cannaboid are shown in Table 1. The laboratory tests are generally within the normal limits, but they should be performed to find additional pathologies. SC can not be determined with standard toxicological screening tests. Table 1. Signs and symptoms reported after use of synthetic cannabinoid (1) The mainstay of treatment consists of supportive therapy. Patients should be monitored in a quiet and calm room at an appropriate temperature and treatment should be planned according to the clinical findings. It has been shown that agitation improves with long-acting benzodiazepines and dystonia improves with diphenhydramine (1). It is important to interrogate patients in terms of abuse of additional substances other than SC and to perform additional therapeutical interventions if necessary. Following urgent treatment and follow-up patients should be referred to appropriate psychiatry and substance addiction treatment centers.

Tekrarlayan Orbital Myozitli Bir Olgu

Non-spesifik orbital inflamasyon sendromlari (orbital psodotumor) oldukca heterojen bir hastalik grubudur. Orbital myozit bu grubun bir ya da birden cok orbital kasini tutan bir alt tipidir. Cocuklarda oldukca ender gorulmektedir. Tedavide ilk tercih olarak kortikosteroidler kullanilir. Tedaviye yanitsiz hastalarda radyoterapi ve bagisiklik sistemini baskilayici gibi tedavi secenekleri denenmektedir. Nadiren de olsa kendiliginden gerileyen olgular bildirilmistir

Strengthening the role of children's emergency services in the prevention of peer abuse.

To the Editor, Peer abuse is harmful and agressive behavior exerted continuously and recurrently by an individual or a group on another person of about the same age who is weaker in which strength is abused. This agressive behavior may emerge with different clinical pictures ranging from emotional trauma to physical trauma and even mortality (1). Children who are exposed to peer abuse and especially the ones with findings of physical injury present to pediatric emergency services. Pediatric emergency physicans should play the role of a bridge by providing assessment of the findings of physical trauma of the child who is the victim as well as assessment of acute and potential chronic psychiatric problems. This case was presented to increase the level of awareness of the physicans who work in emergency services which are the primary centers where children exposed to peer abuse are presented. A 17-year old girl who was attecked in school presented to the pediatric emergency service in accompaniment of her parents. It was learned that the subject was exposed to verbal attack primarily and physical attack secondarily. On physical examination, no pathological finding was observed except for tenderness and limitation in mobility in the neck. Her radiological tests were found to be normal. A forensic report was prepared and the subject was started to be folowed up by the Child Psychiatry and Child Protection Unit. It was learned that the subject was recorded to another school 3 months ago because of change of residence. The family stated that their daughter did not wish to attend school recently, her academic success decreased and they evaluated this status as the adaptation process for the new school. In the interview with the subject, it was learned that she was being indirectly abused (threats, insinuations and glares) for about three months by a group who terrorized school and exhibited agressive behavior. In the following interviews, it was learned that the subject was molested by hand by an adult male who was a friend of the family three years ago, but she could not tell this event to anybody since she was scared. The subject is still being followed up by the Child Protection Unit and Department of Child Psychiatry. Peer abuse is an important public health problem. Repeated attitudes and behaviors directed to harm a weaker individual at about the same age by a stronger individual and group are evaluated as peer abuse (2, 3). In individuals who are exposed to peer abuse, increased risks of depression, anxiety, substance abuse, suicide attempt and delinquency are observed frequently in addition to physical trauma (3, 4). In addition, it should be kept in mind that children who present to emergency services with repeated non-specific physical complaints might have been exposed to peer abuse (1). Children who are found to have unexplained physical injuries, who have low academic success, who have learning difficulty, who do not wish to attend school and who appear sad and depressive are under risk (1, 3). It has been emphasized that peer abuse is a considerably serious threat for our country and prevention and intervention programs should be developed. Our subject was exposed to verbal abuse primarily and physical abuse secondarily. It was learned that the academic success of our subject considerably decreased in the new school she started and she did not wish to attend school. However, these early warning signs which were interpreted as a school adaptation process were ignored by the family and early intervention and suppport were delayed. Therefore, such complaints should be cared about and the subjects should be evaluated in terms of peer abuse. Child victims are usually sensitive and anxious and have a low self-confidence. Children who have weak family relations, who have been exposed to neglect and abuse, who have chronic disease or disability constitute the target group for peer abuse (3, 5, 6). Our subject had no physical defect, but she had been exposed to sexual abuse before, hid this event, since she was scared and blamed herself. The self-confidence of our subject who was not supported at the time of this first event she experienced decreased, her strenght to cope with other problems decreased and she became a target for peer abuse. Peer abuse should not be evaluated as a transient, harmless and normal part of development by physicans working in emergency services who primarily meet child victims. Accordingly, the care of the children in question should not be terminated at discharge and a multidisciplinary approach together with child psychiatry and social units should be planned and initiated. If physicans working in pediatric emergency departments recognize peer abuse and start the necessary initiatives supporting the child at risk, they would play a very important part in solution of this public health problem. Therefore, the level of awareness of physicians working in pediatric emergency services should be increased in the scope of peer abuse prevention and intervention programs.