A Bayesian Network Meta-Analysis of the Effect of Targeted Therapies on the Total Length of Hospital Stay in Children with Drug-Induced Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis Syndrome.

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare potentially life-threatening hypersensitivity disorders characterized by widespread skin and mucosal involvement. However, there is no standardized evidence-based treatment to reduce the complications of SJS/TEN. This article aims to compare the efficacy of different treatments for pediatric SJS/TEN in terms of length of hospital stay (LOS) using a Bayesian network meta-analysis (NMA). A Bayesian NMA is used to compare and combine evidence from multiple studies and allows clinicians to estimate the relative effectiveness of different treatments/interventions while accounting for heterogeneity in the available evidence. Methods: We conducted a comprehensive electronic database search for studies compatible with our inclusion criteria. Six studies with 103 patients were included in the NMA; of them, 37 patients were treated with intravenous immunoglobulin (IVIG), 37 with systemic corticosteroids (CS), 23 with IVIG + CS, and 3 with Etanercept (ET) + CS. Patients with a median age of 10 years were included in the study. Results: CS had the highest probability of being the most optimal treatment for SJS/TEN in terms of shorter LOS based on the Surface Under the Cumulative Ranking curve levels, and CS + IVIG was associated with a statistically nonsignificant trend toward shorter LOS than IVIG alone. Remarkably, none of the treatments showed a significant benefit over the other interventions in terms of LOS. Conclusion: Current evidence suggests that coadministration of CS and IVIG may be associated with a shorter LOS than IVIG alone. Further research with larger randomized controlled trials is needed to reach a definitive conclusion about the efficacy of specific therapy on LOS in pediatric SJS/TEN and to establish more definitive treatment guidelines.

Lower Arginine Bioavailability, Increased FeNO Levels, and Airway Resistance on Impulse Oscillometry Are Characteristics of Asthma in Children and Young Adults with Sickle Cell Disease.

Background and Objectives: Data on characteristics of asthma in children with sickle cell disease (SCD) is conflicting. Recently, the L-arginine pathway has gained attention in the pathogenesis of asthma and SCD. This study aimed to determine the distinctive clinical and laboratory features and the role of arginine metabolism in asthmatic children with SCD. Materials and Methods: A total of 52 children and adolescents with SCD, including 24 with asthma (SCD-A) and 28 without asthma (SCD-NA), and 40 healthy controls were included. A questionnaire, atopy tests, fractional exhaled nitric oxide (FeNO), and lung function tests were employed. Serum metabolites of the arginine pathway were measured. The results of the three groups were compared. Results: The demographic characteristics and atopy markers of the three groups were similar. FEV1%, FEV1/FVC, MMEF%, and total lung capacity (TLC%) values of SCD-A patients were not significantly different from the SCD-NA group, but they were significantly lower than the values measured in the controls. FeNO values greater than 35 ppb were present only in the SCD-A group. In impulse oscillometry, median resistance values at 5 Hz (R5)% were higher in both SCD subgroups than in healthy controls (p = 0.001). The (R5-20/R5)% values were higher in the SCD-A group (p = 0.028). Serum arginine levels and arginine bioavailability indices were significantly lower in the SCD-A group than in the SCD-NA group and healthy controls (p = 0.003 and p < 0.001). Conclusions: Asthma in children with SCD was not associated with atopy or low FEV1/FVC levels. However, lower arginine bioavailability and higher FeNO levels differentiated asthma in patients with SCD. High R5% and (R5-20/R5)% values indicated increased airway resistance in SCD, with a predominance of small airway disease in asthmatics.

Protective effect of paricalcitol in rat testicular damage induced by subchronic 1800 MHz radiofrequency radiation.

In the present study, the possible protective effects of paricalcitol (P) were investigated in testicular damage because of 1800 MHz radiofrequency radiation (RFR) exposure. Male Sprague Dawley rats 8-10 weeks old (n = 28) were randomly divided into four groups as control (C) (n = 7), RFR (n = 7, 1800 MHz RFR 1 h/day for 30 days), P (n = 7, 0.2 µg/kg paricalcitol, 3 times a week for 30 days), and RFR + P (n = 7, 1800 MHz RFR 1 h/day for 30 days +0.2 µg/kg paricalcitol, 3 times a week for 30 days). Testicular tissue was evaluated with histological and biochemical methods. No statistically significant differences were detected between the groups in seminiferous tubule diameters and germinal epithelial thicknesses. While ultrastructural changes were observed in the seminiferous tubule and Leydig cells in the RFR group, these changes were decreased in the RFR + P group. It was found that the Johnsen Score, Ki67, and p63 immunoreactivity scores (IRS), superoxide dismutase (SOD), and catalase (CAT) activities in the RFR + P group were statistically increased as compared to the RFR group and the malondialdehyde (MDA) levels were decreased statistically and significantly. These results show that paricalcitol administration may have an ameliorative effect on testicular damage occurring because of 1800 MHz RFR exposure.

Circulating MicroRNAs in the Screening of Prenatal Down Syndrome.

OBJECTIVE: Screening tests are recommended to identify genetic defects, chromosomal aneuploidies, and structural birth defects. Sonographic and maternal serum-based options are available for the risk assessment of aneuploidy in the first and/or second trimester. Also, invasive diagnostic methods, such as amniocentesis, are used for prenatal diagnosis, but these methods carry a tangible risk to the fetus. However, in recent years, circulating fetal nucleic acids have a promising moleculer tool in the noninvasive prenatal diagnosis of fetal chromosomal aneuploidies. In this study, we aimed to explore the usability of microRNAs (miRNAs) in this process of prenatal diagnosis. METHODS: Fourteen pregnant patients who were found to be carrying fetuses with congenital anomalies were designated as the patient group; 16 pregnant women identified as being at risk of carrying children with such anomalies-but whose fetuses were later found to be anomaly-free-were assigned to control group 1; and 13 pregnant women who had been screened and who had not been identified as being at risk made up control group 2. An analysis of miRNA expression, isolated from maternal plasma and amniotic fluid samples, was performed by quantitative real-time polymerase chain reaction. RESULTS: It was found that hsa-miR-629-5p, hsa-miR-320c, hsa-miR-21-5p, hsa-let-7c-5p, hsa-miR-98-5p, hsa-miR-486-5p, hsa-miR-4732-5p, and hsa-miR-181a-5p levels increased in the patient group's maternal plasma compared to that of the control group. CONCLUSION: In light of these data, we believe that miRNAs may have an important role in the noninvasive prenatal diagnosis of fetal birth defects, especially Down syndrome.

Expression and Characterization of a New Self-Sufficient P450 Monooxygenase (P450 AZC1) from Azorhizobium caulinodans.

Oxyfunctionalization of non-activated carbon bonds by P450 monooxygenases has drawn great industrial attraction. Self-sufficient P450s containing catalytic heme and reductase domains in a single polypeptide chain offer many advantages since they do not require external electron transfer partners. Here, we report the first P450 enzyme identified and expressed from Azorhizobium caulinodans. Firstly, expression conditions of P450 AZC1 were optimized for enhanced expression in E.coli. The highest P450 content was obtained in E.coli Rosetta DE3 plysS when it was incubated in TB media supplemented with 0.75 mM IPTG, 0.5 mM ALA, and 0.75 mM FeCl3 at 25 °C for 24 hours. Subsequently, the purified enzyme showed a broad substrate spectrum including fatty acids, linear and cyclic alkanes, aromatics, and pharmaceuticals. Finally, P450 AZC1 showed optimal activity at pH 6.0 and 40 °C and a broad pH and temperature profile, making it a promising candidate for industrial applications.

Arthroscopic Bankart repair improves upper limb exercise capacity, shoulder function and quality of life.

BACKGROUND: Anterior glenohumeral instability is an important cause of shoulder disability. The aim of the present study was to investigate arm exercise capacity in patients with anterior glenohumeral instability before and after arthroscopic Bankart repair and to compare the results with those of healthy controls. METHODS: The patient group included a total of 11 males between the ages of 18 and 40 years. The control group consisted of 13 healthy males with an age range of 23 to 41 years. An incremental arm crank exercise test was performed to determine upper limb exercise capacity, as expressed by peak oxygen consumption (VO2peak). The shoulder function of the patients was evaluated by the Western Ontario Shoulder Instability Index (WOSI), and the quality of life was assessed with the Short Form-36 (SF-36). All evaluations were performed preoperatively, and at the postop 3rd and 6th months. RESULTS: The patient group had lower VO2peak and exhaustion duration at the preoperative assessment (p = 0.025 and p = 0.007, respectively). SF-36 domains were lower in patients (p < 0.05). There were significant differences in VO2peak between preoperative and postop 6th-month measurements and between postop 3rd and 6th-month measurements (p < 0.001 and p = 0.001, respectively). The total WOSI score increased from preoperative 50.27% to 57.77% at the postop 3rd month, and to 65.56% at the final follow-up. Although improvements were detected in all SF-36 domains at postop follow-ups, they were not statistically significant except role limitations due to the physical problems domain (p = 0.006). There were no significant differences between controls and patients at the postop 3rd and 6th months with regard to exercise test parameters except the peak rating of perceived exertion. DISCUSSION: Shoulder function, exercise capacity, and quality of life were lower in the patient group and improved after arthroscopic Bankart repair. Clinicians should use the exercise capacity assessment for the evaluation of the recovery of shoulder function after providing stabilization.

Evaluation of developmental profiles of children with hydrocephalus.

OBJECTIVE: The objective of this study was to compare the developmental characteristics of children with hydrocephalus with those of healthy children. MATERIAL AND METHODS: A total of 109 children aged between 2 and 46 months were included in the study, 54 patients diagnosed with hydrocephalus and 55 healthy children were evaluated with demographic data forms and Denver Developmental Screening Test II. RESULTS: The mean personal-social (p<0.001), fine motor-adaptive (p<0.001), language (p<0.001), and gross motor subscale scores were significantly lower in children with hydrocephalus than in the control group. Personal-social (p=0.002) and gross motor (p=0.029) subscale scores were significantly lower in children with obstructive hydrocephalus than communicating hydrocephalus. There was a significant negative correlation between language scores and ages of the children with hydrocephalus (r=-0.350, p=0.009). It was found that children with obstructive hydrocephalus carry a 6.7 folds higher risk of experiencing problems in terms of personal-social development compared to those with communicating hydrocephalus (p=0.011). CONCLUSION: We found that patients with hydrocephalus were developmentally retarded compared to the healthy control subjects. Retardation was the most prominent in the obstructive group. Our results showed that neurodevelopmental follow-up should be carried-out regularly in pediatric patients with hydrocephalus, and early intervention should be started in necessary cases.

Beliefs and behaviors of patients' relatives towards childhood epilepsy in Turkey.

BACKGROUND/AIM: Beliefs about health-related problems throughout history are conveyed differently. Unsafe practices based on the superstitious beliefs of patients' relatives in situations requiring emergency medical attention, such as childhood epilepsy, or in the treatment of chronic diseases may be harmful to children's health. Our study aims to determine the superstitious beliefs, attitudes, and behaviours of the relatives of children with epilepsy. METHODS: A total of 252 relatives of patients diagnosed with childhood epilepsy were included in this cross-sectional study conducted between 15 September and 15 October 2019. The data collection form contained questions about the sociodemographic information of the participants and their beliefs and behaviours towards the disease. The frequency (percentage) and mean were used to summarise the data obtained through the application of the questionnaire, and Student's t-test and correlation methods were used for group comparisons; p < 0.05 was considered statistically significant. RESULTS: In the study, 77.0% of the participants were women, 77.4% were mothers, 43.3% were primary school graduates, 71.8% were unemployed, 77.7% had a low income, 52% lived within a distance of less than 1 km, and 157 of them used folk medicine. There was no relationship between education, income, distance from health institutions, occupation, use of traditional methods, and superstitions. A relationship was found between the relatives of patients with resistant epilepsy who stated that the cause of the disease was superstition (p = 0.036). There was also a correlation between the use of traditional methods (p = 0.006), presence of resistant epilepsy, indication of the cause of the disease as superstition (p = 0.004), and use of traditional methods (p = 0.005). CONCLUSION: Our study shows that approximately four-fifths of the participants had superstitious beliefs about epilepsy and exhibited attitudes and behaviours suggestive of neglect that are unsafe for children. Whilst the individual characteristics of the participants did not affect negative attitudes and behaviours, the presence of resistant epilepsy in their children increased the negative attitude tendency.

A combined risk modeling strategy for clinical prediction of beta-lactam allergies in children.

Background: Drug provocation test (DPT) without skin tests is increasingly recommended in the evaluation of children with low-risk beta-lactam (BL) allergies. However, risk definitions are unclear. Objective: The aim of this study was to compose a clinical predictive model that could identify the children at low risk who could safely undergo direct DPT. Methods: The clinical data of 204 children who underwent a full diagnostic algorithm for suspected BL allergy were analyzed. Clinical data were used to construct mathematical predictive model for confirmed BL allergies. A prospective new sample was used for external validation of the final model. Results: The presentations during the index reaction were anaphylaxis in 5.9% and cutaneous reactions in the majority. BL allergy was confirmed in 15.7% of suspected cases. A backward multiple logistic regression model showed that a family history of drug allergy (adjusted odds ratio [aOR], 5.52), anaphylaxis (aOR, 5.14), any atopic disease other than asthma (aOR, 4.38), and a reaction interval of 0-6 hours during the index reaction (aOR, 5.32) were significantly associated with a confirmed BL allergy. A mathematical combined model based on these factors showed a sensitivity of 77.8% and a negative predictive value (NPV) of 94.3%. The validation study replicated sensitivity and NPV values of the main cohort. Conclusion: The risk definition in BL allergies should depend on population-specific predictive models, including a combination of significant risk factors rather than empiric risk approaches. This may help to accurately determinate children at low risk who may safely proceed to direct DPT.

Developmental evaluation in children experiencing febrile convulsions.

BACKGROUND: The objective of this study was to determine the effect of febrile convulsion (FC) on neuromotor development. METHODS: Data of 325 patients, who were followed up at our outpatient clinic and diagnosed with FC between January 2012 and December 2018, were retrospectively evaluated. Of these patients, 203 underwent the Denver Developmental Screening Test II (DDST II) and were included in the study as the patient group and 100 healthy children as the control group. RESULTS: Of the study group, 84 (41.4%) were girls and 119 (58.6%) were boys (B/G: 1.4). Of all patients, 163 (80.3%) were diagnosed with simple FC, 22 (10.8%) with complicated FC, and 18 (8.9%) with FC+. There was no significant relationship found between FC subtypes and gender, family history of FC, family history of epilepsy, iron (Fe) deficiency, and Fe deficiency anemia. DDST II subtest points were significantly lower in all developmental areas in the patient group when compared to the controls (p < 0.001), while suspected and abnormal test results were higher in all developmental areas in the patient group compared to the controls (p=0.01). It was also determined that the language points were lower as the age of first seizure increased (r=- 0.319, p < 0.01). CONCLUSIONS: Although FC is known to usually having a good prognosis, the low DDST II test results measured in this study indicated that the FC may pose a developmental risk and patients with FC should be followed up in terms of developmental features. Because of the retrospective nature of the study, there was no `preconvulsion` developmental evaluation. This is a major limitation of our study.

Neurodevelopmental risk evaluation of premature closure of the anterior fontanelle.

PURPOSE: To evaluate neurological development of completely healthy children with anterior fontanelle premature closure via Denver Developmental Screening Test II and to compare the results with control group. METHOD AND RESULTS: The records of 140 patients applied to Mersin University Pediatric Neurology Outpatient Clinic between 2011 and 2019 with the complaint of premature closure of the anterior fontanelle were retrospectively reviewed. Patients with microcephaly, craniosynostosis, infection, sequelae of hypoxia-ischemia, metabolic disorders, intracranial hemorrhage, epilepsy, endocrine problems, and dysmorphic features were excluded from the study. Sixty-six completely healthy children with anterior fontanelle premature closure were included in the study. Denver Developmental Screening Test II was performed by the same developmental specialist to the children with premature closure of the anterior fontanelle as well as to the healthy control group. For each child included in the case and the control group, 90% of the values for each development area were calculated and recorded. Then, the results were compared. Denver II Developmental Screening Test (p < 0.001) and gross motor subtest (p < 0.001) results showed statistically significant retardation in the case group compared with the control group. CONCLUSIONS: The study was the first study in the literature on the gross motor development of children with premature closure of anterior fontanelle, and it has been found significantly undeveloped compared with the control group, and it has been concluded that similar patients should be evaluated from this view point in pediatric neurology department.

Efficacy of levetiracetam in the treatment of Sydenham chorea.

BACKGROUND: To study the effect of levetiracetam in treating Sydenham chorea. METHODS: We retrospectively collected the data of 140 patients diagnosed with Sydenham chorea in the pediatric neurology and pediatric cardiology outpatient clinics of Van Training and Research Hospital between January 2010 and December 2018. RESULTS: There were 140 patients, 102 (70%) of whom were girls, with mean age of onset 11.8 ± 2.7 years. Symptomatic treatment was initiated in all patients at the time of diagnosis; this medication was changed during follow up in 15 patients. The most frequently prescribed drugs were haloperidol and sodium (Na) valproate, and the most frequently discontinued one was haloperidol, due to side effects. The second-choice drug was most often levetiracetam. Clinical response often began within the first 2 weeks, with Na valproate (P = 0.002), within 4 weeks with carbamazepine (P = 0.037) but 1-6 months with haloperidol (P = 0.018) and levetiracetam (P = 0.008). Time to full remission was similar with Na valproate, carbamazepine, haloperidol, and levetiracetam (P = 0.276). Our study indicated that levetiracetam was as effective as the other commonly used drugs in the symptomatic treatment of Sydenham chorea. CONCLUSION: Levetiracetam might be an option in the treatment of Sydenham chorea because of its acceptable effect and safety profile. This observation needs further support with evidence obtained through controlled and blinded trials.

Topical Application of High-Dose Mesna Prevents Adhesion Formation: An Experimental Animal Study.

BACKGROUND: Adhesion formation is a common complication of abdominal surgeries. Mesna is a drug with fibrinolytic properties which has been used in surgical field to facilitate tissue dissection. The aim of this experimental animal study was to investigate the effect of mesna on prevention of intra-abdominal adhesion in rats. MATERIALS AND METHODS: Twenty-eight Wistar albino rats were used in the study. To create abdominal adhesion, cecum was abraded in all rats. No additional surgical procedure was performed other than adhesion in group 1 (only adhesion). In the other groups, rats were treated topically by administering 0.9% saline (group 2), 40 mg/kg mesna (group 3), and 400 mg/kg mesna (group 4). All rats were sacrificed on postoperative 21st day. Histopathological and macroscopic evaluations of adhesion formation were performed. RESULTS: Quantity of adhesion scores (P = 0.022), severity of adhesion scores (P = 0.041), total adhesion scores (P = 0.023), and histopathological adhesion grading scores (P < 0.001) were reduced by 400 mg/kg mesna. CONCLUSIONS: This is the first study for mesna on prevention of abdominal adhesion formation in rats. We concluded that dose-dependent reduction of adhesion was achieved by mesna. With future studies, topical administration of mesna during open abdominal surgeries may be used to prevent adhesion formation.

Investigation of possible effects of microRNAs involved in regulation of lipid metabolism in the pathogenesis of atherosclerosis.

Due to being stable in the circulatory system plasma miRNAs have been detected in various diseases including coronary artery disease (CAD) which is the major cause of mortality and morbidity worldwide. Atherosclerosis is the major cause of CAD. The first and most important event in the progression of atherosclerosis is endothelial dysfunction and accumulation of the lipids in the arterial wall. Recent studies have shown that different expression levels of lipid metabolism-related miRNAs associated with the pathogenesis of atherosclerosis. Therefore, in this current study, we aimed to investigate the possible effects of lipid metabolism-related miRNAs in plasma of patients with CAD. miRNA analysis was performed by high throughput quantitative PCR method using RNA samples isolated from 46 patients with CAD and 43 non-CAD or control. Data were analyzed using SPSS software version 17 and GeneGlobe Data Analysis Center by Qiagen. Among 40 miRNAs, 4 miRNAs were markedly up-regulated while 4 miRNAs were down-regulated in patients with CAD compared to the control group. The results have shown that, hsa-mir-144-3p, hsa-miR-222-5p and hsa-miR-133a-5p were statistically different in the patient with CAD compared to the control (p = 0.040, 0.030 and 0.005 respectively). Increased expression of hsa-mir-144-3p, hsa-miR-222-5p and hsa-miR-133a-5p would have associated with presence of the CAD. Furthermore, we suggested that these miRNAs might have been useful markers for early detection of the CAD.

Alterations in energy consumption and plantar pressure distribution during walking in young adults with patellofemoral pain syndrome.

OBJECTIVE: The aim of this study was to determine the alterations of walking energy expenditure and plantar pressure distribution in young adults with patellofemoral pain syndrome (PFPS). METHODS: Thirty five individuals (mean age: 21.31 ± 1.76) with PFPS constituted the patient group and forty healthy participants (mean age: 21.40 ± 2.11) the control group. Preferred walking speeds (PWS) were determined on the over ground. Individuals walked on a treadmill for 7 min at their PWS and 30% above PWS and oxygen consumption was recorded via a metabolic analyzer. Net oxygen consumption was calculated for each walking trial. Borg scale was applied to assess perceived exertion during walking trial. Plantar pressure distributions were measured by a pedobarography device. Plantar area was subdivided into six zones to evaluate the dynamic plantar pressure data. RESULTS: The mean PWS of PFPS and control groups were 4.69 ± 0.51 and 4.52 ± 0.60 km/h, respectively (p > .09). No significant difference was observed in energy expenditure during walking at PWS between 2 groups while oxygen consumption during 30% above PWS was higher in patient group (18.72 ± 3.75 and 16.64 ± 3.27) (p = .007). Net oxygen consumption was also found to be higher in PFPS group (15.12 ± 3.62 and 13.04 ± 3.24) (p = .005). The mean Borg scores were significantly higher in PFPS group at each walking trials (p < .001). No statistically significant difference was found between weight distribution (%) of symptomatic and nonsymptomatic extremity (50.45 ± 3.92% and 49.56 ± 3.93%, respectively) (p = .509). Dynamic pedobarography parameters were not different between 2 groups, and also between symptomatic and nonsymptomatic extremities (p > .05). CONCLUSION: Although, rate of perceived exertion and energy expenditure during walking at 30% above PWS are affected negatively in young adults with PFPS, we may speculate that energy consumption and plantar pressure distribution can be compensated by a physiologic adaptation mechanism during walking at PWS. LEVEL OF EVIDENCE: Level III, Therapeutic Study.

Genetic Predisposition to Unexplained Recurrent Pregnancy Loss: Killer Cell Immunoglobulin-Like Receptor Gene Polymorphisms as Potential Biomarkers.

AIM: The aim of this study was to investigate the association between killer cell immunoglobulin-like receptor (KIR) gene polymorphisms and unexplained recurrent pregnancy loss (URPL). MATERIALS AND METHODS: This study included 70 URPL patients with a history of two or more miscarriages and 70 healthy multiparous women as a control group. KIR genotyping was performed in all subjects for the KIRs 2DL1-4 and 2DS1-5 genes using polymerase chain reaction with sequence-specific primers. RESULTS: There was a significant relationship between the KIR genotypes and URPL. We demonstrated that the KIR 2DL1, 2DL2, 2DL3, 2DL4, 2DS1, 2DS2, 2DS4, and 2DS5 polymorphisms are associated with URPL. The 2DS3 genotype was not detected in either the case or control group. Gene-gene interactions for all genes were statistically significant. The KIR Bx genotype was found primarily in the case group, and at a higher frequency when compared with the control group. There was a significant relationship between the URPL cases and Bx haplotypes. CONCLUSION: We demonstrated that the KIR 2DL1, 2DL2, 2DL3, 2DL4, 2DS1, 2DS2, 2DS4, and 2DS5 polymorphisms are associated with URPL. The 2DS3 genotype of the KIR gene, however, was not detected in either the case or control group. The observations reported herein on KIR genotyping offer a new avenue for innovations in biomarker research concerning URPL and other complex obstetrics diseases.

The airway hyperresponsiveness to methacholine may be predicted by impulse oscillometry and plethysmography in children with well-controlled asthma.

OBJECTIVE: Airway hyperresponsiveness (AHR) is a hallmark of asthma. Methacholine challenge test which is mostly used to confirm AHR is not routinely available. The aim of this study was to investigate the predictive values of fractional exhaled nitric oxide (FeNO), impulse oscillometry (IOS), and plethysmography for the assessment of AHR in children with well-controlled asthma. METHODS: 60 children with controlled allergic asthma aged 6-18 years participated in the study. FeNO measurement, spirometry, IOS, and plethysmography were performed. Methacholine challenge test was done to assess AHR. PC20 and dose response slope (DRS) of methacholine was calculated. RESULTS: Mild to severe AHR with PC20 < 4 mg/ml was confirmed in 31 (51.7%) patients. Baseline FeNO and total specific airway resistance (SRtot)%pred and residual volume (RV)%pred levels in plethysmography were significantly higher and FEV1%pred, FEV1/FVC%pred, MMEF%pred values were lower in the group with PC20 < 4 mg/ml. FeNO, SRtot%pred, and RV%pred levels were found to be positively correlated with DRS methacholine. The higher baseline FeNO, frequency dependence of resistance (R5-R20) in IOS and SRtot%pred in plethysmography were found to be significantly related to DRS methacholine in linear regression analysis (ß: 1.35, p = 0.046, ß: 4.58, p = 0.002, and ß: 0.78, p = 0.035, respectively). The cut-off points for FeNO and SRtot% for differentiating asthmatic children with PC20 < 4 mg/ml from those with PC20 ≥ 4 mg/ml were 28 ppb (sensitivity: 67.7%, specificity: 72.4%, p < 0.001) and 294.9% (sensitivity: 35.5%, specificity: 96.6%, p = 0.013), respectively. CONCLUSION: IOS and plethysmography may serve as reliable and practical tools for prediction of mild to severe methacholine induced AHR in otherwise "seemingly well-controlled'' asthma.

Discrepancies in the diagnosis and classification of nonsteroidal anti-inflammatory drug hypersensitivity reactions in children.

BACKGROUND: Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently encountered in daily clinical practice. The aim of this study was to determine the confirmation rates, risk factors of NSAID hypersensitivity in children and to try to classify them with a standardized diagnostic protocol. METHODS: All patients with a suspicion of NSAID-induced hypersensitivity were evaluated with European Network for drug Allergy (ENDA) recommendations. The children were classified as selective responders (SRs) or cross-intolerant (CI) depending on the drug provocation test (DPT) results. RESULTS: We evaluated 106 children with a suspicion of NSAID hypersensitivity. NSAID hypersensitivity was confirmed with tests in 31 patients; 4 (12.9%) were diagnosed by skin tests and 27 (87.1%) by DPTs and two patients with a history of anaphylaxis by medical records. Eleven patients (33.3%) were classified as SRs, whereas twenty-two (66.6%) children as CIs. SRs and CIs were further classified as NSAID-induced urticaria/angioedema (n = 8), NSAID-exacerbated cutaneous disease (n = 6) and NSAID-exacerbated respiratory disease (n = 1) and single NSAID-induced urticaria/angioedema and/or anaphylaxis (n = 11). Eight (24.2%) patients could not be categorized according to ENDA/GA2LEN classification; one CI patient could not be classified based on pathomechanisms, seven CIs could not be categorized based on the underlying disease and clinical manifestations. A reaction within an hour of drug intake (aOR:3.0, 95% confidence interval: 1.18-7.67, p = 0.021), a history with multiple NSAIDs hypersensitivity (aOR:2.9, 95% confidence interval: 1.16-7.60, p = 0.022), and family history of atopy (aOR:4.0, 95% confidence interval: 1.50-10.82, p = 0.006) were found as the independent risk factors related to confirmed NSAID hypersensitivity. CONCLUSIONS: This study suggests the presence of different phenotypes which do not fit into the current classifications in children with NSAID hypersensitivity.

The characteristics of indoor and outdoor fungi and their relation with allergic respiratory diseases in the southern region of Turkey.

Indoor and outdoor fungal exposure has been shown to be associated with the development of allergic respiratory diseases. The aim of the study was to investigate the types and concentrations of airborne fungi inside and outside homes and evaluate the association between fungal levels and allergic diseases in the southern region of Turkey. A total of 61 children admitted with respiratory complaints to the pediatric allergy clinic between September 2007 and November 2008 were included in this study. The air samples were obtained using the Air IDEAL volumetric air sampler longitudinally for 1 year. A comprehensive questionnaire was used for medical history and housing conditions. Skin prick test was performed to determine fungal sensitivity and spirometric indices were employed. The predominant indoor fungal species were Cladosporium (69.3 %), Penicillium (18.9 %), Aspergillus (6.5 %), and Alternaria (3.1 %). A strong correlation between indoor and outdoor fungal levels was detected for the Cladosporium species (p < 0.001, r = 0.72) throughout the year. Living in a detached home (p = 0.036) and the presence of cockroaches (p = 0.005) were associated with total indoor fungal levels. The presence of cockroaches (aOR 3.5; 95 % CI 0.95-13.10, p = 0.059) was also associated with fungal sensitization at the edge of significance. The statistical cutoff values of indoor and outdoor Cladosporium levels to predict symptomatic asthma were found to be >176 CFU/m(3) (p = 0.003, AUC 0.696; sensitivity 65.5 %; specificity 68.7 %) and >327 CFU/m(3) (p = 0.038; AUC 0.713; sensitivity 66.6 %; specificity 76.9 %), respectively. Children with respiratory symptoms are exposed to a considerable level of fungi inside and outside their homes. The prevention of fungal exposure may provide valuable intervention for respiratory diseases.

Folate metabolism gene polymorphisms and risk for down syndrome offspring in Turkish women.

AIMS: Down syndrome (DS) is the most common chromosomal abnormality. Many studies have assessed the association between maternal gene polymorphisms involved in folate metabolism and the risk of having a DS offspring, but data are conflicting. Six common polymorphisms in folate-metabolizing genes were analayzed to determine possible risk factors for a child to be born having DS (DS mothers); these samples were taken from 47 Turkish mothers having DS children (case group) and 49 control mothers. Investigated polymorphisms include methylenetetrahydrofolate reductase (MTHFR) C677T (rs1801133), A1298C (rs1801131), methionine synthase reductase (MTRR) A66G (rs1801394), methylenetetrahydrofolate dehydrogenase (MTHFD1) G1958A (rs2236225), reduced folate carrier (RFC1) A80G (rs1051266), and cystathionine ß-synthase (CBS) 844ins68. RESULTS: The frequency of the MTHFR 677C allele in DS mothers (79.8%) was significantly higher than in controls (66.3%), with a 0.499-fold increased risk of having a DS offspring (p=0.038 and 95% confidence interval [CI], 0.259-0.961). Mothers with the MTHFD1 1958A allele had a 1.880-fold increased risk of having a child with DS (p=0.031 and 95% CI, 1.060-3.335). No significant association was found for the other polymorphic variants in this study. Gene-gene interactions were not statistically significant. CONCLUSION: Polymorphic variants of the enzymes involved in folate metabolism may play an important role in determining the susceptibility of having a DS offspring. The gene-nutrition, gene-gene interactions and ethnicity are important variables to be considered in future studies.