Necla Akçakaya

In a novel form of IFN-γ receptor 1 deficiency, cell surface receptors fail to bind IFN-γ

Complete IFN-gamma receptor ligand-binding chain (IFNgammaR1) deficiency is a life-threatening autosomal recessive immune disorder. Affected children invariably die of mycobacterial infection, unless bone marrow transplantation is undertaken. Pathogenic IFNGR1 mutations identified to date include nonsense and splice mutations and frameshift deletions and insertions. All result in a premature stop codon upstream from the segment encoding the transmembrane domain, precluding cell surface expression of the receptors. We report herein two sporadic and two familial cases of a novel form of complete IFNgammaR1 deficiency in which normal numbers of receptors are detected at the cell surface. Two in-frame deletions and two missense IFNGR1 mutations were identified in the segment encoding the extracellular ligand-binding domain of the receptor. Eight independent IFNgammaR1-specific mAbs, including seven blocking antibodies, gave recognition patterns that differed between patients, suggesting that different epitopes were altered by the mutations. No specific binding of (125)I-IFN-gamma to cells was observed in any patient, however, and the cells failed to respond to IFN-gamma. The mutations therefore cause complete IFNgammaR1 deficiency by disrupting the IFN-gamma-binding site without affecting surface expression. The detection of surface IFNgammaR1 molecules by specific antibodies, including blocking antibodies, does not exclude a diagnosis of complete IFNgammaR1 deficiency.

Prevalence of bronchial asthma and allergic rhinitis in Istanbul school children

The aim of this study was to determine the prevalence of asthma, allergic rhinitis and their related symptoms in Istanbul and to investigate the effect of socioeconomic status on the prevalence of asthma and allergic rhinitis and whether there are differences between the prevalence of childhood asthma in the same and different regions as found in previous studies and our own. The study period was the 1996–1997 school year in three primary schools in Istanbul. For proportional representation of high, middle, and low socioeconomic levels, the schools were selected from three different regions of Istanbul. A translated version of the International Study of Asthma and Allergies in Childhood (ISAAC) was used. The questionnaire was distributed to the parents of 2600 students aged 6–15 years. All of the 2276 children whose parents responded were included in the survey. The overall cumulative and current prevalences of wheezing were 13.7 and 7.2% respectively and the overall cumulative prevalence of allergic rhinitis was 17.6%. There was no statistically significant difference between asthmatics and non-asthmatics by sex, socioeconomic status and passive smoking. Family history of atopy was found to be significantly higher in asthmatics. Although there are differences in the results of studies concerning the prevalence of asthma and allergic rhinitis not only between different countries but also between different regions of the same city, by using a standardized international method, the actual values may be obtained.

Analysis of the CFTR gene in Turkish cystic fibrosis patients: identification of three novel mutations (3172delAC, P1013L and M1028I)

Abstract In order to determine the spectrum of cystic fibrosis (CF) mutations in the Turkish population, a complete coding region of the cystic fibrosis transmembrane conductance regulator (CFTR) gene including exon-intron boundaries, on 122 unrelated CF chromosomes from 73 Turkish CF families was analysed by denaturing gradient gel electrophoresis and multiplex heteroduplex analysis on MDE gel matrix. In addition to 15 previously reported mutations and 12 polymorphisms, three novel mutations, namely 3172delAC, P1013L and M1028I, were detected. ΔF508 was found to be present on 18.8% of CF chromosomes. The second most common mutation was 1677delTA, with a frequency of 7.3%, followed by G542X and 2183AA→G mutations, with frequencies of 4.9%. These four most common mutations in Turkish CF population account for approximately 36% of mutations. This study could only detect 52.5% of disease-causing mutations in this population; 47.5% of CF alleles remain to be identified, reflecting the high molecular heterogeneity of the Turkish population.

Serotype distribution and antibiotic susceptibility of invasive Streptococcus pneumoniae disease isolates from children in Turkey, 2001–2004

Streptococcus pneumoniae is a major cause of childhood invasive infections, including sepsis, pneumonia and meningitis, and of non-invasive disease such as otitis media. Most S. pneumoniae strains from invasive infections capable of creating treatment problems in children because of antibiotic resistance belong to serogroups 14, 6, 9, 19 and 23. Despite progress in antimicrobial therapy, effective treatment is becoming increasingly complicated because of the rising worldwide emergence of pneumococci resistant to penicillin G and other commonly used antimicrobial agents [1, 3, 5].The aim of the present study was to investigate the antibiotic susceptibility pattern and serotype distribution of S. pneumoniae isolates from children younger than 10 years of age hospitalized with invasive pneumococcal disease (IPD) in Turkey during the years 2001–2004. All patients admitted and treated for invasive infections attributable to S. pneumoniae, between November 2001 and April 2004, in the six large university hospitals in Turkey, located in Istanbul, Adana, Ankara and Izmir, were included in this study. The study cohort represents roughly 30% (20 million) of the population of Turkey. Cases were eligible for evaluation if S. pneumonia, isolated from a normally sterile body site, was identified on the basis of typical colony morphology on blood agar as well as Gram strain, optochin sensitivity and bile solubility tests. Isolate identity was confirmed at the central study laboratory (Department of Microbiology and Infection Disease, Istanbul Faculty of Medicine). Susceptibility tests to antimicrobial agents (penicillin G, amoxicillin-clavulanic acid, cefotaxime, erythromycin and trimethoprim-sulfamethoxazole) were performed by standard disc diffusion method on Müller Hinton agar supplemented with 5% sheep blood. The susceptibility for penicillin was detected with a 1-μl oxacillin disc. The minimal inhibitory concentration (MIC) of the antibiotics was determined by the E test. Disc diffusion tests were employed according to the Clinical and Laboratory Standards Institute guidelines (formerly known as the NCCLS guidelines). An inoculum density equivalent to 0.5 MacFarland standard was prepared in Muller Hinton broth. Capsular typing was carried out by the Quellung reaction, using group and factor sera provided by the Statens Serum Institute (Denmark). Vaccine-type strains included serotypes 4, 6B, 9V, 14, 18C, 19F and 23F. We defined vaccine-related strains as pneumococci with serotypes within the same serogroup as the vaccine types (i.e. serotypes 6A, 9A, 9L, 9N, 18A, 18B, 18F, 19A, 19B, 19C, 23A and 23B) [6]. I. Yalçın Department of Paediatrics, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey

Psychological problems in Turkish asthmatic children and their families.

BACKGROUND Asthma is a chronic respiratory disorder characterized by recurrent episodes of impaired breathing. The disease causes psychological problems due to hospitalization, long-term medication use, and restricted social life. OBJECTIVE The aim of this study was to investigate the relationship between the severity and duration of asthma and psychological problems in asthmatic children, as well as the probability of maternal anxiety. METHODS Thirty-seven children with mild asthma, 55 with moderate asthma and eight with severe asthma were compared with 50 healthy children. The severity of asthma was evaluated using the Pearlman-Bierman classification. Psychological adjustment was measured using the Achenback child Behavior checklist and Spielbergers scale. RESULTS Emotional factors and family dynamics were found to be triggering factors for disease attacks in 16% of children with mild asthma, 38% of those with moderate asthma and 63% of those with severe asthma (p < 0.05). There was no significant difference in the mean maternal anxiety score between the disease severity groups (p > 0.05). The mean depression score was significantly higher in children with moderate and severe asthma than in those with mild asthma (p < 0.05). Disease duration showed no effect on depression and anxiety. CONCLUSION Both asthmatic children and their mothers are negatively affected by the disease.

Childhood asthma perception in Turkey under real-life environment (CAPTURE) study

Successful management of asthma requires good communication between patients and the healthcare team. The background and expectations of a patient inevitably influence the success of any partnership. A questionnaire‐based survey was performed to obtain data on the perception of the impact of asthma in daily life among children (age‐range 6–14 years) and adolescents (age‐range 15–20 years). A total of 756 patients (384 children, 372 adolescents) were randomly selected from 11 Turkish cities and interviewed face‐to‐face. Of the total study population, 71.3% received regular follow‐up and 75.9% currently took asthma medication. Almost 50% reported that asthma affected their lives significantly. Even though half of the patients had symptoms at least once a week, one‐third were not receiving regular prophylactic treatment. Exercise produced asthma symptoms in 45.5% of children and 27.4% of adolescents. The finding that asthma continues to be a major health problem clearly indicates an urgent need for further management programs in Turkey.

Local and systemic reactions during immunotherapy with adsorbed extracts of house dust mite in children.

BACKGROUND We retrospectively evaluated the incidence of local and systemic reactions to injections of adsorbed extracts of house dust mites (Dermatophagoides pteronyssinus and Dermatophagoides farinae) applied according to a conventional schedule in children. METHOD Eighty-eight patients aged 6 to 15 years, suffering from allergic asthma or asthma together with rhinitis, at various stages of treatment with immunotherapy from January 1989 to November 1997 were included. RESULTS Out of 5,760 injections, 5,542 (96.21%) were not associated with a reaction, 206 injections (3.57%) caused local reactions (144, <20 mm in diameter; 62, >20 mm), and systemic reactions were seen after 12 injections (0.2%). Twelve patients experienced 12 systemic reactions. Of these, 7 patients (58.3%) experienced no local reactions prior to a systemic reaction. Eleven males and one female had systemic reactions. Most of both local and systemic reactions occurred within less than 30 minutes after the injection. CONCLUSIONS Our study supports the safety of immunotherapy with house dust mites in children. The majority of reactions were local. Although five of 12 patients who experienced systemic reactions had local reactions prior to a systemic reaction, in general the presence of local reactions was not helpful in predicting which patients would develop systemic reactions. Males and patients with asthma together with rhinitis appeared to be at greater risk for systemic reactions.

Relation between serum Insulin‐like growth factor‐I and insulin‐like growth factor‐binding protein‐3 levels, clinical status and growth parameters in prepubertal cystic fibrosis patients

Abstract Background : This study aims to determine the relation between anabolic hormones, Insulin‐like growth factor‐I (IGF‐I) and IGF‐binding protein‐3 (IGFBP‐3), growth parameters, and clinical status in prepubertal cystic fibrosis (CF) patients. This prospective study comprises age/sex‐matched control subjects and was set in a tertiary care teaching hospital.

Cystic fibrosis mutations and associated haplotypes in Turkish cystic fibrosis patients.

AbstractIdentification of mutations causing cystic fibrosis (CF) in the Turkish population is essential for assessment of the molecular basis of CF in Turkey and the development of strategies for prenatal diagnosis and genetic counseling. Here, we present an updated report of mutations found in the Turkish CF population from an extensive screening study of the entire coding region, including exon-intron boundaries and the promoter region. Cases for which mutations could not be identified were also screened for previously defined large alterations and (TG)mTn-M470V loci. This study revealed a total of 27 different mutations accounting for almost 60% of disease genes in the Turkish population. In this study, we also identified the haplotypes associated with 17 mutations and those associated with unknown mutations. The mutation spectrum of CF in Turkey and its associated haplotypes indicated the presence of a major Mediterranean component in the contemporary Turkish population.

Skin test hypersensitivity for childhood asthma in Istanbul during a period of 16 years

BACKGROUND For diagnosis of allergic disorders, besides history and physical examination, many in vivo and in vitro laboratory tests are used. Skin prick test (SPT) is an easily performed and valuable test in children. Our aim was to evaluate the SPT results of asthmatic children according to age and gender, in Istanbul and its neighborhood, followed for a period of 16 years. MATERIAL AND METHODS Consecutive 5080 asthmatic children, aged 1 to 18 years, admitted to Pediatric Allergy Policlinics of Istanbul University Cerrahpasa Medicine Faculty from 1987 to 2003, were screened retrospectively for 10 frequently exposed allergens. RESULTS 3086 cases (61 %) had SPT reactivity for one and/or for multiple allergens; the SPT reactivity percentages of the exposed allergens was 50 % (2554 cases) for house dust mites DP, 49 % (2462 cases) for house dust mites DF, 15 % (784 cases) for cat dander, 10 % (525 cases) for dog dander, 4 % (228 cases) for lamb wool, 10 % (504 cases) for wheat, 3 % (162 cases) for egg white, 6 % (345 cases) for hazelnut pollen, 6 % (318 cases) for Candida Albicans, 6 % (326 cases) for Aspergillus Fumigatus. CONCLUSION While house dust mites were determined as the predominant allergen for each age groups in this study, allergy against cat dander was the third important allergen in sequence, as cat is a domestic pet which is frequently kept at home in Turkey.