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    Clinical features of candidiasis in patients with inherited interleukin 12 receptor ß1 deficiency
    (2014) Ouederni M.; Sanal O.; Ikinciogullari A.; Tezcan I.; Dogu F.; Sologuren I.; Pedraza-Sánchez S.; Keser M.; Tanir G.; Nieuwhof C.; Colino E.; Kumararatne D.; Levy J.; Kutukculer N.; Aytekin C.; Herrera-Ramos E.; Bhatti M.; Karaca N.; Barbouche R.; Broides A.; Goudouris E.; Franco J.L.; Parvaneh N.; Reisli I.; Strickler A.; Shcherbina A.; Somer A.; Segal A.; Angel-Moreno A.; Lezana-Fernandez J.L.; Bejaoui M.; Bobadilla-Del Valle M.; Kachboura S.; Sentongo T.; Ben-Mustapha I.; Bustamante J.; Picard C.; Puel A.; Boisson-Dupuis S.; Abel L.; Casanova J.-L.; Rodríguez-Gallego C.
    Background. Interleukin 12Rß1 (IL-12Rß1)-deficient patients are prone to clinical disease caused by mycobacteria, Salmonella, and other intramacrophagic pathogens, probably because of impaired interleukin 12-dependent interferon production. About 25% of patients also display mucocutaneous candidiasis, probably owing to impaired interleukin 23-dependent interleukin 17 immunity. The clinical features and outcome of candidiasis in these patients have not been described before, to our knowledge. We report here the clinical signs of candidiasis in 35 patients with IL-12Rß1 deficiency.Results. Most (n = 71) of the 76 episodes of candidiasis were mucocutaneous. Isolated oropharyngeal candidiasis (OPC) was the most common presentation (59 episodes, 34 patients) and was recurrent or persistent in 26 patients. Esophageal candidiasis (n = 7) was associated with proven OPC in 2 episodes, and cutaneous candidiasis (n = 2) with OPC in 1 patient, whereas isolated vulvovaginal candidiasis (VVC; n = 3) was not. Five episodes of proven invasive candidiasis were documented in 4 patients; 1 of these episodes was community acquired in the absence of any other comorbid condition. The first episode of candidiasis occurred earlier in life (median age±standard deviation, 1.5 ± 7.87 years) than infections with environmental mycobacteria (4.29 ± 11.9 years), Mycobacterium tuberculosis (4 ± 3.12 years), or Salmonella species (4.58 ± 4.17 years) or other rare infections (3 ± 11.67 years). Candidiasis was the first documented infection in 19 of the 35 patients, despite the vaccination of 10 of these 19 patients with live bacille Calmette-Guérin.Conclusions. Patients who are deficient in IL-12Rß1 may have candidiasis, usually mucocutaneous, which is frequently recurrent or persistent. Candidiasis may be the first clinical manifestation in these patients. © The Author 2013.
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    Il-12rß1 deficiency in two of fifty children with severe tuberculosis from IRN, MAR, and TUR
    (2011) Boisson-Dupuis S.; Baghdadi J.E; Parvaneh N.; Bousfiha A.; Bustamante J.; Feinberg J.; Samarina A.; Grant A.V.; Janniere L.; Hafidi N.; Hassani A.; Nolan D.; Najib J.; Camcioglu Y.; Hatipoglu N.; Aydogmus C.; Tanir G.; Aytekin C.; Keser M.; Somer A.; Aksu G.; Kutukculer N.; Mansouri D.; Mahdaviani A.; Mamishi S.; Alcais A.; Abel L.; Casanova J.-L.
    Background and Objectives: In the last decade, autosomal recessive IL-12Rß1 deficiency has been diagnosed in four children with severe tuberculosis from three unrelated families from MAR, Spain, and TUR, providing proof-of-principle that tuberculosis in otherwise healthy children may result from single-gene inborn errors of immunity. We aimed to estimate the fraction of children developing severe tuberculosis due to IL-12Rß1 deficiency in areas endemic for tuberculosis and where parental consanguinity is common. Methods and Principal Findings: We searched for IL12RB1 mutations in a series of 50 children from IRN, MAR, and TUR. All children had established severe pulmonary and/or disseminated tuberculosis requiring hospitalization and were otherwise normally resistant to weakly virulent BCG vaccines and environmental mycobacteria. In one child from IRN and another from MAR, homozygosity for loss-of-function IL12RB1 alleles was documented, resulting in complete IL-12Rß1 deficiency. Despite the small sample studied, our findings suggest that IL-12Rß1 deficiency is not a very rare cause of pediatric tuberculosis in these countries, where it should be considered in selected children with severe disease. Significance: This finding may have important medical implications, as recombinant IFN-? is an effective treatment for mycobacterial infections in IL-12Rß1-deficient patients. It also provides additional support for the view that severe tuberculosis in childhood may result from a collection of single-gene inborn errors of immunity. © 2011 Boisson-Dupuis et al.
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    Meningitis caused by neisseria meningitidis, hemophilus influenzae type b and streptococcus pneumoniae during 2005-2012 in Turkey: A multicenter prospective surveillance study
    (Landes Bioscience, 2014) Ceyhan M.; Gürler N.G.; Ozsurekci Y.; Keser M.; Aycan A.E.; Gurbuz V.; Salman N.; Camcioglu Y.; Dinleyici E.C.; Ozkan S.; Sensoy G.; Belet N.; Alhan E.; Hacimustafaoglu M.; Celebi S.; Uzun H.; Oner A.F.; Kurugol Z.; Ali M.; Aygun D.; Oncel E.K.; Celik M.; Yasa O.; Akin F.; Coşkun Y.
    Successful vaccination policies for protection from bacterial meningitis are dependent on determination of the etiology of bacterial meningitis. Cerebrospinal fluid (CSF) samples were obtained prospectively from children from 1 month to ? 18 years of age hospitalized with suspected meningitis, in order to determine the etiology of meningitis in Turkey. DNA evidence of Neisseria meningitidis (N. meningitidis ), Streptococcus pneumoniae ( S. pneumoniae), and Hemophilus influenzae type b (Hib) was detected using multiplex polymerase chain reaction (PCR). In total, 1452 CSF samples were evaluated and bacterial etiology was determined in 645 (44.4%) cases between 2005 and 2012; N. meningitidis was detected in 333 (51.6%), S. pneumoniae in 195 (30.2%), and Hib in 117 (18.1%) of the PCR positive samples. Of the 333 N. meningitidis positive samples 127 (38.1%) were identified as serogroup W-135, 87 (26.1%) serogroup B, 28 (8.4%) serogroup A and 3 (0.9%) serogroup Y; 88 (26.4%) were non-groupable. As vaccines against the most frequent bacterial isolates in this study are available and licensed, these results highlight the need for broad based protection against meningococcal disease in Turkey. © 2014 Taylor & Francis Group, LLC
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    Revisiting human IL-12Rß1 deficiency: A survey of 141 patients from 30 countries
    (2010) De Beaucoudrey L.; Samarina A.; Bustamante J.; Cobat A.; Boisson-Dupuis S.; Feinberg J.; Al-Muhsen S.; Jannière L.; Rose Y.; De Suremain M.; Kong X.-F.; Filipe-Santos O.; Chapgier A.; Picard C.; Fischer A.; Dogu F.; Ikinciogullari A.; Tanir G.; Al-Hajjar S.; Al-Jumaah S.; Frayha H.H.; Alsum Z.; Al-Ajaji S.; Alangari A.; Al-Ghonaium A.; Adimi P.; Mansouri D.; Ben-Mustapha I.; Yancoski J.; Garty B.-Z.; Rodriguez-Gallego C.; Caragol I.; Kutukculer N.; Kumararatne D.S.; Patel S.; Doffinger R.; Exley A.; Jeppsson O.; Reichenbach J.; Nadal D.; Boyko Y.; Pietrucha B.; Anderson S.; Levin M.; Schandené L.; Schepers K.; Efira A.; Mascart F.; Matsuoka M.; Sakai T.; Siegrist C.-A.; Frecerova K.; Blüetters-Sawatzki R.; Bernhöft J.; Freihorst J.; Baumann U.; Richter D.; Haerynck F.; De Baets F.; Novelli V.; Lammas D.; Vermylen C.; Tuerlinckx D.; Nieuwhof C.; Pac M.; Haas W.H.; Müller-Fleckenstein I.; Fleckenstein B.; Levy J.; Raj R.; Cohen A.C.; Lewis D.B.; Holland S.M.; Yang K.D.; Wang X.; Wang X.; Jiang L.; Yang X.; Zhu C.; Xie Y.; Lee P.P.W.; Chan K.W.; Chen T.-X.; Castro G.; Natera I.; Codoceo A.; King A.; Bezrodnik L.; Di Giovani D.; Gaillard M.I.; De Moraes-Vasconcelos D.; Grumach A.S.; Da Silva Duarte A.J.; Aldana R.; Espinosa-Rosales F.J.; Bejaoui M.; Bousfiha A.A.; Baghdadi J.E.; Özbek N.; Aksu G.; Keser M.; Somer A.; Hatipoglu N.; Aydogmus C.; Asilsoy S.; Camcioglu Y.; Gülle S.; Ozgur T.T.; Ozen M.; Oleastro M.; Bernasconi A.; Mamishi S.; Parvaneh N.; Rosenzweig S.; Barbouche R.; Pedraza S.; Lau Y.L.; Ehlayel M.S.; Fieschi C.; Abel L.; Sanal O.; Casanova J.-L.
    Interleukin-12 receptor ß1 (IL-12Rß1) deficiency is the most common form of Mendelian susceptibility to mycobacterial disease (MSMD). We undertook an international survey of 141 patients from 102 kindreds in 30 countries. Among 102 probands, the first infection occurred at a mean age of 2.4 years. In 78 patients, this infection was caused by Bacille Calmette-Guérin (BCG; n = 65), environmental mycobacteria (EM; also known as atypical or nontuberculous mycobacteria) (n = 9) or Mycobacterium tuberculosis (n = 4). Twenty-two of the remaining 24 probands initially presented with nontyphoidal, extraintestinal salmonellosis. Twenty of the 29 genetically affected sibs displayed clinical signs (69%); however 8 remained asymptomatic (27%). Nine nongenotyped sibs with symptoms died. Recurrent BCG infection was diagnosed in 15 cases, recurrent EM in 3 cases, recurrent salmonellosis in 22 patients. Ninety of the 132 symptomatic patients had infections with a single microorganism. Multiple infections were diagnosed in 40 cases, with combined mycobacteriosis and salmonellosis in 36 individuals. BCG disease strongly protected against subsequent EM disease (p = 0.00008). Various other infectious diseases occurred, albeit each rarely, yet candidiasis was reported in 33 of the patients (23%). Ninety-nine patients (70%) survived, with a mean age at last follow-up visit of 12.7 years ± 9.8 years (range, 0.5-46.4 yr). IL-12Rß1 deficiency is characterized by childhood-onset mycobacteriosis and salmonellosis, rare recurrences of mycobacterial disease, and more frequent recurrence of salmonellosis. The condition has higher clinical penetrance, broader susceptibility to infections, and less favorable outcome than previously thought. © 2010 Lippincott Williams & Wilkins.
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    Serotypes of Streptococcus pneumoniae isolates from children with invasive pneumococcal disease in Turkey: Baseline evaluation of the introduction of the pneumococcal conjugate vaccine nationwide
    (2011) Ceyhan M.; Gurler N.; Yaman A.; Ozturk C.; Oksuz L.; Ozkan S.; Keser M.; Salman N.; Alhan E.; Esel D.; Gultekin M.; Camcioglu Y.; Gul M.; Sorguc Y.; Aydemir S.; Gunaydin M.; Yakupogullari Y.; Kizirgil A.
    Before use of the pneumococcal conjugate vaccine PCV7 became widespread in Turkey, 202 invasive pneumococcus isolates were analyzed. The most common serotypes were 19F and 6B. In children ?2 years of age, the potential coverage rate of PCV7 was 69.5%. The most frequent non-PCV7 serotypes were 19A, 3, 1, 6A, and 8. Copyright © 2011, American Society for Microbiology. All Rights Reserved.