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      Efeito de fármacos ototóxicos na audição de recém-nascidos de alto risco Translated title: Effects of ototoxic drugs in the hearing of high risk newborns

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          Abstract

          OBJETIVOS: Calcular a incidência da perda auditiva sensorioneural (PASN) em recém-nascidos de alto risco, verificar se existe associação causal entre o uso de fármacos ototóxicos em neonatos de alto risco e a PASN e estabelecer a frequência das mutações genéticas relacionadas à PASN em neonatos de alto risco. MÉTODOS: A pesquisa foi uma coorte retrospectiva e prospectiva realizada em 250 crianças. Foi realizada coleta de dados em prontuários e com os responsáveis, triagem auditiva por emissões otoacústicas-produto de distorção, timpanometria, audiometria com reforço visual, potencial evocado auditivo de tronco encefálico e emissões otoacústicas transientes. A pesquisa das mutações genéticas 35delG e mitocondriais A1555G e A7445G, foi fundamental para avaliar a possibilidade da PASN ser de origem genética não-sindrômica. RESULTADOS: A incidência da PASN foi de 11,6%, as associações causais entre a PASN e os fármacos administrados foram: amicacina e cefotaxima (OR 5,35), cefotaxima e furosemida (OR 7,02), ceftazidima e vancomicina (OR 9,12). A frequência da mutação 35delG foi de 0,8% e para as mutações mitocondriais A1555G e A7445G foi 0%. CONCLUSÃO: A incidência de PASN em recém-nascidos de alto risco foi alta, apresentando importante relação causal com o uso de medicamentos e pequena relação com mutações genéticas.

          Translated abstract

          PURPOSE: To calculate the incidence of sensorineural hearing loss (SNHL), to verify if there is a causal association between the use of ototoxic drugs and SNHL, and to establish the frequency of genetic mutations related to SNHL in high risk newborns. METHODS: The study was a retrospective and prospective cohort research with 250 children. Data was gathered from subjects' charts and with their caregivers. Moreover, subjects were submitted to auditory evaluation with distortion product otoacoustic emissions, timpanometry, visual reinforcement audiometry, auditory brainstem response and transient otoacoustic emissions. The study of the genetic mutation 35delG, and the mitochondrial mutations A1555G and A7445G was essential to evaluate the possibility that SNHL had a non-syndromic genetic origin. The association between the medicine use and the occurrence of hearing loss had been analyzed. RESULTS: The incidence of SNHL in high risk newborns was 11.6%, and causal associations between SNHL and the drugs administered were: amikacin and cefotaxime (OR=5.35), cefotaxime and furosemide (OR=7.02), ceftazidime and vancomycin (OR=9.12). The frequencies of the mutation 35deIG and mitochondrial mutations A1555G and A7445G were, respectively, 0.8% and 0%. CONCLUSION: The incidence of SNHL in high risk newborns was high, showing an important causal relation with the use of ototoxic drugs and a small relation with genetic mutations.

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          Language of early- and later-identified children with hearing loss.

          To compare the language abilities of earlier- and later-identified deaf and hard-of-hearing children. We compared the receptive and expressive language abilities of 72 deaf or hard-of-hearing children whose hearing losses were identified by 6 months of age with 78 children whose hearing losses were identified after the age of 6 months. All of the children received early intervention services within an average of 2 months after identification. The participants' receptive and expressive language abilities were measured using the Minnesota Child Development Inventory. Children whose hearing losses were identified by 6 months of age demonstrated significantly better language scores than children identified after 6 months of age. For children with normal cognitive abilities, this language advantage was found across all test ages, communication modes, degrees of hearing loss, and socioeconomic strata. It also was independent of gender, minority status, and the presence or absence of additional disabilities. Significantly better language development was associated with early identification of hearing loss and early intervention. There was no significant difference between the earlier- and later-identified groups on several variables frequently associated with language ability in deaf and hard-of-hearing children. Thus, the variable on which the two groups differed (age of identification and intervention) must be considered a potential explanation for the language advantage documented in the earlier-identified group.
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            Mutation in TRMU related to transfer RNA modification modulates the phenotypic expression of the deafness-associated mitochondrial 12S ribosomal RNA mutations.

            The human mitochondrial 12S ribosomal RNA (rRNA) A1555G mutation has been associated with aminoglycoside-induced and nonsyndromic deafness in many families worldwide. Our previous investigation revealed that the A1555G mutation is a primary factor underlying the development of deafness but is not sufficient to produce a deafness phenotype. However, it has been proposed that nuclear-modifier genes modulate the phenotypic manifestation of the A1555G mutation. Here, we identified the nuclear-modifier gene TRMU, which encodes a highly conserved mitochondrial protein related to transfer RNA (tRNA) modification. Genotyping analysis of TRMU in 613 subjects from 1 Arab-Israeli kindred, 210 European (Italian pedigrees and Spanish pedigrees) families, and 31 Chinese pedigrees carrying the A1555G or the C1494T mutation revealed a missense mutation (G28T) altering an invariant amino acid residue (A10S) in the evolutionarily conserved N-terminal region of the TRMU protein. Interestingly, all 18 Arab-Israeli/Italian-Spanish matrilineal relatives carrying both the TRMU A10S and 12S rRNA A1555G mutations exhibited prelingual profound deafness. Functional analysis showed that this mutation did not affect importation of TRMU precursors into mitochondria. However, the homozygous A10S mutation leads to a marked failure in mitochondrial tRNA metabolisms, specifically reducing the steady-state levels of mitochondrial tRNA. As a consequence, these defects contribute to the impairment of mitochondrial-protein synthesis. Resultant biochemical defects aggravate the mitochondrial dysfunction associated with the A1555G mutation, exceeding the threshold for expressing the deafness phenotype. These findings indicate that the mutated TRMU, acting as a modifier factor, modulates the phenotypic manifestation of the deafness-associated 12S rRNA mutations.
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              Newborn and infant hearing loss: detection and intervention.American Academy of Pediatrics. Task Force on Newborn and Infant Hearing, 1998- 1999.

              This statement endorses the implementation of universal newborn hearing screening. In addition, the statement reviews the primary objectives, important components, and recommended screening parameters that characterize an effective universal newborn hearing screening program.
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                Author and article information

                Journal
                rsbf
                Revista da Sociedade Brasileira de Fonoaudiologia
                Rev. soc. bras. fonoaudiol.
                Sociedade Brasileira de Fonoaudiologia (São Paulo, SP, Brazil )
                1516-8034
                1982-0232
                2010
                : 15
                : 3
                : 376-382
                Affiliations
                [01] Fortaleza CE orgnameUniversidade de Fortaleza Brasil
                [02] São Paulo SP orgnameUniversidade Federal de São Paulo Brasil
                [03] Fortaleza CE orgnameUniversidade Estadual do Ceará Brasil
                [04] São Paulo SP orgnameUniversidade Estadual de Campinas Brasil
                Article
                S1516-80342010000300011 S1516-8034(10)01500311
                10.1590/S1516-80342010000300011
                10000306-f6b5-42b0-b48f-660618bb8594

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 15 July 2009
                : 26 October 2009
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 29, Pages: 7
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                SciELO Brazil

                Self URI: Texto completo somente em PDF (PT)
                Categories
                Artigos Originais

                Vancomicina,Perda auditiva,Surdez,Prematuro,Amicacina,Furesemida,Gentamicinas,Combinação de medicamentos,Hearing loss,Deafness,Infant, premature,Amikacin,Furosemide,Vancomycin,Gentamicins,Drug combinations

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