ABSTRACT
Objective: Long term goal in early cochlea implantation in children without any additional disabilities is an age-appropriate speech development. Material and Methods: Speech development in deaf children with cochlear-implant(s) (n=60) was examined with the german language test battery SETK-2 ("Sprachentwicklungstest für 2-jährige Kinder") 2 years after first mapping of the speech processor. Results: More than 68% of the subjects show in all 4 subtests hearing-age equivalent results in receptive and expressive language. 12 children were additionally evaluated by chronological age. 4 of these children show age-appropriate results. There is no significant difference between the children implanted earlier in life (≤12 months) and later implanted children (≥13 months). But it must be kept in mind, that children who were implanted earlier show the same results at a younger age. The discrepancy between their chronological age and their speech development-age is smaller. Speech development in children who grow up bilingually was delayed in German. Conclusions: The results lead to the conclusion that the time of the cochlea implantation is crucial for further development of the children who were born deaf. Rehabilitation concepts have to put a special focus on children who grow up with more than one language.
Subject(s)
Cochlear Implantation , Deafness/rehabilitation , Early Medical Intervention , Language Development Disorders/diagnosis , Language Development Disorders/rehabilitation , Age Factors , Child, Preschool , Deafness/diagnosis , Female , Follow-Up Studies , Humans , Male , Reference Values , Speech Discrimination Tests , Speech Production MeasurementABSTRACT
OBJECTIVE: This study's aim is the assessment of language development of children with Cochlea Implant (CI). It focusses on receptive and expressive language development as well as auditory memory skills. MATERIAL AND METHODS: Grimm's language development test (SETK 3-5) evaluates receptive, expressive language development and auditory memory. Data of 49 children who received their implant within their first 3 years of life were compared to the norms of hearing children at the age of 3.0-3.5 years. According to the age at implantation the cohort was subdivided in 3 groups: cochlear implantation within the first 12 months of life (group 1), during the 13th and 24th months of life (group 2) and after 25 or more months of life (group 3). RESULTS: It was possible to collect complete data of all SETK 3-5 subtests in 63% of the participants. A homogeneous profile of all subtests indicates a balanced receptive and expressive language development. Thus reduces the gap between hearing/language age and chronological age. Receptive and expressive language and auditory memory milestones in children implanted within their first year of life are achieved earlier in comparison to later implanted children. CONCLUSION: The Language Test for Children (SETK 3-5) is an appropriate test procedure to be used for language assessment of children who received a CI. It can be used from age 3 on to administer data on receptive and expressive language development and auditory memory.
Subject(s)
Cochlear Implants , Deafness/diagnosis , Deafness/rehabilitation , Language Development Disorders/diagnosis , Language Development Disorders/rehabilitation , Speech Perception , Age Factors , Child, Preschool , Female , Follow-Up Studies , Humans , Infant , Language Tests , Male , Mental Recall , Reference Values , Speech Production Measurement , Speech Reception Threshold Test , Verbal LearningABSTRACT
BACKGROUND: Normal-hearing children show signs of various phonological processes during language development. These processes represent simplifications of articulation, which are overcome at different time points. For the German language, there are currently no reliable data regarding whether these developmental stages also apply to deaf children with cochlear implants (CI). MATERIALS AND METHODS: Phonological development in deaf children with CI was examined and evaluated with the PLAKSS ("Psycholinguistischen Analyse kindlicher Sprechstörungen"). The results of this analysis (time of test 1 = T1, n = 33) were compared to those of a PLAKSS diagnostic evaluation performed 1 year previously (time of test 0 = T0, n = 31). RESULTS: At T1, 76 % of the whole group showed a phonological development that did not correspond to their hearing age (as measured from the time of the first CI implantation). The most frequently observed phonological processes were the reduction of consonant clusters and fronting. However, 83 % of the group had fewer phonological processes inappropriate to their hearing age at T1 than they did at T0. CONCLUSION: The phonological development of children with CI is not equivalent to their hearing age and is structured differently to that of normal-hearing children.
Subject(s)
Aging , Child Development , Cochlear Implants , Deafness/physiopathology , Deafness/rehabilitation , Language Development , Child , Child, Preschool , Deafness/diagnosis , Female , Humans , Male , Treatment OutcomeABSTRACT
BACKGROUND: After cochlear implantation, most parents expect a normal speech and general development of their child. However, it remains unclear how quickly after early cochlear implantation these children can compensate for their deficits compared to normal-hearing children. METHODS: This study retrospectively analyzed ELFRA-1 questionnaire data from 40 children with borderline deafness or high-grade hearing loss (without other known impairments) who had undergone cochlear implantation at a university medical center before reaching 2 years of age. ELFRA-1 questionnaires were filled out parents assisted by specialists 12 months after implantation. Questions assessed the children's speech production and comprehension, as well as their use of gestures and fine motoric skills. RESULTS: At an average hearing-age of 12 months, the children achieved normal values in all of the subgroups that were comparable to those of 12-month-old children without hearing impairments. A significant correlation (p = 0.01) between the individual subgroups of the ELFRA-1 (speech production, speech comprehension, gestures and fine motor skills) was observed. Unilingual educated children performed significantly better overall. CONCLUSION: Within 12 months of receiving a cochlear implant, all children passed the four categories of the ELFRA-1. This demonstrates a rapid compensation of deficits in speech, motor skills and gesture development by children undergoing early cochlear implantation.
Subject(s)
Cochlear Implantation , Hearing Disorders/diagnosis , Hearing Disorders/therapy , Language Development , Speech Disorders/diagnosis , Speech Disorders/prevention & control , Female , Hearing Disorders/complications , Humans , Infant , Male , Speech Disorders/complications , Surveys and Questionnaires , Treatment OutcomeABSTRACT
In recent experiments at the velocity filter Separator for Heavy Ion reaction Products (SHIP) (GSI, Darmstadt), an extended and improved set of α-decay data for more than 20 of the most neutron-deficient isotopes in the region from lead to thorium was obtained. The combined analysis of this newly available α-decay data, of which the (186)Po decay is reported here, allowed us for the first time to clearly show that crossing the Z = 82 shell to higher proton numbers strongly accelerates the α decay. From the experimental data, the α-particle formation probabilities are deduced following the Universal Decay Law approach. The formation probabilities are discussed in the framework of the pairing force acting among the protons and the neutrons forming the α particle. A striking resemblance between the phenomenological pairing gap deduced from experimental binding energies and the formation probabilities is noted. These findings support the conjecture that both the N = 126 and Z = 82 shell closures strongly influence the α-formation probability.
Subject(s)
Alpha Particles , Polonium/chemistry , Neutrons , Nuclear PhysicsABSTRACT
Auditory synaptopathy/neuropathy (AS/AN) is a special subtype of sensorineural hearing disorders with heterogeneous phenotypes and underestimated incidence. AS/AN generally develops in infancy, occasionally in adulthood. Symptoms include fluctuating, mostly bilateral hearing loss and abnormally reduced speech comprehension, especially in noisy environments. Within audiological assessments, patients with AS/AN present otoacoustic emissions (TEOAE; DPOAE) and cochlear microphonics (CM), absence of stapedius reflexes (SR) as well as absent or pathologically altered auditory evoked brainstem potentials (ABR). Children with AS/AN cannot be identified within OAE-based newborn hearing screening programs. Clinical findings, transtympanic electrocochleography (ECoG) and further diagnostic tools permit further identification of individual characteristics. In individual cases conventional amplification and the use of FM systems may improve hearing and communication skills. If these interventions, accompanied by intensive hearing, speech and language therapy are unsuccessful, cochlear implants (CI) or alternative forms of communication may be useful options for rehabilitation.
Subject(s)
Audiometry/methods , Hearing Aids , Hearing Loss, Central/diagnosis , Hearing Loss, Central/therapy , HumansABSTRACT
BACKGROUND: The Functioning After Pediatric Cochlear Implantation (FAPCI) instrument was recently developed to determine the communicative performance of 2-5-year-old prelingually deafened, cochlear-implanted children. Because of its high reliability and validity, as well as possible additional information compared with existing questionnaires, the 23-item parent-proxy questionnaire was translated from U.S. English to German prior to validation. MATERIAL AND METHODS: Initially, the German inventory was qualitatively developed by experts in audiology and speech pathology in collaboration with a professional American translator. Based on a sample of parents' responses, the outcome was quantitatively validated using psychometric methods (Cronbach's alpha, principal components analysis). Finally, the nomological validity was verified by correlating the overall FAPCI value with an external criterion (i.e., hearing age). RESULTS: For almost all age groups, Cronbach's alpha exceeded the minimum value of the original study (0.86). Principal components analysis revealed a two-factor solution (speech perception/production). The fitting of a nonparametric regression line to the data points showed that the total FAPCI score was positively associated with the time of implant use. CONCLUSION: The results show concordance between the German and the English versions of the FAPCI. The two instruments agree in reliability as well as in validity. The suitability of the German version in the clinical and therapeutic routine needs to be confirmed in further investigations.
Subject(s)
Cochlear Implants , Deafness/diagnosis , Deafness/rehabilitation , Hearing Tests/methods , Recovery of Function , Surveys and Questionnaires , Child, Preschool , Humans , Male , Reproducibility of Results , Sensitivity and Specificity , Treatment OutcomeABSTRACT
Starting with methyl 4,6-O-benzylidene-alpha-D-glucopyranoside (4), an optimized procedure is reported for preparation of the bromide 7, which is transformed into the N-acylated heptopyranosamine 9. After introduction of an axially positioned azido moiety in position 3 intramolecular N/O-acetal formation succeeds to provide the morphan analogue 17. In receptor binding studies with radioligands the amines 18b-18d reveal higher affinity for mu-receptors than for kappa-receptors. The most mu-active compound 18b (Ki = 14 nM) contains two aryl substituents, which presumably may occupy both aryl binding sites of mu-receptors.
Subject(s)
Analgesics, Non-Narcotic , Receptors, Opioid, kappa/metabolism , Receptors, Opioid, mu/metabolism , Analgesics, Non-Narcotic/chemical synthesis , Analgesics, Non-Narcotic/chemistry , Analgesics, Non-Narcotic/metabolism , Analgesics, Non-Narcotic/pharmacology , Binding Sites , Receptors, Opioid, kappa/agonists , Structure-Activity RelationshipABSTRACT
BACKGROUND AND OBJECTIVE: This study compares the results of the outpatient-based program of the Cochlear Implant Center Ruhr with inpatient-based rehabilitation, which is almost exclusively performed in Germany. PATIENTS/METHODS: The Department of Otorhinolaryngology at the University of Essen in Germany provided 52 patients with either 22- or 24-channel Nucleus cochlear implants from March 1996 to July 1999. Almost all patients (n = 49) were rehabilitated on an outpatient basis, which is the standard in many cochlear implant centers outside Germany. RESULTS: The longest follow-up period at the University of Essen Department of Otorhinolaryngology was 36 months. Minor complications occurred in 10% of the patients. After 24 months, the first three implanted patients were able to discriminate 100% of numbers and over 60% of syllables in the Freiburg speech discrimination test. The patients who developed an understanding of open speech were able to discriminate 31 words per minute with cochlear implant and without lipreading after 24 months. Children were seen to double their Schmid-Giovannini scores at 6 months postimplantation. CONCLUSIONS: The Essen outpatient-based cochlear implant program demonstrates results in speech development and speech understanding equal to those of centers providing inpatient rehabilitation. A special advantage is continuous rehabilitation with professionals known to the child for several years. In children especially, exhaustive commuting reduces school attendance and is a burden on the accompanying guardians. As an inpatient, however, the child is torn from his familiar environment. Parents with several children have particular difficulties in accompanying their child and indeed this may not always be possible.
Subject(s)
Ambulatory Care , Cochlear Implantation/rehabilitation , Adult , Child , Follow-Up Studies , Germany , Humans , Outcome and Process Assessment, Health Care , Patient Admission , Speech Discrimination TestsABSTRACT
BACKGROUND: Most catalytic RNAs depend on divalent metal ions for folding and catalysis. A thorough structure-function analysis of catalytic RNA therefore requires the identification of the metal-ion-binding sites. Here, we probed the binding sites using Fenton chemistry, which makes use of the ability of Fe2+ to functionally or structurally replace Mg2+ at ion-binding sites and to generate short-lived and highly reactive hydroxyl radicals that can cleave nucleic acid and protein backbones in spatial proximity of these ion-binding sites. RESULTS: Incubation of group I intron RNA with Fe2+, sodium ascorbate and hydrogen peroxide yields distinctly cleaved regions that occur only in the correctly folded RNA in the presence of Mg2+ and can be competed by additional Mg2+, suggesting that Fe2+ and Mg2+ interact with the same sites. Cleaved regions in the catalytic core are conserved for three different group I introns, and there is good correlation between metal-ion-binding sites determined using our method and those determined using other techniques. In a model of the T4 phage-derived td intron, cleaved regions separated in the secondary structure come together in three-dimensional space to form several metal-ion-binding pockets. CONCLUSIONS: In contrast to structural probing with Fe2+/EDTA, cleavage with Fe2+ detects metal-ion-binding sites located primarily in the inside of the RNA. Essentially all metal-ion-binding pockets detected are formed by tertiary structure elements. Using this method, we confirmed proposed metal-ion-binding sites and identified new ones in group I intron RNAs. This approach should allow the localization of metal-ion-binding sites in RNAs of interest.
Subject(s)
Ferrous Compounds/chemistry , Introns , Metals/metabolism , RNA, Catalytic/metabolism , RNA, Protozoan/metabolism , Animals , Base Sequence , Binding Sites , Binding, Competitive , Cations, Divalent , Crystallography, X-Ray , Hydrolysis , Molecular Sequence Data , Nucleic Acid Conformation , RNA, Catalytic/chemistry , RNA, Protozoan/chemistry , Ribonucleotide Reductases/geneticsABSTRACT
BACKGROUND: The peptide antibiotic viomycin inhibits ribosomal protein synthesis, group I intron self-splicing and self-cleavage of the human hepatitis delta virus ribozyme. To understand the molecular basis of RNA binding and recognition by viomycin, we isolated a variety of novel viomycin-binding RNA molecules using in vitro selection. RESULTS: More than 90% of the selected RNA molecules shared one continuous highly conserved region of 14 nucleotides. Mutational analyses, structural probing, together with footprinting experiments by chemical modification, and Pb2+-induced cleavage showed that this conserved sequence harbours the antibiotic-binding site and forms a stem-loop structure. Moreover, the loop is engaged in a long-range interaction forming a pseudoknot. CONCLUSIONS: A comparison between the novel viomycin-binding motif and the natural RNA target sites for viomycin showed that all these segments form a pseudoknot at the antibiotic-binding site. We therefore conclude that this peptide antibiotic has a strong selectivity for particular RNA pseudoknots.
Subject(s)
Anti-Bacterial Agents/metabolism , Nucleic Acid Conformation , RNA/chemistry , RNA/metabolism , Viomycin/metabolism , Base Sequence , Binding Sites , Cloning, Molecular , Conserved Sequence , Enviomycin/analogs & derivatives , Enviomycin/metabolism , Humans , Lead/chemistry , Molecular Sequence Data , Mutation , RNA/isolation & purification , RNA ProbesABSTRACT
Ribosomes have long been known to require divalent metal ions for their functional integrity. Pb2+-induced cleavage of the sugar-phosphate backbone has now been used to probe for metal binding sites in rRNA. Only three prominent Pb2+cleavages have been detected, with cleavage sites 5' of G240 in 16S rRNA and two sites 5' of A505 and C2347 in 23S rRNA. All cleavages occur in non-paired regions of the secondary structure models of the rRNAs and can be competed for by high concentrations of Mg2+, Mn2+, Ca2+ and Zn2+ ions, suggesting that lead is bound to general metal binding sites. Although Pb2+ cleavage is very efficient, ribosomes with fragmented RNAs are still functional in binding tRNA and in peptidyl transferase activity, indicating that the scissions do not significantly alter ribosomal structure. One of the lead cleavage sites (C2347 in 23S RNA) occurs in the vicinity of a region which is implicated in tRNA binding and peptidyl transferase activity. These results are discussed in the light of a recent model which proposes that peptide bond formation might be a metal-catalysed process.
Subject(s)
Lead/metabolism , RNA, Ribosomal, 16S/metabolism , RNA, Ribosomal, 23S/metabolism , Anti-Bacterial Agents/metabolism , Base Sequence , Binding, Competitive , Catalysis , Cations, Divalent , Hydrogen-Ion Concentration , Hydrolysis , Molecular Sequence Data , Nucleic Acid Conformation , RNA, Ribosomal, 16S/chemistry , RNA, Ribosomal, 23S/chemistry , RNA, Transfer/metabolismABSTRACT
Several divalent metal ions (Ca2+, Sr2+ and Pb2+) do not promote splicing, but instead induce cleavage at a single site in the conserved group I intron core in the absence of the guanosine cofactor at elevated pH, generating products with 5'-OH and 3'-phosphate ends. The reaction is competed by Mg2+, which does not cleave at this position, but hydrolyses the splice sites producing 3'-OH and 5'-phosphate ends. Mn2+ promotes both core cleavage and splice site hydrolysis under identical conditions, suggesting that two different metal atoms are involved, each responsible for one type of cleavage, and with different chemical and geometric requirements. Based on the core cleavage position and on the previously proposed coordination sites for Mg2+, we propose a structural location for two metal ions surrounding the splice site in the Michel-Westhof three-dimensional model of the group I intron core. The proposed location was strengthened by a first mutational analysis which supported the suggested interaction between one of the metal ions and the bulged residue in P7.
Subject(s)
Cations, Divalent , Introns/genetics , RNA Precursors/metabolism , RNA Splicing/physiology , RNA, Catalytic/metabolism , Bacteriophage T4/genetics , Base Sequence , Calcium/physiology , Catalysis , Hydrogen-Ion Concentration , Hydrolysis , Lead/physiology , Magnesium/physiology , Manganese/physiology , Models, Molecular , Molecular Sequence Data , RNA Precursors/genetics , RNA, Catalytic/chemistry , Strontium/physiology , Thymidylate Synthase/geneticsSubject(s)
Anti-Bacterial Agents/pharmacology , RNA Splicing/drug effects , RNA, Ribosomal/drug effects , Aminoglycosides , Anti-Bacterial Agents/metabolism , Anticodon/genetics , Binding Sites , Codon/genetics , Introns/genetics , Models, Genetic , RNA, Catalytic/drug effects , RNA, Ribosomal/genetics , RNA, Ribosomal/metabolism , RNA, Ribosomal, 16S/drug effectsABSTRACT
Self-splicing of group I introns requires divalent metal ions to promote catalysis as well as for the correct folding of the RNA. Lead cleavage has been used to probe the intron RNA for divalent metal ion binding sites. In the conserved core of the intron, only two sites of Pb2+ cleavage have been detected, which are located close to the substrate binding sites in the junction J8/7 and at the bulged nucleotide in the P7 stem. Both lead cleavages can be inhibited by high concentrations of Mg2+ and Mn2+ ions, suggesting that they displace Pb2+ ions from the binding sites. The RNA is protected from lead cleavage by 2'-deoxyGTP, a competitive inhibitor of splicing. The two major lead induced cleavages are both located in the conserved core of the intron and at phosphates, which had independently been demonstrated to interact with magnesium ions and to be essential for splicing. Thus, we suggest that the conditions required for lead cleavage occur mainly at those sites, where divalent ions bind that are functionally involved in catalysis. We propose lead cleavage analysis of functional RNA to be a useful tool for mapping functional magnesium ion binding sites.
