Cisplatin-induced ototoxicity in osteosarcoma patients: a report from the late effects surveillance system.

The aim of this study was to analyze cisplatin-induced ototoxicity in a recent study trial. Seventy-four patients who had received cisplatin for the treatment of osteosarcoma (median cumulative dose: 360 mg/m2) were investigated prospectively for ototoxicity in a multicenter trial. Hearing function was tested by audiometry. We evaluated the incidence and dependencies of hearing loss. After cessation of therapy, 51% of the patients showed a hearing loss of >20 dB in the frequency range of 4-8 kHz. Only in one patient a hearing loss was found at 2 kHz, and in none at 1 kHz. At a cumulative cisplatin dose of < or = 240 mg/m2, almost no ototoxicity was found. Incidence and magnitude of hearing loss increased significantly with a higher cumulative dose. Furthermore, hearing thresholds were significantly poorer in children <12 years. A further follow-up investigation showed only a marginal change in hearing function. We conclude that ototoxicity is moderate in our group of patients and probably irreversible.

[Test set for the evaluation of hearing and speech development after cochlear implantation in children]. / Evaluationsset zur Hör-/Sprachentwicklung nach Cochlea-Implantation bei Kindern.

BACKGROUND: Since autumn 1998 the multicenter interdisciplinary study group "Test Materials for CI Children" has been compiling a uniform examination tool for evaluation of speech and hearing development after cochlear implantation in childhood. METHODS USED: After studying the relevant literature, suitable materials were checked for practical applicability, modified and provided with criteria for execution and break-off. For data acquisition, observation forms for preparation of a PC-version were developed. RESULTS: The evaluation set contains forms for master data with supplements relating to postoperative processes. The hearing tests check supra-threshold hearing with loudness scaling for children, speech comprehension in silence (Mainz and Göttingen Test for Speech Comprehension in Childhood) and phonemic differentiation (Oldenburg Rhyme Test for Children), the central auditory processes of detection, discrimination, identification and recognition (modification of the "Frankfurt Functional Hearing Test for Children") and audiovisual speech perception (Open Paragraph Tracking, Kiel Speech Track Program). The materials for speech and language development comprise phonetics-phonology, lexicon and semantics (LOGO Pronunciation Test), syntax and morphology (analysis of spontaneous speech), language comprehension (Reynell Scales), communication and pragmatics (observation forms). The MAIS and MUSS modified questionnaires are integrated. CONCLUSIONS: The evaluation set serves quality assurance and permits factor analysis as well as controls for regularity through the multicenter comparison of long-term developmental trends after cochlear implantation.

Acoustically and electrically evoked responses of the human cortex before and after cochlear implantation.

Multi-channel auditory evoked potentials (AEP) were recorded before and after cochlear implantation (CI) from a patient suffering from severe high frequency hearing loss with residual, but highly fluctuating hearing around 250 Hz. Immediately after CI activation early components of the N1 were present. Later N1 components developed during the use of CI. The unique result of this single case study is the concordance of the cortical AEP pattern obtained by native and artificial peripheral stimulation, which can be regarded as an indicator for the adequate function of the CI.

[Status of hearing aid use by children in schools for the hearing impaired and deaf]. / Zum Stand der Hörgeräteversorgung bei Schülern und Schülerinnen der Schwerhörigen- und Gehörlosenschule.

To evaluate and possibly improve the hearing aid fittings of children attending the Westphalian School for the Hearing Impaired or the Westphalian School for the Deaf, regular pedaudiologic consulting hours were established at both schools. During a 2-year period, 115 children were examined once, 35 children twice, and 5 children three times. The examinations comprised ear microscopy, audiometry, and a check of the hearing aids with a 0.6-cm3 coupler (children up to 7 years) or 2-cm3 coupler, respectively. The following criteria were used to assess the quality of the hearing aid setting: status of the external auditory canal and middle ear, acceptance of wearing the hearing aid, status of the ear mold, technical status of the hearing aid, and its setting. The results were related to four variables: gender, type of school, age, and mean hearing loss. Overall, just 40.9% of all children showed satisfactory hearing aid performance at the first examination and just 37.1% at the second. A significant influence of the variables on the hearing aid performance was documented for hearing loss only. The higher the hearing loss, the more likely the children were to have good hearing aid status. Analysis of the different parameters revealed that an incorrect setting was the main problem, with a rate of 20.9%; the rate of the other parameters varied from 6.1% to 15.7%. Thus, no parameter was of major relevance to the results. The results of the second examination were poorer in most parameters than those of the first. These alarming results, which are probably not only of regional significance, demonstrate that the hearing aid status of children attending schools for the hearing impaired or for the deaf is in urgent need of improvement.

The influence of maxillary central incisor position in complete dentures on /s/ sound production.

STATEMENT OF PROBLEM: The insertion of prosthodontic restorations often leads to speech defects, most of which are transient but nevertheless a source of concern to the patient. For the dental practitioner, there are few guidelines on designing a prosthetic restoration with maximum phonetic success. PURPOSE: This study investigated the effect of different maxillary central incisor positions on phonetic patterns. MATERIAL AND METHODS: The inclination angle of central incisor blocks in duplicate complete maxillary dentures was changed in a range of -30 degrees to +30 degrees from the original position (0 degrees). Test words and sentences were acoustically analyzed. Spectral parameters such as first peak, noise band (defined by upper and lower limits of the most intensively blackened frequency area), Fast Fourier Transformation power spectrum, energy spectrum, and time were investigated. Influences of oral stereognosis, hearing, and age as cofactors on /s/ articulation were also taken into account. RESULTS: The change of incisor block angle in both directions usually caused a poorer execution of the /s/ sound. The labial angulation seemed to have a greater effect than the palatal angulation. The most significant changes were those in the noise band and energy spectrum. CONCLUSION: Immediate phonetic adaptation of prosthetic restorations in the maxillary incisor region can be achieved only if the original position of the natural teeth is transferred to the denture. Although these misarticulations are, in most cases, likely to disappear within a few weeks, they may persist and even lead to psychosocial problems. A better understanding of the causes of misarticulation and the limits of adaptation according to certain morphologic parameters of dentures is important.

The influence of hypothermia on outer hair cells of the cochlea and its efferents.

Transient evoked otoacoustic emissions (TEOAE) were recorded in 21 guinea-pigs undergoing hypothermia. The minimal average body temperature during cooling was 26 degrees C/24.9 degrees C measured orally or rectally, respectively. The animals were subsequently warmed to normal body temperature. A clear influence of body temperature on TEOAE could be documented. During cooling the amplitude and reproducibilities decreased, disappearing completely at a mean temperature below 28.5 degrees C (oral) and 27.3 degrees C (rectal). The emissions reappeared during rewarming at a mean temperature of 30.1 degrees C (oral) and 30.8 degrees C (rectal). Contralateral auditory stimulation (CAS) led to a decrease of the amplitudes of TEOAE during cooling down to a mean of 33 degrees C/32 degrees C (oral/rectal temperature). During rewarming, influences of the CAS could be recognized, again at an oral temperature above 35 degrees C. The changes to the TEOAE observed in these experiments suggest that hypothermia affects not only the outer hair cells (OHC) of the cochlea but also the efferent supply to the cochlea.

A novel locus for autosomal dominant, non-syndromic hearing impairment (DFNA18) maps to chromosome 3q22 immediately adjacent to the DM2 locus.

Investigating a large German pedigree with non-syndromic hearing impairment of early onset and autosomal dominant mode of inheritance, linkage to known DFNA loci was excluded and in a subsequent genomic scan the phenotype was mapped to a 10-cM interval on chromosome 3q22; a maximum two-point lod score of 3.77 was obtained for the marker D3S1292. The new locus, DFNA18, is excluded from neighbouring deafness loci, DFNB15 and USH3, and it overlaps with the recently described DM2/PROMM locus. As hearing loss has been described as one feature of the PROMM phenotype, the DFNA18 gene might also be responsible for hearing loss in DM2/PROMM.

Atypical organisation of the auditory cortex in dyslexia as revealed by MEG.

Neuroanatomical and -radiological studies have converged to suggest an atypical organisation in the temporal bank of the left-hemispheric Sylvian fissure for dyslexia. Against the background of this finding, we applied high temporal resolution magnetoencephalography (MEG) to investigate functional aspects of the left-hemispheric auditory cortex in 11 right-handed dyslexic children (aged 8-13 years) and nine matched normal subjects (aged 8-14 years). Event-related field components during a passive oddball paradigm with pure tones and consonant-vowel syllables were evaluated. The first major peak of the auditory evoked response, the M80, showed identical topographical distributions in both groups. In contrast, the generating brain structures of the later M210 component were located more anterior to the earlier response in children with dyslexia only. Control children exhibited the expected activation of more posterior source locations of the component that appeared later in the processing stream. Since the group difference in the relative location of the M210 source seemed to be independent of stimulus category, it is concluded that dyslexics and normally literate children differ as to the organisation of their left-hemispheric auditory cortex.

Glutathione S-transferase genetic polymorphisms and individual sensitivity to the ototoxic effect of cisplatin.

One of the side effects of cisplatin therapy in malignant neoplasms is ototoxicity. This effect shows a wide inter-individual range which is more variable than the pharmacokinetic parameters. Oxidative stress has been implicated in cisplatin ototoxicity. The glutathione S-transferase (GST) supergene family encodes isoenzymes that appear to be critical in protection against oxidative stress. Certain GST loci are polymorphic, demonstrating alleles that are null (GSTM1 and GSTT1), encode low-activity variants (GSTP1) or are associated with variable inducibility (GSTM3). The aim of our study was to investigate genetic risk factors involved in the ototoxicity of cisplatin and to determine whether the polymorphisms in five GST genes affect the individual risk of ototoxicity by cisplatin. Two groups of patients were analyzed in this study: group H, 20 patients early and highly sensitive to the ototoxicity of cisplatin; and group N, 19 patients with no hearing impairment under comparable doses of the drug. We found a protective effect for the GSTM3*B allele with a frequency of 0.18 in the group with normal hearing after therapy versus 0.025 in the group with hearing impairment. (chi2=5.37; p=0.02).

[Effect of dental prosthesis on the voice]. / Der Einfluss der Zahnprothese auf die Stimme.

It is well known that alterations to the oral cavity caused by dental prostheses may affect speech articulation, although influences on the voice are not assumed. In addition to the vocal fundamental frequency, vibrations of the vocal chords generate overtones. Through the shape of the larynx and the upper airway, resonances and antiresonances are formed, and in this way overtones are amplified to a variable extent. Nozzle changes caused by a dental prosthesis in the oral cavity may possibly influence overtones but influences on the vocal fundamental frequency seem unlikely. The influence of dental prostheses on the voice is demonstrated in a patient who owned two different dental prostheses. The fundamental frequency rose by up to five semitones during speech and his vocal range increased by up to four semitones when a thin denture was used instead of a normal denture. When the position of the mandible was checked by intraoral needle point placement, a more rostral position of the mandible was recorded with the thin denture than with the normal denture. Sagittal magnetic resonance tomography imaging also showed that the larynx was in a more cranial position. This change was presumed to be due to an upward movement of the larynx induced by the tongue, which itself was found to be in a more cranial position with the thin denture. In this situation, increased tension of the laryngeal muscles were believed to induce a rise in fundamental frequency, shifting the voice range toward higher frequencies. These findings show that dental prostheses can cause vocal changes in individual cases. The etiology of this occurrence is still not clear. Its consequences, however, should be known to the dentist, ENT surgeon and phoniatrist if patients notice changes in their voice after having altered or replaced their dentures.

Can dental prostheses influence vocal parameters?

STATEMENT OF THE PROBLEM: Alterations to the oral cavity caused by dental prostheses can affect speech articulation, whereas the influence of dental prostheses on the voice is unknown. For 1 patient, the fundamental frequency rose by up to 5 semitones during speech and his voice range was enlarged by up to 4 semitones when a thin denture was used instead of his normal denture. In this patient, intraoral needlepoint registration revealed a more rostral position of the mandible with the thin denture when compared with the normal denture. PURPOSE: This study evaluated the effects of such changes on phonation by varying the dentures of 20 subjects in line with those of the first patient. MATERIAL AND METHODS: The volumes of the test dentures were reduced and the vertical and horizontal dimensions of occlusion were varied. The influences of these changed dentures on speaking fundamental frequency, voice range (in semitones), and lowest and highest frequencies of the voice range were examined with a Homoth phonomat. RESULTS: A statistically significant influence of the different dentures on the investigated voice parameters was not proven; however, audible changes to the voice parameters for persons were documented. CONCLUSIONS: Variations of thickness and or volume of dentures and of the vertical and horizontal dimension of occlusion may result in unpredictable audible changes to the voice. Patients should be informed about possible effects of modified or new dentures on their voice.

Hearing screening in healthy newborns: feasibility of different methods with regard to test time.

Clicked-evoked otoacoustic emissions and automated auditory brainstem response are both considered appropriate hearing screening tools. The aim of this study was to compare their practicability with respect to test duration. In the first part of the study, clicked-evoked otoacoustic emissions were recorded in 388 healthy infants on the newborn ward in the first days of life. To reduce false positive rates of screening, clicked-evoked otoacoustic emissions combined with automated auditory brainstem response measurement (A-ABR, Algo 1E and Algo 2) were used in a second investigation. Fifty-five newborns screened by this two-stage method recorded an increased pass rate. The new digital technique of automated auditory brainstem response measurement (Algo 1E and Algo 2) employed in the second part of the study has a test time even shorter than that of clicked-evoked otoacoustic emissions and is no longer a time-consuming test due to improved technology of the second generation of automated auditory brainstem response equipment. Screening including preparation and follow-up time took 9.43 min (Algo 1E) and 8.26 min (Algo 2) respectively and was thus less time-consuming than reported in former studies.

Effects of age, gender and ear side on SOAE parameters in infancy and childhood.

We investigated 267 infants and children aged 9 days to 16.8 years to study the spontaneous otoacoustic emission (SOAE) data prevalence, number per ear, level and frequency as a function of growth. Dependence on age, gender and ear side was statistically analyzed using the method of generalized estimation equations. Except in the 1st year of life, SOAE prevalence per ear and SOAE number per ear decreased significantly with increasing age. Both SOAE parameters were significantly higher in female than in male subjects, with gender difference of SOAE prevalence per ear being more distinct in the 1st year of life. Although a clear ear side effect on SOAE prevalence per ear could already be seen in ears of female children in this age group, only SOAE number per ear was significantly higher in right ears than in left ears from the 1st year of life on. Except in the first 12 months, SOAE level and SOAE frequency decreased significantly with increasing age. Neither a significant gender difference nor a significant ear side difference could be determined. Our results found in infancy and childhood are discussed within the framework of the current literature.

Articulation in children with Down's syndrome. A pilot study.

The articulation of children with Down's syndrome (trisomie 21, T21) in comparison to a group of age-matched normal probands was investigated in a clinical study, using digital sonagraphics (recording of frequency, amplitude and time of the speech signal), with peripheral factors taken into consideration. The T21-Group (n = 10) revealed a higher variability as well as a longer articulation of the test word "Tasse" than the Control Group (n = 10). There was no clear-cut dependence of speed and quality of articulation on all of the peripheral factors evaluated (Angle Class, overbite, oral motor ability, hearing disorder, logopedics, Castillo-Morales stimulating plate treatment). The results of our investigation show differing patterns of articulation in T21 children compared with normal probands, using a reproducible method. A clear-cut influence of various influencing peripheral factors as reported in the literature could not be found for the T21-Group. Thus, central factors seem to have a great impact on articulation in T21 patients.

The influence of body temperature on transient evoked otoacoustic emissions.

Thirty patients undergoing open heart surgery under induced hypothermia had transient evoked otoacoustic emissions (TEOAE) recorded during cooling to 26.07 degrees C (standard deviation (SD) 4.25 degrees C) vesically measured temperature and 24.86 degrees C (SD 4.7 degrees C) nasopharyngeally measured temperature respectively. Subsequently tè patients were rewarmed until normal body temperature was reached again. There was a clear influence of body temperature on the amplitudes and reproducibilities of the TEOAE. The relationship of temperature and amplitude or reproducibility during the cooling phase was significantly different from that during rewarming. No TEOAE were measurable during cooling at a mean temperature lower than 33.41 degrees C (SD 2.04 degrees C) vesical temperature and 30.16 degrees C (SD 3.0 degrees C) nasopharyngeal temperature respectively. During rewarming the echoes became recognizable again at a mean temperature of 28.75 degrees C (SD 3.38 degrees C) vesical temperature and 27.49 degrees C (SD 2.99 degrees C) nasopharyngeal temperature. These results suggest a hysteresis in the relationship between the amplitude of TEOAE and temperature, similar to the well-established relationship between evoked potentials and temperature.

Dentistry and speech production. Correlations between the morphology of the articulation zone and acoustics exemplified in /s/ articulation.

Many factors are thought to be responsible for misarticulation. Maxillomandibular or dental irregularities play an important role as one of these factors. Correlations between morphological changes in dental status and speech disorders are well known, but different opinions are discussed in the literature. A reciprocal relationship between dysfunction and various dental irregularities is assumed. The objective of our review and experimental investigations was to document the influence of dental irregularities on speech articulation as exemplified by the second articulation zone and /s/ articulation. The second articulation zone was experimentally changed by application of dental cement to the palatal surface of the upper incisors. Various words were spoken before and just after the change to the frontal teeth. The /s/ articulations were acoustically analyzed by means of sonography and compared with each other. Although this modification of the teeth, which was identical in all probands, leads to /s/ misarticulation from the standpoint of auditory analysis, interindividual differences were recorded by acoustic means. It is thus possible to differentiate objectively between acoustically correct and incorrect /s/ articulation. Speech and articulation are, however, such complex mechanisms that it is impossible to characterize them by simple causal connections with maxillomandibular or dental irregularities.

[Molecular analysis of the heterogeneity of hereditary monosymptomatic sensorineural hearing loss]. / Molekulare Analysen der Heterogenität hereditärer monosymptomatischer Schallempfindungsschwerhörigkeiten.

BACKGROUND: Genetic characterization of hereditary hearing impairment has progressed considerably with the mapping of nine chromosomal loci for monosymptomatic autosomal-inherited hearing loss over the last three years. METHODS: Following thorough clinical evaluation, linkage analysis using microsatellite markers was performed in two large families from Westphalia/West Germany. RESULTS: For all the dominant (DFNA1--4) and three autosomal-recessive loci (DFNB1--3) described to date, linkage was finally excluded. CONCLUSIONS: A high degree of genetic heterogeneity must be assumed. Identification of individual genes for monosymptomatic sensorineural hearing loss by linkage analysis in large pedigrees may help in molecular differentiation of hearing.