DNA polymorphisms of the apolipoprotein B gene in patients with premature coronary artery disease.

Elevated plasma levels of low density cholesterol and their major apolipoprotein (apo B) are associated with an increased risk of coronary artery disease (CAD). We have examined allele frequencies of restriction fragment length polymorphisms (RFLP) of the apo B gene in 111 male Caucasians with premature CAD (mean age 49 +/- 7 years) and in 122 elderly Caucasian males (mean age, 73 +/- 5 years), free of clinical cardiovascular disease. The rare allele (R1) of the EcoR1 RFLP in exon 29, resulting in an amino acid change (Glu----Lys4154) was seen more frequently in CAD than in controls (0.270 vs 0.207, P less than 0.05). The R1 RFLP and the MspI insertion polymorphisms (MI) within the 3' hypervariable region (HVR) were observed together in 87% and are likely in linkage disequilibrium. The MI RFLP were slightly more frequent in CAD than control (0.239 vs. 0.211, P = 0.08). A second MspI RFLP in exon 26 results in an amino acid change (Arg----Glu3611); the rare allele M2 was seen more frequently in patients than in controls (0.150 vs. 0.057, P less than 0.005). No significant differences in allele frequencies were observed for the Xba1 RFLP in exon 26 (0.500 vs. 0.529, P = ns) or for the PvuII RFLP near the 5' end (P2) (0.105 vs. 0.088, P = ns). No statistically significant differences in lipid, lipoprotein cholesterol or apolipoproteins A-I and B were observed in patients or in controls. Two of the RFLPs examined (R1 and M2) result in changes in amino acid sequence and their allele frequencies are increased in CAD cases when compared with controls. Genetic variability within the apo B gene may thus contribute to cardiovascular risk. The physiological effects of individual mutations within apo B remain to be determined. It is unlikely, however that the single site polymorphisms examined in this study, will impart further information about CAD risk than conventional lipid parameters.

Variables affecting implant performance in children.

This study examined the variables that contribute to the large individual differences in the speech perception skills of children with the Nucleus multichannel cochlear implant. Sixty-one children were tested on four measures of speech perception: two tests of closed-set word recognition, one test of open-set recognition of phrases, and one open-set monosyllabic word test, scored on the basis of the percentage of phonemes as well as words identified correctly. The results of a series of multiple regression analyses revealed that the variables of processor type, duration of deafness, communication mode, age at onset of deafness, length of implant use, and age implanted accounted for roughly 35% of the variance on two tests of closed-set word recognition, and 40% of the variance on measures that assessed recognition of words or phonemes in an open set. Length of implant use accounted for the most variance on all of the speech perception measures.

Children with implants can speak, but can they communicate?

English-language skills were evaluated in two groups of profoundly hearing-impaired children with the Reynell Developmental Language Scales, Revised. The first group consisted of 89 deaf children who had not received cochlear implants. The second group consisted of 23 children wearing Nucleus multichannel cochlear implants. The subjects without implants provided cross-sectional language data used to estimate the amount of language gains expected on the basis of maturation. The Reynell data from the group without implants were subjected to a regression by age. On the basis of this analysis, deaf children were predicted to make half or less of the language gains of their peers with normal hearing. Predicted language scores were then generated for the subjects with implants by using the children's preimplant Reynell Developmental Language Scale scores. The predicted scores were then compared with actual scores achieved by the subjects with implants 6 and 12 months after implantation. Twelve months after implantation, the subjects demonstrated gains in receptive and expressive language skills that exceeded by 7 months the predictions made on the basis of maturation alone. Moreover, the average language-development rate of the subjects with implants in the first year of device use was equivalent to that of children with normal hearing. These effects were observed for children with implants using both the oral and total-communication methods.

Long-term intracochlear implantation in man.

Whether long-term intracochlear implantation and direct electrical stimulation of the acoustic nerve will induce intracochlear bone growth or cause further degeneration of a severely compromised auditory system is an important clinical consideration. Thin-section CT evaluations of the cochleas of six subjects who have used their cochlear implant devices on a daily basis for 3 or more years demonstrated no evidence of osteoneogenesis of the cochlea in the vicinity of the active electrode. No corrosion of the electrode or insulation material was noted on electron microscopy of an explanted electrode system. Electrical threshold and dynamic range measurements have remained stable or even improved during the period of observation. Performance measures using a variety of audiologic tests and speech-tracking scores have demonstrated stability of performance.

Comparison of speech perception abilities in deaf children with hearing aids or cochlear implants.

The speech perception abilities of deaf children with a single- or multi-channel cochlear implant are compared with those of deaf children who derive substantial benefit from conventional hearing aids. The children with hearing aids have unaided pure-tone thresholds ranging from 90- to 110-dB HL through at least 2000 Hz, and aided thresholds of 30- to 60-dB HL. The group data show that the speech perception scores of the subjects with hearing aids were significantly higher than those of the subjects with implants on a range of speech perception measures. Although a few subjects with implants achieved scores as high as those who used hearing aids, the majority did not. Even though the children with implants receive substantial benefit from their devices, they continue to have limited auditory perception abilities relative to their peers who derive benefit from conventional hearing aids. The data highlight the importance of establishing hearing aid benefit in potential candidates for implant.

Effect of age at onset of deafness on children's speech perception abilities with a cochlear implant.

The speech perception abilities of 37 children with cochlear implants (single-channel or multichannel) were examined as a function of age at onset of deafness. There was no significant difference in the speech perception abilities of implanted children who were born deaf and those of implanted children who lost their hearing during the first 3 years of life. In contrast, the performance of children whose age at onset of deafness was 5 years or later was significantly better than that of the children with congenital or early-acquired deafness on tests of stress pattern categorization, closed-set word identification, open-set identification of common phrases, and lipreading enhancement.

Enhancement of expressive language in prelingually deaf children with cochlear implants.

Expressive language skills were assessed in two groups of prelingually-deafened children using the Reynell Developmental Language Scales (RDLS). Results from a group of 89 unimplanted subjects provided cross-sectional data which suggested that profoundly deaf children without implants, on average, could only be expected to make 5 months of expressive language growth in one year. Twenty-three children who received cochlear implants made up the second group of subjects and were administered the RDLS at three intervals: preimplant, 6-, and 12-months postimplant. The scores obtained at the post-implant intervals were then compared to scores that would be predicted on the basis of maturation alone, without the implant (these predictions were formulated based on the data obtained from the unimplanted subjects). At the 12-month postimplant interval, the observed mean language score was significantly higher than the predicted score. Although the mean group data were extremely encouraging, wide inter- subject variability was observed. Although the implant subjects, as a group, were substantially delayed compared with their normal hearing peers, their rate of language growth was found to match that of hearing peers, following implantation. Thus, the gap between chronological age and language age, which normally widens over time in deaf children, remained constant. Preliminary analyses over the first 2.5 years post-implant are consistent with this trend. These results suggest that early implantation (before age 3) might be beneficial to profoundly deaf children because the language delays at the time of implantation would be much smaller.

Speech perception and speech production skills of children with multichannel cochlear implants.

The acquisition of speech perception and speech production skills emerges over a protracted time course in congenitally deaf children with multichannel cochlear implants (CI). Only through comprehensive, longitudinal studies can the full impact of cochlear implantation be assessed. In this study, the performance of CI users was examined longitudinally on a battery of speech perception measures and compared with subjects with profound hearing loss who used conventional hearing aids (HA). The average performance of the multichannel cochlear implant users gradually increased over time and continued to improve even after 5 years of CI use. Speech intelligibility was assessed from recordings of the subjects' elicited speech and played to panels of listeners. Intelligibility was scored in terms of percentage of words correctly understood. The average scores for subjects who had used their CI for 4 years or more exceeded 40%.

Language development in children implanted with the CLARION cochlear implant.

This study examined the development of language skills in 23 prelingually, profoundly deaf children following implantation with the CLARION Multi-Strategy Cochlear Implant. Language skills were assessed with the Reynell Developmental Language Scales (RDLS) preoperatively with hearing aids, and compared to postoperative performance after 6 months of Clarion use. The RDLS was administered in each child's preferred mode of communication, either spoken English alone or simultaneous spoken and signed English. Significant improvements were observed in average age-equivalent scores over time, both for receptive and expressive skills, although the absolute language levels of the implanted children remained delayed relative to those of hearing peers of the same chronological age. The children's rate of language growth in the first 6 months of implant use also was calculated. The results from this analysis showed that the Clarion children, on average, progressed at a rate that exceeded that of normal-hearing children of the same language age. There was no significant difference between the language performance of children who used oral versus total communication.

Speech intelligibility of implanted children.

The speech intelligibility of 61 prelingually deaf children was measured prior to their receiving a multichannel cochlear implant (CI) and at subsequent intervals. The speech intelligibility of the implanted subjects was compared to that of three groups of subjects with profound hearing loss who used conventional hearing aids (HAs), grouped on the basis of unaided thresholds: "gold" (pure tone average [PTA] = 93 dB hearing level [HL]), "silver" (PTA = 103 dB HL), and "bronze" (PTA > or = 110 dB HL). Intelligibility was measured in terms of the percentage of words from a set of 10 sentences that were correctly understood by a panel of listeners. The speech intelligibility of the implanted subjects increased gradually over time, remaining relatively low throughout the first 2 years of implant use. After that time, the average speech intelligibility of the CI subjects surpassed that of the silver HA users. The gold HA subjects demonstrated speech intelligibility that was markedly better than that of the CI subjects, even after 3 1/2 or more years of implant use.

Speech intelligibility of children with multichannel cochlear implants.

The purpose of this longitudinal study is to document improvements in speech intelligibility in children who have received multichannel cochlear implants, to compare their performance to that of a matched group of children with different levels of hearing loss who use conventional hearing aids. Speech intelligibility was measured by panels of listeners who analyzed recorded speech samples preimplant and at 6-month intervals following implantation. The results of this study demonstrate that prelingually deafened children with the Nucleus multichannel cochlear implant achieved significant improvements in speech intelligibility. By the 4.5- to 7.5-year intervals, the speech intelligibility exceeded 40%.

Speech perception skills of children with multichannel cochlear implants or hearing aids.

Perceptual skills were evaluated at two intervals of cochlear implant (CI) use in 24 children with prelingual deafness who received the Nucleus multichannel CI. Their performance was compared to that of age-matched children with prelingual profound hearing losses who used conventional hearing aids (HAs). The HA subjects were grouped by unaided thresholds: "gold" subjects (pure tone average of 92 dB hearing level) and "silver" subjects (pure tone average of 104 dB hearing level). The CI users' perceptual abilities increased significantly with time. At the "early" interval (mean, 2 months of CI use), performance of the CI and silver HA groups was similar on measures of phoneme, word, and sentence recognition; the gold HA subjects' performance was superior to that of the other groups. At the "late" interval, (mean, 2.5 years of CI use), CI subjects' performance exceeded that of the silver group on all measures, and was similar to that of the gold group on vowel recognition and auditory-plus-visual sentence recognition measures.

Performance of deaf children with cochlear implants and vibrotactile aids.

A longitudinal study is under way to examine the speech perception and production skills of deaf children who use a single- or multi-channel cochlear implant, or a two-channel tactile aid. The speech perception data showed that the majority of subjects who achieved the highest scores on a range of measures used the multi-channel cochlear implant. The production data showed that all three types of sensory aids were effective in promoting production skills, with the cochlear implant users showing the greatest gains in this area.

Evaluating meaningful auditory integration in profoundly hearing-impaired children.

The Meaningful Auditory Integration Scale (MAIS) was developed to evaluate meaningful use of sound in everyday situations by profoundly hearing-impaired children. Information about the use of sound in everyday situations is obtained with a parent interview technique. Initial findings obtained with this scale are reported in Experiment 1 for children who use a hearing aid, single-channel cochlear implant, multichannel cochlear implant, or two-channel tactile aid. The hearing aid users were perceived by their parents to use sound in everyday situations to a greater extent than were the users of either implant or the tactile aid. There was a trend toward slightly higher performance by the multi- than by the single-channel cochlear implant users. The tactile aid users were perceived by their parents to use sound in a meaningful way to the most limited extent. Scores on the MAIS, which were obtained on a longitudinal basis, are reported in Experiment 2. The findings suggest that meaningful auditory integration continued to develop over time in children who used each type of sensory aid.

Initial findings with a wearable multichannel vibrotactile aid.

Data are presented on the speech perception performance of two profoundly hearing-impaired subjects while using a two-channel vibrotactile aid (Tactaid II) or a new, seven-channel instrument. Both subjects, one a profoundly hearing-impaired teenager and one a postlingually deaf adult, are experienced users of tactile aids. The data suggest better recognition of speech features, words, environmental sounds, and enhancement of lipreading skills with the new multichannel instrument than with the two-channel device.