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Biomedical subjects

S J Norton

Publications and source records attributed to S J Norton.

At least 19 recordsLinked to original sources

Characteristics of transient evoked otoacoustic emissions in normal-hearing and hearing-impaired children.

OBJECTIVE: Transient evoked otoacoustic emissions (TEOAEs) were measured in children with normal hearing and in children with hearing loss to investigate the characteristics of TEOAEs as they relate to overall amplitude and amplitude spectra of evoking stimuli, and to audiometric status. DESIGN: Three parameters of response measure (signal to noise ratio, amplitude and reproducibility) were assessed to determine accuracy of identification of varying degrees of hearing loss for broadband clicks, frequency-specific click bands and tone bursts. Forty-four children (66 ears) between 4 and 13 yr of age were evaluated for participation in the study. Fifty-nine ears with intact tympanic membranes were included in the final analyses: 14 ears with normal hearing and 45 ears with hearing loss. RESULTS: Children with normal hearing had robust responses that displayed nonlinear growth functions for broadband clicks and for tone bursts. Children with hearing loss had responses that decreased rapidly with decreasing stimulus level, if emissions were present at all. Data were analyzed using clinical decision analysis and receiver operator characteristic curves. Broadband clicks presented at 80 and 86 dB peSPL identified a hearing loss > or = 30 dB HL with a high degree of accuracy. Click responses filtered into octave bands centered at 500 and 1000 Hz did not improve classification of hearing loss, in fact, the 500 Hz band was particularly inaccurate. Results for click responses filtered into half-octave bands centered at 2000 and 4000 Hz were comparable with those for the broadband click, although the 2000 Hz band was superior for identification of hearing loss > or = 20 dB HL for an 80 dB peSPL click, and > or = 30 dB HL for an 86 dB peSPL click. Results for tone bursts centered at 500, 1000, 2000 and 4000 Hz, presented at 80 dB peSPL, were similar to results of the filtered click bands. Accuracy for identifying hearing loss increased with increasing center frequency. The 2000 and 4000 Hz tone bursts provided the best separation between normal-hearing and hearing-impaired ears, with 4000 Hz being slightly better. CONCLUSIONS: Data from this study suggest that TEOAEs in children can separate ears with normal hearing from those with hearing loss using a variety of stimulus and response conditions. Moreover, by using multiple stimulus levels it may be possible to distinguish between mild and moderate hearing losses.

Acoustic Stimulation

Fluid flow imaging by means of wide-band diffraction tomography.

The problem of reconstructing a two-dimensional distribution of fluid flow from wide-band scattering measurements is considered. Reciprocal scattering measurements are employed, meaning that scattered waves are recorded between a source and receiver, and again with the source and receiver interchanged. As shown, such measurements allow the reconstruction of a fluid flow image separate from that of a distribution of stationary acoustic velocity inhomogeneities.

Acoustics

Synthesis and study of thiocarbonate derivatives of choline as potential inhibitors of acetylcholinesterase.

Fourteen alkyl and aryl thiocarbonate derivatives of choline were synthesized and studied as potential inhibitors of acetylcholinesterase (AChE). Twelve of the compounds inhibited AChEs derived from calf forebrain, human red blood cells, and octopus brain ranging from low to moderately high inhibition potency. The concentration of each inhibitory compound giving 50% inhibition of enzyme activity (IC50 values, which ranged from 1 x 10(-2) to 8 x 10(-7) M) was determined and is reported; inhibitor constants (Ki values) for the most inhibitory compounds, (1-pentylthiocarbonyl)choline chloride and (1-heptylthiocarbonyl)choline chloride, were calculated from kinetic data and are also reported. The inhibitors are competitive with substrate, and they are not hydrolyzed by the AChE activities. Certain of these new compounds may provide direction for the development of new drugs that have anticholinesterase activity and may be used for the treatment of Alzheimer's disease.

Acetylcholinesterase

Changes in otoacoustic emissions and auditory brain stem response after cis-platinum exposure in gerbils.

Ototoxicity associated with cis-platinum administration commonly presents as hearing loss and tinnitus. The hearing loss is usually an irreversible, high-frequency sensorineural loss. Histologic studies in humans and animals suggest that the outer hair cells (OHCs) are most susceptible to cis-platinum. Evoked otoacoustic emissions (EOAE), as a measure of outer hair cell function, are potentially useful in following ototoxic insults involving OHCs. Distortion-product otoacoustic emissions (DPOAE) test frequency-specific regions of the cochlea and therefore may be particularly well suited for monitoring ototoxic injuries. We measured distortion product otoacoustic emissions, at f2 = 2, 4, 6, 8, 10, and 12 kHz, in gerbils after a single large dose of cis-platinum. Animals treated with saline served as controls. The findings were compared to auditory brain stem evoked response (ABR) thresholds, using tone pips of the same frequencies. The DPOAE and ABR thresholds were measured before treatment and again 2, 5, and 14 days after drug administration. The changes in DPOAE were compared with the changes in ABR. No treatment effect was noted in the 2-day group. Animals treated with cis-platinum demonstrated significant elevation of DPOAE and ABR thresholds compared with control animals at 5 and 14 days. There was no significant difference between the threshold changes in the 5- and 14-day groups.

Animals

Glyoxalase II and glutathione levels in rat liver mitochondria during cold storage in Euro-Collins and University of Wisconsin solutions.

Glutathione and glyoxalase II levels were evaluated in cytosolic and mitochondrial compartments of rat liver after 7 and 24 hr of cold storage in University of Wisconsin (UW) and Euro-Collins solutions. 1-4 A similar time-dependent depletion of cytosolic glutathione up to about 60% of control values was observed in both Euro-Collins and UW solutions. Cytosolic glyoxalase II showed activity oscillations in livers stored in Euro-Collins but not in UW. Mitochondrial glutathione and glyoxalase II were severely depleted soon after 7 hr of cold storage in Euro-Collins, whereas the same parameters did not change in liver stored in UW after 24 hr. UW is confirmed to be the most suitable solution for liver cold storage and we conclude that mitochondrial glutathione and glyoxalase II can be important parameters in assessing mitochondrial and cell function.

Adenosine

The effects of continuous versus interrupted noise exposures on distortion product otoacoustic emissions in guinea pigs.

Distortion product otoacoustic emissions (DPOAE) were measured serially in guinea pigs before and following 4-h exposures to a half-octave band of noise centered at 6 kHz. Stimulus parameters used to elicit the DPOAE were f2/f1 = 1.26 and L2 = L1-10. The 80 dB SPL exposures resulted in attenuation of emissions, which was maximal at the frequency one-half octave above the exposure when referenced to the f2 stimulus, and which recovered back to baseline after 2 days. The 90 dB SPL exposures resulted in a permanent deficit in emissions elicited by high-frequency stimuli, as measured after 8 days of recovery. A statistically significant difference was also found between animals exposed continuously for 4 h versus animals given two 2-h exposures separated by a 1-h break. Measures of f2-f1 and 3f1-2f2 indicated that they were more sensitive than 2f1-f2 to alterations in cochlear function after noise exposure.

Acoustic Stimulation

Isozymes of superoxide dismutase from Aloe vera.

Extracts from the parenchymatous leaf gel and the rind of the Aloe vera plant (Aloe barbadensis Miller) were shown to contain seven electrophoretically-identifiable superoxide dismutases (SODs). The chromatographic elution profiles and the migration of these bands on native polyacrylamide gel electrophoresis (PAGE), for both the gel and rind, are quite similar. Two of these seven activities are insensitive to cyanide treatment, suggesting that they are mangano-SODs. The other five activities are sensitive to cyanide treatment, but insensitive to azide treatment and are presumed to be cupro-zinc SODs. All of the seven proteins appear to be homodimers with apparent native molecular masses centered at approximately 32 and 42 kD as indicated by SDS-PAGE and gel-filtration (FPLC) chromatography. The specific activities of SODs in the A. vera rind and gel are comparable to those of spinach leaves and of rabbit liver.

Aloe

Hearing loss prevalence and risk factors among Sierra Leonean children.

OBJECTIVES: To determine hearing loss prevalence among a group of Third World children, to describe the physical examination and audiometric findings in the hearing-impaired children, and to assess the association of hearing loss with several known risk factors. It was hypothesized that chronic otorrhea would be the risk factor most strongly associated with hearing loss. DESIGN: Community screening program to identify and evaluate hearing-impaired children. Case-control analysis of hearing loss risk factors. A survey taker, blinded to the children's hearing status, ascertained risk factors. SETTING: Rural community in eastern province of Sierra Leone, West Africa. PATIENTS: Population-based sample of 2015 children aged 5 to 15 years. Risk factor analysis was performed in 184 children and an equal number of matched controls. MAIN OUTCOME MEASURE: Hearing loss determined according to World Health Organization, Geneva, Switzerland, definition. RESULTS: A total of 184 (9.1%) of 2015 children were found to have mild or greater hearing loss. The prevalence of bilateral profound hearing impairment was 4.0 per 1000. We assessed physical examination and audiometric findings. The risk factor most strongly associated with hearing loss was a history of otorrhea persisting longer than 1 month (odds ratio, 23.3; 95% confidence limits, 12.11, 45.40). CONCLUSIONS: A high prevalence of hearing loss was identified. Much of this impairment may result from chronic untreated or unrecognized ear infections. Further community-based studies of hearing-impaired children are necessary for planning preventive and curative programs.

Adolescent

"Say-stay" identification and psychoacoustic performance of hearing-impaired listeners.

Controversy exists over the extent to which psychoacoustic abilities explain speech perception. The present study addressed this issue by assessing the contribution of psychoacoustic abilities to speech identification by hearing-impaired listeners. Speech stimuli and nonspeech analogs were presented to normal-hearing and hearing-impaired listeners with varying degrees of hearing loss. Phonemic judgments for synthetic versions of "say-stay" stimuli were evaluated as a function of first formant onset frequency and of silence duration between the /s/ noise and the vocalic portion. Three psychoacoustic measures were obtained: glide onset frequency discrimination, gap detection in noise, and gap detection in speechlike composite signals. Although the resulting difference limens increased with increasing hearing loss, the acoustic cues to the speech contrast were available to all listeners. Nonetheless, the response patterns to the speech stimuli varied among groups in a manner that was not explained by the psychoacoustic results. Thus, although hearing-impaired listeners were able to detect and discriminate essential acoustic cues for speech, the perceptual organization of speech stimuli appeared to differ with degree of loss. Alternative explanations for the findings are considered, including the possible effect of hearing loss on auditory/linguistic experience.

Adolescent

Skin burn injury and oxidative stress in liver and lung tissues of rabbit models.

The effects of burn injury (30% of total body surface area) on the levels of oxidized and reduced glutathione, malondialdehyde, and on the activities of certain glutathione-dependent enzymes, have been determined in tissues of rabbit models. Thus, the malondialdehyde, glutathione (GSH), glutathione disulfide (GSSG) concentrations and the specific activities of glutathione peroxidase, glutathione S-transferase, and glutathione reductase were measured in liver and lung of 24-h burn rabbit models and compared to the corresponding values in 24-h sham burn (medicated, anesthetic/analgesic) rabbit models. It was found that the concentrations of malondialdehyde in liver and lung of burn models were increased by 17% and 29% respectively. Glutathione concentrations were decreased by 29% in liver and 13% in lung, and glutathione disulfide concentrations were increased by 35% in liver and 33% in lung, in burn versus sham burn models. It was also found that the specific activities of glutathione peroxidase decreased significantly, resultant to burn injury, by an average of 35% and 27% in liver and lung, respectively. Burn injury also decreased glutathione S-transferase specific activities by 14% in liver and 23% in lung tissues. In contrast, glutathione reductase specific activity was increased in liver tissues (22%), but was decreased (19%), as with the other enzymes studied, in lung tissues of burn models. Control model studies (no medication, no sham burn) show that these effects of burn injury are additional to effects elicited by medication associated with sham burn models. The data of this study are indicative of a major oxidative stress in liver and lung tissues due to burn injury at a remote site.

Animals

N,S-bis-fluorenylmethoxycarbonylglutathione: a new, very potent inhibitor of mammalian glyoxalase II.

A very potent competitive inhibitor of mammalian glyoxalase II activity, N,S-bis-fluorenylmethoxycarbonylglutathione (DiFMOC-G) has been synthesized and characterized. The Ki value for inhibition of glyoxalase II purified from calf liver is 0.08 microM. The Ki values for glyoxalase I inhibitions range from 285 to 500 fold higher than the values obtained for glyoxalase II inhibitions, depending on the source of the enzyme. Among other enzymes involved in glutathione metabolism, such as glutathione S-transferase, glutathione reductase, and glutathione peroxidase, only glutathione S-transferase is inhibited to a small extent by DiFMOC-G. Diesters of DiFMOC-G were prepared in order to improve transport of DiFMOC-G into mammalian tumor cells (rat adrenal pheochromocytoma, PC-12) in culture. Among the diesters synthesized, diisopropyl DiFMOC-G was found to be the most inhibitory to cell viability, with a [I]0.5 value of 3 microM.

Animals

Effect of perilymphatic fistulas on evoked otoacoustic emissions in the guinea pig.

Round window perilymphatic fistulas were surgically created in 20 guinea pigs. Distortion product otoacoustic emissions (DPOAEs) at 2fl - f2 were recorded prior to and immediately following laceration of the round window. The stimuli were equal level sinusoids (f1 < f2) with f2 ranging from 2 to 10 kHz, a fixed f2:f1 ratio of 1.25, and stimulus levels (L2 = L1) ranging from 20 to 80 dB SPL. After an 18-day survival period, emission measurements were repeated, and fluorescein was infused into the cerebrospinal fluid to verify patency or closure of the fistula. Nine animals demonstrated patent fistulas, whereas 11 had closed fistulas. There was a statistically significant reduction in DPOAE amplitude after an acute fistula across all stimulus levels (p < .001). At 18 days the DPOAE amplitudes in animals with healed fistulas could not be differentiated from controls, whereas DPOAE amplitudes in animals with patent fistulas were statistically different from controls (p < .05). The results suggest that evoked otoacoustic emissions may be useful in detecting perilymphatic fistulas.

Acoustic Stimulation

External and middle ear status related to evoked otoacoustic emission in neonates.

OBJECTIVE: Screening auditory status prior to neonatal hospital discharge to identify newborns with severe hearing impairment is an important pediatric care priority. Evoked otoacoustic emission (OAE) testing is a quick noninvasive method. The purpose of this study was to determine the relationship between external auditory canal and middle ear status with click-evoked OAE. It was hypothesized that vernix caseosa, debris in the ear canal, and middle ear fluid contribute to the OAE fail rate. DESIGN: All neonates had an initial OAE examination. A second investigator, "blinded" to the results, examined all ears otoscopically, cleaned any obstructing debris, and repeated with a second OAE test. SETTING: All neonates were tested in a designated nursery at a mean age of 43 +/- 21 hours. PATIENTS: Forty-one full-term neonates were prospectively enrolled. INTERVENTION: The ear canals with debris were cleaned under direct vision with a pediatric swab dampened by an alcohol wipe. OUTCOME MEASURE: The primary outcome measure was the postcleaning OAE pass rate. RESULTS: The preotoscopic examination pass rate of 82 ears was 76%. The OAE pass rate improved to 91% after debris removal. CONCLUSIONS: The results indicate that the examination and cleaning of the external ear canal are important components of the neonatal screening process.

Acoustic Stimulation

Application of transient evoked otoacoustic emissions to pediatric populations.

Transient evoked otoacoustic emissions (TEOAEs) occur after presentation of brief acoustic stimuli such as clicks and tone pips. They represent physiological activity from within the cochlea, specifically from normal functioning outer hair cells. TEOAEs are frequency specific in that their spectra are determined by the spectra of the evoking stimulus and the audiometric configuration. TEOAEs are sensitive to mild to moderate degrees of cochlear hearing loss up to about 40 to 50 dB HL. They can be measured rapidly and noninvasively in infants and children. Among the potential applications in pediatric audiology are screening for hearing impairment in neonates, separating peripheral hearing loss and central auditory dysfunction, and monitoring cochlear status in children receiving ototoxic drugs.

Acoustic Stimulation

The effects of aging on otoacoustic emissions.

Otoacoustic emissions were measured in 42 normal hearing subjects ranging from 20 to 80 years old. For each subject spontaneous, click-evoked, tone-burst-evoked, stimulus frequency and distortion product emissions were measured across a wide intensity range for frequencies between 1 and 3 kHz. Although there are significant differences between age groups, the results indicate no age effect independent of hearing sensitivity on any type or parameter of otoacoustic emissions (OAE). The effect of increasing age is confounded with the effect of decreasing sensitivity such that post hoc analyses are inadequate to separate the effects of sensitivity and age on otoacoustic emissions. Even within the range of audiometrically normal hearing, OAE characteristics vary with threshold for all age groups. The conclusion is that hearing sensitivity must be included as a controlled variable in order to accurately assess intrinsic aging effects.

Acoustic Stimulation

Vulnerability and adaptation of distortion product otoacoustic emissions to endocochlear potential variation.

The endocochlear potential (EP) was reversibly decreased in adult gerbils by the intraperitoneal injection of furosemide, while cochlear functioning was monitored by measurement of distortion production otoacoustic emissions (DPE) at a range of stimulus intensities. Stimulus frequencies for DPEs were f1 = 6.8 and f2 = 8 kHz (f2/f1 = 1.18). Emissions monitored in the ear canal and scala media were 2f1-f2, 3f1-2f2, 2f2-f1, and f2-f1. Typically, the EP decreased smoothly, reached a minimum one-half hour after injection, then recovered slowly over several hours. Emissions at 2f1-f2 and 3f1-2f2 at low stimulus levels were particularly vulnerable to the change in EP. These vulnerable emissions showed characteristic trajectories in which the amplitudes changed little with the initial EP decrease, then dropped sharply as the EP continued to decrease. However, the amplitudes then began to recover even before the EP reached minimum, and recovered completely while the EP remained subnormal. The trajectories of the other odd order emissions were similar, but lacked the abrupt decrease. The variation of the even order (f2-f1) component was completely different, but appeared related to the odd order trajectories in a complex fashion. During the initial decrease for the vulnerable components, the decrease in emission amplitude (in dB) was found to be proportional to the square of the change in EP (in mV). The recovery with a subnormal EP was interpreted as an adaptive effect with a time constant of about 15 min.

Acoustic Stimulation

Purification and characterization of a glutathione peroxidase from the Aloe vera plant.

Extracts from the parenchymous leaf-gel of the Aloe vera plant (Aloe barbadensis Miller) were shown to contain glutathione peroxidase (GSHPx) activity. The activity was purified to homogeneity by ion exchange and gel filtration (FPLC) chromatography in the presence of 0.5 mM glutathione. The native enzyme has an apparent molecular weight of 62 kD as determined by gel filtration. In the presence of sodium dodecylsulfate (SDS), the molecular weight was estimated to be about 16 kD as determined by polyacrylamide-gel electrophoresis (SDS-PAGE). The native enzyme is proposed to be constituted of four identical subunits; it also contains one atom of selenium per subunit, as found with most glutathione peroxidases from animal sources. The Km values were determined to be 3.2 mM for glutathione and 0.26 mM for the hydroperoxide substrate, cumene hydroperoxide. The enzyme is competitively inhibited by N, S, bis-FMOC glutathione (Ki = 0.32 mM), a potent inhibitor of glyoxalase II. Inhibitors of glyoxalase I (e.g. S-octylglutathione) have no effect on the peroxidase activity.

Aloe