Biomedical subjects

R V Harrison

Publications and source records attributed to R V Harrison.

At least 37 records · Page 2Linked to original sources

PubMed1999

Issues in the development, dissemination, and effect of an evidence-based guideline for managing sore throat in adults.

BACKGROUND: In October 1995 the University of Michigan Healthcare System initiated a program to develop and implement guidelines for primary care in an effort to improve the quality and cost-effectiveness of care for common conditions associated with wide variations in clinical practice. One of these conditions was Group A beta-hemolytic streptococcus (GABHS), present in 5% to 20% of adults complaining of sore throat. METHODS: A draft guideline was developed on the basis of a theoretical model of sore throat management, local data, and research evidence. The guideline was revised to reflect physicians' beliefs and practices regarding sore throat management. Guideline recommendations depended only on the number of clinical signs experienced by the patient and included testing only if it was likely to provide additional information about the probability of GABHS. Data on pre- and postdissemination data on patients presenting with sore throat were collected. RESULTS: When physicians believed testing or antibiotics were unnecessary, only 7% of patients demanded screening and only 6% of patients wanted antibiotics. Physician beliefs about a patient's need for testing agreed with guideline recommendations in 63% of patients both before and after guideline dissemination. DISCUSSION: Disseminating locally modified, evidence-based guidelines may not be sufficient to produce practice changes. If the guideline had been followed, the amount of testing would have been reduced by 17% and the appropriateness of testing improved for 32% of sore throat patients. The results indicate the need for implementation efforts that go beyond presenting evidence, even when that evidence is from both the literature and the local practice setting.

Adult↗

PubMed1999

Middle ear instillation of gentamicin and streptomycin in chinchillas: morphologic appraisal of selective ototoxicity.

OBJECTIVE: To determine selective cochlear and vestibular ototoxicity of two aminoglycoside antibiotics (gentamicin and streptomycin) in the chinchilla model. Middle ear application of these agents mirrors the clinical practice of chemical vestibular ablation used in Meniere's disease. BACKGROUND: Middle ear instillation of gentamicin or streptomycin has become a popular form of vestibular ablative treatment for disabling Meniere's disease. The vestibular selectivity of these two drugs applied in this fashion has clinical support but is not fully established in humans. Our understanding in this regard has largely been limited to animal models exposed to systemic infusion of aminoglycosides. METHOD: Ten chinchillas underwent left middle ear instillation of one of three agents using variable dosing schedules: gentamicin (n = 6), streptomycin (n = 2), and saline (n = 2) as control. Animals were sacrificed for temporal bone studies using scanning electron microscopy. Morphologic changes in the cochlear and vestibular neuroepithelia were identified. RESULTS: Widespread cochlear and vestibular neuroepithelial injuries were observed with both gentamicin and streptomycin. Contralateral ototoxicity was variable and not related to the total dose of drug delivered. The effect of these two aminoglycosides on the dark cells of the vestibular system appeared negligible. CONCLUSION: We were unable to confirm the selective damage of vestibular end-organ in the chinchilla by either gentamicin or streptomycin, a phenomenon that is generally perceived to occur in humans. Chinchillas, like other small mammals, may not be an ideal model for the study of human ototoxicity.

Animals↗

PubMed1998

Plasticity of tonotopic maps in auditory midbrain following partial cochlear damage in the developing chinchilla.

There is substantial reorganization of the midbrain (inferior colliculus) tonotopic map following neonatally induced partial cochlear lesions in the chinchilla. The most obvious feature of this remapping is a large "iso-frequency" region in the ventral sector of the central nucleus of inferior colliculus (ICC). Neurons in this region exhibit similar threshold and tuning properties, with a common characteristic frequency which corresponds to the high-frequency audiometric cutoff. This overrepresented frequency range also corresponds to the high-frequency border of the cochlear lesion. Alterations to the tonotopic map corresponding to lower frequencies, in more dorsal regions of ICC, depend on the extent and degree of the cochlear lesion. When there is minimal damage to apical (low-frequency) cochlear areas, the dorsal ICC has relatively normal frequency representations. With more extensive apical cochlear lesions there is a corresponding disruption of ICC tonotopic representation of the low frequencies. We conclude that the tonotopic map within the ICC can become (re)organized postnatally according to the abnormal pattern of neural activity from the auditory periphery. Similar reorganization can be expected to occur in human infants with a partial cochlear hearing loss from birth.

Age Factors↗

PubMed1998

Comparison of distortion-product and transient evoked otoacoustic emissions with ABR threshold shift in chinchillas with ototoxic damage.

In this study we compare distortion product otoacoustic emissions (DPOAEs), transient evoked otoacoustic emissions (TEOAEs) and ABR threshold shifts in an animal model (chinchilla) of cochlear hearing loss. Subjects were treated with an aminoglycoside (amikacin) to produce basal cochlear lesions of various degree. DPOAE and TEOAE were measured throughout the treatment period and until hearing thresholds stabilized. ABR thresholds to tone pip stimuli were determined. Cytocochleograms of cochleas were prepared using scanning microscopy. DPOAEs (2f1-f2) were compared to fast Fourier transform (FFT)-analyzed TEOAEs components in the 1-, 2-, and 4-kHz frequency regions. Both types of emission were compared with corresponding ABR thresholds. There was no significant linear correlation between these different measures of cochlear function. Moreover, the amplitudes of DPOAEs reflected smaller regions of cochlear outer hair cell (OHC) damage better than TEOAEs. These results suggest that DPOAEs can be used to more accurately monitor hair cell function at specific hearing locations than TEOAEs.

Amikacin↗

PubMed1998

An animal model of auditory neuropathy.

OBJECTIVE: We describe an animal model of auditory neuropathy in which subjects have extensive, scattered inner haircell loss but with a relatively intact outer haircell population. DESIGN: Such a pattern of cochlear haircell damage can be produced in the chinchilla by treatment with the anticancer agent carboplatin. RESULTS: In these subjects, otoacoustic emissions (OAEs) and cochlear microphonics remain normal while auditory brain stem evoked potential (ABR) thresholds are significantly elevated. However, in the same subjects, central auditory neurons (in the inferior colliculus) have response thresholds that are considerably lower (by up to 50 dB) than ABR thresholds. These findings parallel the characteristics of auditory neuropathy in humans, in which absent or abnormal ABRs are recorded in patients with only mild to moderate audiometric thresholds and preserved OAEs. CONCLUSIONS: We suggest that scattered inner haircell lesions also can result from long-term cochlear hypoxia, and we propose that this is a likely candidate for the etiology of many types of auditory neuropathy in human subjects.

Animals↗

PubMed1998

Increased otoacoustic-emission amplitude secondary to cochlear lesions.

OBJECTIVE: The measurements of transient evoked otoacoustic emissions and distortion-product otoacoustic emissions are being used increasingly, both as an objective hearing test clinically, and as a research tool to investigate the micromechanical aspects of cochlear function. We hypothesized that localized damage in the apical or middle cochlear turns may have an influence on the micromechanics and the function of adjacent, apparently normal cochlea. For that purpose, we used an animal model of localized apical and middle-turn cochlear lesions. METHOD: Extent of damage was assessed by scanning electron microscopy and the function of the damaged cochlea by change in the otoacoustic emission (OAE) levels. RESULTS: We found that localized damage to the apical or middle turn may be accompanied by an increase in OAE measured from adjacent apparently normal cochlea. CONCLUSION: Explanations to this phenomenon are suggested, and possible clinical associations such as to Meniere's disease and to sudden hearing loss are reviewed.

Animals↗

PubMed1997

The effects of anesthesia on otoacoustic emissions.

We have measured transient-evoked and distortion-product otoacoustic emissions (OAEs) in the chinchilla and compared them in the awake and anesthetized animal (using either ketamine or barbiturate agents). We report a significant increase in OAE amplitudes during anesthesia, particularly using ketamine. These effects are most evident for transient-evoked otoacoustic emissions (TEOAEs) as measured in the non-linear mode. Our data support the hypothesis that tonic activity levels in cochlear efferents may be reduced by anesthetic effects, either directly or indirectly (e.g., by general reductions in descending pathway activity), and that reduced cochlear efferent activity will result in the observed increase of OAE amplitudes.

Acoustic Stimulation↗

PubMed1997

The effects of crossed olivocochlear bundle section on transient evoked otoacoustic emissions.

The purpose of this study was to investigate the effect of sectioning the crossed olivocochlear bundle (COCB) on transient evoked otoacoustic emissions (TEOAEs) in anesthetized adult chinchillas. Of particular interest is the role of cochlear efferents to the outer haircells (OHCs) and how they control mechanisms responsible for otoacoustic emissions. Specifically the experiment addressed whether a tonic level of inhibitory control is reduced by COCB section. The nonlinear component of TEOAEs was measured before and after COCB section. Analysis was made of the 1, 2, 3, 4, and 5 kHz frequency components and of the total emission, as quantified by fast Fourier transform (FFT) of the raw (time domain) response. After COCB section, the amplitude of the total response and of the 2, 3, 4, and 5 kHz components increased whereas the amplitude of the 1 kHz component decreased. The results indicate that COCB section reduces inhibitory control of the OHC mechanisms responsible for nonlinear TEOAE generation. It is not clear whether the nerve section eliminates a spontaneous level of activity in COCB efferents, or whether it results in the interruption of a stimulus-evoked feedback loop.

Acoustic Stimulation↗

PubMed1997

Total ablation of cochlear haircells by perilymphatic perfusion with water.

Inner and outer haircells are destroyed within one day following perfusion of the perilymphatic spaces with water, otherwise the structural integrity of the cochlea and the organ of Corti are preserved. This technique is a reliable method to create an acute unilateral deafness model for investigations of auditory function.

Animals↗

PubMed1997

The Paediatric Cochlear Implant Program at the Hospital for Sick Children, Toronto.

Ontario has a province-wide program for provision of cochlear implants. Toronto's Hospital for Sick Children is one of three designated centres that service the paediatric population. This cochlear implant program was established in 1989. Since that time, 37 children (as of May 1996) have been provided with cochlear implants. The program also services Ontario residents who were implanted elsewhere. In the following, we provide a detailed description of the program, including the processes through which children are selected as candidates, the follow-up studies that we carry out, and the roles of various health care professionals involved. We present a demographic survey of our patient population to date, and discuss some of the important issues relating to candidacy.

Child, Preschool↗

PubMed1996

Tonotopic mapping in auditory cortex of the chinchilla.

Using single-unit electrophysiological methods we have mapped sound frequency (or cochleotopic) representation in the auditory cortex of the chinchilla. We describe the surgical approach to expose this area. We report on maps from six subjects and note a considerable variation in shape between individuals. In general, the primary area has a cochleotopic/tonotopic organization in which low frequencies are represented rostrally and higher frequencies caudally. Neurons in the primary area have latency and tuning properties comparable to other mammalian species. A region anterior to the primary (AI) auditory are has a reverse tonotopic map and may be analogous to the anterior auditory field (AAF) reported in other species.

Acoustic Stimulation↗

PubMed1996

Otoacoustic emission amplification after inner hair cell damage.

Otoacoustic emissions (OAEs) are considered to originate from active cochlear processes involving the outer hair cells (OHC). These emissions are suppressed by activity in the efferent olivocochlear bundle (OCB) and following OHC damage caused by noise exposure or ototoxic drugs. Temporary enhancement of OAEs may occur following noise exposure, and permanent enhancement of emissions has been associated with primary afferent dysfunction in the auditory system. This suggests that there are active adaptation processes in the cochlea exist that could potentially compensate for loss of afferent input. We have used the anti-cancer drug carboplatin to induce selective inner hair cell (IHC) lesions in the cochleae of chinchilla and measured the elevation of auditory thresholds that occurred using brainstem responses (ABR). Following carboplatin treatment click evoked otoacoustic emissions (CEOAEs) were amplified from cochlear frequency regions, which demonstrated extensive IHC damage but apparently normal OHCs. These results support the theory that OHCs cells are involved in the production of these cochlear emissions but also provides further evidence that active adaptation processes exist in the cochlea. It is postulated that loss of afferent input reduces the activity in the medial efferent OCB resulting in de-suppression of OHC contractility. Enhanced OHC contractility could then produce amplification of CEOAEs.

Acoustic Stimulation↗

PubMed1996

Recording from the inferior colliculus following cochlear inner hair cell damage.

The anti-cancer drug carboplatin has been used to generate inner hair cell (IHC) lesions in the cochleae of chinchilla. This model has provided a valuable physiological tool for the study of the auditory system, particularly concerning the relative roles of IHCs and outer hair cells (OHCs). We recorded responses to contralateral sound stimuli of single units (SU) in the central nucleus (CN) of the inferior colliculus (IC) from normal and carboplatin treated animals. Normal single unit thresholds and frequency tuning curves (FTCs) were found, despite gross IHC damage within the cochleae of carboplatin treated animals. No evoked afferent responses could be detected in CN regions which represented cochlear loci where total IHC loss had occurred. Normal frequency selectivity in the auditory system is possible with small numbers of surviving IHCs provided OHCs remain normal.

Animals↗

PubMed1996

The neonatal chinchilla cochlea: morphological and functional study.

The developmental time scale of the cochlea varies from species to species. We investigate here the condition of the neonatal cochlea in the chinchilla, a species increasingly used in auditory research. We have examined the morphology of cochlear hair cells using scanning microscopy, and the development of auditory function during the first postnatal month by monitoring auditory brainstem evoked responses (ABR). We find that although there were some outer hair cell kinocilia present in middle and apical areas, the hair cells otherwise were mature at 24 hours after birth. Furthermore, cochlear auditory thresholds are adult-like at birth. However, whilst there was little change in ABR thresholds over one month, there is evidence of continued maturation of the central auditory system as shown by the shortening of the PI-P5 latency from 9.1 ms to 7.7 ms.

Animals↗

PubMed1995

Effects of chronic cochlear damage on threshold and frequency tuning of neurons in AI auditory cortex.

We describe the effects of long-term cochlear lesions on the frequency response properties of AI cortical neurons in the cat. Young animals were treated with amikacin to produce bilateral, basal to mid-turn cochlear lesions. After 12-24 months the response properties of single neurons or small unit clusters in primary auditory cortex were recorded in anesthetized animals. Responses to stimulus frequency and intensity were mapped in detail and frequency threshold curves (FTCs) and Q10dB values were derived. Subsequent to recording experiments, scanning electron microscopy of the sensory epithelium was used to characterize the degree and extent of the cochlear damage. In normal control animals, Q10dB values were, on average, lower than those derived by others from cochlear nerve fibre recordings in the same species. In amikacin-treated animals, deterioration was evident in the threshold and tuning properties of cortical neurons, particularly in those cells whose input originated in damaged cochlear regions. Often, neurons associated with 'normal' cochlear areas (as assessed by scanning microscopy) also had poor frequency tuning compared with controls. As an animal model of sensorineural hearing loss, we consider the cat with long-term cochlear lesions to be more appropriate than animals with acute or short-term pathology. We also suggest that in making physiological-psychophysical correlations, neural responses from the central auditory system (e.g. cortex) should perhaps be given more consideration than data derived at the cochlear level.

Amikacin↗

PubMed1995

Carboplatin ototoxicity in the chinchilla: lesions of the vestibular sensory epithelium.

Carboplatin (cis-Diammine-1,1-cyclobutane dicarboxylate platinum II; CBDCA) is a second generation platinum analog with less nephrotoxicity and cochlear ototoxicity than cisplatin, the first generation platinum chemotherapeutic agent. Studies in many animal species have indicated that carboplatin ototoxicity is expressed as damage to cochlear outer hair cells. The lesion is similar, though less severe, than that resulting from cisplatin intoxication. Recent investigations by our laboratory have demonstrated a species-specific ototoxicity of carboplatin in the chinchilla cochlea. Contrary to other animal models, the inner hair cells are the focus of damage; the outer hair cells often sustain little or no damage. Clinical evidence points to vestibular dysfunction in some patients treated with platinum-containing anti-tumoural agents. However, no morphological studies have shown degeneration of the sensory cells in the vestibular labyrinth resulting from carboplatin treatment. The objective of the present study was to determine whether, in view of its unique toxicity in the chinchilla, carboplatin has any toxic effect on the vestibular end organs. Preliminary investigations of the vestibule by light and scanning electron microscopy indicate that sensory cell cilia became exfoliated or deformed in the crista, utricle and in one instance in the saccule. In general the pattern of damage is similar to that caused by other known ototoxic agents including aminoglycosides and cisplatin.

Animals↗

PubMed1994

Cochlear function after selective inner hair cell degeneration induced by carboplatin.

The ototoxicity of carboplatin, a second generation anti-cancer agent, was examined using the chinchilla as an animal model. In animals treated with a clinical therapeutic dose (400 mg/m2), the dominant degenerative change is to inner hair cells (IHCs). This is in sharp contrast to most other ototoxic agents, which damage primarily the outer hair cells (OHCs). Functional changes to the cochlea have been evaluated in carboplatin treated subjects by recording cochlear action potentials (CAP) and cochlear microphonics (CM); cochlear lesions were evaluated using scanning electron microscopy. In carboplatin treated animals, CAP thresholds to tone-pip stimuli were elevated in proportion to IHC damage in corresponding cochlear regions. In contrast, CM amplitudes and 'thresholds' remained close to normal in most cases, reflecting the preservation of OHCs in the basal turn. These results indicate a high degree of independence between the inner and outer hair cell systems in the cochlear transduction mechanism. We suggest that this species-specific preparation with selective IHC loss will provide a valuable tool for studying, separately, the role of OHCs in both afferent and efferent cochlear function.

Acoustic Stimulation↗

PubMed1994

Induction of selective inner hair cell damage by carboplatin.

Carboplatin (diammine [1,1 cyclobutane dicarboxylato (2)-0,0'] platinum) is an anti-cancer agent which can be toxic to the inner ear. We have explored the nature of this ototoxicity in the chinchilla. In this species, initial degenerative changes appear to be restricted to the inner hair cell (IHC) regions of the organ of Corti. This finding is intriguing and unusual since all other known ototoxic drugs, such as aminoglycosides, are predominantly associated with outer hair cell damage. In the present study, the mechanism of ototoxicity was investigated by comparing two different routes of carboplatin administration. Carboplatin was administered either intravenously (i.v.) or intraperitoneally (i.p.). The mode of administration influenced electrophysiological and morphological changes. Hearing thresholds were elevated in the i.v. group significantly more than in the i.p. group at all tested frequencies. The degree of hair cell damage was evaluated by scanning electron microscopy at four frequency regions in each cochlea. IHC damage in the i.v. group was significantly more severe than in the i.p. group. Carboplatin effects on a different species, the guinea pig, were also determined to clarify interspecies differences. In the guinea pig, outer hair cell damage occurred sporadically and inner hair cells remained intact. In contrast, chinchilla inner hair cells are susceptible to the ototoxic effects of carboplatin. The degree of hair cell damage appears to be dependent on the peak level of carboplatin rather than on the total dose. This animal model provides a new tool for the investigation of inner and outer hair cell function.

Animals↗