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Biomedical subjects

R V Harrison

Publications and source records attributed to R V Harrison.

At least 55 records · Page 3Linked to original sources
PubMed1994

Ototoxicity of carboplatin: comparing animal and clinical models at the Hospital for Sick Children.

Carboplatin was introduced to the paediatric population as an alternative chemotherapeutic agent in the management of various malignant neoplasms, including sarcomas of the head and neck, in the hope that it would have fewer side effects than pre-existing agents. While many investigators have considered the ototoxicity of this drug only incidentally, others have presumed it to be of negligible importance. A recent animal model of its use has demonstrated damage to the inner hair cells of the cochlea, particularly at the basal turn, with a corresponding high incidence of hearing loss. Similarly, 11 of 22 patients who received this agent at the Hospital for Sick Children over the past 2 years demonstrated a sensorineural hearing loss in the 4 to 12 kHz range. This complication occurred as early as after the first dose and was generally progressively worse with subsequent doses. Consequently, we recommend careful audiologic monitoring of children receiving this agent.

Adolescent↗
PubMed1993

Job demands and worker health: three-dimensional reexamination of the relationship between person-environment fit and strain.

The most influential study of the person-environment (P-E) fit approach to stress was conducted by J. R. P. French, R. D. Caplan, and R. V. Harrison (1982). Unfortunately, this study operationalized fit using various transformations of difference scores, thereby introducing numerous substantive and methodological problems. In the present study, the authors reanalyze data from French et al., using a procedure described by J. R. Edwards (in press) that avoids problems with difference scores and captures the underlying three-dimensional relationship between E, P, and strain. Results resolve ambiguities in the French et al. findings and identify relationships between E, P, and strain that, although consistent with P-E fit theory, cannot be adequately represented by fit measures such as those used by French et al. Implications for P-E fit research are discussed.

Adaptation, Psychological↗
PubMed1993

Auditory evoked potentials in cats with neonatal high frequency hearing loss. Evidence of abnormal frequency representation in the midbrain.

We have recorded auditory evoked potentials, of both neurogenic and myogenic origin, in cats having neonatal high frequency cochlear hearing loss. Using frequency specific stimuli (tone pips) and by measuring responses near to threshold, we have probed tonotopic (or cochleotopic) representation within the brainstem-midbrain auditory pathway. At stimulus frequencies corresponding to the high frequency cut-off of the cats' audiograms we have observed enhanced amplitudes of both auditory brainstem evoked responses (ABR) and postauricular myogenic (PAM) potentials. We interpret our findings as evidence of a larger than normal population of neurons tuned to this frequency region. We suggest that such abnormal frequency representation results from a long-term sensory deficit caused by lesions to the basal, high frequency region of the cochleas.

Animals↗
PubMed1993

The MRL-lpr/lpr mouse: a potential model of autoimmune inner ear disease.

Most attempts at developing a model of autoimmune inner ear disease have focused on the immunization of healthy animals with cochlear tissue. We have chosen an alternate route of studying this entity utilizing the MRL-lpr/lpr (Lupus) mouse, an animal known to spontaneously develop multisystemic, organ nonspecific autoimmune disease. We report on the auditory pathology found in animals at early stages of this systemic disease. At the onset of clinical signs of illness (cachexia, weight loss, lethargy) animals were sacrificed and their cochleas and kidney prepared for morphologic analysis. Significant pathology was seen in the MRL/lpr animals involving the basal and middle turns of the cochlea which could not be correlated with the presence or degree of glomerulonephritis. Findings included outer and inner haircell degeneration, strial edema and degeneration, and an acellular infiltrate in the tunnel of Corti. Cochlear pathology was not found in control animals. Thus, at early stages of systemic disease, MRL/lpr mice manifest significant cochlear pathology not seen in control animals. The implications of these results with regard to the pathogenesis of these lesions as well as their clinical relevance are discussed.

Animals↗
PubMed1993

Neonatal cochlear hearing loss results in developmental abnormalities of the central auditory pathways.

We have used animal models of long term neonatal cochlear hearing loss to study developmental plasticity of the central auditory pathways. Newborn chinchilla pups and feline kittens were treated with the ototoxic drug amikacin, so as to induce basal lesions in the cochlea. At maturity these animals were used in single unit electrophysiological mapping studies, in which the cochleotopic organization of primary auditory cortex (of the cat) and the inferior colliculus of the midbrain (in the chinchilla) were mapped. We have observed, both in the midbrain and auditory cortex, massive reorganization of frequency representation. Most striking were the presence of large monotonic regions (i.e. large areas in which all neurons have similar tuning properties). Cochlear lesions which involve inner hair cells clearly modify the normal development of cochleotopic representation in the midbrain and cortical regions. We suggest that similar abnormal patterns of frequency representation will exist in human subjects with long term neonatal hearing loss.

Amikacin↗
PubMed1993

Three-dimensional cytoskeletal structures of the chinchilla organ of Corti: scanning electron microscopy application of the polyethylene glycol method.

We describe the application of a polyethylene glycol (PEG) embedding technique to examine the sensory and supporting structures of the inner ear. The chinchilla organ of Corti was exposed by cracking PEG embedded cochleas. A range of PEG molecular weights (2000-8000) were utilized; PEG 2000, with a melting point of 57 degrees C was preferred. After removal of the PEG, the three-dimensional aspects of intracellular structures were observed using scanning electron microscopy. Filamentous elements in the hair cell cuticular plate and in the supporting cells were clearly observed, as was the meshwork of cross-linked actin filaments in the cuticular portion of sensory hair cells. Microtubule and microfilament alignment patterns in pillar and Deiters cells were also clearly demonstrated. Characteristic structures in the outer hair cell synaptic region, such as the post-synaptic cistern and synaptic body, were well preserved using the PEG method.

Actin Cytoskeleton↗
PubMed1993

The effects of long-term cochlear hearing loss on the functional organization of central auditory pathways.

We have developed an animal model of neonatal high-frequency cochlear hearing loss to investigate the long-term effects on the central auditory pathways. Specifically, we have induced basal cochlear lesions in newborn kittens using the ototoxic aminoglycoside, amikacin. We have monitored the consequent auditory threshold elevations using auditory brainstem evoked responses (ABR) to tone pip stimuli. In the mature animal we have mapped tonotopic (cochleotopic) representation in primary auditory cortex (AI) using standard micro-electrode recording techniques, and we show that this map becomes massively re-organized. In particular, one frequency area that corresponds to the high frequency cut-off slope of the subject's audiogram appears to become greatly expanded, in some cases to take up 75% of AI surface. In general, the development of normal cochleotopic or tonotopic representation in cortex appears to depend upon the integrity of ascending sensory input from the cochlea particularly during early stages of development. With the clinician in mind, we discuss our findings in relation to practical issues.

Acoustic Stimulation↗
PubMed1991

Motion sickness. Helping patients tolerate the ups and downs.

The sensory conflict theory provides a useful framework for understanding motion sickness. Few modifications of this model have been proposed since its publication. The weak link in the study of motion sickness has been the failure to delineate the anatomic structures that correspond to the model's components. Effective pharmacotherapy is available for treatment of motion sickness. The choice should be based on the need to provide prophylaxis for or treatment of symptoms and on the side effect profile of the drug.

Adaptation, Physiological↗
PubMed1991

Reorganization of auditory cortex after neonatal high frequency cochlear hearing loss.

Cochleotopic representation in cortex (AI) is extensively reorganized in cats having neonatal, bilateral high frequency cochlear hearing loss. Anterior areas of AI, normally devoted to high frequencies, contain neurons which are almost all tuned to one lower frequency. This frequency corresponds, at the level of the cochlea, to the border between normal and damaged haircell regions.

Amikacin↗
PubMed1991

Developing criteria for ordering common ancillary services.

This article describes the process utilized to develop criteria for appropriately ordering five ancillary services frequently performed in hospitals: 1) arterial blood gases, 2) electrocardiograms (ECGs), 3) serum electrolytes, 4) chest x-rays, and 5) complete blood counts (CBCs). The development of each set of criteria involved an initial consultant, a panel of six additional regional expert consultants, and three national reviewers. Each criteria set was developed through a process involving seven steps: 1) an initial working draft, 2) revisions at an initial meeting of the regional experts, 3) revisions at a second meeting of the regional experts, 4) written comments from the regional experts, 5) written comments from national reviewers, 6) additional written comments from regional experts, and 7) application of the criteria to cases in a community hospital. The change in item content was measured between steps and agreement with individual items was measured at steps 2, 3, and 4. The results indicate that appreciable change in content occurred with each step except step 4. Agreement started fairly high and was over 90% by step 4. The discussion considers the utility of each developmental step, factors affecting the utility of the criteria, the extent to which the results can be generalized, and the need for more research to identify optimal processes for the development of criteria to evaluate quality of care.

Ancillary Services, Hospital↗
PubMed1991

Morphological changes to the cochlea in an animal model of profound deafness.

We have used systemic application of the ototoxic drug amikacin, to induce total cochlear haircell loss in the chinchilla, in order to create an animal model of profound deafness. We have produced models of both neonatal deafness (by treatment of new-born pups), as well as of acquired total hearing loss (by treatment of mature animals). We present a description of our techniques for producing cochlear lesions and for evoked potential monitoring of the resulting threshold elevations. We also give a qualitative description of cochlear haircell damage as viewed by scanning electron microscopy, and a quantitative assessment of the spiral ganglion cell survival after total haircell loss.

Amikacin↗
PubMed1991

Cytoarchitecture of cochlear nucleus in the chinchilla.

The morphology of the cochlear nucleus in the normal, adult chinchilla, as demonstrated by Nissl staining, was examined. The cytoarchitecture was determined from sections viewed at the light microscope level. The chinchilla cochlear nucleus was found to possess most of the features reported in other mammalian cochlear nuclei. It could easily be divided into dorsal and ventral components due to an intervening layer of granule cells, and most cell types previously reported in mammals were also found in the chinchilla cochlear nucleus. A distinct distribution pattern of cell types exists within each part.

Animals↗
PubMed1991

Effects of total cochlear haircell loss on integrity of cochlear nucleus. A quantitative study.

In cochleas of chincillas treated with amikacin, cochlear sensory cells were totally destroyed in all new-born animals. In animals treated as adults some occasional haircells remained in apical turns. In the neonatally treated animals, the resulting auditory deprivation significantly affected the volume of the ventral cochlear nucleus and large-dark spherical cell area. The density of large-dark spherical cells increased significantly from normal in both neonatally and adult treated groups. Our results suggest that the VCN is more dependent on auditory stimulation for proper development than the DCN. In adult chinchillas treated with amikacin there was a significant change in large-dark spherical cell density without a change in total cell numbers or large-dark spherical cell area volume. Our study indicates that the mature cochlear nucleus is much more resistant to the effects of auditory deprivation than the developing cochlear nucleus and that the maintenance of the mature auditory system is not as dependent on auditory stimulation. Studies such as this examining the morphological effects of profound cochlear deafness on higher levels of the auditory system are essential in cochlear implant research.

Amikacin↗
PubMed1991

The effects of long and short term profound deafness on the responses of inferior colliculus to electrical stimulation of the cochlea.

It is widely assumed that adequate sensory stimulation is important for the proper post-natal development of the central nervous system, particularly during certain critical or sensitive periods in development. To examine the functional effects of long-term profound deafness on the development of the auditory system, the response properties of neurons in the inferior colliculus (IC) to electrical stimulation of the cochlea were investigated in chinchillas (i) deaf from birth and (ii) deafened as adults. In animals deafened as adults there was a 50% reduction in the number of neurons activated by electrical stimulation of the cochlea, compared with studies in normal controls. In contrast, very few or no responses could be elicited from IC of animals made deaf from birth. The results imply that lack of neural activity in the ascending auditory pathways from an early stage of development results in an inactivation of IC neurons. It is not clear if such inactivity is temporary or permanent.

Amikacin↗
PubMed1991

Three dimensional intracellular structure of the cochlea using the A-O-D-O method.

We have observed the three-dimensional intracellular structure of the organ of Corti and the spiral ganglion of the chinchilla using the aldehyde osmium-DMSO-osmium (A-O-D-O) method, and compared our findings with previous studies in the guinea pig. In cells of the spiral ganglion and the organ of Corti, microtubules and other cytoplasmic filaments were digested by OsO4 during processing to provide a clear view of membranous structures such as mitochondria, endoplasmic reticulum and Golgi apparatus. The appropriate digestion time with 0.1% OsO4 solution was found to be 60-80 hrs for the organ of Corti and 70-90 hrs for the spiral ganglion. The A-O-D-O method has been especially useful to show the organization of the endoplasmic reticulum of the outer hair cells. We have made a further characterization of the apical cistern, a reticular network which appears to link the basal body of the (vestigial) kinocilium to both Hensen's body and the subsurface cisternae.

Animals↗