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Biomedical subjects

J E Hawkins

Publications and source records attributed to J E Hawkins.

At least 19 recordsLinked to original sources
PubMed1990

Apical hair cells and hearing.

This study assessed the contribution of the apical hair cells to hearing. Guinea pigs, chinchillas and monkeys were behaviorally trained using positive reinforcement to respond to pure-tone stimuli. When a stable audiogram had been determined, each subject received one of three experimental treatments: ototoxic drug administration, low-frequency noise exposure, or the application of a cryoprobe to the bony wall of the cochlear apex. After post-treatment audiograms stabilized, subjects were euthanized and the percentage of hair cells remaining was assessed by light microscopy. Results indicate that a redundancy of encoding mechanisms exist in the mammalian cochlea for low-frequency stimuli. They also suggest that a very small percentage of apical hair cells are sufficient for some low-frequency hearing. Finally, data from this and other studies suggest that the low-frequency threshold shift caused by the loss of a certain percentage of apical hair cells is less pronounced than the high-frequency threshold shift caused by the loss of a comparable percentage of basal hair cells. These data agree with anatomical and electrophysiological evidence that functional as well as anatomical differences may exist between the apex and base of the cochlea.

Animals↗
PubMed1990

Transgenic mouse model of the mild dominant form of osteogenesis imperfecta.

Osteogenesis imperfecta type I is a mild, dominantly inherited, connective tissue disorder characterized by bone fragility. Mutations in type I collagen account for all known cases. In Mov-13 mice, integration of a murine retrovirus within the first intron of the alpha 1(I) collagen gene results in a null allele blocked at the level of transcription. This study demonstrates that mutant mice heterozygous for the null allele are a model of osteogenesis imperfecta type I. A defect in type I collagen production is associated with dominant-acting morphological and functional defects in mineralized and nonmineralized connective tissue and with progressive hearing loss. The model provides an opportunity to investigate the effect of a reduced amount of type I collagen on the structure and integrity of extracellular matrix. It also may represent a system in which therapeutic strategies to strengthen connective tissue can be developed.

Animals↗
PubMed1987

The species-specific nature of the ototoxicity of dihydrostreptomycin in the patas monkey.

The remarkable susceptibility of the inner ear of the patas monkey (Erythrocebus patas) to the ototoxic action of dihydrostreptomycin (DHSM) (and streptomycin (SM)) is well established in this paper and affords a rare example of a species-specific reaction to a restricted class of compounds within the aminoglycoside group of antibiotics. In a series of experiments, behavioral and morphological observations together provided the following profile of DHSM ototoxicity in the patas monkey: Sudden onset of hearing loss beginning after 7-9 weeks of treatment; Substantial, though often partial, hearing impairment beginning at the high frequencies and progressing with or without continued treatment to the low frequencies; In the inner ear, a corresponding and selective loss of nerve fibers and of outer hair cells, relative to inner hair cells, beginning in the base of the cochlea and proceeding toward the apex; Continued and progressive loss of hearing for several months after cessation of drug treatment; and Non-auditory effects in some animals on the kidney and vestibular system. Results from control experiments confirmed this special relationship between the patas monkey and DHSM: Other nonhuman primates (macaques and vervet monkeys) were essentially unaffected by DHSM; The patas showed no equivalent sensitivity to other aminoglycosides such as kanamycin or to other forms of ototraumatic insult such as intense noise.

Animals↗
PubMed1986

Nonweekend schedule for BACTEC drug susceptibility testing of Mycobacterium tuberculosis.

Determination of the drug susceptibility of Mycobacterium tuberculosis by conventional methods using an agar-based medium may take 3 weeks or more to complete. On the other hand, results on positive cultures are generally available in 4 to 7 days with the radiometric (BACTEC, Johnston Laboratories, Towson, Md.) procedure. One disadvantage to the latter is the requirement to determine the quantity of 14CO2 in each test vial on a daily basis from the day of inoculation. Growth index readings often must be made over weekends, adding to the work load of clinical laboratories during periods of reduced staff or necessitating compensatory pay or time. Susceptibility tests with streptomycin, isoniazid, ethambutol, and rifampin against 104 M. tuberculosis strains were performed by the submerged disk method, the recommended BACTEC method with daily growth index readings, and the radiometric procedure with readings delayed for 2 days after inoculation. Criteria for interpretation of "delayed" tests were established. Drug concentrations tested included some modifications of those available commercially. Overall agreement for the four drugs by the three methods was greater than 90%. We conclude that under our test conditions a schedule of inoculation of radiometric test vials on Friday with growth index readings commencing on Monday gives susceptibility results that correlate well with the daily BACTEC method and with a conventional 7H10 agar method.

Dose-Response Relationship, Drug↗
PubMed1985

Radiometric selective inhibition tests for differentiation of Mycobacterium tuberculosis, Mycobacterium bovis, and other mycobacteria.

In the context of a busy reference laboratory, radiometric selective inhibition tests were evaluated for rapid differentiation of Mycobacterium tuberculosis and Mycobacterium bovis and of the M. tuberculosis complex from other mycobacteria. p-Nitro-alpha-acetylamino-beta-hydroxypropiophenone at 5 micrograms and hydroxylamine hydrochloride at 62.5 and 125 micrograms per ml of 7H12 medium were used to separate the M. tuberculosis complex from other mycobacteria (MOTT bacilli). Since it is important epidemiologically to distinguish M. tuberculosis from M. bovis, susceptibility to 1 microgram of thiophene-2-carboxylic acid per ml was also determined radiometrically. By using these three agents as selective inhibitors, M. tuberculosis, M. bovis, and MOTT bacilli were differentiated with a high degree of specificity by a BACTEC radiometric procedure. Results of tests performed on clinical isolates submitted on solid medium to our reference laboratory were available within 5 days.

Hydroxylamine↗
PubMed1985

Evaluation of a simple method for growing Mycobacterium haemophilum.

Surface paper strips containing hemin (X factor) were tested on Middlebrook 7H10 agar and Lowenstein-Jensen medium to determine if the growth requirement of Mycobacterium haemophilum for iron-containing complexes could be met by this simplified method. One reference strain and seven strains of this species isolated from patients showed good growth around the strips on 7H10 within 2 weeks but failed to grow on Lowenstein-Jensen medium with X-factor strips. Middlebrook 7H10 medium with X-factor strips may be a useful alternative to the preparation of specialized media for the recovery of M. haemophilum from clinical specimens.

Culture Media↗
PubMed1985

Interlaboratory drug susceptibility testing of Mycobacterium tuberculosis by a radiometric procedure and two conventional methods.

A total of 224 recent isolates of Mycobacterium tuberculosis from 163 patients selected to have multidrug resistance were tested against streptomycin (SM), isoniazid, rifampin, and ethambutol (EMB) by the rapid radiometric BACTEC method and two conventional proportion methods: the World Health Organization (WHO) method, using Lowenstein-Jensen medium; and the Veterans Administration reference laboratory for mycobacteria (VA) method, using Middlebrook 7H10 agar medium. The results were compared, focusing on the concentrations of the drugs in all three methods. Among the four drugs tested, most of the discrepancies in measured activity were observed with SM and EMB, generally because of differences in the drug concentrations used by the three methods. A 4-micrograms amount of SM in the BACTEC method was found to be slightly less active than 10 micrograms in the VA method and significantly more active than 4 micrograms of dihydrostreptomycin in the WHO method. With EMB, 2.5 micrograms in BACTEC was similar to 5 micrograms in the VA method and 2 micrograms in the WHO method, while 10 micrograms in the BACTEC method was found to be more active than 10 and 2 micrograms in the VA and WHO methods, respectively. To attain close agreement, drug concentrations used in the BACTEC method should be carefully selected when a comparison is to be made with any conventional method employed in a laboratory. Standardization of in vitro susceptibility testing is greatly needed to achieve uniformity among the test methods used to evaluate tuberculosis therapeutics.

Drug Resistance, Microbial↗
PubMed1985

Perivascular demyelinization of cochlear neurons in two neonates.

Localized perivascular demyelinization of the peripheral processes of cochlear neurons was observed in surface preparations of the osseous spiral lamina in two neonates, one a premature infant with erythroblastosis fetalis, the other a full-term infant with cyanotic congenital heart disease. In both cases the cause of the demyelinization was unknown. Both infants had severe edema as a result of congestive heart failure and anoxia. The serum bilirubin level in the erythroblastotic child appeared too low to have caused injury to the nerve fibers. The demyelinization was most striking in the lower half of the basal turn. It was observed only in the immediate vicinity of meandering stretches of capillaries as they crossed the nerve fibers. In the premature infant there was hair cell loss throughout the cochlea; in the other there was no hair cell loss, but a malformed labyrinth of the Mondini type.

Cochlear Nerve↗
PubMed1983

Inner ear pathology associated with Reye's syndrome.

Severe pathological changes were observed in the inner ear tissues of a 2-month-old patient who died of Reye's syndrome after 5 days of hospitalization. In the organ of Corti, the inner hair cells appeared to be more severely damaged than the outer hair cells. Various degrees of degeneration were observed in all non-sensory epithelial cells lining the cochlear duct. In most turns of the cochlear duct, Reissner's membrane was ruptured and/or collapsed onto the organ of Corti. Likewise, both sensory and non-sensory cells of the vestibular end organs were markedly degenerated. These observations suggest that the inner ear tissues are acutely affected in patients with Reye's syndrome, and that the changes may cause impairment of hearing and/or equilibrium in patients who recover.

Acoustic Maculae↗
PubMed1979

"Neural" responses to acoustic stimulation after destruction of cochlear hair cells.

Electrophysiological and histological observations in guinea pig's cochleas after amikacin treatment (14 X 450 mg/kg) confirm the results obtained in a former experiment: clear, short-latency, click-evoked responses were recorded in cochleas with only very few hair cells remaining at the extreme apex. Detailed analysis of these responses strongly indicates a neural origin and confirms their low-frequency sensitivity. Careful histological observations confirm the extensive hair cell loss and the preservation of nerve fibers in the remnants of the organ of Corti and of the vestibular sense organs. These results suggest that the acoustical vibrations either stimulate the vestibular receptors or act directly or through some kind of mechano-electrical transduction on the remaining cochlear nerve fibers.

Amikacin↗
PubMed1979

Hearing thresholds with outer and inner hair cell loss.

Hearing impairment and related cochlear histopathologic changes were evaluated in experimental animals after treatment with aminoglycoside antibiotics or exposure to intense sound. In the course of treatment with kanamycin, neomycin, or dihydrostreptomycin, permanent hearing loss in monkeys and guinea pigs occurred first at the high frequencies and progressed toward the lows. Exposure to different octave bands of noise at 120 dB SPL in monkeys and chinchillas produced permanent hearing loss at frequencies related to the spectral characteristics of the octave band. In most instances loss of outer hair cells was substantially greater than that of inner hair cells. In fact, the pattern and location of missing outer hair cells on the basilar membrane were most often correlated with threshold shifts of 50 dB or less. Generally inner hair cell loss was observed when the threshold shift was greater than 50 dB. Our data support the place principle and the inference that the outer hair cells are essential for hearing from threshold to about 50 dB SL. The inner hair cells, if functioning normally, apparently take over above that level. Although there is little doubt that such a generalization will, in the long term, be found to have been greatly oversimplified, there is every reason to believe that a combination of behavioral and morphologic procedures, as used in this study, will play an important part in elucidating the differences in functional significance of the two types of hair cells.

Animals↗
PubMed1978

Hearing loss and cochlear pathology in the monkey (Macaca) following exposure to high levels of noise.

Eight Old World monkeys were exposed 8 h daily for 20 days to octave-band noise having center frequencies from 0.5--8 kHz at levels of 117--120 dB SPL. Two additional animals received exposures to wide-band, 120-dB SPL noise on the same schedule, and one animal was exposed to the 2-kHz octave band for 40 h continuously. Behavioral audiograms were measured throughout exposure and during a 1-month recovery period. Following recovery, the animals were sacrificed and their ears examined histologically. Monaural audiograms are presented showing initial and final TTS and PTS measured at the end of the recovery period. These are compared with complete cytocochleograms for each ear. Hair cell loss was generally restricted to the outer rows, and was reasonably well correlated with pattern of hearing loss. Some cell loss, including inner hair cells, was found in the extreme basal turn, usually without associated high-frequency hearing loss. The relationships between exposure frequency, hearing loss, and locus of cochlear pathology are discussed, as are changes in TTS during exposure.

Animals↗