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Biomedical subjects

S Carlile

Publications and source records attributed to S Carlile.

32 records · Page 2Linked to original sources

The effects of chronic hypoxia on human auditory system sensitivity.

We have examined the effects of prolonged periods of hypoxia produced at high altitudes on the latency of the auditory brain-stem evoked response (ABER) in 9 subjects at around sea level, 3,500 m, and 4,370 m. Following an ascent from 1,300 m to 3,500 m over 24 h, the mean blood O2 saturation fell to 86.5 +/- 1.2% (+/- S.E.M.) and was associated with a mean prolongation of latency of wave V of the ABER of 0.34 +/- 0.10 ms (p = 0.011 two-tailed paired t-test). Using the stimulus-level/response latency relation determined at around sea-level for each subject, this prolongation of wave V corresponded to a mean reduction in sensitivity of 9.1 dB +/- 1.6 dB. Over a period of 72 h, blood O2 saturation improved slightly (mean 88.1% +/- 1.8%) and mean wave V latency returned to control values. A second rapid ascent to 4,370 m reduced blood O2 to below prerecovery levels (82.5% +/- 1.7%), but in this case there were no significant changes in auditory sensitivity (p = 0.79 two-tailed paired t-test). These data show that mild hypoxia results in an initial decrease in auditory sensitivity. However, the recovery of sensitivity with more prolonged exposure suggests that the auditory system can compensate for chronic mild hypoxia.

Adult↗

The auditory periphery of the ferret: postnatal development of acoustic properties.

The development of the acoustics of the auditory periphery of the ferret was examined by measuring the spectral transfer functions (STFs) and the directional characteristics of the outer ears of animals ranging in age from postnatal day 32 (P32) to P54. Using an impulse response technique the STFs were obtained from up to 250 locations throughout free space. The directional responses were calculated for frequencies between 1 kHz and 30 kHz. The low frequency roll-off of the STF decreased with increasing age from around 15 kHz at P32 to an adult value of around 8 kHz by P51. The directional responses of the outer ear of the immature ferrets differed significantly from adult animals in a fashion that was consistent with the smaller size of the auditory periphery. However, by P51 the responses were generally within the normal adult range. The implications of the relatively rapid development of the acoustics of the auditory periphery are discussed in terms of the development of mechanisms subserving sound localization.

Acoustic Stimulation↗

Auditory brainstem of the ferret: maturation of the brainstem auditory evoked response.

A longitudinal study of developmental changes in the brainstem auditory evoked response (BAER) was made on 19 ferrets between postnatal days 25 (P25) and 50. Responses to free-field click stimuli were recorded from anaesthetized animals, and compared with data obtained from 8 adult ferrets. A reproducible BAER was first recordable on P27, although the response onset was generally later in smaller animals. BAER onset preceded eye opening, which started on P32. Adult-like thresholds were observed in all animals by P40, but the age at which they were attained was also dependent on size. The BAER in the adult ferret consists of 4 main vertex-positive peaks occurring in the first 5 ms following transient acoustic stimulation. In the youngest animals the presence of an additional peak (between II and III) and the slurring of peaks III and IV were consistent features. The individual peaks undergo an asymmetrical pattern of development, with mean peak I latency attaining an adult value at P40, while mean peak IV latency is still 115% of the mean adult value at that age. BAERs could routinely be recorded using high stimulus presentation rates (greater than 40/s), though an increase in absolute and interpeak latencies occurred, the extent of which decreased with age. The pattern of BAER development in the ferret is compared with that in other species, and the concept of the 'silent period' (period between conception and onset of hearing) as a standard unit of auditory development is introduced.

Acoustic Stimulation↗

The auditory periphery of the ferret. I: Directional response properties and the pattern of interaural level differences.

The transformations of sound by the auditory periphery of the ferret have been investigated using an impulse response technique for a large number of sound locations surrounding the animal. Individual frequencies were extracted from the detailed spectral transformation functions (STFs) obtained for each stimulus location and, using sophisticated spatial interpolation routines, were used to calculate the directional response of the periphery at that frequency. The strength of the directional response was directly related to the analysis frequency. Furthermore, as the analysis frequency was increased to 20 kHz, the orientation of the directional response increased in elevation from the horizon (E0 degrees) to about E30 degrees, while the azimuthal location remained fairly constant at 30 degrees to 40 degrees from the midline. For analysis frequencies above 20 kHz, the response became increasingly directional toward the ipsilateral interaural axis. The interaural level differences (ILDs) were also calculated for all animals studied. ILDs increased from around 5 to 25 dB over the range of frequencies from 3-24 kHz. The two-dimensional patterns of iso-ILD contours were roughly concentric and centered on the interaural axis for frequencies below 16 kHz. For higher frequencies, there was a tendency for the ILD contours to be centered on more anterior and inferior locations. The increased directionality of the auditory periphery with increasing analysis frequency, together with the presence of sharp nulls in the response at high analysis frequencies, is consistent with a diffractive effect produced by the aperture of the pinna. However, this simple model does not predict the directional responses over the low to middle frequency range.

Animals↗

The auditory periphery of the ferret. II: The spectral transformations of the external ear and their implications for sound localization.

In the previous paper the directional response characteristics of the ferret auditory periphery were examined. In this study further measurements of the spectral transfer functions (STFs) of the auditory periphery were obtained at locations close to the tympanic membrane. There was considerable variation in the STFs recorded from different animals and between recordings made at each end of the auditory canal in the same animal. However, calculation of the so called "location dependency function" demonstrated that changes in the location of the stimulus produced the same pattern of changes in the STFs in all recordings. Changes in the spectral transformation for azimuth locations in the ipsilateral auditory field were examined by calculating the horizon STF. The gain transformations of frequencies below 20 kHz were found to be asymmetrical about the interaural axis so that maximum gain was obtained for anterior stimulus locations. In contrast, the maximum gain for frequencies above 20 kHz was obtained for stimulus locations about the interaural axis, and movement of the stimulus location into either the anterior or posterior fields produced symmetrical reductions in gain. These changes were related to the directional properties of the periphery examined in the previous paper [S. Carlile, J. Acoust. Soc. Am. 88, 2180-2195 (1990)]. The spatial resolution of the monaural information provided by the peripheral STFs is dependent on the rate of change of the transformations as a function of azimuthal displacement of the stimulus location. This was examined by calculating the unsigned first spatial derivative for each frequency in the horizon STF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Platelet dysfunction associated with Wilms tumor and hyaluronic acid.

Acquired von Willebrand disease (AVWD) has been described in two cases of nephroblastoma. We studied a patient with nephroblastoma who presented with a coagulopathy suggestive of AVWD. The subject had undetectable levels of F.VIIIR:Ag, diminished F.VIIIR:WF (16.3%), F.VIII:C activity (37%), and lack of platelet aggregation to ADP, epinephrine, collagen, and arachidonic acid. These results were associated with abnormally high serum levels (850 mg/dl) of hyaluronic acid (HA), which made the patient's serum hyperviscous. Examination of the neoplasm revealed HA in the tumor matrix. All abnormalities of coagulation resolved after chemotherapy and extirpation of the neoplasm, which produced normal serum HA levels. To study the effects of HA on platelet function, we added HA to normal platelet-poor plasma (NPP), which rendered F.VIIIR:Ag undetectable; treatment of HA with hyaluronidase eliminated F.VIIIR:Ag assay interference caused by HA. F.VIII:C activity decreased in vitro when HA was mixed with normal platelet-poor plasma (NPP). HA reduced the initial slope of normal platelet aggregation. Partial correction of platelet aggregation occurred after hyaluronidase treatment of HA-spiked PRP. Experiments in rabbits exposed to HA (serum level 400 mg/dl) demonstrated abnormalities similar to those noted in the patient. Shear rate studies of whole blood containing HA (500 mg/dl) yielded high shear stress, 27-136 dynes/cm2 over shear rates of 10-216 sec-1. We conclude that the coagulopathy demonstrated in this case is secondary to hyperviscosity produced by elevated levels of HA, which interferes with the assay for F.VIIIR:Ag. Thus the acquired coagulopathy associated with other cases of nephroblastoma may present as spurious von Willebrand disease.

Animals↗

Directional properties of the auditory periphery in the guinea pig.

The directional sensitivity of the outer ear of the guinea pig was determined by recording changes in the amplitude of the cochlear microphonic to frequencies between 1 and 20 kHz as the location of the sound source was changed throughout 360 degrees of horizontal auditory space. The directional responses to frequencies below 3 kHz were almost omnidirectional. The directional responses for frequencies between 3 and 12 kHz were progressively more directional toward the anterior midline. The responses for frequencies above 12 kHz were highly directional along the ipsilateral interaural axis. In contrast, the directional responses to all frequencies in animals whose pinnae had been removed were orientated along the ipsilateral interaural axis. The observations suggest that the orientation and strength of the directional response of the auditory periphery in the guinea pig are dependent on frequency and that this dependence is attributable, at least in part, to the acoustic properties of the pinna. The observations also indicate that there is a substantial change in the interaural intensity difference at various frequencies and in the spectral transfer function of the ear according to the location of the sound source in the ipsilateral hemifield. The observation that these changes are asymmetrical about the interaural axis for a substantial part of the auditory range of the animal is consistent with the hypothesis that the frequency dependent directionality of the auditory periphery provides a spectral cue for the localization of broad band sounds in the free field.

Animals↗

Distribution of frequency sensitivity in the superior colliculus of the guinea pig.

A field potential could be recorded in the deep layers of the superior colliculus (SCd) in the guinea pig following presentation of pure tone bursts at frequencies between 1 and 22 kHz, bursts of white noise, and clicks presented in the free field. The potentials evoked by these stimuli at different intensities had two negative and one positive component associated with the onset of the stimulus. The amplitude of the negative components of the potential varied according to the location of the recording electrode along the dorso-ventral and rostro-caudal axes of the SC and with the frequency of pure tone stimuli. The largest amplitude potentials were recorded in the deep grey layer of the SCd midway along the rostro-caudal axis of the nucleus. The distribution of frequency sensitivity along the rostro-caudal axis of the SCd was determined by recording the amplitude of the negative components of the field potential evoked by 10 ms pure tone bursts at a constant intensity. The distribution of frequency sensitivity across the nucleus was not cochleotopic. The caudal pole of the nucleus had largest responses to frequencies above 15 kHz, with a peak sensitivity around 20 kHz. In contrast, the rostral pole of the nucleus was most sensitive to frequencies around 10 kHz and the sensitivity to frequencies around 20 kHz was relatively low. At a point midway along the rostro-caudal axis of the SCd, the nucleus was sensitive to a broad range of frequencies from 5 to 25 kHz. The patterns of frequency sensitivity recorded in the rostral, middle and caudal SCd are qualitatively similar to the frequency transfer characteristics of the auditory periphery for sounds located in the anterior, orthogonal and posterior regions respectively of contralateral space. The correspondence between these two sets of data suggests that the pattern of frequency sensitivity along the SCd may provide a mechanism by which the nervous system can encode the spectral cues which are generated at the auditory periphery.

Acoustic Stimulation↗

An improved transilial crest bone biopsy drill for quantitative histomorphometry.

Transilial crest bone biopsy with quantitative histomorphometry is an important technique for the assessment of metabolic and endocrine bone disease. The surface area of the histologic section suitable for histomorphometric analysis is reduced by the build-up of bone dust and by trabecular fracture, produced by the conventional Bordier bone drill. We describe here a modification of this drill that both allows escape of dust from around the cutting edge of the teeth and greatly reduces bone dust volume and trabecular fracture. In paired samples the new drill was shown to improve significantly the quality of the biopsy specimens.

Biopsy↗

Auditory responses in the torus semicircularis of the cane toad, Bufo marinus. I. Field potential studies.

Field potentials have been recorded in the torus semicircularis of the toad, Bufo marinus, in response to brief tones presented in the free field. The amplitude of the potentials varied with the frequency of the stimulus and location of the electrode along the rostro-caudal axis of the torus. All frequencies in the auditory range evoked largest potentials when the stimulus was located in the contralateral auditory field. Potentials evoked by low to mid frequencies were largest when the stimulus was located near the line orthogonal to the long axis of the animal. For progressively higher frequencies, the optimal stimulus position was progressively more anterior in the contralateral field. In animals in which one eighth nerve had been sectioned, field potentials evoked by tones of low to mid frequency were less sensitive to changes in stimulus direction than in normal animals. However, the directional sensitivity of field potentials evoked by mid to high frequencies was similar in monaural and normal animals. These observations suggest that binaural neural integration is important in determining the directional sensitivity of field potentials in the torus evoked by low to mid frequencies but not for potentials evoked by mid to high frequencies.

Animals↗

Auditory responses in the torus semicircularis of the cane toad, Bufo marinus. II. Single unit studies.

The responses of single units to brief tone bursts presented in the free field have been recorded in the torus semicircularis of the toad, Bufo marinus. The characteristic frequencies of the units fell into three main groups. The peri stimulus time histograms (p.s.t.h.s) for units in the torus showed a variety of forms but most histograms had a peak near the beginning of the response. The latencies of these peaks varied between 10 and 90 ms after the onset of the stimulus. As the intensity of a stimulus at the characteristic frequency was increased, the number of spikes elicited increased and the latency of the first peak in the p.s.t.h. decreased. All units that exhibited a high sensitivity to changes in stimulus intensity had characteristic frequencies in the low region of the auditory range and relatively long latencies. The number of spikes elicited and the latencies of the responses also varied as the location of the stimulus was changed. For those units whose spike output was highly sensitive to stimulus direction, the latency of the response was longer and showed greater variation with stimulus direction than the less sensitive units. The characteristic frequencies of the more highly sensitive units were also restricted to the low region of the auditory range. The properties of units with a high sensitivity to stimulus intensity were similar to the properties of units that were highly sensitive to stimulus direction. The difference between these properties and those of units with lower sensitivity to stimulus intensity and direction suggests that the auditory system in the brainstem of anura may be composed of at least two functionally distinct pathways. One of these pathways probably involves a more complex neuronal integration of the afferent input following low frequency stimulation.

Animals↗

Serum thyrotropin and thyroid hormone levels in humans receiving chronic potassium iodide.

Serum thyroxine (T4), triiodothyronine (T3) and thyrotropin (TSH) concentrations were measured in 13 patients with chronic obstructive pulmonary disease receiving saturated solution of potassium iodide (SSKI). All had a low serum T4 and a high serum TSH concentration. However, serum T3 levels were normal in eight. Recovery of normal thyroid function was observed in each of the seven patients in whom the iodide was discontinued. The same hormones were measured in four normal subjects who received 30 drops of SSKI daily for 11 weeks. An increase in serum TSH levels was preceded by a fall in serum concentrations of T4 and to some extent, T3. Upon SSKI withdrawal subsequent increases in the serum concentrations of both thyroid hormones, but particularly T3, resulted in the return of serum TSH to baseline levels. None of the subjects developed clinical hypothyroidism. It is not apparent why the normal subjects did not exhibit clinical or laboratory evidence of hypothyroidism while the patients with chronic pulmonary disease did. A younger age and the shorter duration of iodide administration in the normal subjects may have played a role.

Adult↗

Prostaglandin F2alpha (PGF2alpha) and prolactin secretion in rats.

Plasma prolactin and F-prostaglandins (PGF) were measured anesthetized male Sprague-Dawley rats before and at 15, 30, 45 and 60 minutes following i.v. injection of either PGF2alpha (4 mg/kg), chlorpromazine, 1 mg/kg or chlorpormazine (1 mg/kg) after pretreatment with i.p. indomethacin (2 mg/kg). Following PGF2alpha administration, plasma prolactin levels increased significantly only at 15 and 30 minutes in spite of extremely high PGF levels throughout 60 minutes. Besides the expected rise in plasma prolactin, chlorpromazine caused a transient but statistically significant increase in PGF. Indomethacin blocked the chlorpormazine-induced PGF rise but not prolactin increase. Animals stressed with ether anesthesia showed elevation of plasma prolactin, which was not blocked by indomethacin although PGF concentration fell. Theese results indicate that PGF2alpha can stimulate prolactin release. This effect does not appear to be physiologic since very high PGF levels are required. Furthermore, blockade of prostaglandin synthesis by indomethacin does not prevent the release of prolactin in response to chlorpormazine or stress. Our findings do not support a possible role of PGFs as intermediaries in prolactin release. However, it is possible that PGFs may work through other mechanisms not investigated in our study.

Animals↗