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Biomedical subjects

M Gafni

Publications and source records attributed to M Gafni.

34 records · Page 2Linked to original sources

Auditory nerve-brain stem evoked potentials in cats during manipulation of the cerebral perfusion pressure.

In order to study the effects of various degrees of cerebral ischemia on the auditory nerve-brain stem evoked potentials (BAEP), the cerebral perfusion pressure (CPP), defined as the difference between mean arterial blood pressure (MAP) and intracranial pressure (ICP), was systemically manipulated in anesthetized, paralyzed and ventilated cats. The CPP was varied by decreasing MAP, either by hemorrhage or by the infusion of a vasodilating drug, and elevating ICP by infusion of mock CSF into the cisterna magna, or by MAP depression and ICP elevation simultaneously. Even though the lower limit of adequate CPP is considered to be 40 mm Hg, the EEG became isoelectric at an average CPP of 24 mm Hg and the BAEP became isoelectric at an average CPP of 7 mm Hg. These extremely low CPP values of 7-24 mm Hg are far below the range of autoregulation of cerebral blood flow (CBF) so that the brain stem auditory pathway is still capable of generating its electrical response (BAEP) at very low CBF. This is paradoxical since these same regions of the brain have been shown to have the highest levels or regional metabolism as shown by their very high local cerebral blood flow and local glucose utilization.

Animals↗

Early detection of hearing loss in infants by auditory nerve and brain stem responses.

Auditory-nerve and brain-stem-evoked responses (ABR) have been used alongside standard behavioral hearing tests for the early detection of hearing loss in infants and young children. Two comparisons are presented. The first concerns a group of 65 hearing-impaired children for whom we now have complete pure-tone and speech audiograms. There is a good correlation between the two types of hearing tests in 61 children; the lack of correlation in 4 children is discussed. The second comparison was conducted on neonates. Because ABR testing provides information which is far more accurate than behavioral testing, it is recommended for use in high-risk neonates, especially when mass behavioral screening is not feasible.

Audiometry↗

Auditory nerve-brain stem potentials in man and cat under hypoxic and hypercapnic conditions.

In order to study the effects of hypoxic and hypercapnic respiratory gas mixtures on brain activity, the auditory nerve brain stem evoked potentials (ABP) were recorded in 6 human volunteers and in 12 cats while they were breathing various gas mixtures. In humans, no effect of gas mixtures containing 9-13% O2 or 7.5-10% CO2 was observed on the wave form, latency and amplitude of the ABP. The cats were exposed to up to 25% CO2 and down to 5.5% O2 or to combined hypoxic and hypercapnic gas mixtures for up to 45 min while recording ABP and monitoring CO2 and O2 in the respired gases, arterial blood gas levels, pH, arterial blood pressure, body temperature and EEG. The extremes of pH were 6.68 and 7.46. The EEG was depressed or became isoelectric during hypercapnia. In general, the wave form, amplitude and latencies of the ABP waves were not much affected by these conditions. Loss of ABP was observed only when the animal was ventilated with about 5% O2 and this was secondary to and following cardiac failure and depressed arterial blood pressure, presumably leading to brain ischaemia. Thus, even though the cortex (EEG) is depressed, the brain stem seems to be resistant to these alterations in the blood gases in spite of the relatively higher rates of metabolism reported for the brain stem auditory structures.

Adult↗

Contribution of changes in click rate and intensity on diagnosis of multiple sclerosis by brainstem auditory evoked potentials.

Brainstem auditory evoked potentials (BAEPs) were recorded in 51 patients with different degrees of certainty with respect to multiple sclerosis (MS): Definite, probable and possible (McAlpine et al. 1972). Click stimuli were presented at various intensities and rates which were thought to stress the auditory pathways. The main types of abnormal BAEP traces were the absence of some of the brainstem waves (in the presence of a normal audiogram), prolonged brainstem transmission time (BTT) and abnormal amplitude ratio. In the definite MS group, average BTT was prolonged and average amplitude ratio was more than two standard deviations greater than the corresponding parameter in the normal group. The stressful manoeuvres of increasing click repetition rate and lowering click intensity increased the degree of abnormality of BAEP traces. There was no case in which the response to standard click stimuli (75 dB HL, 10 or 20 per sec) showed a normal trace while increasing the stimulus repetition rate and/or decreasing intensity showed a pathological response. The pathophysiology of BAEP traces in MS is discussed.

Adolescent↗

The latency of auditory nerve-brainstem responses in sensorineural hearing loss.

The use of auditory nerve-brainstem responses in differential diagnosis of hearing loss is based on several properties of these responses including response latency. The auditory nerve response latency has been shown to be prolonged in conductive hearing loss. The latency of the brainstem responses is also often prolonged in retrocochlear hearing loss. However, the effect of sensorineural hearing losses on auditory nerve response latency is not clear. Several authors report that response latency is prolonged in sensorineural loss, whereas others claim that it is unchanged. To study this, auditory nerve-brainstem responses to 75 dB HL clicks were recorded in normal-hearing subjects and in those with various degrees of high-frequency sensorineural hearing loss. In the more extreme hearing losses, the auditory nerve response could not be seen in the response trace, so the latency of the earlobe positive wave from the region of the inferior colliculus was considered as mirroring auditory nerve response latency, since the time interval between these two waves has been shown to be constant. The average latency of the more severe hearing loss group (more than 40 dB hearing loss at 4kHz) was found to be only 0.35 ms longer than that of the normal-hearing group. This value is smaller than that seen in most conductive and retrocochlear hearing losses. This result warrants continued use of prolonged auditory nerve response latency (greater than 0.35 ms) as an indicator of conductive hearing loss. Possible explanations for smaller latency prolongation than expected of the auditory nerve response in sensorineural hearing loss are discussed based on the properties of single auditory nerve fibers.

Audiometry↗

Analysis of auditory nerve-brainstem responses (ABR) in neonates and very young infants.

Auditory nerve-brainstem responses (ABR) to click stimuli were recorded in 26 normal infants when they were neonates and again in the same infants when they were 3 months old. The cochlear microphonic potential was also recorded in several of the neonates. The following response parameters were studied: latency and amplitude of the auditory nerve response, amplitude of the brainstem response elicited from the region of the interior colliculus, the ratio of the amplitudes of these two waves and brainstem transmission time (BTT): the time interval between these two responses. It was found that the auditory nerve response is only slightly prolonged in neonates with respect to adults and shortens by a small amount from birth to the age of 3 months. The latency of the auditory nerve response in neonates is only about 0.3 ms longer than in adults. BTT is longest in neonates and shortens significantly in 3-month-old infants.

Acoustic Stimulation↗

The source along the basilar membrane of the cochlear microphonic potential recorded by surface electrodes in man.

In order to determine the region along the basilar membrane which contributes to the recorded CM, an attempt was made to record CM responses in subjects with normal hearing and in subjects with high frequency cochlear hearing losses (e.g. acoustic trauma). In such cases of high frequency hearing loss, one may assume that damage has occurred to the hair cells in the basal turn of the cochlea. The CM, elicited by one cycle sinusoidal stimuli of various frequencies, intensities, phases, etc., was recorded by means of earlobe and scalp vertex electrodes. The CM recorded in subjects with normal hearing to high frequency sounds showed (besides the previously reported properties of the CM) large amplitudes and short latencies in response to low frequency stimuli. On the other hand, the CM recorded in subjects with high frequency hearing loss were either prolonged in latency and small in amplitude or completely absent. A plot of the relationship between CM lastency to high intensity 500 HZ stimuli stimuli and audiometric hearing loss in 66 ears shows clearly that in those cases in which hearing was normal at frequencies up to about 8 kHZ, CM latency was very short. On the other hand, in those cases in which the high frequency hearing loss progressed to include more and more lower frequencies, CM latency was more prolonged and smaller in amplitude until CM could no longer be observed. These results indicate that the CM recorded in normally hearing subjects from skin electrodes in response to low frequency (500 HZ) stimuli is generated in the basal turn of the cochlea. This finding is probably a consequence of the form of the mechanical response of the basilar membrane (travelling wave) to low frequency stimuli.

Acoustic Stimulation↗

A functional measure of brain activity: brain stem transmission time.

Surface-recorded auditory nerve and brain stem responses are being used routinely for diagnostic purposes in man. When interest is in auditory diagnosis, the electric response threshold is of primary importance. However, when used in neurological diagnosis, the wave form of the response is important. As a measure of one aspect of response wave form, this paper suggests the use of brain stem transmission time (BTT), defined as the time interval between the first earlobe-negative wave (response of the auditory nerve--the 'input' to the brain stem) and the earlobe-positive wave from the region of the inferior colliculus (the 'output' of the brain stem). The paper shows that BTT is longest in neonates, approaches adult values at the age of about 3 years, is relatively independent of click intensity, conductive hearing loss (middle ear lesion), click rate (except for high rates) and click frequency (filtered clicks). The finding that in a given age group, BTT is generally independent of most stimulus conditions, makes it a useful functional test of brain stem activity.

Adolescent↗

Auditory nerve and brain stem responses. Comparison in awake and unconscious subjects.

The recording of auditory nerve and brain stem responses to click stimuli is being used for the diagnosis of several conditions such as suspected hearing loss and suspected neurological disorders. The responses obtained in the patient group (often infants and children) are compared with those obtained in normal subjects of similar age who, for ethical reasons, are not sedated. In this study, recordings were made in normal subjects while they were awake and when they were unconscious in drug-induced sleep (being prepared for dental surgery). No significant difference could be observed between the recordings obtained in the awake state and when unconscious in the same subjects. Therefore, one is justified in using recordings made in awake subjects as controls for recordings made in other unconscious patients.

Brain Stem↗

The mechanism of damping of the serum thyroxine and triidothyronine levels caused by increasing thyrotropin dosage in mice.

The time course of the effect of bovine TSH (bTSH) on serum concentrations of thyroxine (T4) and triiodothyronine (T3) was measured in the normal mouse. The basal, unstimulated levels were 3.2+/-1.1 mug/100 ml T4 and 104+/-25 ng/100 ml T3 (mean+/-SD). With doses of bTSH from 0.5 to 100 mU the peak levels of the thyroid hormones were only 2.6 and 1.8 times the basal level for T4 and T3, respectively. With increasing doses of bTSH there was a proportional prolongation of the increased serum levels of thyroid hormones, i.e., about 2 h for 0.5mU to 12 h for 100 mU TSH. The integrated response with time was linearly related to the log dose. This would suggest a control mechanism which prevents excessive concentration of thyroid hormones in the serum. This pattern of response to TSH differs somewhat from that obtained by following radioiodine release in the McKenzie type bio-assay. To avoid the problems of changing blood concentrations of thyroid hormones and TSH, the release of T4 and T3 from the mouse thyroid was measured in vitro. The secretion increased with bTSH concentrations in the range of 0.02-0.8 mU/ml for T4 and 0.02-0.4 mU/ml for T3. The maximal response was 8.8+/-0.5 ng T4/3h/thyroid and 3.6+/-0.3 ng T3/3h/thyroid as against the basal secretion of 2.4+/-0.2ng T4 and 0.8+/-0.1 ng T3 (mean+/-SEM). Further in crease in bTSH concentration was associated with a decreased rate of thyroid hormone release. Thyroidal cAMP accumulation was enhanced with increasing bTSH concentration, even when there was a decrease in secretion. The dichotomy in the dose-response pattern between the two parameters indicated that the effect of high TSH concentrations on the release was induced at a step beyond cAMP accumulation. This was corroborated by the similar pattern of release induced by increasing concentration of DBcAMP. These findings indicate the existence of an intrathyroidal autoregulatory mechanism which prevents excess increase of thyroid hormone levels in the blood.

Animals↗

Inhibition of the response of mouse thyroid to tryrotropin induced by chronic triiodothyronine treatment.

Administration of 1 mU bovine TSH iv to mice resulted, within 1 hour, in the increase of the serum T4 level from 32 +/- 1.4 ng/ml to 53 +/- 2.6 ng/ml (Mean +/- SE, n = 24). Treatment with 1 mug triiodothyronine (T3) per day, for 10 days, abolished the responsiveness of the thyroid to TSH, as measured by thyroxine (T4) release. Thyroidal response to TSH was measured also in vitro. The basal hormonal release was 4.66 +/- 0.55 ng T4 and 0.98 +/- 0.15 ng T3 per thyroid per 3 h (n = 30). In the presence of bovine TSH (0.2 mU/ml) the hormonal secretion increased 3-fold for T4 and 2.5-fold for T3. Thyroids from mice pretreated with T3 for 10 days showed almost no response to TSH. Partial refractoriness to TSH was already significant 5 days after T3 pretreatment. Responsiveness to TSH was restored 3 days after T3 withdrawal or after 3 daily injections of 10 mU bovine TSH, concomitant with the last 3 days of T3 pretreatment. These results indicated that the prolonged absence of an adequate level of trophic hormone may be the cause of thyroidal unresponsiveness to acute TSH treatment. With 20 mU of TSH, cAMP levels rose from 4 +/- 0.5 picomoles to 80 +/- 9.3 picomoles per thyroid (n = 6). In mice subjected to 10 days of T3 pretreatment the response was markedly reduced: 20 +/- 3 picomoles/ thyroid. Thyroids of the T3-treated mice responded normally to 1 mM DBcAMP in vitro. From these results it was concluded that the impaired responsiveness of the thyroids to TSH occurs at a step prior to cAMP accumulation.

Animals↗

The effect of elevated doses of thyrotropin on mouse thyroid.

In the course of validating the McKenzie assay it was found that large doses of bovine or rat TSH have a retarding effect on hormonal secretion from the thyroid. TSH in doses less than 10 mU had a maximal effect on thyroidal secretion at about 2-3 h after administration. Doses of TSH in excess of 10 mU caused the peak of secretion to appear at about 9-10 h and caused, as well, a decreased thyroidal iodine release at earlier times. This effect was not due to changes in the pattern of iodocompounds secreted by the thyroid or to a change in the clearance of the blood [125I] thyroxine. An estimate of the integrated secretion with time was linear with log dose up to 100 mU TSH. This pattern of response to TSH is also seen when colloid droplet formation is the parameter studied. cAMP accumulation shows a different pattern of response to TSH. Control levels of cAMP were 1-2 pmoles/mg thyroid. Doses of TSH smaller than 5 mU caused no significant increase in cAMP. With a further increase in TSH up to 200 mU per mouse, cAMP levels increased linearly with the log of TSH and reached 400 pmoles/mg thyroid. Theophylline administered together with large doses of TSH increased the level of the thyroidal cAMP and further decreased the release of iodocompounds at 2 h. These results indicate that there may be an intrathyroidal mechanism which prevents a surge of secretion of thyroid hormones with acute changes in blood TSH levels. The mechanism sensitive to excess TSH is probably associated with steps in thyroidal activation between the accumulation of cAMP and colloid droplet formation.

Animals↗

Intermediate endocochlear potential levels induced by hypoxia.

It seems that the positive potential of the scala media (endocochlear potential [EP]) and the high potassium concentration in the endolymph are generated and maintained by an electrogenic pump. In order to study its properties, the EP was measured in cats ventilated with low oxygen gas mixtures (2.25-10%). It was found that the EP could be maintained at intermediate levels which were more or less linear functions of blood oxygen tension (25-60 mmHg), showing that the pump can operate on intermediate levels. This hypoxic preparation may contribute to the study of cochlear blood flow.

Acoustic Stimulation↗