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D L Jewett

Publications and source records attributed to D L Jewett.

At least 37 records · Page 2Linked to original sources

Evoked potentials in rats with misonidazole neurotoxicity. I. Brain stem auditory evoked potentials.

Central neurotoxicity produced in rats by daily administration of 300 mg/kg of misonidazole (MISO) 5 times/week for 4-5 weeks (total dose = 6.0 gm/kg) was evaluated weekly wit brain stem auditory evoked potentials (BAEPs). Compared to untreated control rats, all treated rats had a prolongation of the I-IV interpeak latency (p less than 0.005) at a mean of 13.2 +/- 2.7 days at a cumulative dose of approximately 4.0 gm/kg of MISO per rat. In some rats, the I-III and I-II interwave latencies were prolonged and waves III and IV were lost. Control rats did not show any significant alteration in BAEP latency or amplitude. Histopathologic examination of the brain stems of treated rats showed that necrotic lesions were present primarily in the nuclei of the tegmentum of the fourth ventricle, with scattered nuclear involvement in the cerebellar roof nuclei, inferior olive, and nucleus of the spinal tract of the trigeminal nerve. The cerebral cortex appeared to be normal in all treated rats. Changes in BAEPs caused by central neurotoxicity correlated with the histopathologic findings. We conclude that BAEPs are a sensitive method for evaluating MISO central neurotoxicity in the rat model.

Animals↗

Diagnosis of acute nerve compression in the cat with high frequency nerve trains evoked responses.

High frequency nerve trains were evaluated from above and below the site of compression before, during, and after acute compression of the sciatic nerves of six adult cats. Acute nerve compression reduced the ability of axons to conduct high frequency impulse trains: the longer the compression, the lower the frequency of impulses that could be conducted through the region of compression without a decrement in latency and amplitude. Possible mechanisms for alterations of nerve trains and the possible clinical and experimental use of nerve trains analysis are discussed.

Acute Disease↗

Evaluation of misonidazole peripheral neurotoxicity in rats by analysis of nerve trains evoked response.

The clinical use of misonidazole and other nitroimidazole radiosensitizing agents is limited by the peripheral and central neurotoxicity that is produced in animals and humans. In a blinded study, rats treated with misonidazole at either 100 mg/kg or 300 mg/kg, 5 days/week for 3 weeks, were evaluated for peripheral neurotoxicity using nerve trains evoked responses. Only one rat treated at a dose of 100 mg/kg developed symptoms and signs of neurotoxicity, while all rats treated at 300 mg/kg developed these signs and symptoms. Nerve trains analysis made possible a diagnosis of neurotoxicity before overt clinical signs appeared. This test is non-invasive and may be useful for evaluating patients receiving nitroimidazole radiosensitizers as part of a radiation therapy regimen.

Animals↗

The Q10 of auditory brain stem responses in rats under hypothermia.

Auditory brain stem responses (ABRs) were recorded from normal Sprague-Dawley rats ranging in age from 15 to 120 days. Increased latencies for all four waves of the ABR were noted for animals of all ages as their body temperatures were reduced from 38 to 28 degrees C. The Q10S of the latency changes were highly variable but were still significantly higher for the first three waves of the ABR in animals less than 20 days of age compared with older animals. The Q10S for the fourth wave in both groups were alike. Wave heights tended to decrease during cooling, but this effect was inconsistent. The cochlear microphonic was recorded in some animals and tended to decrease in size with cooling. As seen in this study, the significant changes in wave latencies due to small temperature differences underscore the need to carefully control this variable when taking evoked responses from animal preparations and humans subject to variations in body temperature. The interanimal variability of the Q10 precludes any simple 'correction' of latency differences due to temperature for research or clinical purposes.

Animals↗

Planar curve analysis of three-channel auditory brain stem response: a preliminary report.

Recording of auditory brain stem responses (ABRs) were made in guinea pigs by means of far-field computer averaging from three orthogonal electrode pairs. The 'Y' locations were mouth and nuchal ridge, 'X' locations left and right mastoids, and 'Z' locations vertex and throat. Three-dimensional models were constructed to plot simultaneous points from the three averages in a voltage-voltage-voltage space. In all five animals tested, at least three subsets of sequential data points lie in separate planes. The data points in each plane roughly correspond to waves I to III in the guinea pig ABR as recorded from the vertex-throat electrode pair. The planarity of data points is a new observation and is not predicted from the single-channel recordings. Three-dimensional planes are also found by means of vectorcardiography, which suggests some underlying principle, such as synchrony and homogeneity of anatomical position of the generators. Planar analysis of ABRs may be useful in analyzing and utilizing the additional information obtainable from 'non-standard' electrode pairs.

Acoustic Stimulation↗

Effects of undernutrition on development of far-field auditory brain stem responses in rat pups.

Timed-pregnancy Sprague-Dawley rats were placed on special diets on day 15 of their pregnancy. One group received a normal, 24% protein diet, and the second a deficient, 8% protein diet. After birth the litters within each group were cross-fostered, thinned to 8 pups each, and maintained on their respective diets. Beginning with postnatal day 16 the ABR (auditory brain stem response) was repeatedly recorded from the pups until day 43. Undernourished rat pup body weights were less than one-third of those of the well-nourished litters at the conclusion of testing. ABRs taken from the undernourished group were significantly delayed in early development compared with the controls, but the differences decreased with age despite continuation of a deficient diet. A second experiment was run to rule out body temperature differences between the two groups and showed that the ABR effect was not solely due to this variable. These results indicate that undernourishment is one of the factors that can affect the rate of maturation of the ABR.

Acoustic Stimulation↗

Far-field cochlear microphonic responses to continuous pure tones recorded from the scalps of cats.

The cochlear microphonic response to continuous pure tones has been recorded in the 'far field' from the scalps of anesthetized cats. Previous methods for scalp recording used tone pip transients only. Our experiments show that the observed wave forms are not due to electrical or mechanoelectrical artifacts. Neural responses such as brain stem responses or the frequency-following response have been excluded as major contributors to the observed wave forms, which are virtually identical to the round window cochlear microphonic response with respect to (1) wave shape with non-sinusoidal stimuli, (2) intensity-amplitude functions, (3) response phase, and (4) amplitude changes due to superimposed band-limited white noise. The methods of ruling out significant artifacts are applicable to non-invasive recordings from humans.

Animals↗

The effects of ototoxicity on the auditory brain stem response and the scalp-recorded cochlear microphonic in guinea pigs.

The objective determination of hearing impairment with evoled response techniques may be of value in the early detection of ototoxic reactions, especially in infants and other "difficult" patient populations. In this study the auditory brain stem response to "clicks" at two intensities and two repetition rates were recorded from guinea pigs that had been given one of two dosage levels of kanamycin or no drug. The scalp-recorded cochlear microphonic to continuous tones was also recorded. Hearing loss was seen in one-third of the animals receiving kanamycin. The temporal course of the deficit varied considerably between animals. Auditory system change was most readily detected in response to low-intensity stimuli, while change in repetition rate of the clicks did not affect the results. The cochlear microphonic potentials correlated with the auditory brain stem response.

Animals↗

Thermal fields and heat generation effects in tissue, awake and under halothane anesthesia.

In order to further document the heat generation terms used in models predicting heat transmission in tissue, a series of temperature fields were generated and measured in cat brain with an implantable cylindrical source and thermocouple apparatus. The experimental technique allowed measurements to be made under fully awake in vivo conditions as well as for 3 to 45% levels of halothane anesthesia. Fields resulting from probe forcing function temperatures of 4 degrees C, 18 degrees C, and 28 degrees C were warmer in the anesthetized tissue indicating an increase in heat generation resulting from blood flow and metabolic heat. Values of the heat generation were obtained by applying the Bio-Heat Equation directly to the experimental data. A simple blood flow heat generation model gave a reasonable prediction of the heat generation in a temperature range lower than 3 to 4 degrees C below the inlet blood temperature, and with a Q10 equals 3 variation of blood flow rate with temperature. Results also indicate that the heat generation effect under halothane anesthesia conditions are such that the use of the apparent property concept in thermal modeling may not be valid.

Anesthesia, Inhalation↗

Spatio-temporal distribution of auditory-evoked far field potentials in rat and cat.

Short latency (less than 5 msec) auditory-evoked 'far field' potentials were mapped over the head of anesthetized rats and cats using a monaural 'click' stimulus. Significant activity was found over most of the head and, in the rat, on other parts of the body. Different components of the observed waveforms have different spatial distributions, supporting earlier evidence that they come from different generators. No area was found on the head which could be considered as an electrically neutral reference point for all the waves. There was considerable asymmetry in the spatial distribution of the early waves, with the area near the contralateral ear showing larger magnitudes than the area near the ipsilateral ear. It was found that most of the head of the rat is not in the far field, as previously defined. Significant activity was found on the tongue in the cat, which tended to increase the apparent magnitude of waves I and II at the vertex when the tongue was used as a reference. The area near the ear canal was also found to show significant activity, raising questions as to the use of the ear lobe as a reference point in human studies. We conclude that the placement of the electrodes can markedly influence the waveforms obtained, in some cases enhancing detection of early components.

Animals↗