Search PubMedSearch

Biomedical subjects

K C Campbell

Publications and source records attributed to K C Campbell.

16 recordsLinked to original sources

A semiquantitative analysis of the effects of cisplatin on the rat stria vascularis.

Cisplatin (CDDP) is a very effective chemotherapeutic agent but is highly ototoxic. Most studies have focused on the effects of CDDP on the outer hair cells. The purpose of this study was to examine changes in the stria vascularis in cisplatin treated male Wistar rats and to provide semiquantitative analysis of the results. We removed a section of the stria vascularis from the basal turn of five control and five CDDP (16 mg/kg) treated rats. Using transmission electron microscopy (TEM) we analyzed: (1) changes to the strial tissue as a whole; and (2) intracellular changes in the marginal cells. We also subjected the samples to semiquantitative analysis using the MCID, focusing on three aspects of strial profile abnormalities; the number of abnormal marginal cells in CDDP treated tissue, intracellular strial edema and densitometry. Controls appeared normal, but many pathologic changes were apparent in the experimental group. Results from the semiquantitative analysis indicate cisplatin has a deleterious effect on the stria vascularis including strial edema; bulging, rupture and/or compression of the marginal cells and depletion of the cytoplasmic organelles.

Animals

Translating between orthogonally oriented stimulus and response arrays in four-choice reaction tasks.

Three experiments examined performance of four-choice reaction tasks using stimulus and response arrays oriented along parallel or orthogonal axes. All used a procedure in which pairs of locations were precued in advance of the target stimulus. Responses were slower for orthogonal than for parallel stimulus-response sets, but the pattern of relative precuing benefits was similar. Complete transfer occurred when the stimulus array was changed from an orthogonal to a parallel orientation with respect to the response array after three sessions of practice. Transfer was also evident when the orientation of the response array was changed from orthogonal to parallel with respect to the stimulus array, as long as the assignment of stimulus locations to fingers was not altered. The results suggest that coding in the four-choice task is by relative location regardless of whether the stimulus and response sets are oriented orthogonally, and that an additional transformation operation to align the frames of reference is performed for orthogonal orientations.

Cues

D-methionine provides excellent protection from cisplatin ototoxicity in the rat.

Cisplatin (CDDP) is a widely used chemotherapeutic agent. Unfortunately, CDDP is highly ototoxic. We tested D-methionine (D-Met), a sulfur containing compound, as an otoprotectant in male Wistar rats. Complete data sets were obtained for five groups of five animals each, including a treated control group (16 mg/kg CDDP), an untreated control group (administered an equivalent volume of saline) and three groups that received either 75, 150, or 300 mg/kg D-Met 30 min prior to the 16 mg/kg CDDP dosing. Auditory brainstem response (ABR) thresholds were obtained in response to clicks, and 1 kHz, 4 kHz, 8 kHz, and 14 kHz toneburst stimuli, before and 3 days after drug administration. Scanning electron microscopy (SEM) was used to examine the outer hair cells of the apical, middle and basal turns of the cochlea. Animal weight was measured on the first and final day. D-Met provided excellent otoprotection even at the lowest level with complete otoprotection obtained for the 300 mg/kg dosing as measured by both ABR and SEM. D-Met also markedly reduced weight loss and mortality. All animals receiving D-Met (15/15) survived to the end of the study period as opposed to only 5/10 of the treated controls.

Acoustic Stimulation

Technical and editorial administration of a World-Wide-Web site during a period of rapid growth: the OncoLink experience.

OncoLink is a cancer information resource on the World-Wide-Web (WWW) that provides a wide variety of information for cancer patients and healthcare providers. Since its introduction in March, 1994 it has enjoyed success as demonstrated by an over 31-fold increase in usage as of February, 1996. Current utilization exceeds 1.1 million accesses per month. The content of OncoLink has also expanded greatly, with new items being added daily. In addition, OncoLink has been the recipient of numerous awards from a variety of agencies and organizations. During this period of rapid growth, the complexity of managing and maintaining OncoLink has likewise increased. This work may be divided into three categories: content editing, technical (or production) editing, and web site maintenance. Consequently, we have developed numerous administrative procedures to handle this workload. After implementing these new administrative strategies, we were able to greatly reduce the need for face-to-face meetings of our Editorial and Production Staffs. This paper describes our experience with developing efficient strategies for managing the daily operation of OncoLink during a period of rapid growth.

Computer Communication Networks

Comparison of tympanic membrane-recorded electrocochleography and the auditory brainstem response in threshold determination.

The purpose of this study was to evaluate the usefulness of electrocochleography (ECoG) recorded with a tympanic membrane electrode as an adjunctive measure to auditory brainstem response (ABR) in frequency-specific threshold estimation. In a group of 10 normally hearing and 10 sensorineural hearing-impaired subjects, ABR and ECoG were simultaneously recorded in response to tone-burst stimuli centered at 500, 1000, 2000, and 4000 Hz. At each frequency, stimulus intensity was reduced in 12-dB decrements from an initial level of 110 dB SPL until no replicable response could be discerned. Electrocochleography and ABR thresholds were determined at each frequency, and correlation to behavioral audiometric threshold was determined. Input/output functions were also computed. At 2000 and 4000 Hz, both ABR and ECoG thresholds correlated with behavioral audiometric threshold. At 1000 Hz, ABR threshold correlated with behavioral audiometric threshold; ECoG did not. At 500 Hz, neither ABR nor ECoG threshold correlated with behavioral audiometric threshold. Input/output functions were steeper for ECoG than for ABR at all frequencies tested in the normally hearing group.

Auditory Threshold

Electrocochleography with postural changes in perilymphatic fistula. Animal studies.

The present study investigated the effect of altering body position on electrocochleographic findings in the presence and absence of perilymphatic fistula. Three groups of guinea pigs included 1) 10 normal control animals, 2) 10 experimental animals with induced perilymphatic fistula, and 3) 10 control animals with induced perilymphatic fistula. In the first two groups, animals were successively tested in three positions: first with the ventral aspect down, again after 30 minutes with the test ear up, and again after 15 minutes with the test ear down. In the third group, body position was not altered. Stimuli consisted of clicks and 6,000-Hz tone bursts. Data analysis included summating potential (SP) amplitude, action potential (AP) amplitude, and AP threshold for the click stimuli. Only the normal control group showed a significant effect of body position for the SP/AP amplitude ratio. Average change was greater in the experimental group, but high variability precluded statistical significance. Both fistulized animal groups exhibited high variability in the SP/AP amplitude ratio, with and without postural change. The SP/AP amplitude ratio and SP amplitude were significantly larger for the two fistulized groups than for the normal control group. No significant change in threshold occurred across positions for any group.

Acoustic Stimulation

Noninvasive electrodes for electrocochleography in the chinchilla.

This study compares noninvasive vs invasive electrodes for electrocochleography in chinchillas. Summating potential (SP) amplitude, action potential (AP) amplitude, and AP threshold, recorded with five types of noninvasive electrodes, were compared with simultaneous bulla recordings. Noninvasive electrodes included a needle electrode over the bulla, gold Tiptrode (Etymotic Research, Elk Grove Village, Ill), Enhancer I (Nicolet Instrument Corp, Madison, Wis), Coats (Lifetech Inc, Austin, Tex) electrode, and a locally constructed tympanic membrane (TM) electrode. Stimuli included 100-microsecond clicks and 6000-Hz tone bursts (with a 1 millisecond rise/fall time and a 5 millisecond plateau). Stimuli were initially presented at 110 dB peak equivalent sound pressure level for the clicks and 100 dB peak equivalent sound pressure level for the tone bursts. Intensity was then decreased in 10-dB decrements until no replicable AP activity was observed. The TM damping for the TM electrode was measured with 0.5, 1, 2, 4, and 6 kHz and click stimuli. The AP was clear and replicable for all electrodes used in the study, although the amplitude was substantially less for the noninvasive electrodes as opposed to the invasive electrode. The invasive electrode provided the largest amplitude SP recording, but SP could generally be clearly recorded with the needle electrode, Enhancer I, and the Coats electrode. The TM electrode and gold Tiptrode provided SP recordings less consistently. The AP threshold could be recorded with all the electrodes in the study and was generally within 10 dB of threshold recorded invasively. Electrode variables, including ease of electrode placement and potential injury, were examined. The Tiptrode and Enhancer I electrodes posed relatively few problems during placement.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials

Audiologic monitoring for ototoxicity.

In summary, the clinician has a variety of protocols available for monitoring ototoxicity. Depending on the patient's risk factors and ability to be tested, the protocol for a given patient may vary. A flow chart reflecting some of the possible decisions and options is presented in Figure 1. Certainly, as we learn more about ototoxicity and the advantages and disadvantages of the various test methods, further refinements of patient and test selection will ensue. Ototoxicity is a rapidly expanding and interesting area. Hopefully, the care of patients receiving ototoxic medications will continue to improve and will ultimately prevent, or at least ameliorate, ototoxic hearing loss.

Audiology

Electrocochleography with postural changes in perilymphatic fistula and Menière's disease: case reports.

Perilymphatic fistula can be difficult to diagnose differentially prior to exploratory surgery. In this study, we investigated a new test technique in four case studies of subjects with perilymphatic fistula and compared our findings to results obtained in 20 normally hearing subjects with no history of vertigo and 10 subjects with Meniere's disease. Recordings from an eardrum electrode were obtained with the subject in an upright position, after the subject had been lying in a horizontal position for 30 minutes with the test ear up and after 15 minutes with the test ear down. Stimuli consisted of high level clicks and tonebursts. Neither the summating potential (SP) and action potential (AP) amplitudes nor the SP/AP amplitude ratio were significantly affected by postural change in either the normal or Meniere's disease group. The perilymphatic fistula subjects, in general, showed greater changes in the SP/AP, particularly for the 6000 Hz tonebursts, than did the other two groups. More data will be needed to determine if these findings are consistent in a large population of perilymphatic fistula patients.

Adolescent

Electrocochleographic recordings in acute and healed perilymphatic fistula.

In this study, the summating potential (SP) and action potential (AP) amplitude ratio was measured in 15 guinea pigs before and after surgical induction of a round window fistula. The round window fistula was then allowed to heal, and recordings were obtained after 1 month. Stimuli included 8000-Hz and 2000-Hz tone bursts and click stimuli at levels ranging from 100-dB peak equivalent sound pressure level to AP threshold. Immediately after fistula induction, a statistically significant enlargement in the SP/AP amplitude ratio occurred in response to the click and the 8000-Hz tone-burst stimuli. No change in the SP/AP amplitude ratio was observed for the 2000-Hz stimuli. After healing, the SP/AP amplitude ratio generally returned to prelesion values. No unhealed perilymphatic fistulas were observed in any of the 15 guinea pigs at 1 month after fistula induction. Considering the difficulty of diagnosing perilymphatic fistula in humans, it is encouraging to note that, at least in animals, noninvasive electrophysiologic recordings may perhaps be sensitive to the presence of patent perilymphatic fistula.

Action Potentials

Chronic perilymph fistula in the guinea pig with implications in the human.

To improve understanding of the pathophysiology of perilymph fistulas, a predictable animal model of a chronic fistula was developed. Our findings suggest that guinea pig fistulas do not remain patent for prolonged periods. By extrapolating these findings to humans, we postulate that the symptoms and signs of perilymph fistula are possibly due not to one prolonged constant fistula, but rather a series of "blowouts" from an inherent congenital or posttraumatic weak spot in either the round or oval window. We feel that a diagnosis of perilymph fistula must be considered in any patient presenting with a Meniere's-like symptom set concomitant with a congenital inner ear deformity or a history of inner ear trauma.

Acoustic Stimulation

Electrocochleography in the presence and absence of perilymphatic fistula.

The purpose of the present study was to evaluate the effect of an acute perilymphatic fistula on the amplitude ratio (SP/AP) of the summating potential (SP) and action potential (AP). The effect of the acute fistula on AP threshold was also addressed. Electrocochleographic recordings were obtained before and immediately after surgical laceration of the round window membrane in 19 guinea pigs. Stimuli comprised clicks and 2,000-Hz and 8,000-Hz tone bursts, presented initially at 100 dB peak equivalent sound pressure level and in descending 10-dB steps. After fistula induction the SP/AP significantly increased for the click and 8,000-Hz tone burst stimuli but not for the 2,000-Hz tone burst stimuli. No significant change in AP threshold occurred. These findings suggest that the SP/AP may be sensitive to perilymphatic fistula, at least in guinea pigs. The changes in the SP/AP do not appear to be related to changes in threshold.

Action Potentials

Interpretation of electrocochleography in Menière's disease and normal subjects.

Electrocochleographic recordings were obtained from 20 subjects with normal hearing and 10 subjects with Menière's disease by using an eardrum electrode. Stimuli included clicks and 6,000-Hz tone bursts. Results were not significantly different between the two groups for summating potential (SP) amplitude, action potential (AP) amplitude, or the SP/AP amplitude ratio. Interpreting the results in light of symptoms on the date of assessment or hearing threshold did not appear to improve separation between the two groups. Various SP/AP amplitude ratio criteria have been proposed in order to separate normal patients from those with Menière's disease. Applying these proposed criteria to our data did not successfully separate the two groups.

Acoustic Stimulation

Electrocochleographic recordings in chronic and healed perilymphatic fistula.

This study examined electrocochleographic recordings in 15 guinea pigs with perilymphatic fistulas. A chronic round window fistula was induced in each animal by insertion of a sigmoid stainless steel needle with the lumen intact. In the contralateral control ear, a similar needle was inserted with the lumen crushed. In this way the model compared acute (control group) versus chronic (experimental group) perilymphatic fisulae. Electrocochleographic recordings were obtained before, immediately after needle insertion, in a subset at two to three weeks after needle insertion, and again at 17-22 weeks when the fistulas had healed with the needles still in place. Minimal threshold changes were noted from the pre- to the acute post-condition. More marked elevation of threshold was noted for the 17-22 weeks condition. Threshold elevation was greater in the experimental ears but was present in the control ears. The SP/AP amplitude ratio was generally stable for the pre- to post-conditions in both ears. For the 17-22 week epoch the SP/AP amplitude ratio was still fairly stable for the click stimulus but the ratio diminished for the toneburst stimuli. For the subset analyzed at 7-21 days the SP/AP amplitude ratio tended to increase for both groups for all stimuli although AP thresholds were normal.

Animals

Evaluation of six gentamicin nomograms using a bayesian parameter estimation program.

A new set of guidelines for the administration of gentamicin was developed by estimating steady-state peak and trough gentamicin concentrations for simulated patients with known weights and creatinine clearances. The most appropriate doses to achieve target peak concentrations of 5-10 mg/L and troughs of less than 2 mg/L were then tabulated. The performance of these new guidelines was assessed using data collected from 60 patients who had received gentamicin and had at least two serum concentration measurements. Individual estimates of clearance and volume of distribution were obtained using a Bayesian parameter estimation program and these estimates were used to predict the steady-state peak and trough concentrations that would arise from the new guidelines and five other previously published nomograms (Mawer, Chan, Hull-Sarubbi, Rule of Eight, and Dettli). The new guidelines, the Dettli nomogram, and the Hull-Sarubbi table achieved similar percentages (52-57%) of patients within the target ranges (5-10 mg/L for peak and less than 2 mg/L for trough), although 28% of patients had predicted peak concentrations below 5 mg/L with the new method compared to 15% with the other two. Only 38% of patients were within both ranges when the Mawer nomogram and the Rule of Eight methods were used. Since a large percentage of patients would have achieved concentrations outside of the target ranges no matter which nomogram was used, serum concentration monitoring is still recommended to confirm dose requirements.

Bayes Theorem

The effect of stimulus repetition rate on the auditory brainstem response in tumor and nontumor patients.

Auditory brainstem responses were recorded in two groups of adult subjects with asymmetric sensorineural hearing loss. Clicks were presented at repetition rates of 9.7, 39.7, 49.7, and 59.7/s. One group was composed of 20 patients with no known otoneurologic lesion (cochlear group), and one group was composed of 8 patients with a surgically confirmed acoustic neuroma in the ear with poorer hearing sensitivity (retrocochlear group). Detection of wave V at different repetition rates was not significantly different between the two groups. Average wave-V latency shift was not significantly different between the two groups as repetition rate increased from 9.7/s to 39.7/s but was significantly greater for the retrocochlear group as repetition rate increased from 9.7/s to 49.7/s and 59.7/s. However, the wave-V latency shift showed no improvement over the slow-rate interaural wave-V latency difference in discriminating between the two groups of patients. No significant correlation between the amount of wave-V latency shift and hearing loss at 2000 Hz or 4000 Hz was found for the ears with poorer hearing sensitivity.

Acoustic Stimulation