End points for cisplatin ototoxicity.

INTRODUCTION: Hearing loss owing to ototoxicity in humans is usually presumed to be irreversible and stable. Most articles in the literature study the effects of ototoxic agents such as cisplatin only over a few days or weeks. This study focused on the recovery of hearing over several months in mice. The same treatment was applied to guinea pigs to determine whether there were significant differences in response between the two species. METHODS: Thirty-two mice and 37 guinea pigs were randomized to receive either saline or cisplatin (15 mg/kg). After this exposure, we performed auditory brainstem response (ABR) testing on the mice over 8 months and on the guinea pigs for 1 month. RESULTS: Hearing loss owing to cisplatin shows significant variability between and within species. In mice, hearing loss is maximal at about 17 dB during the third month after cisplatin administration but actually improves to the level attributable to presbyacusis. Guinea pigs, however, experience greater, approximately 25 dB hearing loss within a month of administration of the same dose of cisplatin, tested with the same protocol. CONCLUSION: In general, ototoxicity end points should be assessed more than 1 month after exposure for animals. Our observation that hearing loss is incomplete before 1 month in mice opens the possibility of studies for preventive treatment during that time.

Does sodium thiosulphate delay presbyacusis?

INTRODUCTION: This study compares the effects of sodium thiosulphate (STS) and normal saline on the prevention of hearing loss. SETTING: Animal research laboratory. METHODS: Sixteen mice were randomized to receive intraperitoneal injections of either normal saline or STS. Auditory brainstem response testing was used to determine baseline and posttreatment hearing thresholds over the course of 1 year. RESULTS: Compared with saline, treatment with STS resulted in a statistically significant improvement in click and pure-tone thresholds until the end of the year. CONCLUSION: STS can significantly delay hearing loss associated with age in this murine model.

Does intracochlear brain-derived nerve growth factor improve auditory brainstem click thresholds in sensorineural hearing loss?

OBJECTIVE: To determine whether intracochlear administration of brain-derived nerve growth factor (BDNF) is associated with lower auditory brainstem response (ABR) click thresholds after cisplatin-induced sensorineural hearing loss. STUDY DESIGN: Animal research study. METHODS: Fifteen normal hearing guinea pigs were studied. In 11 animals, hearing loss was created using cisplatin. One month later, bilateral cochleostomies were then performed. In one ear, BDNF was injected, and in the other, an equivalent volume of saline was injected prior to plugging with fat. In four animals, no cisplatin or BDNF was given, but the cochleostomies were performed bilaterally as surgical controls. ABR testing was then carried out for two subsequent months using clicks to determine thresholds. RESULTS: There were no statistically significant changes in ABR click thresholds between BDNF-treated versus BDNF-untreated ears. The thresholds for the control group that underwent cochleostomy only were actually worse than those for either of the groups that received cisplatin, and the ears that received BDNF had better hearing than either saline or surgical controls, but the results were not statistically significant. CONCLUSION: Our data do not support the use of intracochlear BDNF for severe hearing loss correction in guinea pigs as used in this protocol.

Brain-derived nerve growth factor in the treatment of sensorineural hearing loss.

OBJECTIVES/HYPOTHESIS: A possible medical treatment for sensorineural hearing loss using brain-derived nerve growth factor (BDNF) was explored. The hypothesis is that direct intracochlear application of BDNF will result in improved hearing. STUDY DESIGN: Animal research study. METHODS: Significant hearing loss was created using cisplatin in 11 guinea pigs. One month later, bilateral cochleostomies were performed placing 0.05 microg of BDNF in one cochlea of each animal prior to plugging with connective tissue. The other cochlea served as a control. Auditory brain-stem response (ABR) testing was then carried out for three months at 6,000, 8,000, 12,000, and 24,000 Hz. RESULTS: ABR thresholds were better in the treated ear for all frequencies. Threshold differences were statistically significantly better two months after treatment (general linear model, repeated measures P = .045). CONCLUSIONS: Intracochlear application of BDNF may prevent hearing loss.

Comparison of three methods of testing hearing in mice.

INTRODUCTION: This study compares the reliability and validity of three methods of testing hearing in mice. SETTING: Animal research laboratory. METHODS: Three methods of testing hearing were used in 18 mice: (1) auditory brainstem response (ABR), (2) electrocochleography with a needle electrode, and (3) electrocochleography with a soft, cotton-wick electrode. RESULTS: Reliability was good for all three tests, but ABR testing was the easiest and provided the lowest thresholds and least variability. The results for these tests under other conditions may vary. CONCLUSION: ABR testing can be considered an optimal test method under the circumstances in this study.

Fatigue in individuals with advanced cancer in active treatment and palliative settings.

Fatigue is associated with cancer, but it also occurs in other illnesses and in work and leisure activities. This article is a report of part of a project comparing fatigue across ill and non-ill populations aimed at identifying the unique features of fatigue in individuals with cancer. The first stage of this work suggested that fatigue is 3 distinct but related concepts-tiredness, fatigue, and exhaustion-which led to the development of the Fatigue Adaptation Model. In this article, the authors report the findings of a qualitative study of fatigue in individuals with advanced cancer in active treatment and palliative settings. It is the first in a series of 5 papers intended to make the boundaries between tiredness, fatigue, and exhaustion more explicit. Here, the authors show that although tiredness, fatigue, and exhaustion are all manifested by the same 5 attributes (changes in emotional, cognitive, and muscular function; decreasing control over body processes; and decreased social interaction), the qualitative differences in the manifestations support the assertion that they are distinct states. This distinction is important, as interventions that could prevent, or at least delay, progression from tiredness to fatigue may be inappropriate for the prevention or delay of progression from fatigue to exhaustion.