Sulfhydryl compounds and antioxidants inhibit cytotoxicity to outer hair cells of a gentamicin metabolite in vitro

Aminoglycoside antibiotics such as gentamicin have long been known to destroy cochlear and vestibular hair cells in vivo. In the cochlea outer hair cells are preferentially affected. In contrast, gentamicin will not damage outer hair cells in vitro unless it has been enzymatically converted to a cytotoxic metabolite. Several potential inhibitors of this enzymatic reaction were tested in an in vitro assay against outer hair cells isolated from the guinea pig cochlea. Viability of hair cells (viable cells as per cent of total number of cells observed) averaged about 70% under control conditions. Addition of metabolized gentamicin significantly reduced viability to less than 50% in one hour. Sulfhydryl compounds (glutathione, dithioerythritol) and antioxidants (vitamin C, phenylene diamine, trolox) prevented the cytotoxic actions of the gentamicin metabolite. Inhibitors of aminc oxidases and compounds reportedly protective against renal and acute lethal toxicity of aminoglycosides (poly--aspartate and pyridoxal phosphate, respectively) were ineffective as protectants. The results reinforce the hypothesis that gentamicin is enzymatically converted to a cytotoxin and imply the participation of sulfhydryl-sensitive groups or free radicals in this reaction. Alternatively or additionally, sulfhydryl compounds or antioxidants may participate in detoxification reactions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31500/1/0000422.pd

Attenuation of gentamicin ototoxicity by glutathione in the guinea pig in vivo

The effect of glutathione co-therapy on the expression of gentamicin ototoxicity was tested in pigmented guinea pigs. The first group of animals was injected with gentamicin (100 mg/kg body weight/day) for two weeks followed by 10 weeks of rest. A second group received glutathione by gastric gavage immediately prior to each gentamicin injection. Two groups of controls were treated either with saline injections or glutathione gavage alone. Auditory brainstem responses, taken at 2-week intervals, revealed a progressive gentamicin-induced hearing loss reaching a 30 to 40 dB threshold shift at 2 kHz, approximately 60 dB at 8 kHz and 80 dB at 18 kHz. Glutathione co-therapy slowed the progression of hearing loss and significantly attenuated the final threshold shifts by 20 to 40 dB. Morphological evaluation confirmed hair cell loss after gentamicin treatment and protection by glutathione. Drug serum levels were assayed at 2 and 7 days of treatment. There were no differences between the gentamicin (mean = 183 [mu]g/ml; range, 90 to 300) and the gentamicin/glutathione group (mean = 164 [mu]g/ml; range, 80 to 320). Antimicrobial activity of gentamicin was tested against Staphylococcus aureus and Pseudomonas aeruginosa. A 30-fold molar excess of glutathione did not influence the efficacy of gentamicin. These studies suggest that glutathione protects against ototoxicity by interfering with the cytotoxic mechanism.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31501/1/0000423.pd

Predictors of poor sleep quality among head and neck cancer patients

Objectives/Hypothesis: The objective of this study was to determine the predictors of sleep quality among head and neck cancer patients 1 year after diagnosis. Study Design: This was a prospective, multisite cohort study of head and neck cancer patients (N = 457). Methods: Patients were surveyed at baseline and 1 year after diagnosis. Chart audits were also conducted. The dependent variable was a self-assessed sleep score 1 year after diagnosis. The independent variables were a 1 year pain score, xerostomia, treatment received (radiation, chemotherapy, and/or surgery), presence of a feeding tube and/or tracheotomy, tumor site and stage, comorbidities, depression, smoking, problem drinking, age, and sex. Results: Both baseline (67.1) and 1-year postdiagnosis (69.3) sleep scores were slightly lower than population means (72). Multivariate analyses showed that pain, xerostomia, depression, presence of a tracheotomy tube, comorbidities, and younger age were statistically significant predictors of poor sleep 1 year after diagnosis of head and neck cancer ( P < .05). Smoking, problem drinking, and female sex were marginally significant ( P < .09). Type of treatment (surgery, radiation and/or chemotherapy), primary tumor site, and cancer stage were not significantly associated with 1-year sleep scores. Conclusions: Many factors adversely affecting sleep in head and neck cancer patients are potentially modifiable and appear to contribute to decreased quality of life. Strategies to reduce pain, xerostomia, depression, smoking, and problem drinking may be warranted, not only for their own inherent value, but also for improvement of sleep and the enhancement of quality of life. Laryngoscope, 2010Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75789/1/20924_ftp.pd

Comparison of Caregiver- and Child-Reported Quality of Life in Children With Sleep-Disordered Breathing

Objective. Caregivers frequently report poor quality of life(QOL) in children with sleep-disordered breathing (SDB).Our objective is to assess the correlation between care-giver- and child-reported QOL in children with mild SDBand identify factors associated with differences between caregiver and child report. Study Design. Analysis of baseline data from a multi-institutional randomized trialSetting. Pediatric Adenotonsillectomy Trial for Snoring, where children with mild SDB (obstructive apnea-hypopnea index\3) were randomized to observation or adenotonsillectomy. Methods. The Pediatric Quality of Life Inventory (Peds QL)assessed baseline global QOL in participating children 5 to12 years old and their caregivers. Caregiver and child scores were compared. Multivariable regression assessed whether clinical factors were associated with differences between caregiver and child report. Results. Peds QL scores were available for 309 families (mean child age, 7.0 years). The mean caregiver-reported PedsQLscore was higher at 75.2 (indicating better QOL) than the mean child-reported score of 67.9 (P \ .001). The agreement between caregiver and child total Peds QL scores was poor, with intraclass correlation coefficients of 0.03 (95%CI, –0.09 to 0.15) for children 5 to 7 years old and 0.21(95% CI, 0.03-0.38) for children 8 to 12 years old. Higher child age and health literacy were associated with closer agreement between caregiver and child report. Conclusion. Caregiver- and child-reported global QOL in children with SDB was weakly correlated, more so for young children. In pediatric SDB, child-perceived QOL may be poorer than that reported by caregivers. Further research is needed to assess whether similar trends exist for disease-specific QOL metrics

Sleep-Disordered Breathing in Michigan: A Practice Pattern Survey

Objectives: This survey sought to determine whether self-professed sleep specialists in the State of Michigan show practice variations in the diagnosis and management of sleep-disordered breathing (SDB), and whether such variations occur between pulmonologists and neurologists. Methods: Questionnaires on practice volume and patterns during the prior 12 months were mailed to physician members of the Michigan Sleep Disorders Association ( n = 119); 67 were completed and returned. Results: Respondents reported that they personally saw a median of 8 new patients each week for suspected SDB; estimates were that 86% of these patients were eventually confirmed to have SDB. Most patients (82%) had laboratory-based polysomnography after an initial clinic evaluation, and most (69%) of those treated for SDB received continuous positive airway pressure. However, practice patterns differed substantially among respondents, even when the analysis was limited to the 42 who reported board certification by the American Board of Sleep Medicine. For example, among all surveyed practices the likelihood that suspected SDB would be evaluated with a split-night diagnostic and treatment polysomnogram varied from 0 to 90%. The likelihood of SDB treatment with bilevel positive airway pressure varied from 0 to 50%, with automatically titrating devices from 0 to 100%, with surgery from 0 to 100% (0 to 50% among certified practitioners), and with oral appliances from 0 to 20%. The practice patterns of pulmonologists and neurologists did not differ significantly. Conclusion: Approaches to SDB vary widely in Michigan, though not according to clinician background in pulmonary medicine or neurology. A patient’s experience, in both assessment and treatment, could differ substantially based on which clinician is consulted.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47959/1/11325_2003_Article_95.pd

Do respiratory cycle-related EEG changes or arousals from sleep predict neurobehavioral deficits and response to adenotonsillectomy in children?

Study Objectives: Pediatric obstructive sleep apnea (OSA) is associated with hyperactive behavior, cognitive deficits, psychiatric morbidity, and sleepiness, but objective polysomnographic measures of OSA presence or severity among children scheduled for adenotonsillectomy have not explained why. To assess whether sleep fragmentation might explain neurobehavioral outcomes, we prospectively assessed the predictive value of standard arousals and also respiratory cycle-related EEG changes (RCREC), thought to refl ect inspiratory microarousals. Methods: Washtenaw County Adenotonsillectomy Cohort II participants included children (ages 3-12 years) scheduled for adenotonsillectomy, for any clinical indication. At enrollment and again 7.2 ± 0.9 (SD) months later, children had polysomnography, a multiple sleep latency test, parent-completed behavioral rating scales, cognitive testing, and psychiatric evaluation. The RCREC were computed as previously described for delta, theta, alpha, sigma, and beta EEG frequency bands. Results: Participants included 133 children, 109 with OSA (apnea-hypopnea index [AHI] ≥ 1.5, mean 8.3 ± 10.6) and 24 without OSA (AHI 0.9 ± 0.3). At baseline, the arousal index and RCREC showed no consistent, significant associations with neurobehavioral morbidities, among all subjects or the 109 with OSA. At follow-up, the arousal index, RCREC, and neurobehavioral measures all tended to improve, but neither baseline measure of sleep fragmentation effectively predicted outcomes (all p \u3e 0.05, with only scattered exceptions, among all subjects or those with OSA). Conclusion: Sleep fragmentation, as refl ected by standard arousals or by RCREC, appears unlikely to explain neurobehavioral morbidity among children who undergo adenotonsillectomy. Clinical Trial Registration: ClinicalTrials.gov, ID: NCT00233194

Do Respiratory Cycle-Related EEG Changes or Arousals from Sleep Predict Neurobehavioral Deficits and Response to Adenotonsillectomy in Children?

STUDY OBJECTIVES: Pediatric obstructive sleep apnea (OSA) is associated with hyperactive behavior, cognitive deficits, psychiatric morbidity, and sleepiness, but objective polysomnographic measures of OSA presence or severity among children scheduled for adenotonsillectomy have not explained why. To assess whether sleep fragmentation might explain neurobehavioral outcomes, we prospectively assessed the predictive value of standard arousals and also respiratory cycle-related EEG changes (RCREC), thought to reflect inspiratory microarousals. METHODS: Washtenaw County Adenotonsillectomy Cohort II participants included children (ages 3-12 years) scheduled for adenotonsillectomy, for any clinical indication. At enrollment and again 7.2 ± 0.9 (SD) months later, children had polysomnography, a multiple sleep latency test, parent-completed behavioral rating scales, cognitive testing, and psychiatric evaluation. The RCREC were computed as previously described for delta, theta, alpha, sigma, and beta EEG frequency bands. RESULTS: Participants included 133 children, 109 with OSA (apnea-hypopnea index [AHI] ≥ 1.5, mean 8.3 ± 10.6) and 24 without OSA (AHI 0.9 ± 0.3). At baseline, the arousal index and RCREC showed no consistent, significant associations with neurobehavioral morbidities, among all subjects or the 109 with OSA. At follow-up, the arousal index, RCREC, and neurobehavioral measures all tended to improve, but neither baseline measure of sleep fragmentation effectively predicted outcomes (all p > 0.05, with only scattered exceptions, among all subjects or those with OSA). CONCLUSION: Sleep fragmentation, as reflected by standard arousals or by RCREC, appears unlikely to explain neurobehavioral morbidity among children who undergo adenotonsillectomy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT00233194 CITATION: Chervin RD, Garetz SL, Ruzicka DL, Hodges EK, Giordani BJ, Dillon JE, Felt BT, Hoban TF, Guire KE, O'Brien LM, Burns JW. Do respiratory cycle-related EEG changes or arousals from sleep predict neurobehavioral deficits and response to adenotonsillectomy in children?. J Clin Sleep Med 2014;10(8):903-911