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Edward A Neuwelt - One of the best experts on this subject based on the ideXlab platform.
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early changes in auditory function as a result of platinum chemotherapy use of extended high frequency audiometry and evoked distortion product otoacoustic emissions
Journal of Clinical Oncology, 2007Co-Authors: Kristin Knight, Dale F Kraemer, Christiane Winter, Edward A NeuweltAbstract:Purpose The objective is to describe progressive changes in hearing and cochlear function in children and adolescents treated with platinum-based chemotherapy and to begin preliminary evaluation of the feasibility of extended high-frequency audiometry and distortion product otoacoustic emissions for Ototoxicity monitoring in children. Patients and Methods Baseline and serial measurement of conventional pure-tone audiometry (0.5 to 8 kHz) and evoked distortion product otoacoustic emissions (DPOAEs) were conducted for 32 patients age 8 months to 20 years who were treated with cisplatin and/or carboplatin chemotherapy. Seventeen children also had baseline and serial measurement of extended high-frequency (EHF) audiometry (9 to 16 kHz). Audiologic data were analyzed to determine the incidence of Ototoxicity using the American Speech-Language-Hearing Association criteria, and the relationships between the different measures of Ototoxicity. Results Of the 32 children, 20 (62.5%) acquired bilateral Ototoxicity i...
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Ototoxicity in children receiving platinum chemotherapy underestimating a commonly occurring toxicity that may influence academic and social development
Journal of Clinical Oncology, 2005Co-Authors: Kristin Knight, Dale F Kraemer, Edward A NeuweltAbstract:Purpose To describe the frequency and severity of Ototoxicity in a series of pediatric patients treated with platinum-based chemotherapy. Patients and Methods Serial audiologic evaluations were conducted for 67 patients aged 8 months to 23 years who received platinum-based chemotherapy. Audiologic data was analyzed to determine time to hearing-loss using American Speech-Language-Hearing Association (ASHA) criteria, and the effects of treatment and patient characteristics on the incidence and severity of Ototoxicity. Results Bilateral decreases in hearing were seen in 61% of patients (median time to hearing loss, 135 days). Children treated for medulloblastoma, osteosarcoma, and neuroblastoma had greater incidence and severity of hearing loss. Agreement between the usually reported National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) and ASHA criteria was inadequate. Conclusion Traditional reporting of toxicity data (CTCAE) has under-reported Ototoxicity and minimized the signif...
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delayed sodium thiosulfate as an otoprotectant against carboplatin induced hearing loss in patients with malignant brain tumors
Clinical Cancer Research, 2001Co-Authors: Nancy D Doolittle, Leslie L Muldoon, Robert E Brummett, Dale F Kraemer, Rose Marie Tyson, Cynthia Lacy, Joseph S Bubalo, Michael Heinrich, James A Henry, Edward A NeuweltAbstract:Carboplatin is effective in the treatment of malignant brain tumors. However, when administered in conjunction with osmotic opening of the blood-brain barrier (BBB), carboplatin is ototoxic. The purpose of this study was to determine whether delayed administration of sodium thiosulfate (STS), given after BBB closure, provided protection against carboplatin Ototoxicity. Patients underwent monthly treatment with intra-arterial carboplatin (200 mg/m2/day x 2) in conjunction with osmotic opening of the BBB, for up to 1 year. Audiological assessment was conducted at baseline and within 24 h before each monthly treatment. STS was administered i.v. as one (20 g/m2) or two (20 g/m2 and 16 g/m2) 15-min doses, depending on baseline hearing status. The initial group received the first STS dose 2 h (or 2 and 6 h) after carboplatin (STS2) and a subsequent group received STS 4 h (or 4 and 8 h) after carboplatin (STS4). Audiological data were compared with a historical comparison group (HCG) treated with carboplatin without STS. Spearman correlation coefficients comparing STS 2 (n = 24), STS4 (n = 17), and HCG (n = 19) indicated significantly lower rates of Ototoxicity with increased delay in STS (P = 0.0006). On the basis of the analysis of hearing levels, there were significant differences among the two STS groups and HCG at 8000 Hz (P = 0.0010) and at 4000 Hz (P = 0.0075). The log-rank test for time to Ototoxicity indicated a significant difference between STS4 and HCG (P = 0.0018). Delayed STS was effective in protecting against carboplatin-induced hearing loss. STS delayed to 4 h after carboplatin significantly decreased time to development of Ototoxicity and rate of Ototoxicity when compared with HCG.
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delayed administration of sodium thiosulfate in animal models reduces platinum Ototoxicity without reduction of antitumor activity
Clinical Cancer Research, 2000Co-Authors: Leslie L Muldoon, Michael A Pagel, Robert A Kroll, Robert E Brummett, Nancy D Doolittle, Eleanor G Zuhowski, Merrill J Egorin, Edward A NeuweltAbstract:Platinum-based chemotherapeutic agents, such as carboplatin and cisplatin, are effective against many human tumors, but their use may be limited by a high incidence of Ototoxicity. Delayed administration of the chemoprotective agent sodium thiosulfate (STS) reduces the Ototoxicity of carboplatin in a guinea-pig model, when given up to 8 h after the chemotherapy, and also reduces hearing loss in patients given carboplatin with osmotic blood-brain barrier opening for treatment of brain tumors. We tested whether STS, given at times that achieved otoprotection, could impact the chemotherapeutic efficacy of carboplatin. The impact of STS was evaluated by measuring the onset of growth of LX-1 human small cell lung carcinoma s.c. xenografts in the nude rat. When STS was administered as two boluses, 2 and 6 h after treatment with carboplatin and etoposide, there was a decrease in the time to tumor progression. In contrast, when STS administration was delayed until 8 h after carboplatin/etoposide, there was no reduction in the antitumor cytotoxicity of the chemotherapy. STS infusion did not significantly affect ultrafilterable platinum pharmacokinetics in the guinea pig. To explore the potential wider applicability of STS, in a pilot study we tested its efficacy against cisplatin Ototoxicity. Delayed administration of STS, 2 h after cisplatin, was protective against cisplatin-induced Ototoxicity in the guinea pig model, as determined by electrophysiological measures. On the basis of these data, we suggest that delayed administration of STS may provide a mechanism to reduce the Ototoxicity caused by administration of carboplatin or cisplatin for both central nervous system and systemic cancer chemotherapy.
Brian W. Blakley - One of the best experts on this subject based on the ideXlab platform.
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systematic review of ototoxic pre surgical antiseptic preparations what is the evidence
Journal of Otolaryngology-head & Neck Surgery, 2018Co-Authors: Shubhi Singh, Brian W. BlakleyAbstract:There is uncertainty regarding the safety of surgical antiseptic preparations in the ear. A systematic review of the literature was conducted to assess the evidence regarding Ototoxicity of surgical antiseptic preparations. A literature search was conducted using the PRISMA methods. Key words included “Ototoxicity” “hearing loss”, “antiseptic”, “surgical preparation”, “tympanoplasty”, “vestibular dysfunction”, “chlorhexidine”, “iodine”, “povidone”, “ethanol”, and “hydrogen peroxide” using Medline, Embase, Cochrane Library, Scopus and Web of Science. We included peer-reviewed papers that 1) objectively measured Ototoxicity in humans or animals through hearing, vestibular function or histologic examination, 2) studied topically applied surgical antiseptic preparations, 3) were either in English or had an English abstract. We excluded papers that were 1) in vitro studies, 2) ear trauma studies, 3) studies of ototoxic ear drops intended for therapy, or 4) case reports. Studies included in the final review were screened using the PRISMA method. Current systematic review registration number pending: 83,675. Fifty-six papers were identified as using PRISMA criteria. After applying our exclusion criteria, 13 papers met overall study criteria. Of these, six papers reported Ototoxicity of iodine based solutions, five papers reported Ototoxicity of chlorhexidine and ethanol and two papers assessed hydrogen peroxide. All papers reviewed were animal studies. Iodine based solutions show least harm overall, while chlorhexidine and high concentrations of alcohol based solutions showed most harm. The evidence on hydrogen based solutions was inconclusive. The overall evidence for anyone antiseptic solution is weak. There is some evidence that iodine, chlorhexidine, hydrogen peroxide and alcohol based antiseptics have Ototoxicity. Conclusive evidence for human Ototoxicity from any solution is not strong.
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Systematic review of ototoxic pre-surgical antiseptic preparations – what is the evidence?
'Springer Science and Business Media LLC', 2018Co-Authors: Shubhi Singh, Brian W. BlakleyAbstract:Abstract Objective There is uncertainty regarding the safety of surgical antiseptic preparations in the ear. A systematic review of the literature was conducted to assess the evidence regarding Ototoxicity of surgical antiseptic preparations. Methods A literature search was conducted using the PRISMA methods. Key words included “Ototoxicity” “hearing loss”, “antiseptic”, “surgical preparation”, “tympanoplasty”, “vestibular dysfunction”, “chlorhexidine”, “iodine”, “povidone”, “ethanol”, and “hydrogen peroxide” using Medline, Embase, Cochrane Library, Scopus and Web of Science. We included peer-reviewed papers that 1) objectively measured Ototoxicity in humans or animals through hearing, vestibular function or histologic examination, 2) studied topically applied surgical antiseptic preparations, 3) were either in English or had an English abstract. We excluded papers that were 1) in vitro studies, 2) ear trauma studies, 3) studies of ototoxic ear drops intended for therapy, or 4) case reports. Studies included in the final review were screened using the PRISMA method. Current systematic review registration number pending: 83,675. Results Fifty-six papers were identified as using PRISMA criteria. After applying our exclusion criteria, 13 papers met overall study criteria. Of these, six papers reported Ototoxicity of iodine based solutions, five papers reported Ototoxicity of chlorhexidine and ethanol and two papers assessed hydrogen peroxide. All papers reviewed were animal studies. Iodine based solutions show least harm overall, while chlorhexidine and high concentrations of alcohol based solutions showed most harm. The evidence on hydrogen based solutions was inconclusive. Conclusions The overall evidence for anyone antiseptic solution is weak. There is some evidence that iodine, chlorhexidine, hydrogen peroxide and alcohol based antiseptics have Ototoxicity. Conclusive evidence for human Ototoxicity from any solution is not strong
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WR-2721 (Amifostine) Ameliorates Cisplatin-Induced Hearing Loss But Causes Neurotoxicity In Hamsters: Dose-Dependent Effects
Journal of the Association for Research in Otolaryngology, 2004Co-Authors: Michael W. Church, Brian W. Blakley, Don L. Burgio, Anil K. GuptaAbstract:Chemoprotective agents reduce the toxic side effects of chemotherapy agents such as cisplatin. The conventional belief is that the chemoprotective agent WR-2721 (Amifostine), while protecting against most cisplatin-induced side effects, does not protect against cisplatin-induced Ototoxicity (i.e., hearing loss). There is no knowledge, however, about the efficacy of high doses of WR-2721 (WR) in possibly protecting against cisplatin-induced Ototoxicity. Thus, the dose-dependent effects of WR in possibly ameliorating cisplatin-induced Ototoxicity were investigated. Hamsters were given a series of 5 cisplatin injections (3 mg/kg/injection once every other day, i.p.) either alone or in combination with 18, 40, 80, or 400 mg/kg/injection of the rescue agent WR ( n = 5 or 10/group). Other groups received either 80 mg/kg/injection WR alone ( n = 5) or were untreated ( n = 14). Ototoxicity was assessed by auditory brain stem responses (ABR). WR provided dose-dependent rescue from cisplatin’s Ototoxicity with no protection at the low dose of 18 mg/kg, moderate protection at 40 mg/kg, and nearly complete protection at 80 and 400 mg/kg. However, WR doses of 40 mg/kg or higher caused neurotoxicity as evidenced by prolongations in the ABR’s interpeak latencies. Thus, high doses of WR provided the beneficial effect of protecting against cisplatin-induced Ototoxicity, but had the harmful side effect of neurotoxicity. Previous failures to find chemoprotection from cisplatin-induced Ototoxicity were likely due to the use of WR doses that were too small. The clinical implications of the beneficial and harmful effects of high doses of WR are discussed.
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the comparative effects of sodium thiosulfate diethyldithiocarbamate fosfomycin and wr 2721 on ameliorating cisplatin induced Ototoxicity
Hearing Research, 1995Co-Authors: Michael W. Church, Brian W. Blakley, James A Kaltenbach, Don L. BurgioAbstract:Abstract The efficacies of four agents in ameliorating cisplatin-induced Ototoxicity were investigated. Hamsters were given a series of 5 cisplatin injections (3 mg/kg/injection once every other day, i.p.) either alone or in combination with 1600 mg/kg/injection sodium thiosulfate (STS), 300 mg/kg/injection diethyldithiocarbamate (DDTC), 18 mg/kg/injection WR-2721, or 300 mg/kg/injection fosfomycin (n = 10/group). Ototoxicity was assessed electrophysiologically by auditory brainstem responses (ABRs) and anatomically by cochlear histology. The greatest auditory protection was given by STS, followed by DDTC. WR-2721 and fosfomycin did not provide any protection. All of the animals in the STS and DDTC groups survived, while some fatalities occurred in the fosfomycin, WR-2721, and cisplatin-only groups. Thus, the agents that were protective against atotoxicity were also protective against mortality. The ABRs also provided evidence of cisplatin-induced neuropathy. In summary, STS and DDTC hold promise for ameliorating the ototoxic effects of cisplatin chemotherapy and the hamster proved to be an excellent model of cisplatin Ototoxicity.
Don L. Burgio - One of the best experts on this subject based on the ideXlab platform.
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WR-2721 (Amifostine) Ameliorates Cisplatin-Induced Hearing Loss But Causes Neurotoxicity In Hamsters: Dose-Dependent Effects
Journal of the Association for Research in Otolaryngology, 2004Co-Authors: Michael W. Church, Brian W. Blakley, Don L. Burgio, Anil K. GuptaAbstract:Chemoprotective agents reduce the toxic side effects of chemotherapy agents such as cisplatin. The conventional belief is that the chemoprotective agent WR-2721 (Amifostine), while protecting against most cisplatin-induced side effects, does not protect against cisplatin-induced Ototoxicity (i.e., hearing loss). There is no knowledge, however, about the efficacy of high doses of WR-2721 (WR) in possibly protecting against cisplatin-induced Ototoxicity. Thus, the dose-dependent effects of WR in possibly ameliorating cisplatin-induced Ototoxicity were investigated. Hamsters were given a series of 5 cisplatin injections (3 mg/kg/injection once every other day, i.p.) either alone or in combination with 18, 40, 80, or 400 mg/kg/injection of the rescue agent WR ( n = 5 or 10/group). Other groups received either 80 mg/kg/injection WR alone ( n = 5) or were untreated ( n = 14). Ototoxicity was assessed by auditory brain stem responses (ABR). WR provided dose-dependent rescue from cisplatin’s Ototoxicity with no protection at the low dose of 18 mg/kg, moderate protection at 40 mg/kg, and nearly complete protection at 80 and 400 mg/kg. However, WR doses of 40 mg/kg or higher caused neurotoxicity as evidenced by prolongations in the ABR’s interpeak latencies. Thus, high doses of WR provided the beneficial effect of protecting against cisplatin-induced Ototoxicity, but had the harmful side effect of neurotoxicity. Previous failures to find chemoprotection from cisplatin-induced Ototoxicity were likely due to the use of WR doses that were too small. The clinical implications of the beneficial and harmful effects of high doses of WR are discussed.
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the comparative effects of sodium thiosulfate diethyldithiocarbamate fosfomycin and wr 2721 on ameliorating cisplatin induced Ototoxicity
Hearing Research, 1995Co-Authors: Michael W. Church, Brian W. Blakley, James A Kaltenbach, Don L. BurgioAbstract:Abstract The efficacies of four agents in ameliorating cisplatin-induced Ototoxicity were investigated. Hamsters were given a series of 5 cisplatin injections (3 mg/kg/injection once every other day, i.p.) either alone or in combination with 1600 mg/kg/injection sodium thiosulfate (STS), 300 mg/kg/injection diethyldithiocarbamate (DDTC), 18 mg/kg/injection WR-2721, or 300 mg/kg/injection fosfomycin (n = 10/group). Ototoxicity was assessed electrophysiologically by auditory brainstem responses (ABRs) and anatomically by cochlear histology. The greatest auditory protection was given by STS, followed by DDTC. WR-2721 and fosfomycin did not provide any protection. All of the animals in the STS and DDTC groups survived, while some fatalities occurred in the fosfomycin, WR-2721, and cisplatin-only groups. Thus, the agents that were protective against atotoxicity were also protective against mortality. The ABRs also provided evidence of cisplatin-induced neuropathy. In summary, STS and DDTC hold promise for ameliorating the ototoxic effects of cisplatin chemotherapy and the hamster proved to be an excellent model of cisplatin Ototoxicity.
Michael W. Church - One of the best experts on this subject based on the ideXlab platform.
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WR-2721 (Amifostine) Ameliorates Cisplatin-Induced Hearing Loss But Causes Neurotoxicity In Hamsters: Dose-Dependent Effects
Journal of the Association for Research in Otolaryngology, 2004Co-Authors: Michael W. Church, Brian W. Blakley, Don L. Burgio, Anil K. GuptaAbstract:Chemoprotective agents reduce the toxic side effects of chemotherapy agents such as cisplatin. The conventional belief is that the chemoprotective agent WR-2721 (Amifostine), while protecting against most cisplatin-induced side effects, does not protect against cisplatin-induced Ototoxicity (i.e., hearing loss). There is no knowledge, however, about the efficacy of high doses of WR-2721 (WR) in possibly protecting against cisplatin-induced Ototoxicity. Thus, the dose-dependent effects of WR in possibly ameliorating cisplatin-induced Ototoxicity were investigated. Hamsters were given a series of 5 cisplatin injections (3 mg/kg/injection once every other day, i.p.) either alone or in combination with 18, 40, 80, or 400 mg/kg/injection of the rescue agent WR ( n = 5 or 10/group). Other groups received either 80 mg/kg/injection WR alone ( n = 5) or were untreated ( n = 14). Ototoxicity was assessed by auditory brain stem responses (ABR). WR provided dose-dependent rescue from cisplatin’s Ototoxicity with no protection at the low dose of 18 mg/kg, moderate protection at 40 mg/kg, and nearly complete protection at 80 and 400 mg/kg. However, WR doses of 40 mg/kg or higher caused neurotoxicity as evidenced by prolongations in the ABR’s interpeak latencies. Thus, high doses of WR provided the beneficial effect of protecting against cisplatin-induced Ototoxicity, but had the harmful side effect of neurotoxicity. Previous failures to find chemoprotection from cisplatin-induced Ototoxicity were likely due to the use of WR doses that were too small. The clinical implications of the beneficial and harmful effects of high doses of WR are discussed.
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the comparative effects of sodium thiosulfate diethyldithiocarbamate fosfomycin and wr 2721 on ameliorating cisplatin induced Ototoxicity
Hearing Research, 1995Co-Authors: Michael W. Church, Brian W. Blakley, James A Kaltenbach, Don L. BurgioAbstract:Abstract The efficacies of four agents in ameliorating cisplatin-induced Ototoxicity were investigated. Hamsters were given a series of 5 cisplatin injections (3 mg/kg/injection once every other day, i.p.) either alone or in combination with 1600 mg/kg/injection sodium thiosulfate (STS), 300 mg/kg/injection diethyldithiocarbamate (DDTC), 18 mg/kg/injection WR-2721, or 300 mg/kg/injection fosfomycin (n = 10/group). Ototoxicity was assessed electrophysiologically by auditory brainstem responses (ABRs) and anatomically by cochlear histology. The greatest auditory protection was given by STS, followed by DDTC. WR-2721 and fosfomycin did not provide any protection. All of the animals in the STS and DDTC groups survived, while some fatalities occurred in the fosfomycin, WR-2721, and cisplatin-only groups. Thus, the agents that were protective against atotoxicity were also protective against mortality. The ABRs also provided evidence of cisplatin-induced neuropathy. In summary, STS and DDTC hold promise for ameliorating the ototoxic effects of cisplatin chemotherapy and the hamster proved to be an excellent model of cisplatin Ototoxicity.
Anil K. Gupta - One of the best experts on this subject based on the ideXlab platform.
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WR-2721 (Amifostine) Ameliorates Cisplatin-Induced Hearing Loss But Causes Neurotoxicity In Hamsters: Dose-Dependent Effects
Journal of the Association for Research in Otolaryngology, 2004Co-Authors: Michael W. Church, Brian W. Blakley, Don L. Burgio, Anil K. GuptaAbstract:Chemoprotective agents reduce the toxic side effects of chemotherapy agents such as cisplatin. The conventional belief is that the chemoprotective agent WR-2721 (Amifostine), while protecting against most cisplatin-induced side effects, does not protect against cisplatin-induced Ototoxicity (i.e., hearing loss). There is no knowledge, however, about the efficacy of high doses of WR-2721 (WR) in possibly protecting against cisplatin-induced Ototoxicity. Thus, the dose-dependent effects of WR in possibly ameliorating cisplatin-induced Ototoxicity were investigated. Hamsters were given a series of 5 cisplatin injections (3 mg/kg/injection once every other day, i.p.) either alone or in combination with 18, 40, 80, or 400 mg/kg/injection of the rescue agent WR ( n = 5 or 10/group). Other groups received either 80 mg/kg/injection WR alone ( n = 5) or were untreated ( n = 14). Ototoxicity was assessed by auditory brain stem responses (ABR). WR provided dose-dependent rescue from cisplatin’s Ototoxicity with no protection at the low dose of 18 mg/kg, moderate protection at 40 mg/kg, and nearly complete protection at 80 and 400 mg/kg. However, WR doses of 40 mg/kg or higher caused neurotoxicity as evidenced by prolongations in the ABR’s interpeak latencies. Thus, high doses of WR provided the beneficial effect of protecting against cisplatin-induced Ototoxicity, but had the harmful side effect of neurotoxicity. Previous failures to find chemoprotection from cisplatin-induced Ototoxicity were likely due to the use of WR doses that were too small. The clinical implications of the beneficial and harmful effects of high doses of WR are discussed.
