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The aminoglycosides are broad-spectrum antibiotics especially effective against many strains of gramnegative bacteria. Since streptomycin was used for tuberculosis treatment, the toxic side effects of such antibiotics were identified. The kidney and the inner ear are affected. The nephrotoxicity is usually reversible, while the chronic ototoxicity is irreversible. Within the inner ear, it is the cochlear and vestibular sensory epithelium that is damaged. A toxic mechanism in which an interference with mitochondrial protein synthesis is central has been inferred. During the last fifty years, risk factors for aminoglycoside-induced-ototoxicity have been identified, including a genetically transmitted hypersensitivity to the ototoxic effect. Although several strategies to prevent the damage have been proposed, today it is not rare that patients suffer permanent loss of hearing and loss of balance due to aminoglycoside toxicity. This review gives a brief background of aminoglycoside ototoxicity, some strategies to prevent it, and the therapeutic use of the vestibulo-toxic effect.
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A review of the ototoxic effects of cis-diamminedichloroplatinum (II) (cis-platinum) is presented. Cis-platinum impairs auditory function by preferentially destroying the outer hair cells of the organ of Corti in the basal turn of the cochlea. Hair cell loss in the vestibular labyrinth has also been observed. Auditory sequelae include tinnitus and/or hearing loss, both of which are usually reversible. The incidence of tinnitus in clinical studies is about 7%. Hearing loss is noted in about 69% of patients, usually in the 4,000-8,000 Hz range, although speech frequencies (1,000-4,000 Hz) may occasionally become involved. The hearing losses range from 15-65 dB, and only 7% of all patients complain of difficulty in understanding speech. A direct dose effect relationship does not appear to exist for either tinnitus or hearing loss. The onset of hearing loss, however, appears to be related to cumulative levels of the drug. Vestibular dysfunction has also been shown to be a side effect of therapy. Case management strategies are discussed.
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Abstract This review introduces the pathology of aminoglycoside antibiotic and the cisplatin chemotherapy classes of drugs, discusses oxidative stress in the inner ear as a primary trigger for cell damage, and delineates the ensuing cell death pathways. Among potentially ototoxic (damaging the inner ear) therapeutics, the platinum‐based anticancer drugs and the aminoglycoside antibiotics are of critical clinical importance. Both drugs cause sensorineural hearing loss in patients, a side effect that can be reproduced in experimental animals. Hearing loss is reflected primarily in damage to outer hair cells, beginning in the basal turn of the cochlea. In addition, aminoglycosides might affect the vestibular system while cisplatin seems to have a much lower likelihood to do so. Finally, based on an understanding the mechanisms of ototoxicity pharmaceutical ways of protection of the cochlea are presented. Anat Rec, 2012. © 2012 Wiley Periodicals, Inc.
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We are concerned to correct a common misconception—namely, that ototoxicity is synonymous with deafness. Except for the rare cases of mitochondrial mutations discussed by Bitner-Glindzicz and Rahman, vestibular function is much more sensitive to aminoglycosides than hearing function.1 Ninety per cent of patients with gentamicin associated vestibular loss will not be deaf.2 …
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Conclusions: Our data indicate that SSSR and SSSR + FGLM-NH2 protect sensory hair cells against neomycin-induced death in the vestibular epithelium. In addition, the results show that SSSR and FGLM-NH2 can be used as protective molecules against aminoglycoside ototoxicity. Objectives: This study investigated the role of the peptides SSSR and SSSR + FGLM-NH2 in mammalian vestibular hair cell death induced by aminoglycoside. Methods: Cultured utricles from mature CBA/N mice were used in this study. The cultured utricles were assigned to five groups (control group, neomycin group, neomycin + SSSR group, neomycin + FGLM-NH2 group, and neomycin + SSSR + FGLM-NH2 group). Aat 24 h after exposure to neomycin, the hair cells were labeled immunohistochemically, and the rate of survival of vestibular hair cells was evaluated using a fluorescence microscope. Results: The rate of survival of vestibular hair cells was significantly higher in the neomycin + SSSR and neomycin + SSSR + FGLM-NH2 groups than in the neomycin group. The results suggest that SSSR could protect hair cells against aminoglycoside ototoxicity.
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To characterize the audiological and vestibular changes associated with a mitochondrial DNA mutation in an Arab-Israeli family and in other families with mitochondrial predisposition to aminoglycoside-induced hearing loss.Evaluation of audiological (pure tone thresholds, speech reception thresholds, speech discrimination, tympanometry, acoustic reflex thresholds, tone decay, and auditory brain-stem evoked response recording) and vestibular (complete history, physical examination, and 2-channel electronystagmography) systems. In 5 patients, structural evaluation of the inner ear was done by magnetic resonance imaging.Fifteen members of an Arab-Israeli family, and 1 Chinese woman with the same mitochondrial DNA mutation who experienced hearing loss after short-term exposure to streptomycin.Most of the patients had a profound hearing loss due to cochlear involvement. The hearing loss usually was not accompanied by notable peripheral vestibular dysfunction. In the patient with severe hearing loss after exposure to aminoglycoside, the vestibular function was completely normal.In most of the Arab-Israeli patients with congenital deafness, the vestibular system function was normal, in contrast to the frequency of vestibular abnormality among deaf children, which was described in the literature. This may be related to genetic predisposition to aminoglycoside-induced deafness.
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It has long been known that the major irreversible toxicity of aminoglycosides is ototoxicity. Among them, streptomycin and gentamicin are primarily vestibulotoxic, whereas amikacin, neomycin, dihydrosterptomycin, and kanamicin are primarily cochleotoxic. Cochlear damage can produce permanent hearing loss, and damage to the vestibular apparatus results in dizziness, ataxia, and/or nystagmus. Aminoglycosides appear to generate free radicals within the inner ear, with subsequent permanent damage to sensory cells and neurons, resulting in permanent hearing loss. Two mutations in the mitochondrial 12S ribosomal RNA gene have been previously reported to predispose carriers to aminoglycoside-induced ototoxicity. As aminoglycosides are indispensable agents both in the treatment of infections and Meniere's disease, a great effort has been made to develop strategies to prevent aminoglycoside ototoxicity. Anti-free radical agents, such as salicylate, have been shown to attenuate the ototoxic effects of aminoglycosides. In this paper, incidence, predisposition, mechanism, and prevention of aminoglycoside-induced ototoxicity is discussed in the light of literature data.
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You have accessThe ASHA LeaderFeature1 Feb 2007The Impact of Ototoxicity on the Vestibular SystemInner Ear Damage can be a Side Effect of Some Medications Jaynee Handelsman Jaynee Handelsman Google Scholar More articles by this author https://doi.org/10.1044/leader.FTR1.12022007.4 SectionsAbout ToolsAdd to favorites ShareFacebookTwitterLinked In Ototoxicity—damage to the inner ear from exposure to toxic agents—is a serious problem and an unfortunate side effect of the use of certain medications that treat serious illnesses, including infection and cancer. Numerous agents are known to be toxic to the delicate structures of the inner ear, including aminoglycoside antibiotics and some chemotherapy agents. Although ample evidence of ototoxicity appears in the literature, and protocols exist for monitoring the effects of toxic agents on hearing, less is known about their impact on the vestibular system. Little information exists about the prevalence of vestibular toxicity among patients who are exposed to toxic agents, and no commonly accepted protocols are in place for monitoring vestibular system function during exposure. Clinical Features of Vestibular Toxicity Oscillopsia and unsteadiness when standing and walking are the two most commonly reported and disturbing symptoms associated with bilateral loss of vestibular system function. Oscillopsia is the perception that viewed stationary objects or surroundings move coincident with head movement. The object movement is in the same plane and in the opposite direction of the head movement. In a classic paper describing his personal experiences following a long course of streptomycin for treatment of knee sepsis (J.C., 1952), the author provided a clear picture of the devastating impact of oscillopsia: the head movement from his pulse was sufficient to prevent him from reading without head stabilization. He also reported severe unsteadiness when attempting to stand and walk. J.C.’s symptoms progressed rapidly over the course of two to three days following the cessation of treatment. It is important to note that vestibular ototoxicity can present suddenly or gradually over an extended period of time. Additionally, the vestibular loss resulting from systemic use of potentially toxic agents is often—but not always—bilateral. In fact, intravenous aminoglycoside use can result in unilateral vestibular loss, an asymmetric bilateral loss, or asymmetric bilateral reduction in function. Patients with asymmetric bilateral vestibular loss experience symptoms consistent with both unilateral and bilateral vestibular paresis. Affected patients might report oscillopsia and unsteadiness characteristic of bilateral loss of function, as well as positional vertigo typically associated with an imbalance between the peripheral vestibular systems. Clinical Implications The use of aminoglycosides in industrialized societies has steadily declined over the past 20 years. However, their use is prevalent in the treatment of tuberculosis; enterococcal, mycobacterial, and severe gram-negative bacterial infections; and cystic fibrosis (CF) (Schacht, 2007). At the Vestibular Testing Center at the University of Michigan, our most recent experiences have been with individuals receiving treatment for pulmonary exacerbations secondary to CF. In a recently initiated clinical protocol for the individuals in our pediatric CF program, we are evaluating hearing and vestibular system function at the beginning of each course of antibiotic treatment and at the three-month follow-up pulmonology visit for each patient. Since patients typically are in the hospital for two to three days at the onset of treatment, after which treatment continues at home for three to four weeks, it is unrealistic to monitor function at shorter intervals. Our goal is to learn more about the incidence of ototoxicity in this patient population, as well as to determine how best to measure incremental changes in function over time. The ultimate desired outcome is to investigate the use of and efficacy of protective agents in limiting the toxic impact of these drugs on hearing and vestibular function. In an effort to summarize vestibular function in our patient group, we devised a method for describing vestibular loss using three categories. The first category includes evidence of peripheral vestibular system involvement that is non specific (e.g. spontaneous, positional, and/or post-head shaking nystagmus and increased phase leads, abnormal time constants, or asymmetries in rotational testing); the second includes evidence of unilateral vestibular loss (e.g. caloric asymmetries and any combination of findings from the first category); and the third category includes evidence of bilateral vestibular loss (e.g. bilaterally reduced caloric results, gain reductions in rotational chair testing, abnormal dynamic visual acuity). To date, we have completed vestibular testing on 23 patients with CF, ranging in age from 10–56 years. Some were referred because of symptoms of vestibular ototoxicity prior to the initiation of this monitoring program; the remainder were asymptomatic and were seen because of this clinical initiative. Preliminary findings are compelling. Only two individuals tested thus far have vestibular test results that are completely normal, and one of the two has never had aminoglycosides. Of the remaining patients, almost half have evidence of bilateral vestibular loss, two have evidence of a unilateral vestibular loss, and each of the others has non-lateralizing evidence of peripheral vestibular system involvement. Three individuals have had repeat testing. Two displayed evidence of bilateral involvement at the time of both tests, and the other moved from the first to the third category following her most recent course of antibiotics. The sample population to date is skewed because some patients were initially referred because of symptoms and because the clinical initiative is relatively new; however, the overwhelming majority of the population displays vestibular system involvement. Two additional findings highlight the need for vestibular testing in this population. First, only four of the 23 patients, all of whom are adults, have documented hearing loss. Second, although most of the patients report no current or past problems with dizziness or balance, they may show evidence of oscillopsia on dynamic visual acuity testing or abnormal postural control test results. Monitoring Vestibular Function The importance of monitoring vestibular system function when potentially toxic agents are used is clear from our limited data in evaluating patients who have been treated with aminoglycoside antibiotics for pulmonary exacerbations secondary to CF. While monitoring hearing also is warranted, the relative paucity of hearing loss in the presence of vestibular system involvement suggests that a monitoring program that includes only hearing is insufficient. Additionally, since patients do not seem to appreciate the impact of the vestibular loss initially, asking patients to notify health care providers at the onset of symptoms is inadequate. It has been our experience that many physicians have been unaware of the role of the vestibular system on maintenance of clear vision during head movement and on postural control. While they may appreciate the potential impact of toxic agents on hearing, many do not understand the risk to the vestibular system, nor do they appreciate the devastating side effects of vestibular loss. For these reasons, it is critical that audiologists and speech-language pathologists take a greater role in educating our colleagues within and outside the professions. For more information about Division 6, go to Division 6’s Web site. References J. C. (1952). Living without a balance mechanism.New England Journal of Medicine, 246, 458–460. CrossrefGoogle Scholar Schacht J. (2007). Aminoglycoside Antibiotics.In Campbell K.C. M. (Ed.) Pharmacology and Ototoxicity for Audiologists (pp.163–176). New York: Thomson Delmar Learning. Google Scholar Author Notes Jaynee Handelsman, is assistant director, Vestibular Testing Center, Department of Otolaryngology, University of Michigan Health System, Ann Arbor. She is a member of ASHA Special Interest Division 6, Hearing and Hearing Disorders: Research and Diagnostics. Contact her at [email protected]. Advertising Disclaimer | Advertise With Us Advertising Disclaimer | Advertise With Us Additional Resources FiguresSourcesRelatedDetails Volume 12Issue 2February 2007 Get Permissions Add to your Mendeley library History Published in print: Feb 1, 2007 Metrics Downloaded 599 times Topicsasha-topicsleader_do_tagasha-article-typesCopyright & Permissions© 2007 American Speech-Language-Hearing AssociationLoading ...
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