title: Preclinical and clinical studies of unrelieved aural fullness following intratympanic gentamicin injection in patients with intractable Ménière's disease.
abstract: OBJECTIVE
  To clarify whether gentamicin affects vestibular dark cells in guinea pigs and relieves patients of aural fullness with intractable Ménière's disease following intratympanic administration.
  
  
  METHODS
  Purified gentamicin-Texas Red (GTTR) was injected intratympanically in guinea pigs that were sacrificed at 1, 3, 7, 14 and 28 days. GTTR uptake was examined in hair cells, and transitional cells and dark cells in vestibular end-organs were examined. Specific attention was paid to its distribution in dark cells under confocal microscopy, and the ultrastructure of dark cells using electron microscopy, following intratympanic injection.
  
  
  RESULTS
  Dark cells in the semicircular canals showed weak GTTR uptake at 1, 3, 7, 14 and 28 days after intratympanic injection, with no significant differences at various time points after injection. However, the adjacent transitional cells demonstrated intense GTTR uptake that was retained for at least 28 days. Ultrastructural studies demonstrated negligible characteristics associated with apoptosis or necrosis in these dark cells. The tight junctions between dark cells showed no signs of disruption at 7 or 28 days after injection.
  
  
  CONCLUSIONS
  Intratympanic gentamicin has little direct impact on vestibular dark cells.
  
  
  METHODS
  A modified low-dose titration intratympanic approach was used in 29 patients with intractable vertigo and the clinical outcomes were followed. Aural fullness following intratympanic gentamicin injection was not relieved based on our subjective scales, demonstrated by no statistically significant difference between preinjection (4.16 ± 3.08) and postinjection (3.58 ± 2.93; p > 0.05) aural fullness scores. Vertigo control was achieved in 88% of patients, with hearing deterioration identified in 16% of patients. Intratympanic gentamicin administration might not lead to relief of aural fullness in patients with intractable vertigo, although it can achieve a high vertigo control rate with some cochleotoxicity.
authors.affiliation: Department of Otology and Skull Base Surgery, Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhai
authors.forename: Ru
authors.initials: R
authors.lastname: Zhang
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.forename: Peter S
authors.initials: PS
authors.lastname: Steyger
authors.forename: Chun-Fu
authors.initials: CF
authors.lastname: Dai
mesh_terms: D000328:Adult; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage / Q000627:therapeutic use*; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D008575:Meniere Disease / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome; D014432:Tympanic Membrane / Q000187:drug effects* / Q000503:physiopathology; D014717:Vertigo / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins