Autologous intratympanic blood patch for presumed perilymphatic fistulas.

OBJECTIVE: To assess an alternative to bed rest and surgery for suspected perilymphatic fistulas using intratympanic blood injections. METHOD: A review was conducted of patients' history, physical and audiometric data, before and after treatment by intratympanic blood injections performed from 2009 to 2015. RESULTS: Twelve ears were identified, with trauma associated with air travel, water sports or nose blowing. Ten of these cases had hearing loss, six had vestibular symptoms. Four cases had audiological and vestibular symptoms, two had vestibular symptoms only, and six had audiological symptoms only. Time-to-treat varied from 1 day to 30 days. Magnetic resonance imaging scans were obtained for five cases. Ten cases received steroids. Six out of seven cases showed improvement of hearing loss. Five cases showed positive fistula test results, four with documented resolution. Seven cases had full resolution of all symptoms, four had near-full resolution and one had no improvement. CONCLUSION: Intratympanic blood injections offer an effective alternative to conservative or surgical therapy. Advantages include sooner time-to-treat, lower financial costs and decreased psychosocial burdens. It allows a more flexible and liberal use of a potential definite treatment for perilymphatic fistula.

Cochlear function and transgene expression in the guinea pig cochlea, using adenovirus- and adeno-associated virus-directed gene transfer.

Development of a viral vector that can infect hair cells of the cochlea without producing viral-associated ototoxic effects is crucial for utilizing gene replacement therapy as a treatment for certain forms of hereditary deafness. In the present study, cochlear function was monitored using distortion-product otoacoustic emissions (DPOAEs) in guinea pigs that received infusions of either (E1(-), E3(-)) adenovirus, or adeno-associated virus (AAV), directly into the scala tympani. Replication-deficient (E1(-), E3(-)) adenovirus-directed gene transfer, using the cytomegalovirus (CMV) promoter, drove transgene expression to inner hair cells and pillar cells of the cochlea. AAV transduction was tested with several promoters, such as platelet-derived growth factor (PDGF), neuron-specific enolase (NSE), and elongation factor 1alpha (EF-1alpha) promoters; which drove transgene expression to cochlear blood vessels, nerve fibers, and certain spiral limbus cells, respectively. AAV transgene expression was visualized by green fluorescent protein immunostaining. Immunocytochemistry to heparan sulfate confirmed the absence of proteoglycans in guinea pig hair cells, indicating that the receptor for AAV was not present on these cells. However, the heparan sulfate proteoglycan expression pattern mimicked the AAV transduction pattern. An overall finding was that cochlear function was not altered throughout the infection period using AAV titers as high as 5 x 10(8) IP/infused cochlea. In contrast, cochlear function was severely compromised by 8 days postinfection with adenoviral titers of 5 x 10(8) PFU/infused cochlea, and outer hair cells were eliminated. Thus, cochlear hair cells are amenable to in vivo gene transfer using a replication-deficient (E1(-), E3(-)) adenovirus. However, replication-defective or gutted adenovirus vectors must be employed to overcome the ototoxic effects of (E1(-), E3(-)) adenovirus vectors.