The Experts below are selected from a list of 279 Experts worldwide ranked by ideXlab platform
Elizabeth M Keithley - One of the best experts on this subject based on the ideXlab platform.
-
am 111 reduces hearing loss in a guinea pig model of acute Labyrinthitis
Laryngoscope, 2007Co-Authors: Gregory C Barkdull, Jeffrey P Harris, Yannick Hondarrague, Thomas Meyer, Elizabeth M KeithleyAbstract:Objectives/Hypothesis: This study investigated the otoprotective properties of AM-111, an inhibitor of c-Jun N-terminal kinase-mediated apoptosis and inflammation. Study Design: A controlled, prospective animal study using a guinea pig model of acute Labyrinthitis. Methods: Acute Labyrinthitis was generated by injection of antigen into the scala tympani of sensitized guinea pigs. Treatment groups received 100 μL of AM-111 at concentrations of 100 μmol/L, 10 μmol/L, and 1 μmol/L in a hyaluronic acid gel formulation delivered over the round window niche within 1 hour of antigen challenge. Cochlear function was monitored over 21 days with serial auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) measurements followed by histologic analysis. Results: The ABR results on day 21 demonstrated that untreated control ears for acute Labyrinthitis had a mean hearing loss (HL) of 68 ± 12 dB. In contrast, ears treated with AM-111 (100 μmol/L) had a mean HL of 39 ± 31 dB. These two groups were statistically different (one-way analysis of variance, P = .03). Secondary outcomes, including DPOAE shift, inner hair cell survival, inflammatory cell counts, and spiral ganglion density, were also statistically significant in favor of an otoprotective effect of AM-111. Lower doses of AM-111 did not produce a statistically significant reduction in HL over controls. Conclusion: AM-111 delivered over the round window membrane in a 100 μL hyaluronic acid formulation at a 100 μmol/L concentration immediately after induction of acute Labyrinthitis in the guinea pig cochlea protects hearing, reduces hair cell loss, and reduces the number of inflammatory cells at 21 days after treatment.
-
AM‐111 Reduces Hearing Loss in a Guinea Pig Model of Acute Labyrinthitis
Laryngoscope, 2007Co-Authors: Gregory C Barkdull, Jeffrey P Harris, Yannick Hondarrague, Thomas Meyer, Elizabeth M KeithleyAbstract:Objectives/Hypothesis: This study investigated the otoprotective properties of AM-111, an inhibitor of c-Jun N-terminal kinase-mediated apoptosis and inflammation. Study Design: A controlled, prospective animal study using a guinea pig model of acute Labyrinthitis. Methods: Acute Labyrinthitis was generated by injection of antigen into the scala tympani of sensitized guinea pigs. Treatment groups received 100 μL of AM-111 at concentrations of 100 μmol/L, 10 μmol/L, and 1 μmol/L in a hyaluronic acid gel formulation delivered over the round window niche within 1 hour of antigen challenge. Cochlear function was monitored over 21 days with serial auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) measurements followed by histologic analysis. Results: The ABR results on day 21 demonstrated that untreated control ears for acute Labyrinthitis had a mean hearing loss (HL) of 68 ± 12 dB. In contrast, ears treated with AM-111 (100 μmol/L) had a mean HL of 39 ± 31 dB. These two groups were statistically different (one-way analysis of variance, P = .03). Secondary outcomes, including DPOAE shift, inner hair cell survival, inflammatory cell counts, and spiral ganglion density, were also statistically significant in favor of an otoprotective effect of AM-111. Lower doses of AM-111 did not produce a statistically significant reduction in HL over controls. Conclusion: AM-111 delivered over the round window membrane in a 100 μL hyaluronic acid formulation at a 100 μmol/L concentration immediately after induction of acute Labyrinthitis in the guinea pig cochlea protects hearing, reduces hair cell loss, and reduces the number of inflammatory cells at 21 days after treatment.
-
immunologic responses in experimental cytomegalovirus Labyrinthitis
American Journal of Otolaryngology, 1990Co-Authors: Jeffrey P Harris, Elizabeth M KeithleyAbstract:Abstract To better understand the pathogenesis of cytomegalovirus Labyrinthitis, a guinea pig model was created. Following inoculation at several sites (cardiac, perilymph, and endolymphatic sac) in both seronegative and seropositive animals, the immunologic, histologic, and electrophysiologic responses were measured. Seronegative animals uniformly showed progressive hearing loss with marked inflammation and degeneration of neural elements. In animals inoculated into the endolymphatic sac, an associated endolymphatic hydrops developed in addition to deafness. Seropositivity protected the hearing, but endolymphatic sac inoculations resulted in mild hydrops due to local inflammation that was devoid of evidence of viral replication. The question of whether hearing loss was attributable to local inflammatory responses rather than the cytopathic effects of the virus was then examined. To test this hypothesis, animals were immunosuppressed with cyclophosphamide prior to intracochlear inoculation of cytomegalovirus. The immunosuppressed animals showed significantly better hearing than the controls, and this correlated directly with the degree of cellular infiltration of the scala tympani. These studies confirm the importance of host immune responses in the pathogenesis of hearing loss due to cytomegalovirus.
Robert J Ruben - One of the best experts on this subject based on the ideXlab platform.
-
acute streptococcus pneumoniae meningogenic Labyrinthitis an experimental guinea pig model and literature review
Archives of Otolaryngology-head & Neck Surgery, 1994Co-Authors: Andrew L Blank, Gustave L Davis, Thomas R Vandewater, Robert J RubenAbstract:Objective: To create an experimental model of Streptococcus pneumoniae type 3 meningogenic Labyrinthitis (a leading cause of deafness) similar to that in human disease. Design: Cohort analytic study of guinea pigs that were inoculated intrathecally with varying dilutions of S pneumoniae type 3; the progress of the disease was compared with that in saline solution–inoculated control animals. Subjects: Healthy adult Hartley guinea pigs without clinical evidence of middle ear disease that were conveniently sampled. Interventions: Intrathecal inoculation of 10 4 to 10 6 colony-forming units of S pneumoniae type 3 into 13 guinea pigs; signs and symptoms of meningitis/Labyrinthitis were observed for 15 days and compared with those in two saline solution–inoculated control animals. Main Outcome Measures: Morbidity—Labyrinthitis, meningitis; end point—death. Results: The 10 4 to 10 6 colony-forming units of S pneumoniae type 3 caused inflammation that extended from the meninges to the inner ear via the cochlear aqueduct within 3 days after inoculation; a dose of 10 7 killed animals within 12 hours after inoculation. Three of five animals that were inoculated with a 10 6 dose died 3 days after inoculation; two of three animals that were inoculated with a 10 5 dose lived to 15 days after inoculation. One of two animals that were inoculated with a 10 4 dose did not become infected. Inflammation extended to the middle ear by round-window destruction. Reactive bone formation simulated labyrinthine osteosclerosis. Observers assessed histologic slides "blindly." Conclusion: Guinea pigs can survive 15 days after intrathecal inoculation of a 10 5 dose, with morphologic features similar to those in human disease. This is an effective model for this study of meningogenic Labyrinthitis. (Arch Otolaryngol Head Neck Surg. 1994;120:1342-1346)
Hilary A Brodie - One of the best experts on this subject based on the ideXlab platform.
-
effects of depletion of complement in the development of Labyrinthitis ossificans
Laryngoscope, 1999Co-Authors: Gregory M Desautel, Hilary A BrodieAbstract:Hypothesis: Labyrinthitis ossificans results in part from the intense inflammatory response to Streptococcus pneumoniae cell wall components. Depletion of complement in Mongolian gerbils following induction of meningitis will reduce the degree of inflammation and subsequent cochlear fibrosis. Study Design: Random prospective study. Histological evaluations were performed with the researcher blinded to the experimental group Methods:S pneumoniae meningitis was induced in 10 control and 18 experimental Mongolian gerbils with an intrathecal injection of the bacteria. Both groups of animals received treatment with penicillin. The experimental group was also treated with cobra venom factor to deplete complement in the animals. Three months after the induction of meningitis, the animals' temporal bones were harvested for histological evaluation. Results: The decomplemented animals developed significantly less intracochlear fibrosis (P < .01). The mortality rate for the experimental group was 11% compared with 40% in the control group (P = .14). Conclusions: Reduction of the intense inflammatory response to the S pneumoniae cell wall components in suppurative Labyrinthitis secondary to bacterial meningitis reduced the degree of Labyrinthitis ossificans.
-
chronology of Labyrinthitis ossificans induced by streptococcus pneumoniae meningitis
Laryngoscope, 1999Co-Authors: Vishad Nabili, Hilary A Brodie, Nikita I Neverov, Steven P TinlingAbstract:Objective: Labyrinthitis ossificans consists of novel osteogenesis that fills the normally patent cochlear and vestibular lumen as an end-stage sequelae to various pathologies. This study was designed to establish the sequence of events and chronology of the osteoneogenesis and calcification. Study Design: A prospective randomized double-blind study. Methods: By using serial application of different colored fluorochromes, which deposit in newly forming bone, the timing of bone deposition and bone remodeling can be established. Labyrinthitis ossificans was induced in she groups (n = 5) of gerbils by an intrathecal injection of live Streptococcus pneumoniae. Group 1 received no fluorochrome labels, group 2 received one label, group 3 received three labels, and groups 4, 5, and 6 received four labels. The temporal bones were harvested after 2 weeks (group 1), 1 month (group 2), 3 months (group 3), 4 months (group 4), 6 months (group 5), and 12 months (group 6). Results: Sixteen of the 25 animals that received labels developed ossification, demonstrated with fluorescent microscopy. In the animals that developed Labyrinthitis ossificans, newly formed disorganized bone began calcifying as early as 3 weeks (label 1) after S pneumoniae injection. Osteoneogenesis continued as evidenced by the presence of the other labels when first applied at 6 weeks (label 2), and 10 weeks (label 3). Ossification, calcification, and remodeling proceeded through a 12-month course, wherein a reduction of labels was present at 6 months and total disappearance by 12 months. Conclusions: The use of fluorescent stains in this animal model provides a means to establish a timeline of the ossification seen in Labyrinthitis ossificans. Key Words: Ossified cochlea, Labyrinthitis, deafness, cochlear implant, meningitis.
-
Induction of Labyrinthitis ossificans after pneumococcal meningitis: An animal model ☆ ☆☆ ★ ★★
Otolaryngology-Head and Neck Surgery, 1998Co-Authors: Hilary A Brodie, Teresa C Thompson, Lara VassilianAbstract:Newly formed disorganized bone fills the open spaces within the otic capsule in various pathologic conditions, resulting in Labyrinthitis ossificans. The pathologic mechanisms of this disease remain poorly understood. To better study the sequence of events and contributing mechanisms involved in Labyrinthitis ossificans, an animal model was developed. Three groups of Mongolian gerbils received either an intralabyrinthine injection of normal saline solution (group 1) or Streptococcus pneumoniae polysaccharide capsule antigens (groups 2 and 3). The temporal bones were harvested after 3 months and serially sectioned. None of the eight control animals (group 1), which received intralabyrinthine injections of normal saline solution, had any histologic changes in their temporal bones. Nine of the surviving 19 animals in groups 2 and 3 had fibrosis or evidence of early ossification. A fourth group of Mongolian gerbils received two intrathecal injections of live S. pneumoniae organisms. The temporal bones were harvested after 3 months and serially sectioned. Fourteen of the surviving 15 animals had fibrosis or ossification or both. This animal model will provide a method for study of the mechanisms of Labyrinthitis ossificans. (Otolaryngol Head Neck Surg 1998;118:15-21.)
-
induction of Labyrinthitis ossificans after pneumococcal meningitis an animal model
Otolaryngology-Head and Neck Surgery, 1998Co-Authors: Hilary A Brodie, Teresa C Thompson, Lara VassilianAbstract:Newly formed disorganized bone fills the open spaces within the otic capsule in various pathologic conditions, resulting in Labyrinthitis ossificans. The pathologic mechanisms of this disease remain poorly understood. To better study the sequence of events and contributing mechanisms involved in Labyrinthitis ossificans, an animal model was developed. Three groups of Mongolian gerbils received either an intralabyrinthine injection of normal saline solution (group 1) or Streptococcus pneumoniae polysaccharide capsule antigens (groups 2 and 3). The temporal bones were harvested after 3 months and serially sectioned. None of the eight control animals (group 1), which received intralabyrinthine injections of normal saline solution, had any histologic changes in their temporal bones. Nine of the surviving 19 animals in groups 2 and 3 had fibrosis or evidence of early ossification. A fourth group of Mongolian gerbils received two intrathecal injections of live S. pneumoniae organisms. The temporal bones were harvested after 3 months and serially sectioned. Fourteen of the surviving 15 animals had fibrosis or ossification or both. This animal model will provide a method for study of the mechanisms of Labyrinthitis ossificans. (Otolaryngol Head Neck Surg 1998;118:15-21.)
Takeshi Kurata - One of the best experts on this subject based on the ideXlab platform.
-
pathogenesis of cytomegalovirus associated Labyrinthitis in a guinea pig model
Microbes and Infection, 2007Co-Authors: Harutaka Katano, Yuko Sato, Yoshihiro Tsutsui, Tetsutaro Sata, Akihiko Maeda, Naoki Nozawa, Naoki Inoue, Yasuya Nomura, Takeshi KurataAbstract:Cytomegalovirus infects fetuses through the placenta, resulting in various congenital disorders in newborns, including hearing loss. We developed a monoclonal antibody to guinea pig cytomegalovirus (GPCMV) that was available for immunohistochemistry, and investigated the expression of the GPCMV antigen in animal models of direct and congenital infections. Injection of GPCMV, directly to the inner ear, increased the sound pressure level and resulted in Labyrinthitis with severe inflammation. Immunohistochemistry detected GPCMV-infected cells mainly in the scala tympani, scala vestibule and spinal ganglion, but rarely in the cochlear duct. Injection of GPCMV to 5-week pregnant guinea pigs resulted in severe Labyrinthitis in fetuses. Immunohistochemistry detected GPCMV-infected cells in the perilymph area and spinal ganglion, but not in the endolymph area, including hair cells. These data suggest that the virus spreads via the perilymph and neural routes in the inner ear of both models of direct and congenital infections.
Jeffrey P Harris - One of the best experts on this subject based on the ideXlab platform.
-
am 111 reduces hearing loss in a guinea pig model of acute Labyrinthitis
Laryngoscope, 2007Co-Authors: Gregory C Barkdull, Jeffrey P Harris, Yannick Hondarrague, Thomas Meyer, Elizabeth M KeithleyAbstract:Objectives/Hypothesis: This study investigated the otoprotective properties of AM-111, an inhibitor of c-Jun N-terminal kinase-mediated apoptosis and inflammation. Study Design: A controlled, prospective animal study using a guinea pig model of acute Labyrinthitis. Methods: Acute Labyrinthitis was generated by injection of antigen into the scala tympani of sensitized guinea pigs. Treatment groups received 100 μL of AM-111 at concentrations of 100 μmol/L, 10 μmol/L, and 1 μmol/L in a hyaluronic acid gel formulation delivered over the round window niche within 1 hour of antigen challenge. Cochlear function was monitored over 21 days with serial auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) measurements followed by histologic analysis. Results: The ABR results on day 21 demonstrated that untreated control ears for acute Labyrinthitis had a mean hearing loss (HL) of 68 ± 12 dB. In contrast, ears treated with AM-111 (100 μmol/L) had a mean HL of 39 ± 31 dB. These two groups were statistically different (one-way analysis of variance, P = .03). Secondary outcomes, including DPOAE shift, inner hair cell survival, inflammatory cell counts, and spiral ganglion density, were also statistically significant in favor of an otoprotective effect of AM-111. Lower doses of AM-111 did not produce a statistically significant reduction in HL over controls. Conclusion: AM-111 delivered over the round window membrane in a 100 μL hyaluronic acid formulation at a 100 μmol/L concentration immediately after induction of acute Labyrinthitis in the guinea pig cochlea protects hearing, reduces hair cell loss, and reduces the number of inflammatory cells at 21 days after treatment.
-
AM‐111 Reduces Hearing Loss in a Guinea Pig Model of Acute Labyrinthitis
Laryngoscope, 2007Co-Authors: Gregory C Barkdull, Jeffrey P Harris, Yannick Hondarrague, Thomas Meyer, Elizabeth M KeithleyAbstract:Objectives/Hypothesis: This study investigated the otoprotective properties of AM-111, an inhibitor of c-Jun N-terminal kinase-mediated apoptosis and inflammation. Study Design: A controlled, prospective animal study using a guinea pig model of acute Labyrinthitis. Methods: Acute Labyrinthitis was generated by injection of antigen into the scala tympani of sensitized guinea pigs. Treatment groups received 100 μL of AM-111 at concentrations of 100 μmol/L, 10 μmol/L, and 1 μmol/L in a hyaluronic acid gel formulation delivered over the round window niche within 1 hour of antigen challenge. Cochlear function was monitored over 21 days with serial auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) measurements followed by histologic analysis. Results: The ABR results on day 21 demonstrated that untreated control ears for acute Labyrinthitis had a mean hearing loss (HL) of 68 ± 12 dB. In contrast, ears treated with AM-111 (100 μmol/L) had a mean HL of 39 ± 31 dB. These two groups were statistically different (one-way analysis of variance, P = .03). Secondary outcomes, including DPOAE shift, inner hair cell survival, inflammatory cell counts, and spiral ganglion density, were also statistically significant in favor of an otoprotective effect of AM-111. Lower doses of AM-111 did not produce a statistically significant reduction in HL over controls. Conclusion: AM-111 delivered over the round window membrane in a 100 μL hyaluronic acid formulation at a 100 μmol/L concentration immediately after induction of acute Labyrinthitis in the guinea pig cochlea protects hearing, reduces hair cell loss, and reduces the number of inflammatory cells at 21 days after treatment.
-
spontaneous remission in experimental autoimmune Labyrinthitis
Annals of Otology Rhinology and Laryngology, 1992Co-Authors: Shigeharu Yamanobe, Jeffrey P HarrisAbstract:We investigated the time course of hearing impairment and cellular infiltration into the inner ear after systemic sensitization of guinea pigs with a single intradermal injection of bovine inner ear antigen (IEAg) in complete Freund's adjuvant (CFA). Lymphocytes and polymorphonucleocytes appeared mainly in the scala tympani on days 7 to 14, and in addition there was thickening and cellular infiltration of the round window membrane at day 14. These cellular infiltrations resolved after day 28. The auditory brain stem response thresholds from IEAg-sensitized animals were significantly elevated after day 7. Some sensitized animals (n = 5) had spontaneous remissions after day 28; however, the hearing thresholds did not completely recover. These results demonstrate that experimental autoimmune Labyrinthitis can be induced by a single inoculation of IEAg-CFA and that remission, as evidenced by clearing of the cochlear cellular infiltration and improved hearing thresholds, can occur spontaneously.
-
immunologic responses in experimental cytomegalovirus Labyrinthitis
American Journal of Otolaryngology, 1990Co-Authors: Jeffrey P Harris, Elizabeth M KeithleyAbstract:Abstract To better understand the pathogenesis of cytomegalovirus Labyrinthitis, a guinea pig model was created. Following inoculation at several sites (cardiac, perilymph, and endolymphatic sac) in both seronegative and seropositive animals, the immunologic, histologic, and electrophysiologic responses were measured. Seronegative animals uniformly showed progressive hearing loss with marked inflammation and degeneration of neural elements. In animals inoculated into the endolymphatic sac, an associated endolymphatic hydrops developed in addition to deafness. Seropositivity protected the hearing, but endolymphatic sac inoculations resulted in mild hydrops due to local inflammation that was devoid of evidence of viral replication. The question of whether hearing loss was attributable to local inflammatory responses rather than the cytopathic effects of the virus was then examined. To test this hypothesis, animals were immunosuppressed with cyclophosphamide prior to intracochlear inoculation of cytomegalovirus. The immunosuppressed animals showed significantly better hearing than the controls, and this correlated directly with the degree of cellular infiltration of the scala tympani. These studies confirm the importance of host immune responses in the pathogenesis of hearing loss due to cytomegalovirus.
