Biomedical subjects

Gordon B Hughes

Publications and source records attributed to Gordon B Hughes.

9 recordsLinked to original sources

PubMed2006

Increased frequencies of cochlin-specific T cells in patients with autoimmune sensorineural hearing loss.

Autoimmune sensorineural hearing loss (ASNHL) is the most common cause of sudden hearing loss in adults. Although autoimmune etiopathogenic events have long been suspected in ASNHL, inner ear-specific Ags capable of targeting T cell autoreactivity have not been identified in ASNHL. In this study, we show by ELISPOT analysis that compared with normal hearing age- and sex-matched control subjects, ASNHL patients have significantly higher frequencies of circulating T cells producing either IFN-gamma (p = 0.0001) or IL-5 (p = 0.03) in response to recombinant human cochlin, the most abundant inner ear protein. In some patients, cochlin responsiveness involved both CD4+ and CD8+ T cells whereas other patients showed cochlin responsiveness confined to CD8+ T cells. ASNHL patients also showed significantly elevated cochlin-specific serum Ab titers compared with both normal hearing age- and sex-matched control subjects and patients with noise- and/or age-related hearing loss (p < 0.05 at all dilutions tested through 1/2048). Our study is the first to show T cell responsiveness to an inner ear-specific protein in ASNHL patients, and implicates cochlin as a prominent target Ag for mediating autoimmune inner ear inflammation and hearing loss.

Aged↗

PubMed2005

Serial audiometry in a clinical trial of AIED treatment.

OBJECTIVE: We analyzed pure-tone and speech audiometric results from a prospective trial of anti-inflammatory treatment of subjects with active autoimmune inner ear disease (AIED). We sought to characterize the pattern and size of the treatment effect as reflected in clinical audiometry and to identify audiometric predictors of response to steroid treatment of AIED. SUBJECTS: Adult participants demonstrated clinically established criteria for AIED (n = 116). Eligibility required audiometric evidence of active AIED as indicated by idiopathic sensorineural hearing loss with threshold elevations within 3 months of enrollment. METHODS: We evaluated audiometric changes after 4 weeks of treatment with pharmacologic doses (60 mg/day) of prednisone. We examined the relationship between audiometric pure-tone thresholds at baseline and changes in word intelligibility score (WIS) using parametric and nonparametric analyses. Magnitudes of change were assessed using independent or paired t-tests. Separate analyses were performed on subgroups that did or did not show improved WIS score with steroid treatment. RESULTS: Overall mean pure-tone averages improved from baseline to closeout of prednisone treatment in better hearing ears from 52.4 to 48.3 dB (p < .0001). Mean WIS improved in the better ear from 71.4% to 78.1% (p < .0001). Of pure-tone measures, only the six-tone average showed significant correlation with both the absolute improvements in WIS and with the percentage change in WIS after treatment. Individual frequencies at baseline showed no significant relationship with changes in WIS score after treatment. In 69 (59.5%) of 116 subjects, WIS improved (range, 2-80%) in the better ear. In these subjects, the baseline pure-tone thresholds and pure-tone averages correlated significantly and positively with improvement in WIS. CONCLUSIONS: Steroid treatment in AIED-mediated hearing loss produce variable but significant hearing gains. Neither a focal, cochleotopic region of greatest vulnerability to AIED nor frequency-specific amenability to treatment were evident. We did observe that analysis of predictors and the degree of treatment effect vary with different approaches to measuring change in the WIS. Depending on the approach adopted, the size of the treatment effect may be greatest across intermediate hearing levels at baseline. These observations offer an audiometric database that may enable greater precision in judging clinically meaningful parameters for future studies of AIED treatment and other interventions for sensorineural hearing loss.

Adolescent↗

PubMed2004

Technical modifications of suboccipital craniectomy for prevention of postoperative headache.

A retrospective review of 53 consecutive patients who underwent a retrosigmoid vestibular nerve section (VNS) or microvascular decompression (MVD) through a modified suboccipital craniectomy with a minimum follow-up of 2 years was performed. Technical modifications to the suboccipital craniectomy included a skin incision designed to avoid the lesser and greater occipital nerves; a small, 2-cm diameter craniectomy with no intradural drilling of bone; and a simplified closure to prevent muscle adhesion to dura without the need for cranioplasty. The presence, duration, and severity of postoperative headache were the primary outcome measures. Craniectomy-related complications, operative time, and length of hospital stay were also reviewed. The incidence of postoperative headache after suboccipital craniectomy was 7.5% at 3 months (4/53), 3.8% at 1 year (2/53), and 3.8% at 2 years (2/53). Complications related to craniectomy included cerebrospinal fluid leakage (5.7%), aseptic meningitis (1.9%), and superficial wound infection (1.9%). The mean operative time was 145 and 98 minutes for VNS and MVD, respectively. The mean hospital stay was 2.2 and 3.6 days for VNS and MVD, respectively. Technical modifications of suboccipital craniectomy during retrosigmoid VNS and MVD lowered the incidence of postoperative headache and craniectomy-related complications and had no adverse effect on operative time or length of hospital stay.

Journal Article↗

PubMed2004

Intratympanic steroid treatment: a review.

OBJECTIVE: To review published literature regarding the use of intratympanic steroids in the treatment of Meniere's disease and sudden sensorineural hearing loss and to make recommendations regarding their use based on the literature review. DATA SOURCES: Literature review from 1996 to 2003, PubMed, Medline Plus, and Web of Science. STUDY SELECTION: Retrospective case series and uncontrolled prospective cohort studies were the only types of studies available for review. CONCLUSION: On the basis of the available literature, a weak recommendation is made to use intratympanic steroid treatment of sudden hearing loss if oral steroid therapy fails or is contraindicated. The available studies regarding intratympanic steroid treatment of Meniere's disease and tinnitus are inadequate to answer the question of the efficacy of this treatment for these conditions. Higher quality studies are needed.

Adrenal Cortex Hormones↗

PubMed2004

Murine autoimmune hearing loss mediated by CD4+ T cells specific for inner ear peptides.

Autoimmune sensorineural hearing loss (ASNHL) is characterized typically by bilateral, rapidly progressive hearing loss that responds therapeutically to corticosteroid treatment. Despite its name, data implicating autoimmunity in the etiopathogenesis of ASNHL have been limited, and targeted self-antigens have not been identified. In the current study we show that the inner ear-specific proteins cochlin and beta-tectorin are capable of targeting experimental autoimmune hearing loss (EAHL) in mice. Five weeks after immunization of SWXJ mice with either Coch 131-150 or beta-tectorin 71-90, auditory brainstem responses (ABR) showed significant hearing loss at all frequencies tested. Flow cytometry analysis showed that each peptide selectively activated CD4(+) T cells with a proinflammatory Th1-like phenotype. T cell mediation of EAHL was determined by showing significantly increased ABR thresholds 6 weeks after adoptive transfer of peptide-activated CD4(+) T cells into naive SWXJ recipients. Immunocytochemical analysis showed that leukocytic infiltration of inner ear tissues coincided with onset of hearing loss. Our study provides a contemporary mouse model for clarifying our understanding of ASNHL and facilitating the development of novel effective treatments for this clinical entity. Moreover, our data provide experimental confirmation that ASNHL may be a T cell-mediated organ-specific autoimmune disorder of the inner ear.

Adoptive Transfer↗

PubMed2003

Treatment of corticosteroid-responsive autoimmune inner ear disease with methotrexate: a randomized controlled trial.

CONTEXT: A number of therapies have been proposed for the long-term management of corticosteroid-responsive, rapidly progressive, bilateral sensorineural hearing loss (autoimmune inner ear disease [AIED]). Methotrexate has emerged as the benchmark agent but has not been rigorously evaluated for hearing improvement in patients with AIED. OBJECTIVE: To assess the efficacy of long-term methotrexate in maintaining hearing improvements achieved with glucocorticoid (prednisone) therapy in patients with AIED. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled trial conducted from February 3, 1998, to November 5, 2001, of 67 patients with rapidly progressive, bilateral sensorineural hearing loss at 10 tertiary care centers in the United States. INTERVENTION: Randomization to either oral methotrexate (15 to 20 mg/wk; n = 33) or placebo (n = 34), in combination with an 18-week prednisone taper. Follow-up examinations, including audiometric evaluation, were performed at 4, 8, 12, 24, 36, 48, and 52 weeks, or until hearing loss was documented. MAIN OUTCOME MEASURE: Maintenance of hearing improvement achieved from prednisone treatment. RESULTS: Sixty-seven patients (57.8%) enrolled in the prednisone challenge experienced hearing improvement. Twenty-five patients (37%) experienced hearing improvements in both ears. Of the individuals who reached study end points, 24 (80%) of 30 end points were because of measured hearing loss in the methotrexate group and 29 (93.5%) of 31 end points were because of measured hearing loss in the placebo group (P =.15). Methotrexate was no more effective than placebo in maintaining the hearing improvement achieved with prednisone treatment (hazard ratio, 1.31; 95% confidence interval, 0.79-2.17; P =.30). CONCLUSION: Methotrexate does not appear to be effective in maintaining the hearing improvement achieved with prednisone therapy in patients with AIED.

Audiometry↗

PubMed2003

Autoimmune sensorineural hearing loss: an immunologic perspective.

Autoimmune sensorineural hearing loss (ASNHL) typically produces a bilateral rapidly progressive loss of hearing that may occur suddenly. The diagnosis is made by excluding ototoxicity, systemic disease, and other factors that mimic ASNHL and by showing a therapeutic response to corticosteroid treatment. Although autoantibodies and autoreactive T cells have been implicated in the etiopathogenesis of ASNHL, several central issues remain unresolved, including the relative prominence of B cell or T cell autoimmunity in the initiation and progression of ASNHL, the identity of the putative inner ear self-antigen(s) that target ASNHL, and the development and application of immunosuppressive therapies for preventing the progressive hearing loss which may be profound and require cochlear implantation. In this review, we will examine the seminal human and animal studies that have led to our current views regarding the autoimmune etiopathogenesis of ASNHL. In addition, we will address the need for developing an inner ear-specific mouse model for ASNHL that may define the stages leading to the development of ASNHL and may also provide new diagnostic markers and help develop novel and effective treatments for preventing progressive hearing loss in ASNHL.

Animals↗

PubMed2002

Interferon-gamma production to inner ear antigens by T cells from patients with autoimmune sensorineural hearing loss.

Autoimmune sensorineural hearing loss (ASNHL) typically produces bilateral rapidly progressive loss of hearing over a few days or weeks, but may also produce sudden loss over a few hours. The diagnosis is made by excluding ototoxicity, systemic disease, and other factors that mimic ASNHL and by showing a therapeutic response to corticosteroid treatment. Antibody production and T-cell proliferative responses to inner ear antigens have been implicated in the etiopathogenesis of ASNHL. In the current study, we have extended these autoimmune investigations by determining the frequencies of inner ear specific IFN-gamma producing T cells in peripheral blood mononuclear cells (PBMC) from ASNHL patients and from age- and sex-matched control subjects. ELISPOT analysis showed that 25% of ASNHL patients have significant increased frequencies of inner ear specific IFN-gamma producing T cells in their PBMC. All control subjects were relatively unresponsive. Our results implicate inner ear specific IFN-gamma producing proinflammatory T cells in the pathogenesis of ASNHL.

Adult↗

PubMed2002

Vestibular nerve sectioning for intractable vertigo: efficacy of simplified retrosigmoid approach.

OBJECTIVE: To determine the surgical efficacy of a simplified retrosigmoid approach for vestibular nerve sectioning. STUDY DESIGN: A retrospective analysis. SETTING: Tertiary academic referral center. PATIENTS: Twenty-eight consecutive patients who underwent vestibular nerve sectioning for intractable peripheral vestibular disorders. INTERVENTION: All patients had a simplified retrosigmoid approach for vestibular nerve sectioning. MAIN OUTCOME MEASURES: Functional outcome after vestibular nerve sectioning was analyzed with respect to improvement in patient disability from vertigo and reduction in the frequency of definitive vertigo attacks. Resolution of lightheadedness provided an additional outcome measure. The incidence of surgical complications, including postoperative headache, was determined, and the operative time was reviewed. RESULTS: Twenty-six patients (92.9%) had an improved functional level postoperatively, 21 (75.0%) had excellent improvement, 4 (14.3%) had significant improvement, 1 (3.6%) had limited improvement, and 2 (7.1%) had no change. No patient was worse postoperatively. Eighteen of 23 Ménière's patients (78.3%) had complete control of definitive vertigo attacks after vestibular nerve sectioning. Improvement in lightheadedness was seen in 23 patients (82.1%), 11 (39.3%) of whom reported complete resolution. Postoperative headache developed in 1 (3.6%) patient. No patients experienced infection, facial weakness, or leakage of cerebrospinal fluid. Mild hearing deterioration was seen in 2 patients (7.1%). The mean operative time was 76.3 minutes. CONCLUSION: With excellent efficacy, short operative time, and a low incidence of postoperative hearing loss or headache, this simplified retrosigmoid technique should be considered for vestibular nerve sectioning in patients with intractable peripheral vestibular disorders.

Adult↗