G Bredberg

Karolinska University Hospital, Tukholma, Stockholm, Sweden

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Publications (33)29.34 Total impact

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    ABSTRACT: Based on in vitro studies, it is hypothesized that neurotrophic factor deprivation following deafferentation elicits an oxidative state change in the deafferented neuron and the formation of free radicals that then signal cell death pathways. This pathway to cell death was tested in vivo by assessing the efficacy of antioxidants (AOs) to prevent degeneration of deafferented CNVIII spiral ganglion cells (SGCs) in deafened guinea pigs. Following destruction of sensory cells, guinea pigs were treated immediately with Trolox (a water soluble vitamin E analogue)+ascorbic acid (vitamin C) administered either locally, directly in the inner ear, or systemically. Electrical auditory brainstem response (EABR) thresholds were recorded to assess nerve function and showed a large increase following deafness. In treated animals EABR thresholds decreased and surviving SGCs were increased significantly compared to untreated animals. These results indicate that a change in oxidative state following deafferentation plays a role in nerve cell death and antioxidant therapy may rescue SGCs from deafferentation-induced degeneration.
    Full-text · Article · Mar 2007 · Neurobiology of Disease
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    ABSTRACT: Benefits of cochlear prostheses for the deaf are dependent on survival and excitability of the auditory nerve. Degeneration of deafferented auditory nerve fibers is prevented and excitability maintained by immediate replacement therapy with exogenous neurotrophic factors, in vivo. It is important to know whether such interventions are effective after a delay following deafness, typical for the human situation. This study evaluated the efficacy of brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor axokine-1 analogue (CNTF Ax1) application, 2 or 6 weeks postdeafening, in preventing further degeneration and a decrease in excitability. Guinea pigs were deafened and implanted with intracochlear stimulating electrodes, a scala tympani cannula-osmotic pump system, and auditory brainstem response (ABR) recording electrodes. Subjects received BDNF + CNTF Ax1 or artificial perilymph (AP) treatment for 27 days, beginning at 2 or 6 weeks following deafening. Electrical (E) ABR thresholds increased following deafening. After 1 week, in the 2-weeks-delayed neurotrophic factor treatment group, EABR thresholds decreased relative to AP controls, which were statistically significant at 2 weeks. In the 6-week delay group, a tendency to enhanced EABR sensitivity began at 2 weeks of treatment and increased thereafter, with a significant difference between neurotrophic factor- and AP-treated groups across the treatment period. A clear, statistically significant, enhanced survival of spiral ganglion cells was seen in both neurotrophic factor treatment groups relative to AP controls. These findings demonstrate that BDNF + CNTF Ax1 can act to delay or possibly even reverse degenerative and, likely apoptotic, processes well after they have been activated. These survival factors can rescue cells from death and enhance electrical excitability, even during the period of degeneration and cell loss when the spiral ganglion cell population is reduced by >50% (6 weeks). It is noteworthy that this same degree of ganglion cell loss, secondary to receptor damage, is typically observed after a period equivalent to some years of deafness in humans.
    No preview · Article · Oct 2004 · Journal of Neuroscience Research
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    ABSTRACT: This study describes open-set speech recognition in cochlear implant subjects with ossified cochleae and compares it to a control group with open cochleae. Twenty-one postlingually deafened adults with a Med-El Combi 40/40+GB split- electrode implant were matched to patients using a Med-El cochlear implant with a standard electrode. Speech recognition was assessed over an 18-month period. Split- electrode patients improved significantly over time, but their scores were significantly lower and increased significantly slower than those of controls. Of 14 patients with a duration of deafness less than 20 years, average sentence test scores were 50%, and average monosyllabic word test scores were 31%. This study provides evidence that cochlear implantation is beneficial to patients with ossified cochleae, but early implantation is advisable.
    No preview · Article · Jun 2003 · Cochlear Implants International
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    ABSTRACT: Pneumococcal otogenic meningitis is a rare postsurgical complication that can develop following stapedectomy or after cochlear implantation. The bacterial infection can be fatal in some instances. A recent increase in the incidence of otogenic meningitis among cochlear implant wearers is of concern. The majority of meningitis cases are associated with a 2-component electrode manufactured by one cochlear implant company. The device with the added 'positioner' component has been withdrawn from the market (FDA Public Health Web Notification: Cochlear Implant Recipients may be at Greater Risk for Meningitis, Updated: August 29, 2002, www.fda.gov/cdrh/safety/cochlear.html). Not all cases have been subsequent to otitis media and symptoms have developed from less than 24 h up to a few years after implantation. The purpose of this paper is to review and discuss the pathogenesis, pathology/bacteriology and to elaborate on some clinical features of otogenic meningitis in implanted children and adults. Essential aspects of surgery, electrode design, and cochleostomy seal are discussed. Conclusions are drawn from the available data and recommendations are made for good practice in cochlear implantation and follow-up.
    No preview · Article · Nov 2002 · ORL
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    ABSTRACT: A primary cause of deafness is damage of receptor cells in the inner ear. Clinically, it has been demonstrated that effective functionality can be provided by electrical stimulation of the auditory nerve, thus bypassing damaged receptor cells. However, subsequent to sensory cell loss there is a secondary degeneration of the afferent nerve fibers, resulting in reduced effectiveness of such cochlear prostheses. The effects of neurotrophic factors were tested in a guinea pig cochlear prosthesis model. After chemical deafening to mimic the clinical situation, the neurotrophic factors brain-derived neurotrophic factor and an analogue of ciliary neurotrophic factor were infused directly into the cochlea of the inner ear for 26 days by using an osmotic pump system. An electrode introduced into the cochlea was used to elicit auditory responses just as in patients implanted with cochlear prostheses. Intervention with brain-derived neurotrophic factor and the ciliary neurotrophic factor analogue not only increased the survival of auditory spiral ganglion neurons, but significantly enhanced the functional responsiveness of the auditory system as measured by using electrically evoked auditory brainstem responses. This demonstration that neurotrophin intervention enhances threshold sensitivity within the auditory system will have great clinical importance for the treatment of deaf patients with cochlear prostheses. The findings have direct implications for the enhancement of responsiveness in deafferented peripheral nerves.
    Full-text · Article · Mar 2002 · Proceedings of the National Academy of Sciences
  • Christina Stjernholm · Catharina Muren · Göran Bredberg
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    ABSTRACT: Children with CHARGE have multiple disabilities. Impairments of vision and hearing, balance problems and facial palsy are common. Few reports have dealt with their radiological temporal bone changes and none with cochlear implant surgery. The pre-operative temporal bone computed tomography (CT) and surgical findings of one child with CHARGE and one with a CHARGE-like condition who have received cochlear implants are reported. The findings include absent semicircular canals, narrow orifice for the cochlear nerve, and abnormalities of the oval and round window, the facial canal and the ossicles. CT can be used as a diagnostic tool as these combinations of temporal bone changes are extremely rare in other materials. Cochlear implants may help these often very isolated children to communicate. Copyright © 2001 Whurr Publishers Ltd.
    No preview · Article · Mar 2001 · Cochlear Implants International
  • C. Stjernholm · C. Muren · G. Bredberg
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    ABSTRACT: The process of implantation is fraught with expectations. To ensure continued parental commitment and motivation, it is important to have insight into expectations and the factors that influence them. This study investigated the expectations of mothers whose children used a cochlear implant, and the influence that satisfaction with outcomes had on expectations over time. A qualitative research methodology was used. In-depth interviews were undertaken with eight mothers of pre-school children. The data were analysed according to a detailed qualitative analysis procedure. Findings revealed changing expectations over time, based either on hope or knowledge. Many variables influenced expectations, including response to deafness, anxiety and performance outcomes. Theoretical and clinical implications include the dynamic nature of expectations and the impact these have on counselling.
    No preview · Article · Jan 2001
  • Y Hinohira · K Gyo · N Yanagihara · G Bredberg · E Alsterborg
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    ABSTRACT: The effects of obliteration of the mastoid cavity on the growth of residual cholesteatoma were histologically studied in an animal model. A dermal cyst was produced by grafting a piece of autologous auricular skin in the otic bulla of 11 guinea-pigs. Three weeks after grafting, part of the cyst wall facing the cavity was removed and the debris accumulated inside was inserted into the surrounding granulation using a micropick. This procedure simulates the growth mechanism of cholesteatoma residue which sometimes occurs after middle ear surgery in human subjects. In six animals, the bulla was then obliterated with plaster of Paris. The remaining five animals were used as controls. Animals were killed for histological study at 2, 4 or 8 weeks postoperatively. Microscopic examinations revealed that in the obliteration group, severe inflammatory reactions were induced in the otic bulla, although the graft epithelium survived there; dermal cyst reformed in only one of six animals. In the controls, cyst reformation was recognized in all animals. This indicated that severe inflammation induced by plaster prevented growth of the graft epithelium in the otic bulla.
    No preview · Article · Jan 1998 · Acta Oto-Laryngologica
  • G Linde · G Bredberg · B Lindström
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    ABSTRACT: To evaluate the effectiveness of the Nucleus 20 + 2 implant in a group of patients. Fifteen children and 11 adults who have received the Nucleus 20 + 2 implant since late 1993. The outcome in most patients has been favorable.
    No preview · Article · Dec 1997 · The American journal of otology
  • B Lindström · G Bredberg
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    ABSTRACT: To describe the use of intraoperative electrical stimulation on the stapedius reflex in children. Hospital cochlear implantation center. Eighteen children under the age of 10 years, who have undergone cochlear implantation, have been examined during surgery with the electrically elicited stapedius reflex in the monopolar stimulation mode. A stapedius reflex could visually be detected for all subjects. The responses serve to test the implant, provide guidance in avoiding overstimulation of the child when the device is switched on, and estimate the optimal C-levels.
    No preview · Article · Dec 1997 · The American journal of otology

  • No preview · Article · Dec 1997 · The American journal of otology

  • No preview · Article · Dec 1997 · The American journal of otology
  • T Kobayashi · Y Hinohira · M Hyodo · G Bredberg · E Alsterborg
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    ABSTRACT: The inner ear toxicity of ionomeric cement (Ionocem) when used as a reconstructive material in ear surgery was evaluated in 47 guinea pigs used in a morphological study. The cement was implanted on either the promontory, the round window membrane or the stapes. There was no significant hair cell loss compared with the control ear at three weeks, two months or three months after implantation. Using electrocochleography, the hearing thresholds before, and three weeks, two and three months after the implantation were compared in an additional seven animals. No evident hearing loss was observed in any animal during the study period. No morphological or functional evidence for an ototoxic effect of the ionomeric cement was found in this study.
    No preview · Article · May 1997 · Ear, nose, & throat journal
  • C Muren · G Bredberg
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    ABSTRACT: In a series of six cochlear-implant candidates, including three small children, labyrinthine ossification in various stages of development was observed at CT. In four of the candidates the ossifying process was more advanced in the semicircular canals than in the cochleae, and in two equally distributed. The ossifying process developed during a period of 4-5 months in two of the children. Asymmetry of its extension was found in four patients. The causative organisms were Hemophilus influenzae and Streptococcus pneumoniae. The radiologic assessment of cochlear-implant candidates should include the semicircular canals where the ossification may start, and herald the development of cochlear ossification.
    No preview · Article · Feb 1997 · European Radiology
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    ABSTRACT: A model of auditory performance and a model of ganglion cell survival in postlinguistically deafened adult cochlear implant users are suggested to describe the effects of aetiology, duration of deafness, age at implantation, age at onset of deafness, and duration of implant use. The models were compared with published data and a composite data set including 808 implant users. Qualitative agreement with the model of auditory performance was found. Duration of deafness had a strong negative effect on performance. Age at implantation had a slight negative effect on performance, increasing after age 60 years. Age at onset of deafness had little effect on performance up to age 60. Duration of implant use had a positive effect on performance. Aetiology had a relatively weak effect on performance.
    No preview · Article · Jan 1996 · Audiology and Neurotology
  • G Bredberg · B Lindström

    No preview · Article · Oct 1995 · The Annals of otology, rhinology & laryngology. Supplement
  • B Lindström · G Bredberg · M Vainio · G Beidestam · B Rollvén

    No preview · Article · Oct 1995 · The Annals of otology, rhinology & laryngology. Supplement
  • S A Counter · E Borg · G Bredberg · G Linde · M Vainio
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    ABSTRACT: Electromagnetically induced auditory perception was investigated in 18 deaf patients who were candidates for cochlear implants. In the extracranial magnetic stimulation (EMS) procedure, patients were stimulated with time-varying magnetic field brief pulses from a coil positioned at the i) auricle, ii) the mastoid, and iii) the temporal lobe area. EMS elicited auditory sensations in 26 ears (of 14 patients/subjects). The lowest threshold of auditory sensation (TAS) was found to be at the 20% EMS level, with a range of 20-50% of the maximum level (2.0 Tesla), and approximately equal sensitivity in each coil position. Eleven of the subjects hearing EMS-induced sound perceived changes in pitch while 6 heard "clicks" or clicks and tones. Spearman Rho correlation analysis showed a mild negative correlation between the EMS/TAS and the pre-implant FFA, best tone threshold (BTT), and direct promontorial electrical stimulation (ES) thresholds at 250 Hz and 500 Hz. No correlation was found between EMS or ES and performance on the pre-implant or post-implant psychacoustic tests (MAC VIII or 3-Digit speech tests) or the measurements of the thickness of cutaneous and osseous tissue from the stimulation sites at the mastoid and ear canal to the cochlear and 8th nerve. A fair positive correlation was found between the EMS/TAS and the post-implant (6 months) ES threshold when the electrodes allocated the 500 Hz frequency range were stimulated. A mild positive correlation between the pre-cochlear-implant promontorial electrical stimulation (ES) at 250 Hz and the four frequency tone average (FFA: 0.5, 1, 2, 4 kHz) was also found.(ABSTRACT TRUNCATED AT 250 WORDS)
    No preview · Article · Oct 1994 · Acta Oto-Laryngologica
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    ABSTRACT: A multicentre study of the inner ears of an 88-year-old patient with vertiginous spells and severe hearing loss in the left ear was performed, employing regular and block surface preparations, light and electron microscopy with qualitative and quantitative evaluation of the cochlear and vestibular nerves. There was severe hydrops of the left cochlea and saccule. Reissner's membrane extended into the vestibule and herniated into the perilymphatic space of the non-ampullated end of the horizontal canal. Furthermore, the short canal connecting the posterior ampulla with the utricle had a small, exceedingly thin balloon-like expansion. Only slight hydrops limited to the cochlea was found in the right ear. Sensorineural degeneration was much more pronounced in the left cochlea than in the right. The number of cochlear and vestibular nerve fibres was greatly reduced in the left ear where more fibres with degenerative changes were present. In both specimens the number of myelinated nerve fibres in osseous spiral lamina was smaller than that in the cochlear nerve in the internal auditory canal. Changes occurred in the endolymphatic sacs but were considered non-specific. In this case severe, apparently progressive hydrops and sensorineural degeneration, characteristic of Menière's disease, were associated with atypical onset of clinical symptoms at a late age.
    No preview · Article · Feb 1992 · Acta oto-laryngologica. Supplementum
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    ABSTRACT: A multicentre study of the inner ears of an 88-year-old patient with vertiginous spells and severe hearing loss in the left ear was performed, employing regular and block surface preparations, light and electron microscopy with qualitative and quantitative evaluation of the cochlear and vestibular nerves. There was severe hydrops of the left cochlea and saccule. Reissner's membrane extended into the vestibule and herniated into the perilymphatic space of the non-ampullated end of the horizontal canal. Furthermore, the short canal connecting the posterior ampulla with the utricle had a small, exceedingly thin balloon-like expansion. Only slight hydrops limited to the cochlea was found in the right ear. Sensorineural degeneration was much more pronounced in the left cochlea than in the right. The number of cochlear and vestibular nerve fibres was greatly reduced in the left ear where more fibres with degenerative changes were present. In both specimens the number of myelinated nerve fibres in osseous spiral lamina was smaller than that in the cochlear nerve in the internal auditory canal. Changes occurred in the endolymphatic sacs but were considered non-specific. In this case severe, apparently progressive hydrops and sensorineural degeneration, characteristic of Menièe's disease, were associated with atypical onset of clinical symptoms at a late age.
    No preview · Article · Jan 1992 · Acta Oto-Laryngologica

Publication Stats

675 Citations
29.34 Total Impact Points

Institutions

  • 2004-2007
    • Karolinska University Hospital
      Tukholma, Stockholm, Sweden
  • 2002-2003
    • Akademiska Sjukhuset
      Uppsala, Uppsala, Sweden
  • 1983-1997
    • Karolinska Institutet
      • Division of Audiology
      Сольна, Stockholm, Sweden
  • 1992
    • University of Innsbruck
      Innsbruck, Tyrol, Austria
  • 1990
    • Università degli Studi di Bari Aldo Moro
      • Dipartimento di Scienze Biomediche ed Oncologia Umana (DIMO)
      Bari, Apulia, Italy
    • KTH Royal Institute of Technology
      Tukholma, Stockholm, Sweden
  • 1987
    • Södersjukhuset
      Tukholma, Stockholm, Sweden