PubMed HealthSearch

Biomedical subjects

R A Schindler

Publications and source records attributed to R A Schindler.

At least 19 recordsLinked to original sources

Hyaluronan synthesis in the adult guinea pig endolymphatic sac.

The endolymphatic sac is believed to play a major role in membranous labyrinth homeostasis by controlling the volume of endolymph, removing debris, and participating in the immune response of the inner ear. The endolymphatic sac is postulated to absorb endolymph and to synthesize and secrete high-molecular-weight and osmotically active glycosaminoglycans (GAGs). The present study examines the ability of in vitro adult guinea pig endolymphatic sac cells to synthesize complex proteins and polysaccharides. The intent is to characterize the nature of these compounds by studying carbon-14 (14C) glucose incorporation in tissue cultured endolymphatic sac specimens using autoradiographic and specific enzymatic digestion techniques. Our results suggest that sac cells can synthesize GAGs and proteins in vitro in proportionately larger amounts than surrounding connective tissue and dura. The principal GAG synthesized by the endolymphatic sac appears to be hyaluronan.

Amylases

Preliminary results with the Clarion cochlear implant.

A new cochlear implant has become available. This device, called the Clarion Multichannel Cochlear Implant, is the result of collaborative efforts between the University of California, San Francisco (UCSF), the Research Triangle Institute (RTI), Research Triangle Park, North Carolina, and the device manufacturer and sponsor, MiniMed Technologies of Sylmar, California. The Clarion represents a new generation of multi-programmable cochlear implant systems. Options in waveform, the stimulation mode, and the temporal distribution of the signal permit the device to be optimally customized for each individual patient. The speech coding scheme offering the greatest opportunity for speech recognition can be selected. The first Clarion recipient has recently been implanted at UCSF, initiating the Clarion's investigational clinical trials. A description of the device and preliminary patient results are presented.

Aged

Hyaluronan synthesis by in vitro cultured endolymphatic sac cells.

The endolymphatic sac (ELS) has been the subject of investigation for many years and yet its overall function remains unclear. It is believed mainly to be involved in the regulation of endolymph through fluid resorption and secretion of osmotically active substances. The present study was performed using in vitro cultured, fetal ELSs of 18 to 19 day gestational mice, to assess whether the ELS cells can synthesize the osmotically active polysaccharide, hyaluronan (HA). The ELS and portions of the membranous labyrinth were dissected from whole otocyst specimens and placed in 14C glucose-enhanced tissue culture media. A light microscopic (LM), autoradiographic study was performed to assess whether 14C glucose could be incorporated by the tissue into HA. Both the ELS cells and the adjacent cartilage demonstrated radiolabel incorporation within 4 hours of incubation in tissue culture medium, with increased radiolabel density in ELS cells after 24 hours of incubation. HA-specific hyaluronidase (HAase) resulted in removal of HAase-sensitive compounds in the ELS in both 4-hour and 24-hour cultured specimens when compared to adjacent cartilage cells (p = 0.001). Approximately 43 percent of the radiolabel was incorporated into HA in ELS specimens, as compared to a 22 percent HA synthesis in the adjacent cartilage tissue, suggesting preferential synthesis by ELS cells. The dissected murine otocysts demonstrate viability in vitro as measured by their ability to incorporate 14C glucose from tissue culture medium. Under these conditions the cultured ELS demonstrates an ability to synthesize HA. A theory of ELS function is proposed.

Animals

Changes in hyaluronan synthesis by in vitro cultured endolymphatic sac cells.

The endolymphatic sac (ELS) has been implicated in the maintenance of endolymph volume and pressure in the membranous labyrinth through fluid resorption and secretion of osmotically active substances, known as glycosaminoglycans (GAGs). To assess whether the ELS cells synthesize the GAG, hyaluronan (HA), and to further elucidate the secretory function of the ELS, a series of experiments were carried out on in vitro tissue-cultured, fetal murine ELSs. In phase 1 of the investigation, the ELSs that were attached to a small portion of the posterior labyrinth, were resected from whole otocyst specimens and studied in tissue culture. This model was chosen to determine whether a change in endolymph homeostasis affects ELS activity. Radiolabeled 14C glucose incorporation was used to evaluate HA synthesis by ELS cells when cultured in vitro. Approximately 43 percent of the incorporated 14C glucose radiolabel was digested by Streptomyces hyaluronidase (an HA-specific hyaluronidase), suggesting HA synthesis by sac cells. In phase 2 of our experiments, the ELSs were not resected from the otocysts. Instead, they were left attached to intact membranous labyrinths, and whole otocysts were cultured. Studies analogous to those of phase 1, assessing the ability of the ELS cells to incorporate 14C glucose into HA, were performed on these specimens. Streptomyces hyaluronidase treatment of these ELS specimens resulted in a reduction in the removal of radiolabel. Therefore, the ELS cells of intact otocysts incorporated less 14C glucose into HA when compared to the ELS cells of the resected specimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

State of the art of cochlear implants. The UCSF experience.

Clinical trials with the University of California, San Francisco (UCSF)/Storz multichannel cochlear implant began in February 1985. A total of 16 patients were implanted with this four channel unit, a vocoder-based, compressed-analog system. Twelve of the 16 patients have had their 1-year postoperative evaluations, which permitted observations of their performance over time. Of these 12 patients, 10 (83%) are able to obtain a considerable degree of speech recognition. This represents the achievement of some level of auditory-only understanding in a very high proportion of the implant population. Results are measured with a battery of speech reception tests, including monosyllabic word recognition (the standard clinical "speech discrimination" list), the recognition of key words in sentences, and connected discourse tracking. Conventional audiologic test procedures are used. The objective of the clinical trial was to evaluate the strategies developed by the UCSF implant team through neurophysiologic, histopathologic, and psychophysical investigations over the past 18 years. The UCSF/Storz trials have helped to clarify and to define the specifications for our next generation implant, an electrically transparent eight (bipolar) or 16 (monopolar) channel system.

Adult

Comparative studies of speech processing strategies for cochlear implants.

A wide variety of speech processing strategies for multichannel auditory prostheses were compared in studies of two patients implanted with the UCSF electrode array. Each strategy was evaluated using tests of vowel and consonant confusions, with and without lipreading. Included among the strategies were the compressed analog processor of the present UCSF/Storz prosthesis and a group of interleaved pulses processors in which the amplitudes of nonsimultaneous pulses code the spectral variations of speech. For these patients, each with indications of poor nerve survival, test scores were significantly higher with the interleaved pulses processors. We believe this superior performance was a result of 1. the substantial release from channel interactions provided by nonsimultaneous stimuli and 2. a fast enough rotation among the channels to support adequate temporal and spectral resolution of perceived speech sounds.

Cochlear Implants

Surgical considerations and hearing results with the UCSF/Storz cochlear implant.

Sixteen patients have been implanted with the UCSF/Storz multichannel implant, 11 of whom have been fitted with their external speech processors and transmitters and administered postoperative audiological evaluations. Both the surgical procedures used and the hearing results for these patients are presented. The potential medical/surgical complications of implant surgery and the future direction of research and development within the UCSF/Storz implant program are discussed.

Adult

Cochlear patency problems in cochlear implantation.

Sensory deafness may be associated with partial or total obliteration of the cochlear scalae. Before undertaking cochlear implant surgery, a preoperative assessment of cochlear patency with high-resolution computed tomography (CT) is indicated. To determine the accuracy of pre-implant CT, a review of the radiographic and surgical findings in 36 implanted ears was performed. An abnormal CT scan was found to be a reliable predictor of compromised cochlear patency at operation. These findings help the surgeon to select the side most favorable for implantation and to anticipate problems that may be encountered during device insertion. A normal pre-implant CT scan, however, does not exclude the possibility of compromised cochlear patency. A 46% false negative rate was encountered, presumably because subtle degrees of osseous or fibrous obliteration of the cochlea are beyond the resolution by current generation CT scanners. In our opinion, the radiographic finding of cochlear ossification is not a contraindication to an attempt at cochlear implantation. The only assured way of determining the extent of cochlear patency is by performing an "exploratory cochleostomy" with fenestration of the basal cochlear turn. Drilling anteriorly through an ossified basal scala tympani will often expose an adequate lumen and permit insertion of even a long multichannel electrode into a partially ossified cochlea. Nevertheless, it is essential that the implant team be prepared with devices appropriate for whatever existing or surgically created lumen may be available.

Cochlea

The UCSF/Storz cochlear implant: patient performance.

Clinical trials of the UCSF/Storz multichannel cochlear implant were initiated in February 1985, under the sponsorship of Storz Instrument Company. This four-channel device uses simultaneous bipolar, radial stimulation and a vocoder-based speech processing scheme. To date, eighteen patients have been implanted with the UCSF/Storz implant at four clinical centers in the United States. Based on data accumulated through June 1986, fifteen of these patients had received their speech processors and were given at least an initial evaluation of their performance with the implant. Results have been very encouraging, with all but two of these patients obtaining some degree of open-set auditory-only speech recognition. Most patients have demonstrated improvement over time without extensive rehabilitative intervention and all patients have attained an enhancement in lip-reading ability, as measured with a tracking procedure. According to a self-rated performance scale, all patients have experienced improvement in general communicative function since receiving the implant.

Adult

Cochlear implantation in children: the problem of head growth.

Successful implantation in children requires that provision be made for later head growth. The timing and magnitude of this growth was determined by measurements made from high-resolution computerized tomographic images of developing temporal bones. The temporal bone scans of 103 children of varying ages were studied. The development of the petrous and squamous portion of the temporal bone was at its greatest in the first 2 years of life. The order of magnitude of growth varied with the different axes measured.

Adolescent

The UCSF/Storz multichannel cochlear implant: patient results.

Using the four channel cochlear implant system with a vocoder-based processor developed at UCSF over an extensive period of research, clinical trials of the UCSF/Storz device were initiated in February 1985, under the sponsorship of Storz Instrument Company. To date, 13 patients have been implanted with this device, nine of whom have been fitted with their external processor and transmitter and have received at least their initial postoperative evaluation. Patient results have been extremely promising, with eight of the nine patients obtaining some open-set auditory only speech understanding. Most patients have demonstrated improvement over time and all patients have attained an enhancement in lipreading ability with the use of the UCSF/Storz device.

Adult

The University of California, San Francisco/Storz cochlear implant program.

Using a four-channel implant system with a vocoder-based processor developed at UCSF over an extensive period of research, clinical trials of the UCSF/Storz device were initiated in February 1985 under the sponsorship of Storz Instrument Company. To date, 13 patients have been implanted with the UCSF/Storz device, 10 of whom have been fitted with their external processor and transmitter and have received at least their initial postoperative evaluations. Of these 10 patients, nine are able to use all four channels of their implant system. The device fitting/adjusting process for these patients has been remarkably easy, requiring only approximately 30 to 60 minutes. Patient results have been extremely good, with eight of the 10 patients obtaining some open-set auditory only speech understanding. Without extensive rehabilitation and training, most patients have demonstrated an improvement in speech reception over time. Lip-reading and tracking results indicate that all patients have attained an enhancement of lip-reading ability with the use of the device, suggesting that improved general communication skills have been provided for each UCSF/Storz patient.

Adult

Mondini's dysplasia with recurrent meningitis.

This report describes the diagnosis and surgical management of two patients with similar inner ear malformations resulting in recurrent otitic meningitis. Each patient had a meningocele presenting through the oval window associated with Mondini's anomaly. Details of radiographic diagnosis and surgical management strategies will be discussed and long-term follow-up presented.

Ear, Inner

The ultrastructure of the endolymphatic sac in Meniere's disease.

Biopsies of the endolymphatic sac were performed in 6 patients undergoing endolymphatic sac decompression and/or drainage procedures. Electron microscopy revealed extensive subendothelial fibrosis with loss of vascularity, heavy deposition of collagen and flattening of luminal cells. In patients with long-standing disease, complete obliteration of the endolymphatic sac lumen appeared to occur. There was poor correlation between the surgeon's ability to identify the lumen of the endolymphatic sac and its presence in the biopsy specimen.

Collagen

The ultrastructure of the endolymphatic sac in Ménière's disease.

Meniere's disease is a well recognized clinical entity, yet the etiology and pathophysiology of the disease is not fully understood. Impaired endolymphatic sac function resulting in faulty reabsorption of endolymph has been implicated in the production of the disease. The histopathological findings from biopsied sac specimens and observed by transmission (TEM) and scanning (SEM) electronmicroscopy in two patients with early Meniere's disease are presented and discussed. Extensive subepithelial fibrosis with loss of vascularity and obliteration of portions of the lumen of the endolymphatic sac by an ingrowth of collagen is noted in both specimens. The implications of these findings are discussed and the need for more TEM and SEM studies of inner ear disorders is stressed.

Adult

Multielectrode intracochlear implants. Nerve survival and stimulation patterns.

A series of neurophysiological and anatomical experiments have been performed on cats implanted on a long-term basis with scala tympani electrodes. Auditory nerve survival was assessed for both neomycin sulfate-deafened and previously normal-hearing cats three weeks to 30 months after electrode implantation. Acute neurophysiological experiments were performed on nearly all of the cats and the spatial response to electrical stimulation was determined. The results of these experiments suggest that the auditory nerve can withstand surgical implantation and the long-term interface with scala tympani electrodes. In addition, restricted portions of the auditory nerve can be discretely excited with bipolar stimulation. Monopolar stimulation produced a very broad excitation pattern. These findings have important implications for the application of multielectrode prosthetic devices to the profoundly deaf.

Animals

The cochlear histopathology of chronic intracochlear implantation.

A fundamental question regarding the feasibility of artificial electrical stimulation of auditory nerve in cases of sensory deafness is the fate of that nerve after electrode implantation. The results of chronic scala tympani electrode implantation in normal and neomycin-deafened cats indicate that the vast majority of primary auditory neurons will survive the initial surgical implantation and the long-term interface with the molded silastic electrode for periods of at least 30 months (the longest normal-implant survivors). While there is histologic evidence that some neurons are lost in the basal coil, especially in neomycin-deafened animals, the majority of spiral ganglion cells and their radial fibres survived neomycin administration and surgical implantation even in this region. The implantation of electrodes in neomycin-deafened cats did not result in heavy neuronal degeneration. Indeed, there was little apparent difference in nerve survival between the implanted and unimplanted ears of the neomycin animals for periods up to five months (the longest neomycin implant survivor). Traumatic electrode insertion with injury to the boney covering of the modiolus or disruption of the basilar membrane resulted in extensive nerve loss in the traumatized region. When carefully inserted by an experienced otologist, the molded-silastic scala tympani electrode permitted discrete differential stimulation of restricted segments of auditory nerve and produced little or no neural degeneration.

Animals