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Biomedical subjects

P A Wackym

Publications and source records attributed to P A Wackym.

At least 19 recordsLinked to original sources

Expression and distribution of mu opioid receptors in the inner ear of the rat.

Opioid peptides have demonstrated modulatory effects on the vestibular afferent discharge and are putative vestibular efferent neuromodulators. The distribution of their receptors in the mammalian vestibular epithelia is not known. We used reverse transcriptase-polymerase chain reaction (RT-PCR), in situ hybridization, Western blots and immunohistochemistry to study the expression of mu opioid receptor (MOR) in the Scarpa's ganglia and cristae ampullares of rats. MOR transcript was only detected in the somata of the vestibular afferent neurons. MOR-like immunoreactivity was observed in the somata of vestibular afferents and in nerve terminals in the cristae ampullares epithelia both in the center and peripheral regions. Double labeling of cristae sections with the MOR1 antibody in combination with antibodies against calretinin (a marker for vestibular afferents terminating in calices) and peripherin (a marker for afferents terminating in boutons), respectively showed that MOR1 immunoreactivity was in calyx, dimorphic and bouton vestibular afferents. MOR immunoreactivity was not detected in vestibular efferent fibers identified with choline acetyltransferase immunohistochemistry. These results indicate that MOR may mediate effects of vestibular efferents on afferents.

Animals↗

Radiation hybrid mapping of 11 alpha and beta nicotinic acetylcholine receptor genes in Rattus norvegicus.

Acetylcholine is the main neurotransmitter of the vestibular efferents and a wide variety of muscarinic and nicotinic acetylcholine receptors are expressed in the vestibular periphery. To date, 11 nicotinic subunits (alpha and beta) have been reported in mammals. Previously, our group [Brain Res. 778 (1997) 409] reported that these nicotinic acetylcholine receptor alpha and beta subunits were differentially expressed in the vestibular periphery of the rat. To begin an understanding of the molecular genetics of these vestibular efferents, this study examined the chromosomal locations of these nicotinic acetylcholine receptor genes in the rat (Rattus norvegicus). Using radiation hybrid mapping and a rat radiation hybrid map server (www.rgd.mcw.edu/RHMAP SERVER/), we determined the chromosomal position for each of these genes. The alpha2-7, alpha9, alpha10, and beta2-4 nicotinic subunits mapped to the following chromosomes: alpha2, chr. 15; alpha3, chr. 8; alpha4, chr. 3; alpha5, chr. 8; alpha6, chr. 16; alpha7, chr. 1; alpha9, chr. 14; alpha10, chr. 7; beta2, chr. 2; beta3, chr. 16; and beta4, chr. 8. With the location for each of these nicotinic subunits known, it is now possible to develop consomic and/or congenic strains of rats that can be used to study the functional genomics of each of these subunits.

Animals↗

Adjunctive use of endoscopy during posterior fossa surgery to treat cranial neuropathies.

OBJECTIVE: The objective of this study was to determine the utility and safety of rigid endoscopy as an adjunct during posterior fossa surgery to treat cranial neuropathies. METHODS: A suboccipital craniotomy was performed for 19 patients with non-neoplastic processes involving the Vth, VIIth, and/or VIIIth cranial nerves. Ten patients with trigeminal neuralgia (n = 8), hemifacial spasm (n = 1), or intractable tinnitus (n = 1) underwent primarily microvascular decompression procedures. One patient with geniculate neuralgia underwent nervus intermedius sectioning combined with microvascular decompression. Eight patients underwent unilateral vestibular nerve neurectomies for treatment of Meniere's disease. A 0- or 30-degree rigid endoscope was used in conjunction with the standard microscopic approach for all procedures. RESULTS: All patients experienced resolution or significant improvement of their preoperative symptoms after posterior fossa surgery. The endoscope allowed improved definition of anatomic neurovascular relationships without the need for significant cerebellar or brainstem retraction. Cleavage planes between the cochlear and vestibular nerves entering the internal auditory canal and sites of vascular compression could not be microscopically observed for several patients; however, endoscopic identification was possible for all patients. There were no complications related to the use of the endoscope. CONCLUSION: The rigid endoscope can be used safely during posterior fossa surgery to treat cranial neuropathies, and it allows improved observation of the cranial nerves, nerve cleavage planes, and vascular anatomic features without significant cerebellar or brainstem retraction.

Adolescent↗

Hearing rehabilitation using the BAHA bone-anchored hearing aid: results in 40 patients.

OBJECTIVE: This study evaluates the U.S. experience with the first 40 patients who have undergone audiologic rehabilitation using the BAHA bone-anchored hearing aid. STUDY DESIGN: This study is a multicenter, nonblinded, retrospective case series. SETTING: Twelve tertiary referral medical centers in the United States. PATIENTS: Eligibility for BAHA implantation included patients with a hearing loss and an inability to tolerate a conventional hearing aid, with bone-conduction pure tone average levels at 60 dB or less at 0.5, 1, 2, and 4 kHz. INTERVENTION: Patients who met audiologic and clinical criteria were implanted with the Bone-Anchored Hearing Aid (BAHA, Entific Corp., Gothenburg, Sweden). MAIN OUTCOME MEASURES: Preoperative air- and bone-conduction thresholds and air-bone gap; postoperative BAHA-aided thresholds; hearing improvement as a result of implantation; implantation complications; and patient satisfaction. RESULTS: The most common indications for implantation included chronic otitis media or draining ears (18 patients) and external auditory canal stenosis or aural atresia (7 patients). Overall, each patient had an average improvement of 32+/-19 dB with the use of the BAHA. Closure of the air-bone gap to within 10 dB of the preoperative bone-conduction thresholds (postoperative BAHA-aided threshold vs. preoperative bone-conduction threshold) occurred in 32 patients (80%), whereas closure to within 5 dB occurred in 24 patients (60%). Twelve patients (30%) demonstrated 'overclosure' of the preoperative bone-conduction threshold of the better hearing ear. Complications were limited to local infection and inflammation at the implant site in three patients, and failure to osseointegrate in one patient. Patient response to the implant was uniformly satisfactory. Only one patient reported dissatisfaction with the device. CONCLUSIONS: The BAHA bone-anchored hearing aid provides a reliable and predictable adjunct for auditory rehabilitation in appropriately selected patients, offering a means of dramatically improving hearing thresholds in patients with conductive or mixed hearing loss who are otherwise unable to benefit from traditional hearing aids.

Acoustic Stimulation↗

Ligand-gated purinergic receptors are differentially expressed in the adult rat vestibular periphery.

To further characterize the pattern of expression of the ligand-gated purinergic P2X receptors in the peripheral vestibular system, we conducted reverse transcription-polymerase chain reaction amplification of P2X1 and P2X2 messenger RNA extracted from adult rat vestibular ganglia (Scarpa's ganglia) and vestibular end organs. Transcripts encoding P2X1 were found in both Scarpa's ganglia and the end organs, but transcripts encoding P2X2 were found only in the vestibular end organs. These results support previous electrophysiological data, and they provide a more complete understanding of the specific role of purinergic (adenosine-5'-triphosphate) transmission in the vestibular periphery.

Animals↗

Adenylyl cyclase isoforms in the vestibular periphery of the rat.

The expression of adenylyl cyclase (AC) isoforms in the adult rat vestibular periphery was investigated using reverse transcription polymerase chain reaction (RT-PCR). AC II, IV and V mRNAs were expressed in both Scarpa's ganglion and vestibular end organs. In addition, in the vestibular end organs, an AC mRNA not previously reported in the rat was identified. The cloned sequence (GenBank accession no. AF184150) represented 95 amino acids with 100% similarity to the human AC VII and 94% to the bovine AC VII. AC VII mRNA also was found in the cerebellum but was undetectable in heart, kidney, liver and Scarpa's ganglion.

Adenylyl Cyclases↗

Partial cDNAs encoding G-protein alpha subunits in the rat vestibular periphery.

To begin understanding what G-proteins are involved in signal transduction in the vestibular periphery, the expression of Galpha subunits in rat primary afferent neurons (Scarpa's ganglia) and end-organs was studied. Reverse transcription-polymerase chain reaction (RT-PCR) with degenerate primers corresponding to two conserved regions of the Galpha protein coding sequence produced partial cDNAs encoding two distinct forms of Galpha(s) subunit (Galpha(s2) and anove) Galpha(s2) subunit,GenBank accession number AF1841510); and two forms of Galpha(i2) subunits. A novel truncated form of Galpha(i2) (designated Galpha(i2(vest)),Gen Bank accession number AF189020) was detected in the vestibular periphery. Galpha(i2(vest)) was also expressed in rat cerebellum and heart. The possible role of the identified Galpha protein cDNAs in the function of the vestibular periphery is discussed.

Amino Acid Sequence↗

Topographic distribution of nicotinic acetylcholine receptors in the cristae of a turtle.

The neurochemical basis of cholinergic efferent modulation of afferent function in the vestibular periphery remains incompletely understood; however, there is cellular, biochemical and molecular biological evidence for both muscarinic and nicotinic acetylcholine (ACh) receptors (nAChRs) in this system. This study examined the topographic distribution of alpha-bungarotoxin (alpha-BTX) nAChRs in the cristae of a turtle species. Cristae were perfusion-fixed, cut at 20 micrometer on a cryostat and incubated with alpha-BTX or polyclonal antibodies raised against Torpedo nAChR. Light microscopy showed abundant specific labeling of nAChR in the central zone of each hemicrista on the calyx-bearing afferents surrounding type I hair cells and on the base of the type II hair cells. Within the peripheral zone, dense labeling of type II hair cells near the torus and sparse or no label was observed on type II hair cells near the planum. The alpha-BTX binding showed a similar pattern within the cristae. The similarity between the topographic distribution of alpha-BTX binding nAChR and of efferent inhibition of afferents supports the notion that the inhibitory effect of afferents is mediated by nAChR.

Afferent Pathways↗

Cochlear implantation for auditory rehabilitation in Camurati-Engelmann disease.

Camurati-Engelmann disease (progressive hereditary diaphyseal dysplasia) is a rare sclerotic bone disease involving the diaphyses of the long bones, skull base, and clavicles. Progressive sclerosis of cranial nerve foramina has been implicated in cranial nerve deficits. including facial nerve palsy, vestibular disturbances, and hearing loss. Two patients with Camurati-Engelmann disease and concomitant sensorineural hearing loss are presented. Both patients were evaluated for cochlear implantation. One patient was successfully implanted after preoperative imaging revealed no involvement of the internal auditory canals. The porous nature of the affected bone, however. necessitated the inactivation of 1 electrode to prevent facial nerve stimulation. A second patient was rejected as a potential implant recipient due, in part, to narrow internal auditory canals and rapidly progressive disease. The otologic manifestations of Camurati-Engelmann disease are reviewed, and issues related to cochlear implantation in this rare disease are discussed.

Adult↗

Isolated primary unilateral stenosis of the internal auditory canal.

Congenital primary stenosis of the internal auditory canal (IAC) may exist in isolation or along with a number of other osseous anomalies of the temporal bone. Most of the literature on IAC stenosis is concerned with its effect on the outcome of cochlear implantation (i.e. patients with profound bilateral hearing loss). In addition, some degree of canal asymmetry has been noted in patients with normal hearing, questioning the causal relationship of this finding to deafness. We describe two children with computed tomography (CT) documented severe primary unilateral narrowing of the IAC and an associated ipsilateral sensorineural hearing loss. Typical radiographic findings are described, and the relevant developmental pathology is discussed. The ipsilateral association of stenosis and hearing loss strengthens the link between narrowing of the IAC and deafness.

Adolescent↗

Evaluation of surgical approaches to endoscopic auditory brainstem implantation.

OBJECTIVES: This study investigates the use of endoscopy for the placement of an auditory brainstem implant by translabyrinthine, retrosigmoid (suboccipital), and middle cranial fossa approaches. STUDY DESIGN: Cadaver dissection and endoscope-assisted placement of the auditory brainstem implant. METHODS: Translabyrinthine, retrosigmoid, and middle cranial fossa dissections were performed bilaterally in five cadaveric heads. An auditory brainstem implant was placed within the lateral recess of the fourth ventricle under endoscopic visualization. The implantation was performed with all approaches and documented by digital image capture followed by production of dye-sublimation photographic prints. RESULTS: The lateral recess was visualized with the endoscope in all three approaches to the brainstem. The 30 degrees endoscope provided the best visualization by translabyrinthine and retrosigmoid dissection and was essential for the middle cranial fossa approach. Refinement of implant position was readily achieved, as even the deepest portion of the recess could be seen with all three approaches. CONCLUSIONS: This study finds that endoscopy provides superior visualization of the lateral recess of the fourth ventricle than the operating microscope with all approaches. The retrosigmoid approach is recommended, as it provides the best view of the implantation site and the easiest angle for placement of the prosthesis. The use of the endoscope may allow for a smaller craniotomy than with conventional microscopic techniques, depending on tumor size. The translabyrinthine approach provides a good view of the lateral recess but had no advantage over other approaches. The middle cranial fossa approach is only possible with angled endoscopes; however, it is technically the most difficult and places the facial nerve at greatest risk.

Acoustic Stimulation↗

Adjunctive use of endoscopy during acoustic neuroma surgery.

OBJECTIVE/HYPOTHESIS: In specific clinical situations, endoscopes offer better visualization than the microscope during acoustic neuroma (vestibular schwannoma) surgery and can therefore decrease the incidence of the postoperative complications of cerebrospinal fluid (CSF) leakage and recurrence of tumor. This study was undertaken to determine if the use of adjunctive endoscopy provides complementary information to the operating surgeon during surgery for acoustic neuromas. METHOD: Seventy-eight patients with acoustic neuromas underwent tumor excision by two neurotologists (PAW., D.S.P.), together with their respective neurosurgical partners, via a retrosigmoid (suboccipital) approach (n = 68), translabyrinthine approach (n = 7), or middle cranial fossa approach (n = 3). Endoscopy with a rigid glass lens endoscope was used during tumor removal to examine posterior fossa neurovascular structures, and after tumor excision to inspect the internal auditory canal (IAC), inner ear, and middle ear, depending on the approach used. One of the authors (D.S.P.) has not used adjunctive endoscopy during resections via the translabyrinthine and middle cranial fossa approaches, and therefore, these cases were excluded from the data collection and analysis. RESULTS: Complete tumor excision was achieved in 73 patients. Endoscopy allowed improved identification of tumor and adjacent neurovascular relationships in all cases. In addition, residual tumor at the fundus of the IAC (n = 11) and exposed air cells (n = 24) not seen with the microscope during retrosigmoid approaches were identified endoscopically. In one of the translabyrinthine cases, the endoscope allowed identification of open air cells not visualized with the microscope. None of the 78 patients developed CSF rhinorrhea. Incorporating the endoscope did not significantly increase operative time. CONCLUSIONS: Endoscopy can be performed safely during surgery to remove acoustic neuromas. The adjunctive use of endoscopy may offer some advantages including improved visualization, more complete tumor removal, and a lowered risk of CSF leakage.

Adolescent↗

Endoscope-assisted surgery for acoustic neuromas (vestibular schwannomas): early experience using the rigid Hopkins telescope.

OBJECTIVE: Endoscopes have been increasingly used during neurosurgical procedures. Previously, they have been shown to offer better visualization than the microscope in selected situations and frequently have allowed less invasive surgery. This study was undertaken to determine whether endoscopy is safe and effective during suboccipital surgery for vestibular schwannomas. METHODS: Ten patients with vestibular schwannomas underwent suboccipital transmeatal craniotomies for tumor excision. Endoscopy with a rigid glass lens endoscope (Hopkins telescope) was used during tumor removal to examine posterior fossa neurovascular structures and after tumor excision to inspect the internal auditory canal. RESULTS: Complete tumor excision was achieved in nine patients. Endoscopy allowed improved identification of tumor and adjacent neurovascular relationships in all cases without the need for significant retraction of the cerebellum or brain stem. In addition, residual tumor at the fundus of the internal auditory canal (n = 2) and exposed petrous air cells (n = 3) not seen with the microscope were identified endoscopically. Operative time was not significantly increased by incorporating the endoscope. CONCLUSION: Posterior fossa endoscopy can be performed safely during surgery for tumor removal. Endoscope-assisted surgery for vestibular schwannomas may offer some advantages over standard microsurgery in selected cases. The advantages may include improved visualization, more complete tumor removal, and a lowered risk of cerebrospinal fluid leakage.

Adult↗

A critical appraisal of spontaneous perilymphatic fistulas of the inner ear.

OBJECTIVE: This article provides an overview of relevant data supporting and refuting the existence of spontaneous perilymph fistula, as well as critically reviewing the literature pertaining to their evaluation and management. DATA SOURCES: Sources used were relevant English language clinical and basic science publications. STUDY SELECTION: A Medline search dating back to 1966 for articles concerning perilymphatic fistula, including both human and animal data, was performed. Articles were included if they contained relevant data or were significant reviews of the subject. A traditional bibliography search was then completed to acquire articles missed by the computerized search, including works published before 1966. DATA EXTRACTION: The data from each publication were critically reviewed. Emphasis on understanding the clinical features of surgically created perilymph fistulas was used to more objectively assess the data regarding spontaneous perilymph fistulas. DATA SYNTHESIS: The data were not amenable to formal meta-analysis or valid data summarization; however, when possible trends and contrasting data were emphasized. CONCLUSIONS: Spontaneous perilymph fistulas are very rare occurrences and the majority are likely incited by a pressure-altering event. Current methodologies do not provide sufficient specificity and sensitivity to accurately diagnose perilymph fistulas. The results of endoscopic studies of the middle ear in the evaluation of perilymphatic fistula suggest a low incidence compared with the large number of fistulas reported in the literature. A high index of suspicion must be maintained, and appropriate preoperative counseling should reflect the current controversies. Questions must continue to be asked and further research pursued to help distinguish reality from myth.

Fistula↗

Clinical and molecular pathology of aggressive Schneiderian papilloma involving the temporal bone.

BACKGROUND: Inverting papilloma is a benign but locally aggressive sinonasal tumor that rarely involves the middle ear or temporal bone. METHODS: A report of a case and the molecular pathology of the tumor is presented. RESULTS: A 35-year-old woman with a history of recurrent inverting papilloma of the left paranasal sinuses was found to have evidence of extension through the eustachian tube and extensive involvement of the temporal bone. Surgical management resulted in the patient being disease-free at 14 months. Molecular pathology studies of the resected tumor suggest an association with human papillomavirus. CONCLUSIONS: Direct extension of the sinonasal tumor through the eustachian tube may represent the pathologic mechanism involved in the development of inverting papilloma involving the middle ear and temporal bone.

Adult↗

Molecules, motion, and man.

The application of cell and molecular biology techniques to vestibular research is resulting in rapid changes in our understanding of the fundamental mechanisms of vestibular function. The clinical problems encountered in space travel together with the acute and chronic vestibular dysfunction affecting many of the patients otolaryngologists care for have driven this research at a rapid pace. A review of these methods and highlights of the major advances are discussed.

Animals↗