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Objective To present a logical algorithm for management of postoperative cerebrospinal fluid (CSF) leak that occurs after acoustic tumor removal, and to describe a method for eustachian tube resection. Clinical presentation We present an algorithm in the form of a flow chart, describe middle fossa craniotomy for eustachian tube resection, and present three cases in which this technique was used. Technique For CSF leak, pressure dressing at the wound and bed rest for the patient are advised; lumbar drain is indicated if the leak does not resolve. Occasionally, wound exploration is required. CSF rhinorrhea is treated first with a lumbar drain. If this approach is unsuccessful, the choice of treatment depends on the patient's hearing status. If a patient has no hearing, we perform a blind sac closure of the ear canal and pack the eustachian tube. If a patient has hearing, wound reexploration and lumbar drainage are advised. When conservative and initial surgical procedures for resolving CSF leak fail, we perform a middle fossa craniotomy to identify, divide, and remove a segmental portion of the cartilaginous eustachian tube and then cauterize and occlude both ends. Conclusion At centers where surgical removal of acoustic tumors is frequently performed, a logical protocol should be in place for treatment of postoperative CSF leak. The leak location and the patient's hearing status are factors in determining the appropriate treatment method. Middle fossa craniotomy for resection of the eustachian tube is a safe, definitive management option for treatment of recalcitrant CSF rhinorrhea that occurs after acoustic tumor surgery.

The present study was conducted to evaluate whether the administration of ciprofloxacin 0.3%/dexamethasone 0.1% (Ciprodex)-soaked gelfoam during tympanoplasty has adverse effects on graft healing. Records of patients who had undergone tympanoplasty with Ciprodex-soaked gelfoam packing placed in the middle and external ear canal were reviewed. The time to heal for each patient and the number of postoperative perforations/complications were recorded. Sixty-four charts met the inclusion criteria. Most procedures were primary type I tympanoplasties with temporalis fascia grafts. Healing of the tympanic membrane was documented in 95.3% of patients, and mean time to healing was 49 d. Two patients who underwent revision tympanoplasty failed to exhibit healing at any visit after surgery. Postoperative complications were infrequent. Patients with Ciprodex-soaked gelfoam packing placed during tympanoplasty showed an overall rate of healing of 95%. Although this study is limited by its retrospective design, the data suggest that the use of Ciprodex during tympanoplasty has no detrimental effect on postoperative graft healing.

Objectives: Chondroblastoma is a rare tumor accounting for 1% of primary bone tumors. Chondroblastoma involving the skull base is exceedingly rare with approximately 60 cases reported. We reviewed our experience with chondroblastoma of the skull base with an emphasis on current lateral skull base approaches and long-term tumor control. Study Design and Setting: A retrospective case review at a tertiary neurotology private practice group was performed over a 20-year period. Five patients were identified with skull base chondroblastoma. All patients underwent surgical intervention, and success of surgery was determined by disease-free status at last follow-up. Mean follow-up time was 5.8 years. Results: Two patients underwent gross tumor removal as primary therapy. One patient underwent partial tumor removal at an outside institution, and follow-up magnetic resonance imaging demonstrated rapid growth of residual tumor. This patient was successfully treated with gross total removal of residual tumor with an infratemporal craniotomy approach. Near total tumor removal was performed in two patients because of intimate involvement of vital structures. At last follow-up, no patient had radiographic evidence of tumor recurrence. There were no significant postoperative complications. Conclusions: Gross total or near total resection of skull base chondroblastomas through lateral skull base approaches results in long-term tumor control and low complication rates.

Several approaches to the internal auditory canal and cerebellopontine angle for acoustic neuroma removal have been described. We prefer the translabyrinthine approach in patients with tumors larger than 2 cm or poor preoperative hearing, since both factors predict poor hearing preservation. Many surgeons perceive this approach as confining and consider it contraindicated in large tumors or contracted mastoids. We have recently described the utility of the translabyrinthine approach for the removal of large (>4 cm) acoustic neuromas. In more than 5000 tumor excisions performed by the senior author (W.E.H.), no cases required a modification of the approach because of anatomic constraints within the mastoid. We describe our techniques for the management of the low-lying tegmen, the anterior sigmoid sinus, and the high jugular bulb, alone or in combination, during translabyrinthine removal of acoustic neuromas. Arch Otolaryngol Head Neck Surg. 1997;123:342-344

Objectives/Hypothesis: Compare vestibular schwannoma (VS) surgical outcome between patients with prior irradiation and those not previously treated. Study Design: Retrospective review with matched control group. Methods: Review of tumor adherence to the facial nerve, facial nerve grade, and complications in 38 patients with radiotherapy as a primary procedure before VS surgical removal and a matched random sample of 38 patients with primary surgery. The majority of the irradiated group had gamma knife radiation therapy. Mean time from irradiation to surgical salvage was 3.3 years (SD = 3.2), with a minimum of 5.2 months and a maximum of 15.8 years. Most (89.5%) patients in each group underwent a translabyrinthine approach. Mean tumor size at surgery was 2.6 cm in each group. Results: The irradiated group had more moderate to severe adherence of tumor than the controls (89% vs. 63%, P ≤ .01). They also had a lower rate of good facial function (House-Brackmann grade I/II) (37% vs. 70%) and a higher rate of poor function (grades V or VI) (50% vs. 18%) at follow-up (P ≤ .019). Results were similar when including only those with good preoperative function (50% vs. 72% and 32% vs. 15%) but did not achieve statistical significance. Surgical time and complications did not differ. Conclusion: Patients who have undergone irradiation for VS and require surgical salvage may have a more difficult surgery and poorer outcomes than those not previously irradiated. When making their initial choice of treatment, patients should be counseled that surgery might be more difficult after failed stereotactic irradiation.

Objective To conduct a clinical trial of intratympanic steroid injection for idiopathic sudden sensorineural hearing loss in subjects who failed oral steroid therapy. Study design and setting Open-label methylprednisolone injection clinical trial in a tertiary neurotologic referral center. Twenty subjects (14 males; 6 females) received 4 injections within a 2-week period (4 days apart). Hearing, dizziness, and tinnitus were evaluated before and after treatment. Results There were no serious unexpected adverse events and 2 types of expected adverse events (tympanic membrane perforation, nausea after injection). No increases in dizziness or tinnitus lasting longer than 24 hours were observed after injections. One of 20 (5%) improved to near-normal hearing. In addition, there was statistically significant improvement in 4-frequency pure-tone average and speech discrimination score at 1 month after treatment. Conclusion Four intratympanic injections of methylprednisolone improved pure-tone average or speech discrimination scores for a subset of sudden hearing loss subjects that failed to benefit from oral steroids. Significance A clinical trial of intratympanic injections for idiopathic sudden hearing loss was successfully completed and promising results were found.

Allele variants of EYA1 and EYA4, two members of the vertebrate Eya gene family, underlie two types of inherited human deafness, branchio-oto-renal (BOR) syndrome and DFNA10, respectively. To clarify how mutations in these two genes and their encoded proteins impact the normal biology of hearing, we completed a number of functional studies using the yeast-two-hybrid system. We verified that bait constructs of the homologous region ( Eya1HR and Eya4HR) interact with Six1 prey constructs, although no interaction with Dach1 prey was demonstrable. To compare interaction affinities, we evaluated alpha-galactosidase activity after cotransformation of Eya1HR/Six1 and Eya4HR/Six1 and found that the latter interaction was weaker. By immunofluorescence staining, we showed Eya4HR localization to the cytoplasm. After coexpression of Six1, Eya4HR was translocated to the nucleus. Results with Eya1HR were similar. Translation of mutant constructs ( Eya4HR(R564X) and Eya1HR(R539X)) could not be demonstrated. Using dual Eya-containing constructs (with two wild-type alleles or wild-type and mutant alleles), we confirmed no translation of the mutant allele, even if the mutation was nontruncating. These results are consistent with clinical data and implicate haploinsufficiency as the cause of BOR syndrome and DFNA10.

OBJECTIVE To evaluate surgical outcomes for the treatment of posterior fossa meningiomas at the House Ear Clinic from 1987 to 2001. We review our current treatment algorithm and present our postoperative outcomes with attention to facial and auditory neural preservation. STUDY DESIGN Retrospective review. SETTING Tertiary care center. PATIENTS Medical records of 71 patients who underwent posterior fossa meningioma surgery at the House Ear Clinic were reviewed. INTERVENTION All patients had surgical removal of their meningioma via translabyrinthine, transcochlear, retrosigmoid, extended middle fossa, or combined petrosal approaches by House Ear Clinic neurotologists and neurosurgeons. MAIN OUTCOME MEASURES Preoperative and postoperative auditory and facial nerve function data were collected. Patient and tumor characteristics including presenting symptoms, completion of tumor resection, and complications secondary to surgery were also recorded. RESULTS The most common presenting symptoms in this series were otologic, with hearing loss (61%), tinnitus (58%), and imbalance (58%) as the three most common. Gross total resection was achieved in 67 (94%) patients. Hearing-preservation surgery was attempted in 37 (52%) patients (68% via extended middle fossa or combined approach). Twenty-one patients with preoperative Class A hearing had follow-up audiometric data and 18 (86%) had serviceable hearing preserved. Excluding transcochlear craniotomies, 85% of patients had normal facial nerve function postoperatively. Cerebrospinal fluid leak (6%) was the most common complication. CONCLUSIONS Advances in microsurgical techniques have greatly changed our management of patients with posterior fossa meningiomas. These changes have reduced postoperative morbidity. Specifically, use of the anterior and posterior petrosal approaches has facilitated facial and auditory neural preservation while not compromising the extent of tumor excision.

Objective There is growing concern over the use of systemic antibiotics and the development of bacterial resistance. The question remains as to whether ototopical medications may also promote antibiotic-resistant organisms, either on a local level (in the ear) or in other areas of the aerodigestive tract. We performed an evidence-based review to answer the following clinical question, “Do antibiotic ototopical medications induce antibiotic resistant organisms?” Study design We performed a MEDLINE search of the published literature from 1966 to the present. We used appropriate search terms such as “ototopical antibiotics,” “ototopical drops,” “antibiotic resistance,” “topical antibiotics and otitis externa,” “otitis externa and treatment,” “otitis externa and antibiotic drops,” “otitis externa and ototopical drops,” “otitis media,” “otitis media and treatment,” “otitis media and antibiotic drops,” “chronic suppurative otitis media,” “chronic suppurative otitis media and treatment,” “chronic suppurative otitis media and antibiotic drops,” “ otitis externa and resistant organisms,” “otitis media and resistant organisms,” “chronic suppurative otitis media and resistant organisms,” “ophthalmic antibiotic drops,” “draining ear,” “P.E. tube otorrhea,” “pressure equalizing tube otorrhea,” “pressure equalizing tube otorrhea and treatment,” and “pressure equalizing tube otorrhea and ototopical therapy” to identify pertinent articles. These articles were reviewed and graded according to the evidence quality. Results After an initial screening of over 2,500 articles, 38 articles were analyzed further; of these, 11 were determined to warrant extensive review. Eight articles evaluated chronic suppurative otitis media; 2, otitis externa; and 1, post–tympanostomy tube otorrhea, whereas 3 others studied systemic absorption. Of the 8 chronic suppurative otitis media studies, there were thought to be 5 grade 2B studies, 1 grade 1B study, and 1 grade 2C study. These studies did not demonstrate a propensity for the development of resistant organisms. No study answered the question as to whether resistance to systemic antibiotics might occur in otitis externa. Conclusions Overall grade B evidence seems to indicate that no significant antibiotic resistance develops from the use of ototopical antibiotic treatment.

Objective We sought to determine the incidence of injury to the cochlea or vestibular system from the use of ototopic antibiotic ear drops. Study design We conducted a MEDLINE search of the published literature from 1966 to the present using the search items of “ototopic antibiotics,“ “ototopic drops,” “antibiotic resistance,” and others to identify pertinent articles. These articles were reviewed and graded according to evidence quality. Forty-four articles were found; 27 articles were considered appropriate for review and 14 of these articles were thought to warrant further extensive review. The latter 14 articles dealt directly with the evaluation of either hearing loss or changes in vestibular function after the use of ototopic ear drops. We eliminated studies that did not consider hearing or vestibular function. We considered only articles in the English language, eliminating articles that not address the ototoxicity of ototopical ear drops. Results Most of these articles were in the level 3 to 3b category. Two of the articles were in the 1b category, evaluating evidence-based studies. An article that reviewed case reports of ototopical ototoxicity and a survey article are included in this study, as case reports of ototopical ototoxicity and survey articles. Conclusion We found a total of 54 cases of gentamicin vestibular toxicity and, in 24 of these patients, cochlear toxicity was also documented. Our review also found 11 cases of cochlear and 2 cases of vestibular toxicity in neomycin-based ear drops.

A special consensus panel of the American Academy of Otolaryngology-Head and Neck Surgery was appointed by Academy President Dr Jonas Johnson (2003) to determine the appropriate role of potentially ototoxic topical antibiotics in the treatment of ear disease. The consensus panel wished to determine, using current best evidence, if there were differences in efficacy between the potentially ototoxic and the nonototoxic topical antibiotics. This evidence-based review is designed to answer the specific question, ”Are there differences in clinical treatment efficacy between the aminoglycoside based ototopical antibiotic drops and the fluoroquinolone based antibiotic drops?“ A MEDLINE literature review was performed in September 2002. MeSH search terms included ”ototopical antibiotics“ and ”efficacy,“ with limits for human subjects and titles with abstracts. Fifty publications were identified. Four publications were eliminated from the review process because they were not in English (1 each in Japanese, French, Polish, and Hebrew) and 6 others were eliminated because they did not address the question of efficacy. A total of 40 relevant publications were reviewed and graded according to the standards established by the Centre for Evidence-based Medicine. Each article was reviewed and graded independently by 2 reviewers.

Objective The objective of this study was to systematically review the literature on animal ototoxicity from ototopical medications. A secondary objective was to assess the relevance of animal data to the use of ototopical drops in clinical situations involving humans. Study design We performed a MEDLINE search of the published literature using appropriate search terms to identify pertinent articles, which were reviewed, summarized, and tabulated. Results One hundred seventy-three articles were reviewed; 61 articles were appropriate to the study question and were further analyzed. Conclusions Virtually all studies demonstrate that aminoglycoside antibiotics, when applied topically into the middle ear space, are ototoxic in experimental animals.

Objective We sought to determine long-term hearing preservation in vestibular schwannoma patients after undergoing middle fossa resection. Study design, setting, and outcome measures We conducted a retrospective chart review of patients undergoing middle fossa resection from 1990 to 1995 at a tertiary care center. Pure-tone thresholds, before resection and at least 5 years after resection, and speech discrimination scores are reported. Results Seventy percent of patients with immediate postoperative hearing maintained serviceable hearing at more than 5 years after surgery. Pure-tone average in the operative ear changed at the same rate as hearing in the unoperated ear during this follow-up period. Conclusions More than two thirds of patients who underwent middle fossa resection of a vestibular schwannoma with some hearing postoperatively maintain that hearing at greater than 5 years of follow-up. Surgery alone does not have a negative impact on long-term hearing preservation.

Endogenous retroviruses have shaped the evolution of mammalian genomes. Host genes that control the effects of retrovirus insertions are therefore of great interest. The modifier-of-vibrator-1 locus (Mvb1) controls levels of correctly processed mRNA from genes mutated by endogenous retrovirus insertions into introns, including the Pitpn(vb) tremor mutation and the Eya1(BOR) model of human branchiootorenal syndrome. Positional complementation cloning identifies Mvb1 as the nuclear export factor Nxf1, providing an unexpected link between the mRNA export receptor and pre-mRNA processing. Population structure of the suppressive allele in wild Mus musculus castaneus suggests selective advantage. A congenic Mvb1(CAST) allele is a useful tool for modifying gene expression from existing mutations and could be used to manipulate engineered mutations containing retroviral elements.

Hearing loss is the most common sensory disorder in humans. About one in every 1000 children is affected by severe deafness at birth or during early childhood. A further one in 1000 children becomes deaf before adulthood.More than 50% of all cases are due to genetic cause. These latter forms are usually less severe and progressive. In adults, the prevalence of hearing loss increases with age. By the eighth decade, approximately half of the population has a hearing loss severe enough (>25 dB) to compromise their ability to communicate. These late onset forms are generally considered result from a combination of genetic and environmental causes. Tremendous progress has been made during the last few years in mapping and cloning genes responsible for hearing loss. In this article, we focus on nonsyndromic hearing impairment, since a dramatic progress has been made in this area recently.

Objectives/Hypothesis To clone and characterize the integration site of an insertional inner ear mutation, produced in one of fourteen transgenic mouse lines. The insertion of the transgene led to a mutation in a gene(s) necessary for normal development of the vestibular labyrinth. Study Design Molecular genetic analysis of a transgene integration site. Methods Molecular cloning, Southern and northern blotting, DNA sequencing and genetic database searching were the methods employed. Results The integration of the transgene resulted in a dominantly inherited waltzing phenotype and in degeneration of the pars superior. During development, inner ear fluid homeostasis was disrupted. The integration consisted of the insertion of a single copy of the transgene. Flanking DNA was cloned, and mapping indicated that the genomic DNA on either side of the transgene was not contiguous in the wild-type mouse. Localization of unique markers from the two flanks indicated that both were in the proximal region of mouse chromosome 1. However, in the wild-type mouse the markers were separated by 6.3 cM, indicating a sizable rearrangement. Analysis of the mutant DNA indicated that the entire region between the markers was neither deleted nor simply inverted. Conclusions These results are consistent with a complex rearrangement, including at least four breakpoints and spanning at least 6.3 cM, resulting from the integration of the transgene. This genomic rearrangement disrupted the function of one or more genes critical to the maintenance of fluid homeostasis during development and the normal morphogenesis of the pars superior.

Trigeminal neuromas are slow-growing benign tumors representing approximately 10% of all intracranial neuromas and less than 0.5% of all intracranial tumors. Historically, excision of these tumors through traditional neurosurgical routes—including the frontotemporal transsylvian, subtemporal-intradural, subtemporal-transtentorial, or suboccipital approaches—has resulted in an unsatisfactorily high rate of recurrence. In this study we compare contemporary skull base/neurotologic approaches with conventional procedures for trigeminal neuroma extirpation. (Otolaryngol Head Neck Surg 1999;120:355-60.)

We sought to investigate the functional integrity of the auditory nerve in patients with postoperative hearing loss after middle cranial fossa acoustic-tumor removal in a case-series descriptive study. The study setting was a tertiary referral center, a private otologic practice. The study population comprised seven patients who underwent a middle-cranial-fossa approach for unilateral acoustic-tumor resection and sustained postoperative anacusis with an anatomically intact auditory nerve. Four were men and three women; they ranged in age from 30 to 60 years; all underwent surgery between 1990 and 1994 and agreed to return to the center to participate in the study during 1995. Diagnostic electrical promontory stimulation was used to determine the functional integrity of the auditory nerve. Our main outcome measures were the presence or absence of discrete tone perception, electrical threshold, maximum acceptable level and dynamic range, gap detection and temporal difference limen during electrical promontory stimulation. Three of the seven patients demonstrated positive responses to electrical promontory testing (e.g., discrete tone perception). All three were able to perform the gap-detection and temporal difference limen tests. None of the preoperative characteristics was related to performance on promontory stimulation testing. We conclude that the middle cranial fossa approach permits anatomic—and, in some cases, functional auditory-nerve preservation. These data suggest that auditory rehabilitation in some patients who sustain anacusis after the middle cranial fossa approach to acoustic tumors, as in neurofibromatosis 2, may be provided with cochlear implantation. (Otolaryngol Head Neck Surg 1998;119:588-92.)

Schwannomas are peripheral nerve tumors that typically have mutations in the NF2 tumor suppressor gene. We compared cultured schwannoma cells with Schwann cells from normal human peripheral nerves (NHSC). Both cell types expressed specific antigenic markers, interacted with neurons, and proliferated in response to glial growth factor, confirming their identity as Schwann cells. Schwannoma cells frequently had elevated basal proliferation compared to NHSC. Schwannoma cells also showed spread areas 5-7-fold greater than NHSC, aberrant membrane ruffling and numerous, frequently disorganized stress fibers. Dominant negative Rac inhibited schwannoma cell ruffling but had no apparent effect on NHSC. Schwannoma cell stress fibers were inhibited by C3 transferase, tyrphostin A25, or dominant negative RhoA. These data suggest that the Rho and Rac pathways are abnormally activated in schwannoma cells. Levels of ezrin and moesin, proteins related to the NF2 gene product, merlin, were unchanged in schwannoma cells compared to NHSC. Our findings demonstrate for the first time that cell proliferation and actin organization are aberrant in schwannoma cells. Because NF2 is mutant in most or all human schwannomas, we postulate that loss of NF2 contributes to the cell growth and cytoskeletal dysfunction reported here.

Plasma membrane Ca2+-ATPase isoform 2 (PMCA2) exhibits a highly restricted tissue distribution, suggesting that it serves more specialized physiological functions than some of the other isoforms. A unique role in hearing is indicated by the high levels of PMCA2 expression in cochlear outer hair cells and spiral ganglion cells. To analyze the physiological role of PMCA2 we used gene targeting to produce PMCA2-deficient mice. Breeding of heterozygous mice yielded live homozygous mutant offspring. PMCA2-null mice grow more slowly than heterozygous and wild-type mice and exhibit an unsteady gait and difficulties in maintaining balance. Histological analysis of the cerebellum and inner ear of mutant and wild-type mice revealed that null mutants had slightly increased numbers of Purkinje neurons (in which PMCA2 is highly expressed), a decreased thickness of the molecular layer, an absence of otoconia in the vestibular system, and a range of abnormalities of the organ of Corti. Analysis of auditory evoked brainstem responses revealed that homozygous mutants were deaf and that heterozygous mice had a significant hearing loss. These data demonstrate that PMCA2 is required for both balance and hearing and suggest that it may be a major source of the calcium used in the formation and maintenance of otoconia.

Disease that lies in the posterior mesotympanum, including inflammatory polyps, cholesterol granuloma, and cholesteatoma, is often difficult to extirpate. The literature reflects a divided and often controversial opinion regarding the removal of the bony posterior canal wall to reach this disease. Recently, endoscopic visualization has been advocated to enhance exposure. Employing a fallopian bridge technique wherein the bone medial to the facial nerve is opened into the posterior mesotympanum the authors have used this approach in selective circumstances to optimize the eradication of disease. Three hundred patients undergoing tympanomastoidectomy were included in this analysis. The fallopian bridge technique was attempted in 58 cases and was successfully employed in 42 patients. Indications as well as limitations for this procedure are discussed.

Aneurysms of the basilar artery are uncommon. Historically, because of the central location of these basilar lesions, surgical access has been difficult. Moreover, while this disease and its surgical management inherently carry a high risk of patient morbidity, the presence of neighboring vital neural and vascular structures introduces additional intraoperative challenges. Since 1986 we have employed a transpetrous approach for access to selective aneurysms involving the basilar artery. Removal of the petrous apex has provided an expanded deep window through which infraclinoidal basilar artery aneurysms can be controlled. Reported herein are our results utilizing an anterior petrosectomy approach to the management of infraclinoidal artery aneurysms.

Nager acrofacial dysostosis, first described by Nager and deReynier in 1948, is a rare syndrome characterized by mandibulofacial dysostosis with associated radial defects. The facial features include downward slanting palpebral fissures, absent eyelashes in the medial third of the lower lids, mandibular and malar hypoplasia, dysplastic ears with conductive deafness, and variable degrees of palatal clefting. Upper limb malformation is a constant feature of Nager syndrome and ranges from thumb hypoplasia to absence of the radial ray. The maxillo-mandibular hypoplasia and associated retroplaced tongue set the stage for early and significant upper airway obstruction. The craniofacial anomalies and associated trismus make emergent airway intubation challenging. We present a case of Nager syndrome with life threatening airway obstruction unresponsive to conservative management. This case and a review of the literature emphasize the importance of early tracheotomy for these patients.

Transforming growth factor beta (TGFß) genes are linked to a variety of developmental processes and are the subject of in vivo and in vitro transgene research studies. We are evaluating TGFß-2 effects on mouse inner ear development, with emphasis on the cochlear duct (CD), by comparing plastic sections of intact inner ears from developmental day (D) 16.5,18.5 and 19.5 littermates with wildtype (+/+), heterozygous (+/−) and mutant (−/−) TGFß-2 genotypes as determined by polymerase chain reaction analysis of tail digests. Auditory and vestibular organs of all D16.5 mice appear similar: membranous labyrinth epithelium varies from simple cuboidal/low columnar to pseudostratified/stratified columnar. Surrounding mesenchyme varies in cell density regionally, the most cellular mesenchyme underlies areas of sensory epithelium. Sparse mesenchymal cell distribution in the vestibule and basal CD indicates sites of perilymph channel formation. The spiral and vestibular ganglia and their unmyelinated fibers are prominent. Otoconia and hair cells are present in the utricle (U) and saccule (S) maculae; hair cells are less easily identifiable in the CD.

The Eya1 bor mutant hypomorph contains an intracisternal A particle insertion in intron 7 of the Eya1 gene that results in a 50% reduction in wild-type mRNA levels. The homozygous mutants have middle and inner ear defects and variable kidney abnormalities. The severity of the disorder is affected by genetic background. In contrast to complete deafness and cochlear agenesis in the C3HeB/FeJ strain, F2 Eya1 bor/bor mutants from an intercross between C3HeB/FeJ- Eya1 bor/+ and C57BL/6J showed variable auditory brain-stem responses and cochlear coiling. In this study, using these F2 Eya1 bor/bor mutants, we have identified two major loci, Mead1 ( modifier of Eya1-associated deafness 1 ) and Mead2, that are responsible for suppression of the original phenotypes. We have narrowed these two loci to 5.4 and 4.4 cM, respectively, in congenic lines. Quantitative PCR demonstrated that this modifying effect did not result from an increase in wild-type Eya1 mRNA, suggesting Mead1 and Mead2 are interacting directly or indirectly with Eya1 during inner ear development.

Morbidity and mortality associated with all-terrain vehicular accidents is climbing at a steady rate. These accidents frequently result in multiorgan system trauma. A retrospective study of all victims involved in three-wheel motor vehicle accidents admitted to the UCSD Trauma Unit between July 1980 and July 1985 is presented. Injury severity was assessed using the Abbreviated Injury Scale (AIS) and the Injury Severity Score (ISS). The average patient age was 23.3 years with 30% under 16 years of age. There was a male to female ratio of 14:1. The average hospital stay was 12.4 days. Six percent died as a result of their injuries. Injuries to the head and neck were sustained by 83.3% of patients, facial injuries by 46.6%, injuries to the chest by 13.3%, and injuries to the pelvis and abdomen by 13.3%. Thirty percent suffered injuries to the extremities and over 50% had abrasions, contusions, and/or lacerations. Physicians, the public, and state and federal agencies are urged to promote safer use of these recreational vehicles.