Antibodies to HSP-70 in normal donors and autoimmune hearing loss patients.

OBJECTIVE: To evaluate serum antibody to heat shock protein (HSP) 70 as a marker for autoimmune sensorineural hearing loss (AISNHL). DESIGN: Sera from 20 patients with rapidly progressive sensorineural HL and 20 control volunteers without HL were tested for antibody reactivity against multiple HSP 70 substrates. Substrates included recombinant human HSP (rHuHSP) 72, purified bovine brain heat shock cognate (HSC) 73 and HSP 72, as well as heat-shocked and non-heat-shocked protein extracts from bovine kidney (MDBK) cells. All serum donors were previously tested for antibody to guinea pig inner ear supporting cells; 17 of 20 patients but none (0 of 20) of the controls were positive. METHODS: Sera were tested using Western blots. RESULTS: Reactivity with rHuHSP 70 was observed in 16 patients and 17 controls. Similarly, 15 of 20 patients and 17 of 20 controls stained for both HSP 72 and HSC 73 from the bovine brain. When tested against the heat-shock-induced and control MDBK extracts, six patients and nine controls had greater reactivity with the induced HSP 72. CONCLUSION: The frequency of antibodies to HSP substrates did not differ in patients and controls. Prior studies reported that HSP 72 is the 68 kD antigen commonly detected by AISNHL sera. However, we show that HSP 72 antibodies are no more prevalent in patients than in normal controls. Thus, it is unlikely that the 68 kD protein is HSP 72. Therefore, HSPs are not appropriate substrates for serodiagnosis of AISNHL.

Spontaneous vertigo and headache: endolymphatic hydrops or migraine?

We undertook a study to assess whether patients who had both spontaneous vertigo and headache would respond to treatment for endolymphatic hydrops rather than treatment for migraine. We also attempted to discover if there were any individual characteristics that might predict which patients with an equivocal history and symptoms would be more likely to have either of the two conditions as opposed to the other. All patients were initially treated for endolymphatic hydrops with sodium restriction and increased water intake. Response to treatment was assessed by three tools: the Dizziness Handicap Inventory, a symptom severity scale, and a disability scale. Patients who did not respond to treatment for endolymphatic hydrops were switched to treatment for migraine. At the first follow-up period, 23 patients were available for analysis by telephone survey. According to data obtained by the three assessment tools, 14 patients (60.9%) improved after initial therapy and six (26.1%) improved following subsequent migraine treatment; the remaining three patients (13.0%) did not comply with their initial treatment regimen, and they showed no improvement. Although no statistically significant conclusions can be drawn because of the small sample size, there were trends to suggest that certain demographic, clinical, and objective-testing characteristics might predict which patients are likely to have one of these two conditions as opposed to the other. We conclude that a stepwise approach to treatment, beginning with therapy for endolymphatic hydrops, is an appropriate strategy. Also, the fact that no improvement was seen among the three patients who did not comply suggests that improvement is indeed the result of treatment rather than simply a function of the passage of time.

Adenoid cystic carcinoma of the paranasal sinuses.

Adenoid cystic carcinoma of the paranasal sinuses is a rare neoplasm whose propensity for perineural spread frequently results in positive surgical margins at the skull base. Radiation therapy (RT) may be used to treat unresectable tumors or as an adjuvant for positive surgical margins after attempted resection. A retrospective review of the experience at the University of Michigan Medical Center was undertaken to study the factors influencing survival and to compare the efficacy of RT alone versus as an adjuvant treatment to surgical resection. All patients selected for review (n = 17) had a histologically confirmed diagnosis of adenoid cystic carcinoma arising from the paranasal sinuses with an average follow-up of 6 years. The choice of treatment modality was based upon the resectability of the tumor by clinical and radiologic parameters. This was therefore not a randomized study and there was a clear bias against the radiation only group, which contained the more advanced and locally aggressive tumors. The 6-year survival for the combined surgery + RT group was 73% compared with 50% for the radiation only group (p = NS). The overall local recurrence rate was 76% and the rate of distant metastases was 18%. Of the 10 patients who underwent surgical resection eight (80%) had positive surgical margins at the skull base.

Hearing improvement after resection of cerebellopontine angle meningioma: case study of the preoperative role of transient evoked otoacoustic emissions.

In a retrospective case study of a patient with a right-sided cerebellopontine angle mass lesion, transient evoked otoacoustic emissions were robustly present despite a severe to profound sensorineural hearing loss and abnormal auditory brainstem response. These results were interpreted as suggestive of a neural site of lesion, and the potential for planned, preserved, or improved hearing by a suboccipital surgical craniotomy was considered. A gross total resection was successful. Three years postoperatively, the patient has normal hearing sensitivity and word recognition ability.

AP30, a differential protein marker for perilymph and cerebrospinal fluid in middle ear fluid, has been purified and identified as human apolipoprotein D.

Using two-dimensional (2-D) gel electrophoresis, human perilymph and cerebrospinal fluid have been shown to be highly enriched for an acidic protein with MR 30,000, we designated it as AP30. The protein exhibits charge heterogeneity, with at least eight isoforms visible between pI 4.5 to 5.5 on 2-D gels. Purification of the protein was carried out by ammonium sulfate precipitation, polybuffer exchanger column chromatofocusing, and acetone fractional precipitation. The resulting preparation also contains eight spots in the acidic area of 2-D gels, and one broad band located at Mr 30,000 by SDS-PAGE. Digestion of AP30 with neuraminidase causes the isoforms to shift to a more basic position and to consolidate into two primary spots, indicating that AP30 is a variably sialylated glycoprotein. Amino acid analysis of AP30 revealed an amino acid content very similar to that of human apolipoprotein D. Attempts to determine the amino acid sequence demonstrated that the N-terminus is blocked. Edman sequencing of two peptide fragments, generated by cyanogen bromide cleavage of AP30, both revealed sequences having 100% identity to human apolipoprotein D. Western blot analysis of AP30 with the antibody against authentic human apolipoprotein D demonstrated a high degree of cross-reactivity. These studies indicate that AP30 from human perilymph and cerebrospinal fluid is a member of the apolipoprotein D family.

Two types of oscillopsia in a patient with idiopathic vestibulopathy.

A patient with an idiopathic bilateral vestibulopathy described two types of oscillopsia, one induced by head movement, the other induced by changing pressure in the right external auditory canal. This is the first report of both types of oscillopsia occurring in the same individual and illustrates their different mechanisms and symptomatology.

Human autoantibodies and monoclonal antibody KHRI-3 bind to a phylogenetically conserved inner-ear-supporting cell antigen.

Autoimmunity is thought to be one cause of sensorineural hearing loss (SNHL). Sera from patients with rapidly progressive hearing loss have been shown to contain antibodies to a 68-kD protein in heterologous inner-ear tissue. Using guinea pig inner-ear tissue as the antigenic substrate and either Western blot or immunofluorescence (IF) or both, we tested sera from 74 patients suspected to have autoimmune hearing loss for inner-ear antibodies. Sera from 73 patients were tested by Western blot, and sera from 36 were tested by IF. Thirty-seven of 73 (51%) had antibody to a 68-70-kD protein by Western blot. Sera positive by IF stained supporting cells with a staining pattern like that previously observed with the KHRI-3 monoclonal antibody. There was concordance between Western blot and IF assays. Of 36 patients tested by both assays, 29/31 (94%) that were positive in Western blot were also positive by IF, three were negative by both tests, and two each were positive by one assay but negative by the other. Absorption of patient sera with human inner-ear tissue removed antibody reactivity to the guinea pig supporting cells, indicating that the antigen detected by the autoantibody is also present in the human inner ear. Absorption with an equal volume of white or red blood cells from the tissue donor did not remove the antibody reactivity to inner ear, showing that the absorption by inner-ear tissue is specific. Sera from three patients positive in both assays also stained a 68-70-kD inner-ear protein immunoprecipitated by the KHRI-3 monoclonal antibody, indicating that the monoclonal and human antibodies recognize the same antigen. The results support the hypothesis that patients with autoimmune sensorineural hearing loss produce autoantibodies to an inner-ear supporting cell antigen that is phylogenetically conserved and defined by the murine monoclonal antibody KHRI-3. Since KHRI-3 can induce hearing loss after infusion into the inner ear, it is likely that autoantibodies with the same antigenic target are also pathogenic in humans.

Laryngeal liposarcoma.

Laryngeal liposarcomas are rare, with only 13 previously well-documented cases (to our knowledge). We report an additional case, which documents the use of computed tomography for treatment planning. Laryngeal liposarcomas appear to have a better prognosis than nonlaryngeal liposarcomas; therefore, a critical analysis of reported cases enabled us to identify clinical characteristics that contribute to the favorable prognosis. We also propose a rational therapeutic approach.

Indications for the AO plate with a myocutaneous flap instead of revascularized tissue transfer for mandibular reconstruction.

Our preferred technique for mandibular reconstruction uses a revascularized osseomyocutaneous flap. However, to reconstruct small lateral defects in dentulous patients, the AO mandibular reconstruction plate (MRP) is used. Its advantages include quick, reliable placement without a donor site or the need for advanced technical training. This review examines 16 patients who underwent primary mandibular reconstruction after ablative oncologic surgery using an AO MRP without a bone graft. The average follow-up was 32 months. Twelve patients (75%) had successful reconstructions, while 4 (25%) developed serious complications resulting in failure of the MRP. The most significant factor limiting rehabilitation was disease progression, affecting 12 (75%) of the 16 patients. In this subgroup of selected patients with small (< 6 cm) lateral mandibular defects, useful dentition, and advanced disease, or whose general medical condition precludes prolonged general anesthesia, primary mandibular reconstruction using an AO MRP and a myocutaneous flap without a bone graft is a viable reconstructive alternative.

Evaluation of acute vertigo: unusual lesions imitating vestibular neuritis.

The acute onset of vertigo is a common clinical problem presenting to primary care physicians or otologists for evaluation. Usually the underlying disease process is benign and self-limited in nature. In the absence of hearing loss or additional neurologic findings, a common initial diagnosis is vestibular neuritis. The patient is treated symptomatically and observed for spontaneous resolution. However, other more serious disease processes may mimic the presentation of vestibular neuritis and be misdiagnosed. Five cases of serious central nervous system disorders that were similar to vestibular neuritis in their initial presentation are reviewed to illustrate this point. Each patient presented with the acute onset of continuous vertigo without associated hearing loss. The correct diagnosis was established only after further evaluation was pursued. Recommendations for the initial and subsequent evaluation of these patients are discussed.

Identification of perilymph proteins by two-dimensional gel electrophoresis.

Perilymph has a total protein component that is quantitatively distinct from serum and cerebrospinal fluid (CSF). The goal of this research was to determine if perilymph contains any qualitatively unique protein constituents that will distinguish it from serum or CSF. To test this hypothesis, matched sets of perilymph, serum, and CSF were obtained from 18 guinea pigs and seven human subjects. The purity of each sample was assured by measurement of the protein concentration of each sample and comparison of this parameter to known normal values for perilymph, serum, and CSF. Each sample was then subjected to two-dimensional gel electrophoresis, separating proteins by isoelectric point in the horizontal dimension and by relative molecular weight in the vertical dimension. All gels were processed under precisely identical physical conditions by use of a diamine silver stain. A small number of perilymph proteins not found in plasma were identified in both the guinea pig and the human specimens. The finding of unique perilymph proteins may permit the development of a sensitive marker that will aid in the diagnosis of perilymph fistula.