Generation of azines by the reaction of a nucleophilic carbene with diazoalkanes: a synthetic and crystallographic study.

Reactions of the nucleophilic carbene 1,3-dimesityl-imidazol-2-ylidene (1) with diazofluorene, diphenyldiazomethane, and azidotrimethylsilane were examined. Specifically, carbene 1 reacts with diazofluorene and diphenyldiazomethane to give addition products (azines: 3 and 4, respectively). Compounds 3 and 4 were further characterized in the solid-state by single-crystal X-ray crystallographic studies. [3 (a = 9.7936(6) A, b = 10.0529(7) A, c = 16.251(1) A, alpha = 75.765(1) degrees, beta = 79.711(1) degrees, gamma = 64.321(1) degrees, Z = 2, space group P1); 4 (a = 11.681(3) A, b = 11.861(4) A, c = 21.186(3) A, alpha = 90 degrees, beta = 97.05(2) degrees, gamma = 90 degrees, Z = 4, space group P2(1)/n)]. The structural parameters of 3 and 4 are discussed with reference to previously characterized symmetrical and unsymmetrical azines. Structural data suggest that charge separation is possible in 3.

Outcomes and quality of life in conductive hearing loss.

OBJECTIVE: The goal was to measure quality of life (QOL) and hearing-specific functional status before and after treatment of conductive hearing loss (CHL). STUDY DESIGN AND SETTING: A prospective, longitudinal, outcomes-based study was performed at an academic medical center. RESULTS: Mean baseline QOL scores in CHL patients were comparable with those of the general population. Audiometric studies indicated significant improvements in hearing threshold in all treated patients. There was no significant improvement in mean global QOL scores after treatment of CHL, although there was little room for improvement over baseline. The hearing-specific instrument did demonstrate significant improvements in emotional and social/situational hearing status after treatment. Patients treated with hearing aids had poorer baseline QOL and hearing status than patients treated with surgery and tended to show declines in QOL and only partial improvement in hearing-specific functional status after treatment. CONCLUSIONS: Treatment of CHL resulted in improvements in hearing-specific functional status, although changes were difficult to detect with a global QOL instrument.

Hearing preservation in conservation surgery for vestibular schwannoma.

OBJECTIVE: To evaluate preservation of hearing in the resection of vestibular schwannomas. STUDY DESIGN: A retrospective case review. SETTING: Tertiary-care medical center. PATIENTS: Forty-seven patients (25 men, 22 women) were studied; mean age was 46 years, mean tumor diameter 9.8 mm (range 3-30 mm.) INTERVENTIONS: All patients underwent resection of vestibular schwannomas by the middle cranial fossa (MCF) or the retrosigmoid (RS) approach. MAIN OUTCOME MEASURES: Hearing preservation was classified by the criteria outlined by the American Academy of Otolaryngology-Head Neck Surgery. Hearing was assessed preoperatively and postoperatively at 1 month and 1 year. Facial function was graded according to the House-Brackmann scale. Minimum follow-up was 18 months. RESULTS: Hearing was preserved in 69% of patients who underwent the MCF approach but in only 33% of patients for whom the RS approach was used. The RS approach was used for larger tumors (mean diameter 15 mm) and the MCF procedure for smaller tumors (mean diameter 9 mm). One hundred percent of patients had facial function H/B grade II or better, regardless of approach. CONCLUSION: Hearing function can be reliably preserved in a high percentage of selected patients undergoing resection of vestibular schwannoma.

Unrecognized benign paroxysmal positional vertigo in elderly patients.

Balance disorders in elderly patients are associated with an increased risk of falls but are often difficult to diagnose because of comorbid chronic medical problems. We performed a cross-sectional study to determine the prevalence of unrecognized benign paroxysmal positional vertigo (BPPV) and associated lifestyle sequelae in a public, inner-city geriatric population. Dizziness was found in 61% of patients, whereas balance disorders were found in 77% of patients. Nine percent were found to have unrecognized BPPV. Multivariate analysis demonstrated that the presence of a spinning sensation and the absence of a lightheadedness sensation predicted the presence of unrecognized BPPV. Patients with unrecognized BPPV were more likely to have reduced activities of daily living scores, to have sustained a fall in the previous 3 months, and to have depression. These data indicate that unrecognized BPPV is common within the elderly population and has associated morbidity. Further prospective studies are warranted.

Harvesting human hair cells.

The sensory hair cells of the inner ear are responsible for converting balance and hearing stimuli into electrical signals. Until recently, all previous studies of hair cell physiology had been performed on tissue obtained from non-mammals and rodents. In primates, hair cells are difficult to access, because they rest within the densest structure of the body, the otic capsule of the temporal bone. In this report, we describe a technique that we have used in physiological studies to harvest living human hair cells. We collected vestibular and cochlear tissue specimens from adult humans undergoing translabyrinthine and transotic surgical approaches for resection of lateral skull base tumors. Viable hair cells were identified and visualized with light microscopy. The ability to study normal hair cells from humans may further the study of normal and pathological human sensation, hair cell regeneration, and genetic causes of balance and hearing disorders.

Long-term vestibulo-ocular reflex changes in patients with vestibular ablation.

Long-term changes in the parameters of the vestibulo-ocular reflex (VOR) were evaluated using recently developed multilevel statistical modelling techniques in a group of patients who had undergone ablative inner ear procedures. Data from 84 patients were available for study. The most dramatic recovery in the VOR occurred during the first 60 postoperative days, however, slow changes continued, levelling off at about 120 days. While frequency was a highly significant predictor of outcomes in all parameters, age showed significant predictive value only to phase measures (p = 0.006) and gender had no effect. Sum gain at the lowest frequency tested remained below the 5th percentile and at the higher frequencies remained below the 50th percentile for normal subjects. Phase decreased exponentially, but remained above the 95th percentile for normal subjects, except at the highest frequency where it remained above the 50th percentile. DC bias decreased exponentially, dropping to the 50th percentile by day 146. Asymmetry stayed between the 50th and 95th percentile, except at the highest frequency, where it was at the 50th percentile by day 125.

An N2S2 bifunctional chelator for technetium-99m and rhenium: complexation, conjugation, and epimerization to a single isomer.

A bifunctional chelator 6 was prepared bearing an N2S2 core for binding rhenium or technetium and a carboxylic acid group for conjugation to amino groups of biomolecules. Complexation of 6 with rhenium(V) resulted in two kinetic isomers, anti-7 and syn-7, being formed in approximately equal amounts. Epimerization with 0.5 M NaOH yields a single isomer anti-7, as determined by NMR spectroscopy and single-crystal X-ray analysis. The 99mTc complex was prepared at the tracer level by reaction of the ligand with 99mTcO4-, tin(II) chloride and sodium gluconate giving a mixture of two isomers, but showing a preference for the anti isomer. Chelation in the presence of 1 M NaOH results in anti-8 being formed as the sole product. The bifunctional ability of the ligand was explored by amide formation with (S)-alpha-phenethylamine, either by direct DCC coupling or through the N-hydroxy succinimidyl ester 9 intermediate. The deprotected bioconjugate 11 was complexed with rhenium, yielding similar amounts of two isomeric rhenium complexes, anti-12 and syn-12, which were isolated and characterized by NMR spectroscopy. Treatment of the kinetic mixture of anti-12 and syn-12 with 1 M NaOH resulted in quantitative conversion to a single rhenium complex anti-12. With technetium-99m in 0.1 M sodium acetate, bioconjugate 11 yielded both technetium-99m complexes anti-13 and syn-13, in a 2:1 ratio, respectively. In contrast, complexation in the presence of 1 M NaOH gave only one technetium-99m complex, assigned the structure anti-13.

Cost-effectiveness of the diagnostic evaluation of vertigo.

OBJECTIVE: To evaluate the cost-effectiveness of several diagnostic tests used in the evaluation of vertigo. STUDY DESIGN: Cost-effectiveness analysis, using data from retrospective case review. METHODS: Charts and test results were reviewed from 192 outpatients seen in an academic tertiary referral center for evaluation of vertigo. Cost-effectiveness analysis was performed using decision analysis software, data from office and hospital charges, and expert-based estimations of the utility of different test outcomes. Sensitivity analysis was performed using standard algorithms and wide variable ranges. RESULTS: We found that audiologic testing, posturography, and electronystagmography were the most cost-effective tests, and that magnetic resonance imaging and blood tests had the lowest cost-effectiveness. The analysis was sensitive to the effects of financial costs of tests but, with a few exceptions, was typically not sensitive to the utility of test outcomes or the distribution of test results. CONCLUSIONS: The use of cost-effectiveness analysis, the estimation of utility of test outcomes, and techniques of sensitivity analysis should help guide the clinician's decision making on appropriate testing for patients with vertigo.

Ionic currents and electromotility in inner ear hair cells from humans.

The upright posture and rich vocalizations of primates place demands on their senses of balance and hearing that differ from those of other animals. There is a wealth of behavioral, psychophysical, and CNS measures characterizing these senses in primates, but no prior recordings from their inner ear sensory receptor cells. We harvested human hair cells from patients undergoing surgical removal of life-threatening brain stem tumors and measured their ionic currents and electromotile responses. The hair cells were either isolated or left in situ in their sensory epithelium and investigated using the tight-seal, whole cell technique. We recorded from both type I and type II vestibular hair cells under voltage clamp and found four voltage-dependent currents, each of which has been reported in hair cells of other animals. Cochlear outer hair cells demonstrated electromotility in response to voltage steps like that seen in rodent animal models. Our results reveal many qualitative similarities to hair cells obtained from other animals and justify continued investigations to explore quantitative differences that may be associated with normal or pathological human sensation.

Development of a new outcomes instrument for conductive hearing loss.

OBJECTIVE: The objective was to design and validate a disease-specific outcomes instrument for use in conductive hearing loss (CHL). STUDY DESIGN: The study was a retrospective survey of 47 patients recently treated for CHL with either a hearing aid or surgery. Patients were tested with the newly designed instrument (the Hearing Satisfaction Scale [HSS]), previously validated hearing-specific instruments, and a generic quality-of-life instrument. SETTING: The study was performed in an academic tertiary referral center. MAIN OUTCOME MEASURES: These included test-retest reliability, internal consistency reliability, content validity, criterion validity, and construct validity of the HSS. RESULTS: Test-retest reliability (r = 0.72, p < 0.001) and internal consistency reliability were adequate (Cronbach's alpha was 0.83 and 0.74 for the two subscales of the HSS). Criterion validity for individual items was adequate (r = 0.45, p = 0.02) using audiometric data as the criterion standard. Construct validity was also high using results from other instruments; both convergent and divergent validity of the HSS was demonstrated. In addition, the HSS demonstrated the ability to differentially discriminate between subgroups when grouped by level of hearing loss. CONCLUSIONS: The HSS is a valid and reliable instrument for use in outcomes research on conductive hearing loss.

Iron deficiency anemia and hearing.

Iron deficiency anemia is a frequently occurring clinical disorder. Despite the suggested association with hearing loss in the literature, cochlear sequelae of iron deficiency have yielded conflicting results in experimental studies. Auditory function was tested in iron-deficient and normal male Wistar albino rats using distortion product otoacoustic emissions and auditory brainstem response audiometry for the clarification of the opposing results in the literature. Hemoglobin, hematocrit, serum iron and albumin levels were monitored to verify iron deficiency. Although dramatic differences in weight gain and blood test parameters were noted, no significant change in auditory function due to iron deficiency was detected.

Virtual reality surgical simulation and otolaryngology.

Large-scale flight simulation was pioneered in the 1940s to help meet the training requirements and demand for pilots in World War II. Flight simulators have been effective for training, evaluating, and certifying military and commercial pilots. Accurate scenarios have been developed that allow pilots in training to gain experience without the risk and expense of learning while in flight. The research in aviation simulation suggests a transfer effectiveness ratio of 0.48. This means that 1 hour in the simulator saves a half hour in the air. Because of the successful use of flight simulation as a training technique, computer-based simulators are now used in a variety of domains.

Barotrauma after stapes surgery: a survey of recommended restrictions and clinical experiences.

OBJECTIVE: To identify a consensus on the postoperative barorestrictions after stapes surgery and to examine the clinical barotrauma experience within this patient population encountered by the surveyed physicians. DATA SOURCE: A 34-item survey was developed, allowing for detailed analysis of physician demographic data, practice characteristics, surgical experience, and clinical experience with barotrauma after stapes surgery. The postoperative restrictions addressed by the survey included those for air travel, snorkeling, and scuba diving. Recommendations for the use of ventilation tubes and hyperbaric oxygen therapy were investigated as well. STUDY SELECTION: Surveys were mailed to 419 active members of the American Otological Society and the American Neurotology Society as listed in the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) 1994-1995 Conjoint Directory. A total of 284 (67.8%) surveys were returned, of which 53 were not sufficiently completed and were excluded in the statistical analysis. DATA EXTRACTION: The demographic data and clinical experience were analyzed to determine statistical association with the postoperative recommendations using chi 2 or Fisher's exact tests. The kappa statistic was used as a measure of consistency between physicians' recommended restriction for a specific activity after a stapedectomy or stapedotomy. CONCLUSION: No consensus was demonstrated as to restrictions from activities such as air travel, snorkeling, or scuba diving. Despite this lack of consensus, no significant difference was demonstrated in the prevalence of barotrauma reported within the responding physicians' practices based on their individual recommendations for these activities.

Dimensions of the sinus tympani and its surgical access via a retrofacial approach.

The sinus tympani (ST) is a critical anatomic region of the temporal bone. It lies medial to the facial nerve, between the ponticulus and the subiculum, and therefore is not easily visualized by routine surgical approaches to the middle ear and mastoid. This limited access makes the ST a site that is notorious for residual cholesteatoma. An extensive evaluation of the anatomic dimensions of the ST was made from human temporal bones. Three hundred twenty-seven bones were examined at four standardized levels to describe the dimensions and anatomic relationships of the ST with other structures of the temporal bone. The region of the stapedial tendon was found to be the most limited anatomic substructure in the vicinity of the ST. This study demonstrates the feasibility of a retrofacial approach to the ST as an aid in eradication of otherwise hidden disease.

The use of E-mail by otolaryngologists.

Electronic mail (e-mail) is an extremely powerful form of communication and the most frequently used application on the Internet. While e-mail is not the appropriate mode of communication for every situation, there are many instances where its use is invaluable.

Endoplasmic reticulum protein expression in recombinant NS0 myelomas grown in batch culture.

During batch growth of two recombinant NS0 myelomas, an increase in the expression of the endoplasmic reticulum (ER) proteins (GRP78/BiP, GRP94, and ERp72) was observed. A marked increase in these proteins was associated with the decline phase of growth, an increase in the production rate of chimeric antibody, and a marked slowing or halt in the uptake of glucose and glutamate. Refeeding with glucose, glutamate, or a mixture of amino acids just prior to the onset of decline phase failed to repress induction. Although refeeding with glutamate led to an increase in specific productivity, there was no significant difference in the pattern of ER protein induction. These results indicate that an increase in ER protein expression is not solely related to productivity but also to certain changes that occur during the course of batch growth.

Changes in sensory organization test scores with age.

The goals of this study were to collect normative data on asymptomatic, ambulatory, community-dwelling adults on a standard diagnostic test of vestibular function in balance and to determine if their responses differ significantly from younger adults. Subjects were divided into four age groups, 18-44 years (young), 45-69 years (middle-aged), 70-79 (old), and 80-89 (elderly). Subjects were seen in the neurotologic diagnostic laboratory at a tertiary care facility. Their dynamic balance was tested under a variety of sensory conditions using the EquiTest (NeuroCom), a standard diagnostic test. The data from one subtest, the Sensory Organization Test (SOT) were evaluated. These data showed significant age-associated declines in overall score and changes in movement strategy. These results suggest that those parts of the vestibular system involved with balance have age-related declines through the end of the life span, even in asymptomatic people, and that these changes do not level off but continue into the ninth decade. Therefore, when elderly people are evaluated for balance disorders age-appropriate norms should be used. These results also suggest that declines in motor performance on laboratory tests are not directly related to reduced independence in essential activities of daily living in elderly people.

Progressive hearing loss after transverse temporal bone fracture.

Transverse fractures often violate the otic capsule and commonly, although not invariably, result in immediate and profound sensorineural hearing loss. The pathogenic mechanisms producing sensorineural hearing loss include direct trauma to the cochlear nerve, disruption of the membranous labyrinth, vascular compromise or hemorrhage into the inner ear, perilymphatic fistula, and endolymphatic hydrops. The last two mechanisms account for the occasional patient who develops progressive sensorineural hearing loss after the initial insult. On early posttraumatic evaluation three patients were discovered to have transverse fractures and residual auditory function. Deterioration of hearing led to middle-ear exploration with closure of perilymphatic fistulas. Hearing was preserved in two patients. Diagnosis of posttraumatic perilymphatic fistulas requires early audiometric assessment, high-resolution computed tomographic scanning of the temporal bones to detect fracture of the otic capsule and pneumolabyrinth, and a high index of clinical suspicion.

Radiation therapy in the management of paragangliomas of the temporal bone.

The use of radiation therapy for the treatment of paragangliomas of the temporal bone remains controversial. Few studies exist that provide sufficient information on staging the long-term follow-up to clarify this issue. A retrospective study was undertaken of 38 patients with temporal bone paragangliomas treated with radiation therapy between 1956 and 1991. All patients received radiation therapy, either as a primary modality (14 patients), in combination treatment with surgery (13 patients), or as salvage therapy (11 patients). Mean disease stage (Fisch classification system) for each group was C2, B, and C1, respectively. The follow-up period ranged from 1 to 27 years (median 11.5 yr). Local control was achieved in 79% of the primary radiation therapy group, 100% of the combined treatment group, and 91% of the salvage therapy group. Complications resulting from radiation therapy were few and minor. This study demonstrates that the use of radiation therapy for temporal bone paragangliomas offers effective local control as a primary treatment modality, in combination with surgery, and as salvage therapy with few long-term complications.