Distortion-product otoacoustic emissions and cochlear microphonics: relationships in patients with and without endolymphatic hydrops.

OBJECTIVES: Because endolymphatic hydrops causes cochlear malfunction, and both otoacoustic emissions and cochlear microphonics measure specific cochlear activities, some insight into the pathology of Meniere's disease might be gained by using these two test modalities. Specifically, the involvement of cochlear outer hair cells in patients with endolymphatic hydrops may be detected. Furthermore, it is hoped that these two tests might help determine which regions of the cochlea are affected by endolymphatic hydrops, as well as where along the auditory pathway abnormalities are present. STUDY DESIGN: Data were gathered prospectively on patients presenting to a private, tertiary referral otology/neurotology practice. METHODS: From February 1999 to April 2000, clinical information was collected on patients presenting with vertigo, hearing loss (HL), sudden HL, fluctuant HL, aural fullness, and/or tinnitus. Data included demographics, diagnosis, pure-tone and speech audiometry, tympanometry, summating potential, action potential, cochlear microphonic, and distortion-product otoacoustic emissions. Descriptive statistics were calculated, and relationships between distortion-product otoacoustic emissions and cochlear microphonics in patients with hydrops (defined as summating potential to action potential ratio > or =0.40) and without hydrops were analyzed. RESULTS: Distortion-product otoacoustic emissions were present more often and had larger amplitudes at the lower frequencies. No differences were found in the presence of distortion-product otoacoustic emissions across the frequencies for the two groups, but larger mean amplitudes were found for hydropic ears at 7966 Hz. As hearing levels worsened, both hydropic and nonhydropic ears were less likely to have emissions present; however, 18% of hydropic ears had emissions unexpectedly present when the pure-tone thresholds were > or =50 dB. The cochlear microphonic from the hydrops group tended to be smaller, but this was not statistically significant. Analysis of variance showed a small negative correlation between summating potential to action potential ratio and level of emission at 1968 Hz in hydropic ears; otherwise, there was no relationship between the ratio and emissions. The only statistically significant finding when analyzing the relationship between cochlear microphonic and otoacoustic emission was a small positive correlation between level of microphonic and level of emission at 1406 Hz in hydropic ears. No significant relationships were found between hearing thresholds and emissions or microphonics. CONCLUSIONS: Even though both distortion-product otoacoustic emissions (DPOAEs) and cochlear microphonics (CMs) measure specific cochlear activities, they were not found to be useful for differentiating patients with hydrops from those without. In some patients, however, unexpected distortion-product otoacoustic emissions were present. This may represent localizing information about which regions of the cochlea are being affected by hydrops in these patients. Also, a small positive correlation between the CM and the DPOAE at 1406 Hz was detected in the hydrops group, which may represent the effects of endolymphatic hydrops on the outer hair cell. Future investigations involving hydropic patients with unexpected DPOAEs and studies looking for more DPOAE and CM correlations at frequencies surrounding 1406 Hz are being planned.

Atypical glandular cells of undetermined significance (AGUS): cytopathologic features, histopathologic results, and human papillomavirus DNA detection.

We intensively reviewed 137 smears initially classified as atypical glandular cells of undetermined significance (AGUS) to refine cytological criteria for evaluating these cases, evaluate histological outcomes, and assess the value of human papillomavirus (HPV) DNA testing in management. Consenting, nonpregnant study participants were identified from a cohort of 46,009 women receiving routine Pap smear screening in a managed care setting. Colposcopy was performed on all women, and at least one histological sample was obtained from each. Review diagnoses were assigned to smears and biopsy specimens by two separate panels of pathologists. DNA testing for cancer-associated HPV types was performed on rinses of cytological samplers after a smear and thin-layer slide had been made. On review, 47 (34%) smears were reclassified as negative, 44 (32%) as AGUS, 30 (22%) as atypical squamous cells of undetermined significance (ASCUS), and 16 (12%) as squamous intraepithelial lesions (SIL). The 19 smears interpreted as high-grade intraepithelial lesions on review included 13 high-grade SIL (HSIL), two HSIL with AGUS, favor neoplastic (endocervical adenocarcinoma in situ [AIS]), and four AGUS, favor neoplastic (AIS). Review histological diagnoses were negative in 105 (77%), squamous or glandular atypia in four (3%), low-grade SIL (LSIL) in nine (7%), HSIL in 12 (9%), AIS in five (4%, including two with concurrent HSIL), and endometrial carcinoma in one (1%). HPV testing identified 11 (92%) of 12 women with histologically confirmed HSIL and all five with AIS (100%). A high-grade intraepithelial lesion or carcinoma is detected in approximately 14% of women with community-based diagnoses of AGUS who are referred for immediate evaluation. Use of refined cytological criteria and HPV DNA testing may permit improved management of women with AGUS.

Identifying women with cervical neoplasia: using human papillomavirus DNA testing for equivocal Papanicolaou results.

CONTEXT: A Papanicolaou (Pap) test result of atypical squamous cells of undetermined significance (ASCUS) presents a clinical challenge. Only 5% to 10% of women with ASCUS harbor serious cervical disease, but more than one third of the high-grade squamous intraepithelial lesions (HSILs) in screening populations are identified from ASCUS Pap test results. OBJECTIVE: To determine whether human papillomavirus (HPV) DNA testing of residual material from liquid-based Pap tests and referral of cases found to be HPV-positive directly to colposcopy could provide sensitive detection of underlying HSILs in women with ASCUS Pap results, compared with repeat Pap testing. DESIGN AND SETTING: Natural history of women with ASCUS Pap smear results, all of whom had liquid-based cytology, HPV testing, and subsequent repeat Pap tests and colposcopy with histologic evaluation, conducted at 12 gynecology clinics in a large managed care organization between October 1995 and June 1996. PARTICIPANTS: From a cohort of 46009 women who had routine cervical examinations, 995 women with Pap test results of ASCUS who consented to participate were identified. MAIN OUTCOME MEASURES: Cervical histology, HPV test results, and repeat Pap smear results, and sensitivity of HPV testing to identify patients found to have HSIL+ histology. RESULTS: Of 995 participants with ASCUS Pap test results, 973 had both a definitive histologic diagnosis and HPV result. Sixty-five (6.7%) had histologic HSIL or cancer. For women with histologic HSIL+, the HPV test was positive in 89.2% (95% confidence interval [CI], 78.4%-95.2%), and the specificity was 64.1 % (95% CI, 60.9%-67.2%). The repeat Pap smear result was abnormal in 76.2% (95% CI, 63.5%-85.7%). Triage based on HPV testing only or on repeat Pap testing only would refer similar proportions (approximately 39%) to colposcopy. The sensitivity of HPV DNA testing for HSIL was equivalent to, if not greater than, that of the repeat Pap test. We further estimated that an HPV-based algorithm including the immediate colposcopy of HPV-positive women, and then repeat Pap testing of all others, would provide an overall sensitivity of 96.9% (95% CI, 88.3%-99.5%). CONCLUSIONS: For women with ASCUS Pap tests, HPV DNA testing of residual specimens collected for routine cervical cytology can help identify those who have underlying HSIL. By testing the specimen collected at initial screening, the majority of high-risk cases can be identified and referred for colposcopy based on a single screening.

Determining the utility and effectiveness of the NeoPath AutoPap 300 QC System used routinely.

OBJECTIVE: To evaluate routine use of the NeoPath AutoPap 300 QC System (AP 300) as it influences diagnostic quality and operations in a large cytology laboratory. STUDY DESIGN: During a three-month period, 35,143 conventionally prepared consecutive cervical cytologic smears taken from non-high-risk women and evaluated as negative by our staff of 25 cytotechnologists were selected for processing by four AP 300 instruments. Slides flagged for review by the AP 300 were reevaluated by our five quality control (QC) cytotechnologists. False negative (FN) results were compared with results of our current practice (CP), random-selection QC method, used during the preceding six months. RESULTS: A 240% increase was seen in the FN detection rate for atypical squamous cells of undetermined significance (ASCUS) and squamous intraepithelial lesions (SIL) (n AP = 65 FN in 5,034 QC, n CP = 77 FN in 22,052 QC) and a 744% increase in the FN detection rate for low and high grade SIL (n AP = 24 FN/5,034 QC, n CP = 12 FN/22,052 QC). The rate of overcall by cytotechnologists did not increase. The QC ASCUS/SIL ratio improved. FN biopsy correlation increased from 45% to 85% (n CP = 17/38 agreement, n AP = 23/27 agreement). Turnaround time increased by one or more days for negative and 1.5 days for QC result reporting. Sensitivity varied among instruments. CONCLUSION: More FN results and greater specificity were seen using the AP 300 than using CP. As with other instrumentation, each laboratory should establish acceptable ranges of performance and baseline values for sensitivity and specificity.

The rehabilitation of conductive hearing impairment.

Conductive hearing loss (CHL) usually is amenable to surgical correction. At times, patients with CHL may not be candidates for surgical correction, or they may refuse to undergo the procedure. In such a situation, the patient should be encouraged to try hearing aids, either conventional or bone conduction, depending on the pathologic condition. After a discussion of bone-conduction implantable hearing aids, the article discusses congenital aural atresia, otosclerosis, and the management of CHL after infratemporal fossa approach and transtemporal approaches.

Management of external penetrating injuries into the hypopharyngeal-cervical esophageal funnel.

OBJECTIVE: To compare outcomes related to observation versus exploration for the hypopharynx and the cervical esophagus as the site of proven external penetrating injuries. METHODS: The records of 70 patients (47 with hypopharyngeal and 23 with cervical esophageal wounds) were retrospectively reviewed. RESULTS: No patient, observed or explored, who sustained a penetration into the hypopharynx above the level of the tips of the arytenoid cartilages of the larynx developed a complication. However, 22% of the patients with a hypopharyngeal injury below this level and 39% of patients with a cervical esophageal injury developed either a deep neck infection that required drainage or a postsurgical salivary fistula. CONCLUSIONS: Overall, the consequences of an external penetrating injury become more serious in the descending levels of the funnel formed by the hypopharynx and cervical esophagus. Injuries located in the upper portion of the hypopharynx can be routinely managed without surgical intervention. Neck exploration and adequate drainage of the deep neck spaces are, however, mandatory for all penetrating injuries into the cervical esophagus and most injuries into the lower portion of the hypopharynx.

Predicting rodent carcinogenicity from mutagenic potency measured in the Ames Salmonella assay.

Many in vitro tests have been developed to identify chemicals that can damage cellular DNA or cause mutations, and secondarily to identify potential carcinogens. The test receiving by far the most use and attention has been the Salmonella (SAL) mutagenesis test developed by Ames and colleagues [(1973): Proc Natl Acad Sci USA 70:2281-2285; (1975): Mutat Res 31:347-364], because of its initial promise of high qualitative (YES/NO) predictivity for cancer in rodents and, by extension, in humans. In addition to the initial reports of high qualitative predictivity, there was also an early report by Meselson and Russell [in Hiatt HH et al (1977): "Origins of Human Cancer, Book C: Human Risk Assessment," pp 1473-1481] of a quantitative relationship between mutagenic potency measured in SAL and carcinogenic potency measured in rodents, for a small number of chemicals. However, other reports using larger numbers of chemicals have found only very weak correlations. The primary purpose of this study was to determine whether mutagenic potency, as measured in a number of different ways, could be used to improve predictivity of carcinogenicity, either qualitatively or quantitatively. To this end, eight measures of SAL mutagenic potency were used. This study firmly establishes that the predictive relationship between mutagenic potency in SAL and rodent carcinogenicity is, at best, weak. When predicting qualitative carcinogenicity, only qualitative mutagenicity is useful; none of the quantitative measures of potency considered improves the carcinogenicity prediction. In fact, when qualitative mutagenicity is forced out of the model, the quantitative measures are still not predictive of carcinogenicity. When predicting quantitative carcinogenicity, several possible methods were considered for summarizing potency over all experiments; however, in all cases, the relationship between mutagenic potency predictors and quantitative carcinogenicity is very weak.

Relief of headache by cranioplasty after skull base surgery.

Headache after skull base surgery can cause profound morbidity in certain patients, resulting in significant impairment of their quality of life. Several methods to prevent postoperative headache have been described, including a modification of the skin/muscle incision replacing the craniotomy bone flap replacing the bone flap and filling in the residual defect with methyl methacrylate, using hydroxyapatite cement (HAC) to fill the craniectomy defect, and wiring hardened methyl methacrylate (MMA) into the defect. Ten patients with severe headache following craniectomy for a posterior fossa lesion underwent cranioplasty with MMA, which was placed exactly within the craniectomy defect and secured rigidly with miniplates and screws. The headache decreased in severity in all patients and resolved completely in 90%. Also, 78% of patients with dizziness improved. The procedure and its effect on headache and dizziness will be described.

Sudden bilateral sensorineural hearing loss.

Most cases of sudden sensorineural hearing loss (SHL) remain idiopathic, and the majority are unilateral. From 1989 to 1993, 823 patients with sudden SHL were evaluated. Of these, 14 (1.7%) had sudden bilateral SHL. We reviewed the charts of these 14 patients to compare sudden bilateral SHL with sudden unilateral SHL. Usually, bilateral SHL was asymmetric. Most bilateral cases received combined steroid and vasodilator treatment, while unilateral cases were more likely to receive only one of these treatments. By audiological criteria, 67% of bilateral SHL cases improved, while the improvement rate in unilateral SHL was 52%; however, this difference was not statistically significant. In bilateral SHL patients showing improvement, both ears responded. Bilateral SHL patients were older at the onset of hearing loss, had a higher incidence of vascular disease, and were more likely to have positive antinuclear antibody titer. Recognition of similarities and differences between sudden unilateral and bilateral SHL can help in counseling patients.

Prognosis and treatment of sudden sensorineural hearing loss.

Most cases of sudden sensorineural hearing loss (SHL) are idiopathic. Consequently, the otologist may be asked to predict hearing recovery and select a treatment strategy without fully understanding the disease process. We retrospectively reviewed the charts of 837 patients with SHL to evaluate the prognostic value of specific clinical parameters and the effectiveness of steroid and vasodilator treatments. Treatment response was defined by the patient's subjective response and audiological criteria. Patients who were treated with steroids and/or vasodilators were more likely to improve. Patients who improved had a worse initial pure-tone average (PTA) than those who did not improve. In addition, those with poorer initial speech discrimination scores, worse initial thresholds at 4,000 Hz, younger age, and greater number of treatments were more likely to improve. Neither the electronystagmogram results nor the initial audiogram shape were valuable indicators. Recognition of prognostic indicators can help in counselling patients and in the evaluation of treatment response.

Sudden hearing loss in acoustic neuroma patients.

Patients with acoustic neuroma may have sudden sensorineural hearing loss. Most patients with sudden hearing loss seek medical attention promptly, but the diagnosis of an acoustic neuroma may be delayed for months or years because sudden hearing loss is an unusual initial symptom of an acoustic neuroma. In a retrospective review of 836 cases of sudden hearing loss, we found 13 patients with acoustic neuromas. The prevalence of acoustic neuromas for those screened with auditory brain stem response or magnetic resonance imaging was 2.5%. In addition to these 13 patients, 79 acoustic neuroma patients treated in our clinic had well-documented sudden hearing loss as the initial symptom. Hearing loss in these 92 patients ranged from mild to profound. Associated symptoms of pain, facial paresthesia, or unilateral tinnitus preceding the sudden hearing loss were suggestive of an acoustic neuroma, as was a midfrequency (U-shaped) hearing loss. A history of other diseases or events that might explain the sudden hearing loss, a normal electronystagmogram, or recovery of hearing does not eliminate the possibility of a tumor. Because there are no clinical findings that clearly distinguish those patients with acoustic neuromas from other patients with sudden hearing loss, we recommend either an evaluation with auditory brain stem response or gadolinium-enhanced magnetic resonance imaging for any patient with sudden hearing loss.

Gunshot wounds of the temporal bone: a rational approach to evaluation and management.

Gunshot injuries of the temporal bone are uncommon but are being seen more frequently with the increasing incidence of violent crimes and use of firearms. A retrospective analysis of 43 consecutive patients treated at our institution with this injury was undertaken to determine the clinical symptoms, associated injuries, and treatment outcome. This is the largest series from a single institution treated by a single group during a brief period of time. Most of these patients had injury to various structures within and around the temporal bone, including hearing loss (29), intracranial injury (23), facial nerve injury (22), vascular injury (14), and mandible fracture (6). Ocular trauma and paralysis of cranial nerves V and IX, X, XI, and XII were rare occurrences. A rational approach to the evaluation and management of these injuries will be discussed in detail to optimize outcome.

Management of traumatic hypopharyngeal injuries.

Violation of the hypopharynx by external penetrating trauma is an uncommon occurrence that may lead to life-threatening infectious complications if not recognized promptly and treated appropriately. A retrospective review of 48 such injuries seen during a 10-year period showed that flexible fiberoptic endoscopic examination is the best screening tool for recognition of a possible hypopharyngeal mucosal violation. Direct laryngopharyngoscopy is the best method of definitively diagnosing the injury. Size of the visualized mucosal violation alone is not sufficient information on which to base the decision for medical management versus surgical intervention (i.e., immediate exploration and drainage). Rather, the size, exact site of injury, and mechanism of the injury must be considered to have equal importance. Associated vertebral body fractures may negatively influence acute outcome if diagnosis and treatment of the hypopharyngeal injury are delayed by the cervical spine injury.

Metabolic influences on satiety in rats receiving parenteral nutrition.

Food intake is reduced during parenteral nutrition (PN) proportionally to the amount of calories or composition of the solution infused. The relative importance of infused glucose and lipid, 50 and 30% of PN kilocalories, respectively, in reducing food intake during PN was examined. Glycolysis, fatty acid oxidation, or both were acutely disrupted with 2-deoxy-D-glucose (2-DG) and mercaptoacetate (MA). Rats receiving intravenous infusions of saline or a PN solution providing 100% of total daily calories (PN-100) received a single intraperitoneal injection of saline, 2-DG, and/or MA during the early light phase. 2-DG (1.4 or 2.2 mmol/kg) did not initiate feeding in PN-100 rats, although hyperglycemia was evident in all rats 1 h after 2-DG. Food intake of PN-100 rats after MA (0.4 mmol/kg) was approximately 50% that of control rats. When 2-DG (1.4 mmol/kg) and MA (0.4 mmol/kg) were administered concomitantly, PN-100 and control rats consumed the same amount of food. During PN-100, rats appeared to be more sensitive to losing metabolic energy derived from lipid than from glucose.

Some comments on potency measures in mutagenicity research.

In this article, the measurement of the potency of a chemical or mixture from its dose response in a particular assay is addressed. Attention is focused on data from the Ames Salmonella assay. Three measures of potency are explored and shown to be highly correlated. The presentation then discusses specific areas of research that might benefit from a study of potency.