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Background: Tinnitus is a leading cause of disease burden globally. Several therapeutic strategies are recommended in guidelines for the reduction of tinnitus distress; however, little is known about the potentially increased effectiveness of a combination of treatments and personalized treatments for each tinnitus patient., Methods: Within the Unification of Treatments and Interventions for Tinnitus Patients project, a multicenter, randomized clinical trial is conducted with the aim to compare the effectiveness of single treatments and combined treatments on tinnitus distress (UNITI-RCT). Five different tinnitus centers across Europe aim to treat chronic tinnitus patients with either cognitive behavioral therapy, sound therapy, structured counseling, or hearing aids alone, or with a combination of two of these treatments, resulting in four treatment arms with single treatment and six treatment arms with combinational treatment. This statistical analysis plan describes the statistical methods to be deployed in the UNITI-RCT., Discussion: The UNITI-RCT trial will provide important evidence about whether a combination of treatments is superior to a single treatment alone in the management of chronic tinnitus patients. This pre-specified statistical analysis plan details the methodology for the analysis of the UNITI trial results., Trial Registration: ClinicalTrials.gov NCT04663828 . The trial is ongoing. Date of registration: December 11, 2020. All patients that finished their treatment before 19 December 2022 are included in the main RCT analysis., (© 2023. The Author(s).)

Purpose of Review: To provide an update on the most frequent peripheral vestibular disorders., Recent Findings: The on-going classification of vestibular disorders by the Bárány Society represents major progress. The diagnosis of bilateral vestibulopathy (BVP) requires quantitative testing of vestibular function. 'Acute unilateral peripheral vestibulopathy' (AUPVP) is now preferred over 'vestibular neuritis.' Menière's disease is a set of disorders with a significant genetic contribution. The apogeotropic variant of horizontal canal benign paroxysmal positional vertigo (hcBPPV) and anterior canal BPPV (acBPPV) can be distinguished from a central vestibular lesion. Vestibular paroxysmia is now an internationally accepted clinical entity. The diagnosis of SCDS is based on conclusive findings., Summary: Diagnosis of BVP requires significantly reduced vestibular function. The clinical picture of AUPVP depends on how much the vestibular end organs or their innervation are affected. Menière's disease phenotype is a constellation of symptoms. Although diagnostic and therapeutic criteria for pc and hcBPPV are well defined, a number of less frequent and controversial are increasingly diagnosed and can be treated. Diagnosis of vestibular paroxysmia requires that a patient responds to treatment with a sodium channel blocker. The diagnosis of SCDS requires conclusive findings with various methods. There is still a great need for state-of-the-art randomized controlled treatment trials in most peripheral vestibular disorders.

Objective: To assess the effect of intratympanic methylprednisolone (ITMP) in posterior canal benign paroxysmal positional vertigo (BPPV) that fails treatment involving repositioning maneuver in a case series., Materials and Methods: Nine patients with persistent posterior canal BPPV after 6 or more repositioning maneuvers were treated by ITMP (two weekly doses of 0.3-0.4 mL at 40 mg/mL) before repeating the repositioning procedures., Results: Following ITMP treatment, 7 out of 9 patients were relieved of their symptoms and did not exhibit positional nystagmus after 1 or 2 repositioning maneuvers. The number of positional maneuvers performed before and after ITMP treatment in these 7 patients showed a statistically significant (p=0.016) reduction in the amount of repositioning treatments required. None of the 7 respondent patients showed any relapses during the follow-up period (follow-up range: 11-95 months)., Conclusion: Administering ITMP before resuming repositioning procedures can be a useful treatment for persistent BPPV of the posterior canal.

Introduction: Chronic tinnitus affects 5-15% of the general population; in 1% of individuals with tinnitus this condition severely affects their quality of life. Pharmacological treatment is one of the options for the management of tinnitus patients, but their efficacy remains controversial. AIM. To evaluate the level of evidence to support the use of different drugs in reducing the severity of tinnitus., Development: The pharmacological groups that have been investigated for the treatment of tinnitus include anesthetics, anticonvulsants, antidepressants, antihistamines, benzodiazepines, diuretics, corticosteroids, and of other substances. Intravenous lidocaine seems to be effective, but the short duration of the effect and the adverse reactions prevent its use. Compared with placebo, carbamazepine and gabapentine have not demonstrated effectiveness although they may be effective in some patients with auditory nerve vascular compression or myoclonus. Tricyclic antidepressants are no more effective than placebo at reducing tinnitus severity although they may improve comorbid depression. There is insufficient evidence to evaluate the effectiveness of selective serotonin reuptake inhibitors and benzodiazepines. Acamprosate may decrease the severity of tinnitus, but the level of evidence is low. There are no consistent results in the studies with intratympanic gentamicin or steroids in tinnitus associated with Meniere's disease., Conclusions: The use of pharmacotherapy in reducing the severity of tinnitus is not well supported by prospective, randomized, placebo-controlled clinical trials. Various drugs have been shown to be effective in some studies, but the clinical evidence is limited. Large randomized clinical trials are needed.

Introduction: In 2008, the Otoneurology committee of the SEORL-PCF published a classification of peripheral vertigo, based on clinical criteria. The objective of this study was to validate this classification through analysing the diagnostic agreement among several medical assessors., Methods: Seven medical assessors, all with clinical experience, from 6 different hospitals, participated in the study. One of them selected the clinical histories of 50 consecutive patients who had consulted as a result of balance disorders (24 men and 26 women) with an average age of 53.5 years. These clinical histories -without any information that would identify the patient, the diagnosis established and the treatment- were sent to another 6 assessors. Each of these investigators established their own diagnosis, trying to adjust it to the epigraphs of the classification., Results: Of the 50 patients, there was substantial agreement as to the diagnosis (4 or more evaluators indicated the same one) in 31 cases (26 with a positive diagnosis and 5 with a negative one, which could not be included in any epigraph). The kappa index, which measures the level of accordance between 2 or more assessors, was 0.4198 (moderate level of agreement). Unanimity was achieved in only 7 cases (4 BPPV, 2 Ménière's disease and 1 vertigo associated with migraine)., Conclusions: The current classification, with the criteria it includes, allows labelling with an acceptable consensus to only 62% of the patients. Therefore, a modification in the classification is proposed in relation with the probable BPPV epigraph, as well a revision of the entries for vertigo-migraine and vertigo associated with migraine., (Copyright © 2011 Elsevier España, S.L. All rights reserved.)

Introduction and Objectives: Ménière's disease (MD) is a chronic disorder of the inner ear affecting health-related quality of life in 85% of patients. Although different studies have evaluated the impact of MD on quality of life, sexual health has not been investigated in these patients. The aim of this study was to assess sexual health in patients with MD., Material and Methods: A cross-sectional pilot study was carried out using the general health instrument SF-36, the Dizziness Handicap Inventory Short Form (DHI-S) and two specific questionnaires on sexual functioning, the Female Sexual Function Index (FSFI) for women and the International Index of Erectile Function (IIEF) for men. A statistical analysis of domains of the instruments was performed to compare the score obtained to reference values, and correlation coefficients were calculated to determine the association among different instruments. The level of significance accepted was p<0.05., Results: Forty-eight individuals (26 women and 22 men) with a mean age of 55 and a low-medium culture level were studied. Men showed a high prevalence of erectile dysfunction, twice the national reference values; women had alterations in the sexual satisfaction and pain domains. In both situations, sexual function disorders were dependent upon the SF-36 emotional domains., Conclusions: Emotional problems associated with Ménière's disease may be associated with sexual function disorders, including sexual desire in women and erectile dysfunction in men., (Copyright © 2010 Elsevier España, S.L. All rights reserved.)

Benign paroxysmal positional vertigo is the most common vestibular disorder and it has a significant impact on health-related quality of life. The disease is probably caused by the accumulation of lithiasis material from the otolithic membrane of the utricle. Patients experience multiple short vertigo crises lasting seconds when they go to bed or turn over. There are several clinical variants affecting posterior, horizontal or anterior canals and in some cases vestibular lithiasis can occur in two canals simultaneously. Diagnosis is by video-oculographic recording of positional nystagmus during positional tests to identify the canal affected. There are specific treatment manoeuvres for each clinical variant, which a high degree of short-term effectiveness.

Objective: To analyze the time course of caloric response in patients with Benign Paroxysmal Positional Vertigo (BPPV)., Patients: Seventy-four individuals with diagnosis of BPPV during Dix-Hallpike (DH) test., Study Design: A prospective, longitudinal study., Setting: A tertiary referral center., Intervention: Patients were treated by particle repositioning maneuvers according to the affected canal, and the effectiveness was evaluated at 180 and 360 days. Bithermal caloric response was obtained by using 44 and 30 degrees C water irrigations at diagnosis, 6 months, and 1 year after., Main Outcome Measure: Canal paresis (CP) and response to DH after treatment., Results: The effectiveness of the treatment for BPPV (absence of vertigo and positional nystagmus during DH) was 65.2% (45 of 69) after 1 year of follow-up. Twenty-five percent of (16 of 64) individuals with BPPV presented CP at diagnosis, 27% (12 of 44) at 6 months, and 16% (9 of 56) 1 year after. One year after, seven individuals with CP showed a normal caloric response, another seven demonstrated persistent CP, and one case developed a bilateral CP. The effectiveness of particle repositioning maneuvers was not significantly different between subjects with or without CP after 1 year of follow-up (odds ratio, 1.31 [95% confidence intervals, 0.35-4.89], p = 0.88)., Conclusion: Canal paresis is not associated with a lower outcome to repositioning.

Objective: To evaluate the eye movement response to the head auto-rotation test (HART) in the vertical plane in patients with benign paroxysmal positional vertigo., Design: A transversal, descriptive study. SETTING UP: Outpatient clinic in a general Hospital., Individuals: 34 posterior canal BPPV cases with a video-oculographic diagnosis, older than 18 years old, 7 of them were not able to perform the HART., Intervention: HART was performed by a an electrooculographic system with simultaneous recording of head movement by an acelerometer in the vertical plane (Vorteq, Micromedical Instruments). The HART with eyes fixation was performed 3 times to determine its reliability., Main Outcome Measures: Gain, asymmetry and phase for the vertical VOR respectively. A statistical analysis was carried out to determine the test reliability and the number of individuals with an abnormal result., Results: Gain is the only variable that showed a reproducible result in the HART for the active head movement at 1-2 Hz (test-retest reliability 0.83-0.89). The values of gain showed a moderate correlation at the frequencies 1-3 Hz (correlation 0.60-0.87). Asymmetry and phase were not reproducible variables (correlation < 0.55). Thirteen of 27 (48%) patients presented a decrease of the vertical gain, another 13 showed normal values and one case showed raised values., Conclusion: Gain is the only useful variable in the vertical HART. Forty-eight percent of patients with posterior canal BPPV have a reduced vertical gain, suggesting an impairment of inferior vestibular nerve function.

Objective: To obtain reference values for the vestibulo-ocular reflex response to the head-shaking nystagmus and the bithermal caloric test in the spanish population., Design: A descriptive study. SET UP: General hospital., Individuals: One hundred and seven healthy sex and age stratified voluntiers were included. The final sample included 97 individuals over 18 years of age., Intervention: Spontaneous nystagmus (SN), head-shaking nystagmus (HSN) and caloric induced nystagmus were explored. The eyes movement was recorded by a video-oculographic system. The SN or HSN was considered significant when at least 6 consecutive beats with a slow phase velocity of 2 degrees/sec were detected. The caloric test was performed with water flow at 250mL/20 s at 30 degrees C and 44 degrees C with an interval of 10 minutes between irrigations. The percentage of canal paresis (CP) and directional preponderance (DP) was calculated using maximum slow phase velocity and the Jongkees index formula., Main Outcome Measurements: Presence of SN, horizontal and vertical SHN, percentage of CP and DP., Results: SN was found in 10,3% individuals (6 women and 4 men). Horizontal HSN was also observed in 9 women and 10 men (19,5%), and vertical HSN in 8 women and 10 men (18,6%). The mean and 95 percentil for CP were 13,10 and 28,60 in women and 11,02 and 27,30 in men. For DP, the mean and 95 percentil were 11,76 and 35,80 in women and 11,58 and 28,65 in men. The 5 percentils for slow phase velocity of nystagmus after each irrigation were 6,30; 5,14; 5,96; 4,02 degrees/s (left ear 44 degrees, right ear 44 degrees, left ear 30 degrees, right ear 30 degrees, respectively) in the group of women; and 5,82; 6,99; 5,67; 4,55 degrees/s in men (with the same irrigation sequence)., Conclusion: Results presented should be considered as a population-based norms and may be useful as references for water bithermal test for VOG studies. The SN or HSN could be observed in subjects without vestibular pathology.

Missense mutations in the coagulation factor C homology (COCH) gene (14q12-q13) cause the autosomal dominant sensorineural hearing loss and vestibular disorder DFNA9 (OMIM 603196), and a high prevalence of symptoms of Meniere disease (MD) has been described in families with a mutation in the COCH gene. In this study, we search for mutations in the COCH gene in peripheral blood from patients with definite MD. DNA was extracted from peripheral blood cells of 30 individuals with MD and 30 controls. Exons 4 and 5 of the COCH gene were amplified by PCR reaction, using primer pairs flanking both exons. Sequences were analysed by a DNA sequencing system and compared with the published COCH cDNA sequence. No differences were found in the nucleotide sequences of exons 4 and 5 in the COCH gene in patients with definite sporadic MD when they were compared with the control group. Patients with definite MD have a low prevalence of mutations in exons 4 and 5 of the COCH gene.

Objective: The purpose of this study was to identify pre- or intraoperative markers for post-tonsillectomy haemorrhage (PTH) that may help to define in-/outpatient tonsillectomy., Design: A retrospective case-control study of tonsillectomized patients., Setting: A tertiary referral university hospital., Methods: Twenty-three children with PTH were compared with 69 tonsillectomized age- and sex-matched children without bleeding. The cohort consisted of 559 individuals under 18 years old who were scheduled for tonsillectomy or adenotonsillectomy between 1996 and 2000., Main Outcome Measures: Physical and analytical variables were investigated, including blood pressure, haemoglobin and haematocrit levels, coagulation profile, American Society of Anesthesiology (ASA) physical status classification, indications for surgery, obstructive sleep apnea and snoring, surgical experience, addition of adenoidectomy, method of tonsillectomy, type of anaesthesia, method of haemostasis, and total surgical time. Statistical significance was calculated by the Mann-Whitney U test and Fisher's exact test., Results: The incidence of PTH was 4.11%, and all but one case were primary bleedings. Nineteen cases occurred within the first 8 hours. A possible risk marker identified was ASA class 2 (odds ratio = 5.69, p = .04). Other investigated factors were not significant., Conclusions: The ASA classification may be a predictor for PTH and could be used to select outpatients before tonsillectomy.

To analyze the associations of HLA class I and II antigens in patients with Meniere's disease (MD) in southern Spain, 54 patients with definite MD according to the diagnostic scale of the AAO-HNS were compared with 534 normal controls in a prospective multicenter study. We performed a serological typing for A, B, C and DR specificities of the major histocompatibility complex and allele-specific amplification for HLA-DRB1. No differences were found in the distribution of class I antigens or DR antigens in patients with definite MD when they were compared with the control group. Our results suggest that HLA antigens do not determine an increased susceptibility to develop MD.

Objective: To identify pre or intraoperative risk factors that could indicate a higher risk for post-tonsillectomy hemorrhage (PTH) in children undergoing electrocautery dissection. SET-UP: Primary referral hospital., Design: A retrospective study of 163 post-tonsillectomy children comparing 7 cases of PTH with 156 cases with no PTH., Sample: This study includes children under the age of 18 that underwent tonsillectomy by dissection between 1997 and 2000., Outcome Parameters: Age, sex, height, weight, body mass index, hemoglobin level, hematocrit, platelet count activated partial thromboplastin time (APTT), fibrinogen, ASA index (physical state classification of the American Society of Anesthesiology) and type of hemostasis., Results: Prevalence of PTH was 4.29% in the cohort sample. The risk of PTH in children following tonsillectomy by electrodissection is significantly increased in patients over 15 years of age (OR = 8.46, p = 0.04) and when ligatures are used for hemostasis (OR = 8.62, p = 0.02). Activated partial thromboplastin time > or = 32 seconds is marginally significant (OR = 7.82, p = 0.05)., Conclusions: Our findings show that tonsillectomy by electrodissection has an increased risk of bleeding in older children and when ligatures are used for hemostasis.

Benign paroxysmal positional vertigo (BPPV) is a recurrent chronic disease and its handicap is usually underestimated. The aim of this study is to determine the impact of the treatment by Epley maneuver on short-term BPPV-related quality of life. Forty-two individuals with BPPV were included: 39 with posterior canal affected, 2 with the lateral canal and one with the anterior canal. Diagnosis was established if a consistent clinical history was found and Dix-Hallpike test (DHT) in cases with canal posterior involvement. Subjects with positive DHT were treated by a single Epley maneuver and were recommended to avoid supine for the next 48 hours. The BPPV relapses were investigated at 7th and 30th day post-treatment. BPPV-associated quality of life was evaluated by the Dizzness Handicap Inventory Short-form (DHI-S) at days 1st and 30th post-treatment. Total and partial scores for emotional, physical and functional subscales were compared by Wilcoxon test for paired samples. Dix-Hallpike test was found positive in el 59% individuals (23/39), and 41% cases did not required any treatment. Among 23 patients treated with Epley maneuver, DHT was found negative in 90% at 30th day follow-up. Mean and standard deviation of the total scores obtained in the DHI-S at the first day were 19.22 +/- 9.66 in the DHT positive-patients and 19.79 +/- 10.14 in the whole group (DHT positive or negative). These scores significantly decreased to 10.84 +/- 10.99 at 30 days post-treatment (p = 0.002 and p = 0.001, respectively). In conclusion, the DHI-S is a specific health questionnaire able to assess BPPV-related health and the effectiveness of treatment.

Objective: To identify preoperative markers indicative of an increased risk of postoperative hemorrhage after tonsillectomy in adults., Setting: Tertiary referral hospital., Design: A retrospective 1:3 case-control study (19 post-tonsillectomy hemorrhage [PTH] cases versus a sample of 58 controls stratified by age and sex)., Subjects: Adults over 17 years of age who underwent tonsillectomy from 1989 to 1999 were included., Main Outcome Measurements: Height, weight, percentage of excess weight, body area, systolic and diastolic blood pressure, smoking, drinking, hemoglobin and hematocrit levels, platelet count, partial thromboplastin time, prothrombin activity, fibrinogen, ASA index (physical state classification of the American Society of Anesthesiology), and history of peritonsillar abscess., Results: The risk of PTH in adults was greater in patients with systolic blood pressure > or = 140 mm Hg (OR = 9.46, p = 0.01) and low hematocrit (< 37 for women and < 42 for men, OR = 3.46, p = 0.04). Hemoglobin levels < 12.5 also resulted in an increased risk of PTH in women (OR = 4.79, p = 0.058)., Conclusions: Our findings show that systolic hypertension and anemia may be significant risk factors for PTH in adults.

Sensorineural hearing loss (SHL) of autoimmune origin is characterized by a rapidly progressive onset. Diagnosis is difficult and the condition responds to corticoids or immunosuppressant agents. Two cases with an onset over weeks and progressive hearing loss are reported. Both patients had SHL associated with another autoimmune disease. Laboratory findings were abnormal (immunoglobulins and lymphocyte populations), suggesting an immune disorder. Treatment with 1 mg/kg/day of deflazacort restored hearing to normal. Both patients are currently asymptomatic. The clinical and laboratory response of patients to deflazacort supported the diagnosis of autoimmune SHL.

Headache and episodic vertigo are common symptoms in adults. Migraine-related dizziness and vertigo is a clinical process that is difficult to assess because specific diagnostic criteria are lacking. Although studies have demonstrated a relationship between migraine and dizziness, the prevalence of headache among patients with episodic vertigo is underestimated. A clinical inventory was used to determine the prevalence of headache among 150 patients with episodic vertigo and the impact that dizziness had on the quality of life using an ordinal scale for disability. Patients were questioned about drug use and self-perceived effectiveness. Twenty-three percent of the patients experienced a severe problem that disabled them for work. The prevalence of headache was 68.6% (71% of women and 64% of men). Forty-five percent of patients with episodic vertigo and 44% with headache did not obtain any benefit from symptomatic treatment. A subset of patients suffered from migraine-related dizziness and vertigo and were able to control their balance disorder with migraine therapy.

A structured questionnaire of vertigo (SQV) was used to search patients with Menière's disease (MD) in the first visit. One-hundred consecutive outpatients that complained of dizziness or vertigo were studied. Diagnosis of MD was accepted if three investigators independently recorded it among a list of 29 diagnostic categories after reviewing the SQV. The AAO criteria for definite MD defined by the Committee on Hearing and Equilibrium after 10 months or more of follow-up were the gold standard to contrast questionnaire-based diagnosis. Seven patients were considered as MD with the SQV. The sensitivity (Sn), specificity (Sp) and positive predictive value of the SQV for definite MD were 80%, 97% and 57% respectively, being the false positive rate 3%. The probability for diagnosis of definite MD using the SQV in the first visit was 58% in a set up with a 5% of prevalence. The best predictor selected by all investigators was the presence of hearing loss (Sn 100%, Sp 85%, positive likelihood ratio 6.67). Because of the high specificity, the SQV of vertigo results a useful test to advance the diagnosis of definite MD.

The structured clinical history is the most sensitive test for diagnosing vertigo. Its diagnostic effectiveness on the first visit was analyzed and key signs and symptoms with high predictive value for common causes of vertigo were identified. One hundred outpatients who complained of dizziness or loss of balance were evaluated using a structured clinical interview. Each questionnaire was examined independently by three blinded investigators, who assigned a diagnosis and identified the elements of the history that figured most prominently in the diagnosis. The gold standard was defined as independent selection of the same diagnostic category by all three investigators. A first-visit diagnosis was obtained in 40% of patients (95% confidence interval 30-50%): 38% women and 42% men. Causes included benign positional paroxysmal vertigo (BPPV, 13 patients), headache-associated vertigo (9), Meniere disease (7), cervical vertigo (3), psychiatric dizziness (2), post-traumatic vertigo (2), vertebro-basilar transient ischemic attack (1), vestibular neuritis (1), convulsive seizure (1), and presyncope (1). The best predictors of BPPV were the precipitating mechanism (specificity [SP] 100%), positional nystagmus (sensitivity [SE] 90%, SP 63%), and the Dix-Hallpike test (SE 82%, SP 71%). Elements predictive of headache-associated vertigo were duration of the attack (minutes) and a personal history of headache (both, SP 100%). Other predictors were facial hypoesthesia (SE 92%, SP 47%) and associated neurological disease (SE 82%, SP 58%).

A case of left horizontal-canal benign paroxysmal positional vertigo (HC-BPPV) in a woman with a 7-year history of episodic vertigo when turning over in bed is reported. The diagnosis was established with the patient lying down with her head raised 30 degrees with respect to the horizontal plane. Treatment with positional maneuvers (270 degrees contralateral head rotation in 3 steps) resolved the attacks. Positional testing failed to elicit symptoms 7 days, 14 days, 1 month, and 2 months after treatment. Four months after treatment, the patient remains asymptomatic. Published cases of HC-BPPV are discussed, as well as the differential diagnosis with posterior semicircular canal BPPV.

An occult, laterocervical papillary thyroid carcinoma tissue was found in a functional neck dissection for larynx cancer. The patient was a 76-year-old man with a history of smoking and alcohol ingestion who presented with a supraglottic carcinoma of the larynx located at the laryngeal surface of the epiglottis, left aryepiglottic fold, band and left ventricle with extension to the left vocal cord. Light microscopy showed a lymph node with a fibrous stroma with lymphoid follicles that presented a total substitution of the parenchyma by a papillary thyroid carcinoma. Although examination of the thyroid gland by seriated sections did not reveal any neoplasm, we argue that the papillary thyroid tissue is metastatic.

Latencies of auditory brainstem response are known to be affected by age and sex. We have investigated the effects of age and sex on absolute latencies of waves I, III and V, the interpeaks intervals I-V, I-III and III-V for left and right ears in 67 healthy subjects with normal hearing. We evaluated the reproducibility of the response between ears which showed consistent data. Latency-intensity plots for waves I, III and V were compared among men and women by estimating the regression equations, with no significant difference in the slopes. Regression analysis revealed that latencies of waves I and V were increased with age in men from childhood up to fifties, according to a linear function. However, in women latencies were not dependent on age. The intervals I-V, I-III and III-V were independent on age for both men and women. The latencies of waves III and V and the I-III and I-V intervals were significantly shorter in women than in men in both ears. The findings obtained in the present study show that gender have a stronger effect on latencies of waves III and V, shortening the I-III and I-V intervals in women. Moreover, latencies of waves I and V increase with age in men.

A case of permanent pulsatile tinnitus of the left ear in a patient with hypertriglyceridemia is reported. The combined radiological study with computed tomography, magnetic resonance imaging, and digital angiography excluded a glomus tumor and revealed an enlarged, high-position jugular bulb with slow blood flow. Causes of pulsatile tinnitus are discussed. We conclude that imaging techniques play a major role in the diagnosis of head and neck vascular abnormalities.

Intracellular Ca2+([Ca2+]i) is elevated by depolarization or mechanical stimulation in some hair cell systems. It is not clear whether both these stimuli promote Ca2+ entry in mammalian vestibular hair cells. We monitored [Ca2+]i with the indicator fluo-3 in isolated type I vestibular hair cells of the guinea pig maintained in Hanks' balanced salt solution (HBSS). Mechanical stimulation by bolus application of HBSS led to an immediate rise of [Ca2+]i. The effect depended upon the presence of extracellular Ca2+([Ca2+]o) and no increase occurred in calcium-free HBSS supplemented with calcium-chelators. When the cells were depolarized by bolus application of KCl (final concentration, 100 mM KCl in modified HBSS), the increase in [Ca2+]i was similar to that elicited by HBSS. In the absence of [Ca2+]o, the application of KCI/HBSS led to a slow sustained increase in the fluorescence of the cells suggesting release of calcium from intracellular stores. Finally, treatment of cells with BAPTA prior to mechanical stimulation prevented the rise in [Ca2+]i indicating the need for intact stereociliary tip-links. The results are consistent with the hypothesis that mechanical stimulation elevates [Ca2+]i in isolated vestibular hair cells via calcium influx through mechanotransduction channels.

Human natural killer cells and polymorphonuclear neutrophils constitutively express the low-affinity IgG Fc receptor (Fc gamma RIII, CD16 molecule). To investigate cell surface morphology, antigenic receptor density, and topographical distribution of Fc gamma RIII on the plasma membrane of natural killer cells and polymorphonuclear neutrophils, conventional scanning electron microscopy (SEM), flow cytometry, and immunoscanning electron microscopy were used. Fc gamma RIII was detected with an indirect immunogold labeling procedure, and receptors were visualized in the backscattered and secondary electron imaging mode of SEM. Natural killer cells showed a cell surface morphology compatible with lymphocytic differentiation characterized by microvilli and microridges. Polymorphonuclear neutrophils showed surface features characterized by ridges with folds and scattered short microvilli. Natural killer cells displayed a lower cell labeling density, whereas polymorphonuclear neutrophils showed a high level of expression of Fc gamma RIII on the plasma membrane by quantitative analysis with SEM in the backscattered electron imaging mode. Flow cytometry analysis confirmed these findings. Analysis of the topographical distribution of Fc gamma RIII antigenic receptor sites by SEM in the backscattered and secondary electron imaging modes showed that Fc gamma RIII on natural killer cells are randomly distributed, whereas Fc gamma RIII are located on ridges and folds of the plasma membrane of polymorphonuclear neutrophils. These observations suggest that natural killer cells and polymorphonuclear neutrophils differ in their levels of expression and topographic distribution of Fc gamma RIII on the plasma membrane. This different spatial distribution of Fc gamma RIII would provide morphological evidence of certain cellular functions mediated by natural killer cells and polymorphonuclear neutrophils.

Gentamicin-induced changes in ionic composition in the otolithic membrane of adult OF1 mice were evaluated in the gelatinous layers of the saccule and utricle by quantitative electron probe X-ray microanalysis. The otolithic membranes were plunge-frozen and freeze-dried to prevent the redistribution of elements. Quantitative analysis was carried out with an energy dispersive detector using the peak-to-background (P/B) ratio method and different salts dissolved in dextran as standards to calibrate the P/B ratio against the concentration of the elements P, S and K in the microprobe. Gentamicin selectively decreased the concentrations of P (P < 0.001) and S (P < 0.01) in the gelatinous membrane of the saccule, and had no effect in the utricle. The concentration of K also increased in the utricular gelatinous membrane (P < 0.05). The mechanism of ototoxicity in the gelatinous membrane is unknown, but the ability of aminoglycosides to block calcium channels may induce disturbances in the ionic equilibrium of the endolymphatic fluid, and thus affect the biochemical composition of the gelatinous membrane. This technique can be useful to evaluate the distribution of ions in the process of drug-induced ototoxicity.

Chronic gentamicin ototoxicity was evaluated in the otolithic membrane of adult OF1 mice at the otoconial layer of the saccule and utricle by quantitative electron probe X-ray microanalysis of Ca and K. The otolithic membranes were plunge-frozen and freeze-dried. The analysis was carried out with an energy dispersive detector using the peak-to-back-ground ratio method and different inorganic salts of Ca and K as standards to calibrate the microprobe. Ca and K in the otoconia are related via a linear function in both the saccule and the utricle. This association is not maintained after exposure to gentamicin, which suggests that this aminoglycoside antibiotic interferes with the Ca-K equilibrium in the otoconia. A dose of 200 mg/kg gentamicin twice a day for 5 days did not affect Ca in the mineral phase of the otoconia, but did increase K in both saccular (p < 0.05) and utricular (p < 0.01) otoconia. These increases in K may reflect a modification in the composition of the endolymph, resulting from cellular damage at the plasma membrane.

An absolute quantitative standardization technique has been developed to measure Ca and K weight fractions (WF) in the otolithic membrane of the saccule and utricle by scanning electron microscopy and electron probe X-ray analysis using the peak-to-background (P/B) ratio method. Microcrystalline salt standards were used to calibrate Ca and K K alpha P/B or Y = (P/B).Z2/A (Z = atomic number; A = atomic weight) against WF at 10, 15, 20 and 25 kV accelerating voltage. The effect of voltage on the calibration, plotting the coefficient of correlation (r) as a function of voltage, was not dependent on the voltage in the range 10-25 kV for Ca standards. K standards were also independent when P/B was corrected for Z2/A. Background counts in the otoconia (Bo) were obtained at 5, 25, 50, 100, 200 and 500 s and used to test the electron beam sensitivity of saccular and utricular otoconia. Bo was not dependent on the spectra acquisition time, with the exception of Bo under K alpha K peak in the saccule at 10 kV. Ca and K WF were determined at 10, 15, 20 and 25 kV in the saccule and utricle, showing similar values regardless of the voltage used. This method of calibration offers several advantages, such as stability, homogeneity, known composition of the standards, high reproducibility at different voltages even without Z2/A correction and the similarity between the otoconia and crystal standards. We recommend the application of this method for other elements and biomineral systems.

Electron probe X-ray microanalysis was used to study the phosphorus concentration in the otolithic gelatinous membrane of the saccule and the utricle with scanning electron microscopy. The otolithic membranes were plunge-frozen in liquid N2 and freeze-dried. Quantitative analysis was carried out with an energy dispersive detector using the peak-to-background ratio method and different concentrations of KH2PO4 salts dissolved in dextran solutions. The otolithic gelatinous membrane consists of a 25-30 microns-thick layer overlying the cilia of the hair cells. Elements detected in the gelatinous membrane are: Na, P, S, Cl, K and Ca. Although Student's t-test did not show significant differences between saccular and utricular concentrations of phosphorus, the distribution of this element in the two organs was different. Regression analysis established that the concentrations of phosphorus in the saccular and utricular gelatinous membrane were dependent. The regression equation was: y = 18.02x2 + 133.9 (r = 0.83, P < 0.05) where y is the concentration of phosphorus in the utricle, and x2 the concentration of phosphorus in the saccule. The findings obtained in the present study could be related to structural differences in organic phosphate residues of the phosphoproteins associated to collagen, or to different polyphosphoinositide turnover rates in the cell membrane.

We used scanning electron microscopy to study the morphological surface patterns of cells that cover the attached gingiva and intervestibular papilla of the human oral gingival epithelium. Five patterns are described on the basis of the overall appearance of morphological surface markers: microvilli, parallel, fingerprint, reticular and pitted. Statistical analyses detected significant differences in the frequency of each pattern in both regions of the oral gingival epithelium, and showed the reticular and fingerprint types to predominate. We propose that our description of the different morphological surface types may be of use as a standard for subsequent cytological studies and characterizations of morphological alterations in diseased gingiva.

The effect of tissue preparation on calcium and potassium weight percent in the otoconial layer in the utricle and saccule was studied in four groups of OF1 mice with electron probe X-ray microanalysis. Glutaraldehyde and freeze-drying, glutaraldehyde and air-drying, air-drying, and cryo-fixation and freeze-drying were compared. Ca and K changed significantly in the utricle depending on the method used (P < 0.001), and K changed significantly in the saccule (P < 0.001). We chose cryo-fixation with freeze-drying for the quantitative analysis of the otolithic membrane because this method provided the highest values of Ca and K with minimum loss of Ca and K. Microcrystalline salt standards mounted on scanning electron microscopy holders were used for the quantification of Ca and K by the peak-to-local-background (P/B) ratio method. The P/B ratio in standards with reproducible results, when plotted against weight percent, gave a straight line for Ca (r = 0.99, P < 0.001) and K (r = 0.98, P < 0.001). The Ca and K weight percent in otoconia showed similar frequency distributions in the utricle and saccule.