Prevalence of potential candidates for electric-acoustic stimulation implant in a hearing-impaired population.

OBJECTIVE: To estimate the prevalence of potential electric-acoustic stimulation (EAS) implant candidates in a hearing-impaired population through a review of auditory examinations. METHODS: In total, 7356 patients underwent audiometric examination in our department between 2011 and 2014. The prevalence of patients meeting the audiometric criteria for EAS and standard cochlear implant (CI) was assessed. RESULTS: The percentage of EAS implant candidates meeting the pure-tone audiometric criteria was 0.71% (n=34) among the hearing-impaired individuals (n=4758) examined in our department, whereas 2.52% (n=120) met the criteria for standard CI. Among the 34 EAS implant candidates, 2 individuals (5.83%) received EAS implant surgery after approval of the EAS device in Japan. CONCLUSIONS: There was a lower prevalence of EAS implant candidates than standard CI candidates. Nevertheless, healthcare professionals should carefully examine the audiograms of patients with high frequency hearing loss with regard to meeting the indication criteria for EAS implant. This will enable patients to gain access to adequate information relating to further examinations and treatment options.

Furosemide-loading vestibular evoked myogenic potential testing can suggest developing bilateral involvement of unilateral Meniere's disease.

CONCLUSIONS: Patients with positive results of furosemide-loading vestibular evoked myogenic potential (F-VEMP) testing in the unaffected ears of unilateral Meniere's disease have a high incidence of developing bilateral lesions. OBJECTIVE: To clarify the meaning of positive results of F-VEMP testing of the unaffected ear of patients with unilateral Meniere's disease. METHODS: Twenty-five patients with unilateral Meniere's disease were investigated in this study. The positive group consisted of 6 patients with positive results of F-VEMP testing in the contralateral ear and the negative group consisted of 19 patients with negative results. The incidence of contralateral involvement was compared in both groups by the Kaplan-Meier method. RESULTS: Contralateral involvement was seen in three cases (50%) in the positive group after 2, 12, and 26 months and in three cases (16%) in the negative group after 27, 56, and 78 months. The positive group had a higher incidence of contralateral involvement than the negative group (p = 0.0017, according to a log-rank test).

n-3 Fatty acids decrease arterial low-density lipoprotein cholesterol delivery and lipoprotein lipase levels in insulin-resistant mice.

OBJECTIVE: To determine whether n-3 fatty acids (n-3) influence arterial cholesterol delivery and lipoprotein lipase (LpL) levels in insulin-resistant mice. METHODS AND RESULTS: Insulin resistance contributes to risk of cardiovascular disease. It was previously reported that saturated fat (SAT) diets increased, but n-3 diets decreased, arterial low-density lipoprotein (LDL) cholesterol deposition from LDL total and selective uptake; this was associated with increased or decreased arterial LpL, respectively. Insulin receptor transgenic knockout mice (L1) were fed a chow, SAT, or n-3 diet for 12 weeks. Double-fluorescent boron dipyrromethene (BODIPY)-cholesteryl ester (CE) and Alexa dye-labeled human LDL were injected to separately trace LDL-CE and LDL-apolipoprotein B whole particle uptake. In contrast to SAT, n-3 diets markedly reduced all plasma lipids, ameliorating progression of insulin resistance. As opposed to SAT, n-3 reduced arterial LDL uptake, CE deposition, and selective uptake. Disparate patterns of CE deposition between diets were comparable with arterial LpL distribution; SAT induced high LpL levels throughout aortic media; LpL was limited only to intima in n-3-fed mice. CONCLUSIONS: n-3 diets diminish arterial LDL-cholesterol deposition in mice with insulin resistance, and this is associated with changes in arterial LpL levels and distribution.

n-3 fatty acids reduce arterial LDL-cholesterol delivery and arterial lipoprotein lipase levels and lipase distribution.

OBJECTIVE: We previously reported that saturated fat (SAT)-enriched diets increase arterial cholesteryl ester (CE) deposition, especially from LDL-selective uptake (SU), and this was associated with increased arterial lipoprotein lipase (LpL). We now question how n-3 fatty acid rich diets influence arterial cholesterol delivery and arterial LpL levels. METHODS AND RESULTS: C57BL/6 mice were fed chow or eucaloric high-fat diets enriched in SAT or fish oil (n-3) for 12 weeks, and then injected with double radiolabeled or fluorescent-labeled human LDL to separately trace LDL-CE and LDL-apoB uptake. SAT and n-3 diets increased plasma cholesterol levels similarly; n-3 diets lowered plasma triglyceride concentrations. SAT increased arterial LDL-SU with significantly higher CE infiltration into aortic media. In contrast, n-3 markedly reduced total LDL uptake and CE deposition and abolished SU with LDL localized only in aortic intima. Disparate patterns of CE deposition between diets were consistent with distribution of arterial LpL-SAT diets induced higher LpL levels throughout the aorta; n-3 diets decreased LpL levels and limited LpL expression to the aortic intima. CONCLUSIONS: n-3 rich diets decrease arterial total LDL delivery and abrogate LDL-SU in parallel with changing arterial wall LpL expression and distribution.

Vestibular evoked myogenic potentials of undiagnosed dizziness.

OBJECTIVE: Recording of vestibular evoked myogenic potentials (VEMP) can facilitate the evaluation of otolith function. The dizziness caused by otolith lesions is not completely understood. To clarify which symptoms of dizziness originate from the otolith organs, we examined the relationship between symptoms and VEMP results in patients with undiagnosed dizziness. METHODS: The subjects were 18 patients with undiagnosed dizziness aged less than 40 years who underwent VEMP examination. The VEMP results were evaluated using the interaural ratio of p13-n23 amplitude. RESULTS: Abnormal VEMP results were obtained in five of seven patients who experienced a sensation of falling (p=0.013), in none of the three patients who experienced a swaying sensation (p>0.05), and in one of eight patients who experienced a floating sensation (p>0.05). Five of six patients with abnormal VEMP results complained of disequilibrium lasting a few seconds. CONCLUSIONS: Dizziness with a sensation of falling lasting for a few seconds was related to abnormal VEMP results, suggesting that it resulted from saccular dysfunction. VEMP examination may be considered a useful modality in the diagnosis of dizziness of unknown origin.

Frequency dynamics shift of vestibular evoked myogenic potentials in patients with endolymphatic hydrops.

OBJECTIVE: To measure the frequency dynamics of the vestibular evoked myogenic potential in patients with endolymphatic hydrops. STUDY DESIGN: A prospective study. SETTING: A university hospital. SUBJECTS: The endolymphatic hydrops group consisted of 28 affected ears of patients with definite unilateral Ménière's disease and a control group of 36 ears of 20 healthy volunteers. INTERVENTIONS: Vestibular evoked myogenic potentials generated by tone bursts at 250, 500, 700, 1,000, 1,500, 2,000, and 4,000 Hz were measured in both groups. Vestibular evoked myogenic potentials were also measured after furosemide administration in six patients in the endolymphatic hydrops group. MAIN OUTCOME MEASURE: The frequency sensitivity of vestibular evoked myogenic potential, as evaluated by p13-n23 normalized amplitude. RESULTS: Peak amplitudes were noted at 500 Hz in the control group and at 1,000 Hz in the endolymphatic hydrops group. After furosemide loading, peak amplitude shifted to a lower frequency in four of six ears. CONCLUSION: The peak amplitude of vestibular evoked myogenic potentials in the endolymphatic hydrops group was at a higher frequency than in the control group. The frequency of the saccule (nu) should be proportional to radical(tau/sigma), where tau is the tension of membrane and sigma is its density. We advocate the hypothesis that the shift in frequency dynamics of vestibular evoked myogenic potential in patients with endolymphatic hydrops originates from the morphologic features of the saccule, analogous to an expanded balloon.

Omega-3 fatty acids: molecular approaches to optimal biological outcomes.

PURPOSE OF REVIEW: This review discusses recent advances in delineating basic mechanisms underlying the beneficial effects of omega-3 fatty acids on health and on disease. RECENT FINDINGS: While a substantial number of studies have delineated many differences between the biological effects of saturated versus polyunsaturated fatty acids, less is known about the long-chain omega-3 fatty acids commonly present in certain fish oils. In this review, we focus on recent studies relating to basic mechanisms whereby omega-3 fatty acids modulate cellular pathways to exert beneficial effects on promoting health and decreasing risks of certain diseases. We will use, as examples, conditions of the cardiovascular, neurological, and immunological systems as well as diabetes and cancer, and then discuss basic regulatory pathways. SUMMARY: Omega-3 fatty acids are major regulators of multiple molecular pathways, altering many areas of cellular and organ function, metabolism and gene expression. Generally, these regulatory events lead to "positive" endpoints relating to health and disease.

Selective uptake from LDL is stimulated by unsaturated fatty acids and modulated by cholesterol content in the plasma membrane: role of plasma membrane composition in regulating non-SR-BI-mediated selective lipid transfer.

We previously reported that unsaturated fatty acids stimulated low-density lipoprotein (LDL) particle uptake in J774 macrophages by increasing LDL receptor activity. Since free fatty acids (FFA) also change plasma membrane properties, a putative cholesteryl ester (CE) acceptor for selective uptake (SU), we questioned the ability of FFA to modulate SU from LDL. Using [(3)H]cholesteryl ether/(125)I-LDL to trace CE core and whole particle uptake, we found that oleic acid and eicosapentaenoic acid, but not saturated stearic acid, increased SU by 30% over control levels. An ACAT inhibitor, Dup128, abolished FFA effects on SU, indicating that increased SU by FFA was secondary to changes in cell-free cholesterol (FC). Consistent with these observations, ACAT inhibition increased cell FC and reduced LDL SU by half. The important role of plasma membrane composition was further demonstrated in that beta-cyclodextrin- (beta-CD-) mediated FC removal from the plasma membrane increased SU from LDL and was further stimulated by U18666A, a compound that inhibits FC transport between lysosomes and the plasma membrane. In contrast, cholesterol-saturated beta-CD markedly reduced LDL SU. In contrast to LDL SU, oleic acid, ACAT inhibition, U18666A, or beta-CD had no effects on HDL SU. Moreover, HDL SU was inhibited by antimouse SR-BI antibody by more than 50% but had little effect on LDL SU. In C57BL/6 mice fed a high fat diet, plasma FFA levels increased, and SU accounted for an almost 4-fold increased proportion of total cholesterol delivery to the arterial wall. Taken together, these data suggest that LDL SU is mediated by pathways independent of SR-BI and is influenced by plasma membrane FC content. Moreover, in conditions where elevated plasma FFA occur, SU from LDL can be an important mechanism for cholesterol delivery in vivo.

Omega-3 triglycerides modify blood clearance and tissue targeting pathways of lipid emulsions.

Omega-3-rich (n-3) triglycerides (TG) are increasingly recognized as having modulating roles in many physiological and pathological conditions. We questioned whether the catabolism of lipid emulsions would be changed after enrichment with fish oil (n-3) TG as compared to enrichment with omega-6-rich soy oil (n-6) TG. Phospholipid-stabilized emulsions of n-3 TG and n-6 TG were labeled with [(3)H]cholesteryl oleoyl ether and administered by bolus injection to wild-type (WT) mice, mice lacking the low-density lipoprotein receptor (LDL-R) (LDL-R -/-), and apolipoprotein E (apoE) knockout mice (apoE -/-). The effects of exogenous apoE, heparin, Triton WR 1339, and lactoferrin on catabolism of emulsions were also assayed. n-3 TG emulsions were cleared faster from blood and had different extrahepatic tissue targeting compared to n-6 TG emulsions. In apoE -/- and LDL-R -/- mice, blood clearance of n-6 TG emulsions slowed with decreased liver uptake, but no changes were observed in n-3 TG emulsion clearance and tissue uptake compared to WT mice. In WT mice, addition of exogenous apoE to the emulsion increased liver uptake of n-6 TG emulsions but had no impact on n-3 TG emulsions. Pre-injection of heparin increased and Triton WR 1339 and lactoferrin decreased blood clearance of n-6 TG emulsions with little or no effect on n-3 TG emulsions. Liver uptake of n-6 TG emulsions increased after heparin injection and decreased after Triton WR 1339 injection, but uptake of n-3 TG emulsions was not changed. These data show that the catabolism of n-3 TG emulsions and the catabolism of n-6 TG emulsions occur via very different mechanisms. Removal of chylomicron-sized n-6 TG emulsions is modulated by lipoprotein lipase (LPL), apoE, LDL-R, and lactoferrin-sensitive pathways. In contrast, clearance of chylomicron-sized n-3 TG emulsions relies on LPL to a very minor extent and is independent of apoE, LDL-R, and lactoferrin-sensitive pathways.