Prognostic Value of Labyrinthine 3D-FLAIR Abnormalities in Idiopathic Sudden Sensorineural Hearing Loss.

BACKGROUND AND PURPOSE: According to recent research, modern MR imaging can detect the presense of abnormalities on labyrinthine. Our aim was to report the patterns and prognostic role of abnormal findings on labyrinthine imaging in patients with sudden sensorineural hearing loss. MATERIALS AND METHODS: This study comprised 113 patients who were diagnosed with unilateral sudden sensorineural hearing loss and underwent 3T MR imaging, including pre-/postcontrast 3D fluid-attenuated inversion recovery and T1-weighted imaging. We analyzed abnormalities on MR imaging and correlated them with audiometric results. RESULTS: Thirty-one (27%) patients showed abnormal findings on labyrinthine MR imaging in the affected ear. The initial/final hearing levels of the MRI+ group (91 ± 25/73 ± 27 dB hearing loss) were significantly worse than those of the MRI- group (69 ± 30/48 ± 24 dB hearing loss). The incidence of abnormalities on labyrinthine MR imaging was significantly lower (3 of 40, 8%) in 40 patients with initial mild-to-moderate hearing loss than in those with profound hearing loss (16 of 34, 47%). Considering hearing improvement by the Siegel criteria, the rate of complete or partial recovery was significantly higher in the MRI- group (34%) than in the MRI+ group (10%). In patients with initial severe or profound hearing loss, the MRI- group showed greater hearing improvement (38 ± 21 dB) than the MRI+ group (23 ± 22 dB). CONCLUSIONS: Abnormalities on labyrinthine MR imaging were found in 27% of patients with sudden sensorineural hearing loss. The initial hearing loss was worse in the MRI+ group than in the MRI- group. In patients with initial severe and profound hearing loss, the presence of abnormalities on labyrinthine MR imaging indicated a poor prognosis.

Quantitative analysis of gains and catch-up saccades of video-head-impulse testing by age in normal subjects.

OBJECTIVES: To evaluate video-head-impulse test (vHIT) results in normal subjects, to determine the normative values of vHIT for the vestibulo-ocular reflex (VOR) and to characterise the catch-up saccades (CSs). DESIGN: Prospective cohort study. SETTING: Tertiary care academic referral centre. PARTICIPANTS: Fifty healthy subjects with no history of vestibular impairment, ten each in their 20's, 30's, 40's, 50's and 60's, underwent vHITs in the lateral semicircular canal plane. MAIN OUTCOME MEASURES: vHIT gains and the incidence and amplitudes of covert and overt CSs. RESULTS: The mean vHIT gain was 1.02 ± 0.07, and the mean gain asymmetry was 2.39 ± 1.96%, with no significant differences among age groups. CSs were observed during 22.6% of the trials and in 49% of the ears. The incidence of CSs was not associated with age. The mean velocity of CSs was 55.5 ± 16.9°/s, and its mean interaural difference was 11.8 ± 10.7°/s. CONCLUSIONS: vHIT gains were consistently equal to 1.0 in all age groups (20's to 60's), suggesting that abnormal criteria for vHIT gain (e.g. 0.8) and gain asymmetry (e.g. 8%) can be used, regardless of age. CSs were observed in about half of normal ears, suggesting that VOR is a hypometric system. The amplitudes and interaural difference of CSs were also similar in all age groups, suggesting that abnormal criteria for CS amplitude (e.g. 100°/s) and interaural difference (e.g. 40°/s) can be used, regardless of age.

Vertical components of head-shaking nystagmus in vestibular neuritis, Meniere's disease and migrainous vertigo.

OBJECTIVES: To describe vertical and horizontal components of head-shaking nystagmus (HSN) in various vestibular disorders. DESIGN: Retrospective case review. SETTING: Tertiary care academic referral centre. PARTICIPANTS: Head-shaking nystagmus was assessed in 66 vestibular neuritis (VN) patients at acute (<7 days) and follow-up (2 months), and 65 Meniere's disease (MD) and 76 migrainous vertigo (MV) in interictal period. MAIN OUTCOME MEASURES: Head-shaking nystagmus was categorised as pure horizontal, pure vertical or mixed. Horizontal HSN was classified as monophasic or biphasic and paretic or recovery. Vertical HSN was classified as upbeat or downbeat. RESULTS: Abnormal HSN (pathologic monophasic, biphasic or delayed-peak HSN) showed different positive rates depending on the vestibular disorders and compensation (94% in acute VN; 89% in FU VN; 78% in MD; 50% in MV). Paretic HSN with the nystagmus towards the lesioned side was the most common type in VN and MD; however, recovery HSN with the nystagmus towards the intact side could be rarely observed especially in patients with MD or compensated VN. Vertical nystagmus could be combined with horizontal HSN, and upbeat HSN was observed in most (83%) of the patients with acute VN, but downbeat HSN was common in follow-up VN (83%), MD (97%) and MV (85%). Weak perverted HSN, which is assumed to be a central nystagmus, was rarely observed in MD and MV (6-9%), but not in VN. CONCLUSIONS: Head-shaking nystagmus (HSN) in horizontal plane is a valuable tool in the assessment of vestibular imbalance. Common observation of upbeat HSN in acute VN and downbeat HSN in follow-up VN, MD and MV suggests that vertical components are possibly related to the involvement of vestibular apparatus and compensation. Weak perverted HSN and delayed-peak HSN were rarely observed in MD and MV, and never observed in VN, suggesting that it is possibly related to either asymmetrically impaired vertical canals or misorientation of the velocity-storage system.

Coenzyme Q10 in combination with steroid therapy for treatment of sudden sensorineural hearing loss: a controlled prospective study.

OBJECTIVE: To evaluate the therapeutic efficacy of coenzyme Q10 added to systemic steroid in patients with idiopathic sudden sensorineural hearing loss. DESIGN: A controlled prospective study. SETTING: Asan medical center, University of Ulsan College of Medicine. PARTICIPANTS: Between August 2007 and October 2008, the first 60 patients diagnosed with sudden sensorineural hearing loss were managed with systemic steroid treatment for 2 weeks including 5-day hospitalisation. And the second 60 patients were managed with coenzyme Q10 for 2 weeks added to previous management. MAIN OUTCOME MEASURES: We evaluated auditory function by pure tone audiometry and speech discrimination score. Auditory evaluations were performed before and 3 months after treatment using Siegel's criteria. The degree of improvement in four-tone average hearing and speech discrimination score was calculated from the results before and after treatment. RESULTS: The total hearing improvement rate after the treatment was 75.0% (90/120 patients) in this study. Although 47 patients (78.3%) of coenzyme Q10 group showed better hearing improvement than 43 patients (71.7%) of control group, there was no significant difference. However, the coenzyme Q10 group showed significantly higher improvement in speech discrimination score. CONCLUSION: From this study, we suggest that coenzyme Q10 may have beneficial effects in the treatment of sudden sensorineural hearing loss.

Endoscopic transnasal reduction of an anterior table frontal sinus fracture: technical note.

Repair of an isolated anterior table frontal sinus fracture traditionally requires a coronal incision, which results in a large scar, alopecia and paresthesias, because of these problems, endoscopic approaches have been attempted. These approaches still involve small incisions at the forehead or behind the hairline so might be better described as endoscopy-assisted surgery. This report describes the reduction of an isolated anterior table frontal sinus fracture in a 14-year-old boy using an endoscopic procedure that involves a transnasal approach with no external incisions. Endoscopic instruments were used under 25 and 70 degrees endoscope guidance. A custom-made latex glove balloon was inserted into the frontal sinus, and then expanded and maintained for 20 days to support the reduced bony fragments. Postoperatively, the reduction was successful. The cosmetic deformity was repaired and there was no postoperative morbidity. This case indicates that endoscopic reduction may be a valuable treatment option for certain types of frontal sinus fractures.

Implication of the small GTPase Rac1 in the apoptosis induced by UV in Rat-2 fibroblasts.

Exposure of mammalian cells to ultraviolet (UV) light elicits a cellular response and also lead to apoptotic cell death. However, the role of Rac, a member of Rho family GTPases, in the UV-induced apoptosis has never been examined. In UV-irradiated Rat-2 fibroblasts, nuclear fragmentation began to be observed within 2 h and the total viability of Rat-2 cells were only about 15% at 6 h following by UV irradiation, whereas the total viability in Rat2-Rac(N17) cells stably expressing RacN17, a dominant negative Rac1 mutant, was almost close to 67%. Pretreatment with SB203580, a specific inhibitor of p38 kinase, likewise attenuated UV-induced cell death, but PD98059, a MEK inhibitor, did not. Thus, Rac1 and p38 kinase appear to be components in the apoptotic signaling pathway induced by UV irradiation in Rat-2 fibroblasts. In addition, our results show that p38 kinase stimulation by UV is dramatically inhibited by RacN17, suggesting that p38 kinase is situated downstream of Rac1 in the UV signaling to apoptosis.

Codon 54 polymorphism of the fatty acid binding protein 2 gene is associated with increased fat oxidation and hyperinsulinemia, but not with intestinal fatty acid absorption in Korean men.

The alanine to threonine substitution at codon 54 (Ala54Thr) of the fatty acid binding protein 2 (FABP2) gene has been reported to be associated with increased fat oxidation and insulin resistance in several populations. It has been hypothesized that Ala54Thr substitution results in enhanced intestinal uptake of fatty acids and thereby an impairment of insulin action, but this hypothesis has not been proven in vivo. We studied the association between the Ala54Thr polymorphism of the FABP2 gene and intestinal (3)H-oleic acid absorption, as well as basal insulin level, basal metabolic rate, and fat oxidation rate in 96 healthy young Korean men. Among our subjects, the allele frequency of the Ala54Thr substitution was 0.34. Subjects with Thr54-encoding allele were found to have a higher mean fasting plasma insulin concentration and a higher basal fat oxidation rate compared with the subjects who were homozygous for the Ala54-encoding allele. However, there was no significant difference in basal metabolic rate or (3)H-oleic acid absorption according to the FABP2 gene polymorphism. These results suggest that the Ala54Thr substitution in the FABP2 gene is associated with increased fat oxidation and hyperinsulinemia in normal Korean men, but these effects are not mediated by an increase in the intestinal fatty acid absorption.

Role of the cytosolic phospholipase A2-linked cascade in signaling by an oncogenic, constitutively active Ha-Ras isoform.

Activation of Ras signaling by growth factors has been associated with gene regulation and cell proliferation. Here we characterize the contributory role of cytosolic phospholipase A(2) in the oncogenic Ha-Ras(V12) signaling pathway leading to activation of c-fos serum response element (SRE) and transformation in Rat-2 fibroblasts. Using a c-fos SRE-luciferase reporter gene, we showed that the transactivation of SRE by Ha-Ras(V12) is mainly via a Rac-linked cascade, although the Raf-mitogen-activated protein kinase cascade is required for full activation. In addition, Ha-Ras(V12)-induced DNA synthesis was significantly attenuated by microinjection of recombinant Rac(N17), a dominant negative mutant of Rac1. To identify the mediators downstream of Rac in the Ha-Ras(V12) signaling, we investigated the involvement of cytosolic phospholipase A(2). Oncogenic Ha-Ras(V12)-induced SRE activation was significantly inhibited by either pretreatment with mepacrine, a phospholipase A(2) inhibitor, or cotransfection with the antisense oligonucleotide of cytosolic phospholipase A(2). We also found cytosolic phospholipase A(2) to be situated downstream of Ha-Ras(V12) in a signal pathway leading to transformation. Together, these results are indicative of mediatory roles of Rac and cytosolic phospholipase A(2) in the signaling pathway by which Ha-Ras(V12) transactivates c-fos SRE and transformation. Our findings point to cytosolic phospholipase A(2) as a novel potential target for suppressing oncogenic Ha-Ras(V12) signaling in the cell.

Tumor necrosis factor-alpha generates reactive oxygen species via a cytosolic phospholipase A2-linked cascade.

Reactive oxygen species (ROS) are important regulatory molecules implicated in the signaling cascade triggered by tumor necrosis factor (TNF)-alpha, although the events through which TNF-alpha induces ROS generation are not yet well characterized. We therefore investigated selected candidates likely to mediate TNF-alpha-induced ROS generation. Consistent with the role of Rac in that process, stable expression of Rac(Asn-17), a dominant negative Rac1 mutant, completely blocked TNF-alpha-induced ROS generation. To understand better the mediators downstream of Rac, we investigated the involvement of cytosolic phospholipase A(2) (cPLA(2)) activation and metabolism of the resultant arachidonic acid (AA) by 5-lipoxygenase (5-LO). TNF-alpha-induced ROS generation was blocked by inhibition of cPLA(2) or 5-LO, but not cyclooxygenase, suggesting that TNF-alpha-induced ROS generation is dependent on synthesis of AA and its subsequent metabolism to leukotrienes. Consistent with that hypothesis, TNF-alpha Rac-dependently stimulated endogenous production of leukotriene B(4) (LTB(4)), while exogenous application of LTB(4) increased levels of ROS. In contrast, application of leukotrienes C(4), D(4), and E(4) or prostaglandin E(2) had little effect. Our findings suggest that LTB(4) production by 5-LO is situated downstream of the Rac-cPLA(2) cascade, and we conclude that Rac, cPLA(2), and LTB(4) play pivotal roles in the ROS-generating cascade triggered by TNF-alpha.

Role of cytosolic phospholipase A(2) as a downstream mediator of Rac in the signaling pathway to JNK stimulation.

Rac is an important regulatory molecule implicated in c-jun N-terminal kinase (JNK) activation in response to stress and cytokines. However, the signaling events that mediate the activation of JNK by Rac are not yet well characterized. To broaden our understanding of downstream mediators that link Rac signals to the JNK pathway, we investigated whether cytosolic phospholipase A(2) (cPLA(2)) is involved in Rac activation of JNK. In this report we demonstrate that either co-transfection with antisense cPLA(2) oligonucleotide or pretreatment with arachidonyltrifluoromethyl ketone (AACOCF3), a potent and specific inhibitor of cPLA(2), inhibits Rac-mediated JNK activation, implying a potential role of cPLA(2) in Rac-signaling to JNK activation. In accordance with this observation, we demonstrate that the addition of exogenous arachidonic acid (AA), a principal product of Rac-activated cPLA(2), or leukotrienes, products of 5-lipoxygenase (5-LO) of AA, caused a specific stimulation of JNK. Together, our findings suggest that cPLA(2) mediates, at least partly, the signaling cascade by which Rac stimulates JNK.

The Arabidopsis thaliana plasma membrane H(+)-ATPase multigene family. Genomic sequence and expression of a third isoform.

The plasma membrane of higher plants contains a H(+)-ATPase as its major ion pump. This enzyme belongs to the P-type family of cation-translocating enzymes and generates the proton-motive force that drives solute uptake across the plasma membrane. In Arabidopsis thaliana the plasma membrane H(+)-ATPase is encoded by a multigene family (Harper, J. F., Surowy, T. K., and Sussman, M. R. (1989) Proc. Natl. Acad. Sci. U. S. A. 86, 1234-1238). The complete genomic sequence of a third Arabidopsis H(+)-ATPase isoform (referred to as AHA2) is presented here, and the predicted protein sequence is compared with previously published AHA1, AHA3, and tobacco Nicotiana plumbaginifolia NP1 isoforms. The AHA2 gene is most similar to AHA1, with predicted proteins containing 95% amino acid identity. The mRNA start site and 5'-untranslated sequence for AHA2 were determined from cDNA amplified by the polymerase chain reaction. The 5' region contains a 23-base pair (bp) polypyrimidine sequence and a short upstream reading frame. In comparison with the 16 introns reported in AHA3, AHA2 is missing one intron in the 5'-untranslated region and a second intron in the C-terminal coding region. An unusually large intron for Arabidopsis (greater than 1000 bp) is present at the beginning of the coding sequence of both AHA2 and AHA3. In the 3'-untranslated sequence of AHA1 and AHA2 but not AHA3, there is a 65-bp region of 85% identity and a second shorter region of 16-bp identity harboring an unusual putative poly(A) addition signal (dTTTGAAGAAACAAGGC). Northern blot analysis indicates that AHA2 mRNA relative to total cellular RNA is expressed at significantly higher levels in root tissue as compared with shoot tissue.