Comparison of Balloon Dilation and Laser Eustachian Tuboplasty in Patients with Eustachian Tube Dysfunction: A Meta-analysis.

Objective We aimed to perform a meta-analysis examining balloon dilatation and laser tuboplasty for the treatment of eustachian tube dysfunction (ETD). Data Sources PubMed, Cochrane, and Embase search up to April 18, 2016, with the following keywords: eustachian, middle-ear, eustachian tuboplasty, balloon tuboplasty, laser tuboplasty, laser dilatation, and balloon dilatation. Review Methods Randomized controlled trials and prospective, retrospective, and 1-arm studies of patients with ETD treated with balloon dilatation or laser tuboplasty were included. Outcome measures were improvement of eustachian tube score (ETS) and tympanometry and Valsalva maneuver results. Results Two retrospective and 11 prospective studies were included (1063 patients; 942 treated with balloon and 121 with laser tuboplasty). Balloon tuboplasty resulted in a significant improvement of ETS (pooled standardized mean difference [SMD], 0.94; 95% confidence interval [CI], 0.23-1.66; P = .009) and, compared with laser tuboplasty, a greater tympanometry improvement rate (pooled event rate = 73% vs 13%; P = .001). Valsalva maneuver improvement rate was not different between the group results (pooled event rate = 67% vs 50%; P = .472). The maximum number of studies that provided outcome data for any one measure was only 4, and sensitivity analysis indicated ETS results may have been overly influenced by 2 studies. No balloon tuboplasty studies reported ETS data, preventing comparison between the 2 procedures. Conclusion Both procedures can improve symptoms of ETD; however, because of the limited numbers of studies reporting data of the outcomes of interest, it remains unclear if one procedure provides greater benefits.

Effect of Transcranial Direct Current Stimulation in Patients With Tinnitus: A Meta-Analysis and Systematic Review.

OBJECTIVES: Subjective tinnitus is a phantom sensation experienced without any external source of sound that profoundly impacts the quality of life. Some investigations have claimed that transcranial direct current stimulation (tDCS) reduces tinnitus, but studies on tDCS have demonstrated variable results. This meta-analysis aimed to examine the effect of tDCS on patients with tinnitus. METHODS: We searched for articles published through January 5, 2016, in Medline, Cochrane, EMBASE, and Google Scholar using the following keywords: tinnitus, transcranial direct current stimulation, and tDCS. The study outcomes were change in magnitude estimates of loudness (loudness), tinnitus-related distress (distress), and Tinnitus Handicap Inventory (THI). RESULTS: Pooled results demonstrated that tDCS did not have a beneficial effect on loudness (pooled standardized difference in means = 0.674, 95% CI, -0.089 to 1.437, P = .083). Further, the pooled results demonstrated a greater reduction in distress for the tDCS group (pooled standardized difference in means = 0.634, 95% CI, 0.021-1.247, P = .043). CONCLUSIONS: We conclude that the pooled results demonstrated a greater reduction in distress for groups treated with tDCS as compared with those administered a sham treatment.

Predictors of hearing outcomes following low-dose stereotactic radiosurgery in patients with vestibular schwannomas: A retrospective cohort review.

OBJECTIVES: Hearing deterioration is a major concern for hearing-preserved patients with vestibular schwannomas who are treated with stereotactic radiosurgery (SRS). Thus, determining which patients are more likely to have worse hearing outcomes following SRS may facilitate clinicians in deciding whether conservative policy should be applied in the interest of hearing preservation. This study aimed to define the predictors of hearing outcomes following SRS. PATIENTS AND METHODS: This retrospective study included 100 patients who underwent low-dose SRS (12- to 13-Gy marginal dose) for vestibular schwannomas between January 2004 and January 2014. Clinical factors and hearing outcomes following radiosurgery were reviewed. RESULTS: All patients had serviceable hearing at diagnosis and prior to SRS. The median follow-up period was 6.5years (range, 3-10years). The hearing preservation rate in the first, third, and fifth year after radiosurgery was 89%, 68%, and 63%, respectively. A mean cochlear dose lower than 4Gy was a favorable predictor of hearing outcome. Maximal cochlear dose, patient age, pre-treatment pure-tone average, and imaging characteristics were not associated with post-treatment hearing preservation. Our study showed an accelerated rate of deterioration of serial pure-tone average in the first 3years, followed by a more gradual decline after radiosurgery. CONCLUSION: Our results suggest that cochlear dose constraint is the most crucial factor for hearing preservation. This study provides insight into the rate of hearing preservation and the pattern of hearing deterioration following radiosurgery and can help clinicians advise patients of hearing outcomes following SRS.

Increased Acquired Cholesteatoma Risk in Patients with Osteoporosis: A Retrospective Cohort Study.

OBJECTIVE: Clinically, we found the increased incidence of acquired colesteatoma in the patients with osteoporosis. In this study, we used a retrospective cohort to examine this association and to investigate the possible mechanism. METHODS: We conducted a population-based retrospective cohort study by using the National Health Insurance Research Database (NHIRD). We identified an osteoporosis cohort comprising 37 124 patients newly diagnosed with osteoporosis aged 20 years or older. Patients in the comparison cohort had no history of osteoporosis and were frequency matched with the patients in the osteoporosis cohort according to sex, age, and index year. RESULTS: The acquired cholesteatoma incidence rates for the osteoporosis and comparison cohorts were 1.12 and 0.83 per 1000 person-years, respectively. After we adjusted for confounding factors, the osteoporosis cohort exhibited a 1.32-fold increased acquired cholesteatoma risk relative to the comparison cohort (hazard ratio [HR] = 1.32, 95% confidence interval [CI] = 1.11-1.57). In addition, patients with no history of otitis media (HR = 1.33, 95% CI = 1.11-1.59), cancer (HR = 1.34, 95% CI = 1.12-1.60), or COPD (HR = 1.26, 95% CI = 1.05-1.52) in the osteoporosis cohort exhibited an increased risk of subsequent acquired cholesteatoma relative to those in the comparison cohort. CONCLUSIONS: Our cohort study indicated that patients with osteoporosis had a 1.31-fold increased acquired cholesteatoma risk relative to the comparison cohort. This risk was further increased in patients with comorbid otitis media. Hence, we recommend that otolaryngologists evaluate the condition of the middle ear of patients with osteoporosis.

Spontaneous bilateral dural arteriovenous fistulas with pulsatile tinnitus.

Pulsatile tinnitus with normal otoscopic findings often presents a diagnostic challenge to otolaryngologists and can be attributed to serious vascular malformations such as dural arteriovenous fistulas (DAVFs). Spontaneous DAVFs are relatively rare. A 65-year-old woman presented with sudden-onset subjective/objective pulsatile tinnitus on the right side that had persisted for 2 months. Angiography and magnetic resonance angiography revealed DAVF formation. Stereotactic radiosurgery was performed, and total remission of the DAVFs was achieved.

Safrole suppresses murine myelomonocytic leukemia WEHI-3 cells in vivo, and stimulates macrophage phagocytosis and natural killer cell cytotoxicity in leukemic mice.

Many anticancer drugs are obtained from phytochemicals and natural products. However, some phytochemicals have mutagenic effects. Safrole, a component of Piper betle inflorescence, has been reported to be a carcinogen. We have previously reported that safrole induced apoptosis in human oral cancer cells in vitro and inhibited the human oral tumor xenograft growth in vivo. Until now, there is no information addressing if safrole promotes immune responses in vivo. To evaluate whether safrole modulated immune function, BALB/c mice were intraperitoneally injected with murine myelomonocytic WEHI-3 leukemia cells to establish leukemia and then were treated with or without safrole at 4 and 16 mg/kg. Animals were sacrificed after 2 weeks post-treatment with safrole for examining the immune cell populations, phagocytosis of macrophages and the natural killer (NK) cells' cytotoxicity. Results indicated that safrole increased the body weight, and decreased the weights of spleen and liver in leukemic mice. Furthermore, safrole promoted the activities of macrophages phagocytosis and NK cells' cytotoxicity in leukemic mice when compared with untreated leukemic mice. After determining the cell marker population, we found that safrole promoted the levels of CD3 (T cells), CD19 (B cells) and Mac-3 (macrophages), but it did not affect CD11b (monocytes) in leukemic mice. In conclusion, safrole altered the immune modulation and inhibited the leukemia WEHI-3 cells in vivo.

cDNA microarray analysis of the gene expression of murine leukemia RAW 264.7 cells after exposure to propofol.

Propofol (2,6-diisopropylphenol) is the most extensively used general anesthetic-sedative agent and it is employed in clinical patients. It has been shown that propofol exhibits anticancer activities. However, there is no available information to address propofol-induced cytotoxic effects and affected gene expressions on murine leukemia cells. Therefore, we investigated the effects of propofol on the levels of protein and gene expression, which are associated with apoptotic death in mouse leukemia RAW 264.7 cells in vitro. Results indicated that propofol induced cell morphological changes, cytotoxicity, and induction of apoptosis in RAW 264.7 cells in vitro. Western blot analysis demonstrated that propofol promoted Fas, cytochrome c, caspase-9 and -3 active form and Bax levels, but inhibited Bcl-xl protein level which led to cell apoptosis. Furthermore, cDNA microarray assay indicated that propofol significantly enhanced 5 gene expressions (Gm4884; Gm10883; Lce1c; Lrg1; and LOC100045878) and significantly suppressed 26 gene expressions (Gm10679; Zfp617; LOC621831; LOC621831; Gm5929; Snord116; Gm3994; LOC380994; Gm5592; LOC380994; Gm4638; LOC280487; Gm4638; Tex24; A530064D06Rik; BC094916; EG668725; Gm189; Hist2h3c2; Gm8020; Snord115; Gm3079; Olfr198; Tdh; Snord115; and Olfr1249). Based on these observations, propofol-altered apoptosis-related proteins might result from induction of apoptotic gene expression and inhibition of cell growth gene expression, which finally led to apoptosis in a mouse leukemia cell line (RAW 264.7) in vitro.

Safrole induces G0/G1 phase arrest via inhibition of cyclin E and provokes apoptosis through endoplasmic reticulum stress and mitochondrion-dependent pathways in human leukemia HL-60 cells.

Safrole, a component of Piper betle inflorescence, is a carcinogen which has been demonstrated to induce apoptosis on human oral cancer HSC-3 cells in vitro and to inhibit HSC-3 cells in xenograft tumor cells in vivo. In our previous study, safrole promoted phagocytosis by macrophages and natural killer cell cytotoxicity in normal BALB/c mice. The cytotoxic effects of safrole on HL-60 cells were investigated by using flow cytometric analysis, comet assay, 4',6-diamidino-2-phenylindole (DAPI) staining, western blotting and confocal laser microscopy. The obtained results indicate that safrole induced a cytotoxic response through reducing the percentage of viable cells and induction of apoptosis in HL-60 cells in a dose-dependent manner. DAPI staining and comet assay also showed that safrole induced apoptosis (chromatin condensation) and DNA damage in HL-60 cells. The flow cytometric assay showed that safrole increased the production of reactive oxygen species (ROS) and Ca(2+) and reduced the mitochondrial membrane potential in HL-60 cells. Safrole enhanced the levels of the pro-apoptotic protein BAX, inhibited those of the anti-apoptotic protein BCL-2 and promoted the levels of apoptosis-inducing factor (AIF) and endonuclease G (Endo G) in HL-60 cells. Furthermore, safrole promoted the expression of glucose-regulated protein 78 (GRP78), growth arrest- and DNA damage-inducible gene 153 (GADD153) and of activating transcription factor 6α (ATF-6α). Based on these findings, we suggest that safrole-induced apoptosis in HL-60 cells is mediated through the ER stress and intrinsic signaling pathways.

Effectiveness of theta-burst repetitive transcranial magnetic stimulation for treating chronic tinnitus.

OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS), a noninvasive method for altering cortical excitability, is becoming a therapeutic strategy in auditory research institutions worldwide. Application of inhibiting rTMS on these overactive cortical regions can result in effective tinnitus suppression. The aim of this study is to investigate the efficacy of theta-burst rTMS in patients with chronic tinnitus. STUDY DESIGN: Parallel randomized control study. SETTING: Tertiary referral center. PATIENTS: We enrolled 2 female and 20 male patients in this study. The evaluative tools included tinnitus frequency- and loudness-matching, tinnitus questionnaires (TQ), and the Tinnitus Handicap Inventory (THI). METHODS: The orthogonal projection of the auditory cortex on the scalp was focalized. A figure-eight coil was placed on the surface of the skull over the targeted region with the intensity setting at 80% of the resting motor threshold. We delivered 900 pulses of theta-burst rTMS daily for 10 business days. MAIN OUTCOME MEASURES: Nine of twelve patients (75%) in the active-stimulation group reported tinnitus suppression following treatment with rTMS. The treatment led to reductions of 8.58 and 8.33 in the mean TQ global and THI scores, respectively. Tinnitus loudness also decreased significantly after delivering rTMS. RESULTS: Descriptive analysis of the TQs revealed that patients experienced significant improvements in emotional distress levels and somatic symptoms. CONCLUSIONS: Our preliminary results demonstrate that theta-burst rTMS treatments offer a method of modulating tinnitus. Patients could benefit from emotional improvements, even more than auditory perceptive relief. Further studies are needed to establish a standard protocol and to clarify nervous propagation along the auditory and psychological projection following treatment with rTMS.

Induction of apoptotic death by curcumin in human tongue squamous cell carcinoma SCC-4 cells is mediated through endoplasmic reticulum stress and mitochondria-dependent pathways.

Curcumin from the rhizome of the Curcuma longa plant has been noted for its chemo-preventative and chemo-therapy activities, and it inhibits the growth of many types of human cancer cell lines. In this study, the mechanisms of cell death involved in curcumin-induced growth inhibition, including cell cycle arrest and induction of apoptosis in human tongue cancer SCC-4 cells, were investigated. Herein, we observed that curcumin inhibited cell growth of SCC-4 cells and induced cell death in a dose-dependent manner. Treatment of SCC-4 cells with curcumin caused a moderate and promoted the G(2) /M phase arrest, which was accompanied with decreases in cyclin B/CDK1 and CDC25C protein levels. Moreover, curcumin significantly induced apoptosis of SCC-4 cells with a decrease of the Bcl-2 level, reduction of mitochondrial membrane potential (ΔΨ(m) ), and promoted the active forms of caspase-3. Curcumin also promoted the releases of AIF and Endo G from the mitochondria in SCC-4 cells by using confocal laser microscope. Therefore, we suggest that curcumin induced apoptosis through a mitochondria-dependent pathway in SCC-4 cells. In addition, we also found that curcumin-induced apoptosis of SCC-4 cells was partly through endoplasmic reticulum stress. In conclusion, curcumin increased G(2) /M phase arrest and induced apoptosis through ER stress and mitochondria-dependent pathways in SCC-4 cells.

Exponential modeling of human frequency-following responses to voice pitch.

OBJECTIVE: Recent studies have shown that the frequency-following response (FFR) to voice pitch can be a useful method to evaluate the signal-processing mechanisms and neural plasticity in the human brainstem. The purpose of this study was to examine the quantitative properties of the FFR trends with an exponential curve-fitting model. DESIGN: FFR trends obtained with increasing number of sweeps (up to 8000 sweeps) at three stimulus intensities (30, 45, and 60 dB nHL) were fit to an exponential model that consisted of estimates of background noise amplitude, asymptotic response amplitude, and a time constant. Five objective indices (Frequency Error, Slope Error, Tracking Accuracy, Pitch Strength and RMS Ratio) were used to represent different perspectives of pitch processing in the human brainstem. STUDY SAMPLE: Twenty-three native speakers (16 males; age = 24.7 ± 2.1 years) of Mandarin Chinese were recruited. RESULTS: The results demonstrated that the exponential model provided a good fit (r(2) = 0.89 ± 0.10) to the FFR trends with increasing number of sweeps for the five objective indices. CONCLUSIONS: The exponential model, combined with the five objective indices, can be used for difficult-to-test patients and may prove to be useful as an assessment and diagnostic method in both clinical and basic research efforts.

Possible reduction of hepatoma formation by Smmu 7721 cells in SCID mice and metastasis formation by B16F10 melanoma cells in C57BL/6 mice by Agaricus blazei murill extract.

Agaricus blazei Murill extract (ABM) has been reported to possess antitumor effects. In this study, the role of ABM in tumor growth and metastasis in vivo was evaluated in experimental Smmu 7721 hepatoma cells in severe combined immunodeficiency (SCID) mice and B16F10 melanoma cells lung metastasis in C57BL/6 mice. For the tumor growth model, the size of the liver tumor mass was about 10 mm to 20 mm in the control group. In comparison with the control group, the tumor mass seem to grow slowly with ABM treatment, especially at the high dose. For the tumor metastasis model, after a six-week treatment, the survival rates of B6 mice were 0%, 30%, 10% and 50% for control group, low, median and high concentration ABM treatment groups, respectively. The survival rate showed that pretreatment of C57BL/6 (B6) mice with ABM lengthened their lifespan after tumor cell inoculation, which supports the notion that ABM successfully reduced lung metastasis formation by B16F10 melanoma cells. The treatment effect was dependent on the concentration of ABM for tumor growth and metastasis in these models.

Zanthoxylum ailanthoides Sieb and Zucc. extract inhibits growth and induces cell death through G2/M-phase arrest and activation of apoptotic signals in colo 205 human colon adenocarcinoma cells.

The effects of 50% ethanolic stem extracts of Zanthoxylum ailanthoides Sieb and Zucc. (ZASZ) on the cell viability, cell cycle and apoptosis were investigated in a human colon adenocarcinoma cell line (colo 205). The results demonstrated that ZASZ induced morphological changes and decreased the cell viability. ZASZ promoted Wee1, checkpoint kinase 2 (CHK2), p21 and p53 levels, decreased cyclin B and cdc25c associated with that led to G(2)/M phase arrest. ZASZ-triggered apoptosis was confirmed by 4' -6-diamidino-2-phenylindole (DAPI) staining and DNA gel electrophoresis. ZASZ increased the levels of glucose-regulated protein 78 (GRP78) and growth arrest and DNA damage inducible gene 153 (GADD153), and promoted an increase of reactive oxygen species (ROS) and Ca(2+) release, and loss of mitochondrial membrane potential (ΔΨ(m)) accompanied by cytochrome c release that was due to the decrease of Bcl-2 and increase of Bax levels in the colo 205 cells. ZASZ also induced the protein levels of apoptosis-inducing factor (AIF) and endonuclease G (Endo G), increased the levels of caspase-3, -7 and -9, and stimulated the levels of fatty acid synthase (Fas) and Fas ligand in the colo 205 cells. ZASZ contains phenolic compounds, including flavone, chlorogenic acid and isofraxidin, among which, flavone was found to be the most effective in reducing cell viability and proliferative responses in the colo 205 cells. ZASZ induces cytotoxicity and apoptosis in colo 205 cells which provides the rationale for studies in animal models on the utilization of ZASZ as a potential cancer therapeutic compound.

Evaluation of two algorithms for detecting human frequency-following responses to voice pitch.

OBJECTIVE: Voice pitch carries important cues for speech perception in humans. Recent studies have shown the feasibility of recording the frequency-following response (FFR) to voice pitch in normal-hearing listeners. The presence of such a response, however, has been dependent on subjective interpretation of experimenters. The purpose of this study was to develop and test an automated procedure including a control-experimental protocol and response-threshold criteria suitable for extracting FFRs to voice pitch, and compare the results to human judgments. DESIGN: A set of four Mandarin tones (Tone 1 flat; Tone 2 rising; Tone 3 dipping; and Tone 4 falling) were prepared to reflect the four contrastive pitch contours. Two distinctive algorithms, short-term autocorrelation in the time domain and narrow-band spectrogram in the frequency domain, were used to estimate the Frequency Error, Slope Error, Tracking Accuracy, Pitch Strength and Pitch-Noise Ratio of the recordings from individual listeners as well as the power and false-positive rates of each algorithm. STUDY SAMPLE: Eleven native speakers (five males; age: mean ± SD = 31.4 ± 4.7 years) of Mandarin Chinese were recruited. RESULTS: The results demonstrated that both algorithms were suitable for extracting FFRs and the objective measures showed comparable results to human judgments. CONCLUSIONS: The automated procedure used in this study, including the use of the control-experimental protocol and response thresholds used for each of the five objective indices, can be used for difficult-to-test patients and may prove to be useful as an assessment and diagnostic method in both clinical and basic research efforts.

Early maturation of frequency-following responses to voice pitch in infants with normal hearing.

Neural plasticity of pitch processing mechanisms at the human brainstem, as reflected by the scalp-recorded frequency-following response (FFR) to voice pitch, has been reported for normal-hearing adults. Characteristics and maturation of such a response during the first year of life have remained unclear. The purpose of this study was to examine the characteristics of FFR to voice pitch in normal-hearing infants and to make a direct comparison with adults using the same stimulus and recording parameters. 9 infants and 9 adults were recruited. A Chinese monosyllable that mimics the English vowel /i/ with a rising pitch was used to elicit the FFR to voice pitch. The results demonstrated that infant FFRs showed slightly larger Pitch Strength but comparable Frequency Error, Slope Error, and Tracking Accuracy to those obtained from adults. Early maturation of FFRs was also observed in the infants starting from 1 to 3 mo. of age.

Improvement in otitis media with effusion in patients undergoing tracheostomy after prolonged endotracheal intubation.

OBJECTIVES: Otitis media with effusion (OME) has a higher incidence in adult intensive care unit (ICU) patients. This observational study sought to examine the effect of tracheostomy on OME in critically ill patients and explore the predisposing factors. MATERIALS AND METHODS: Twenty-seven ICU patients who had undergone prolonged intubation (more than 14 days) received traditional tracheostomies. Otoscopic examination, tympanometry, and spectral gradient acoustic reflectometry were performed both at the time of the tracheostomy and 7 days later. We collected data on the patients' demographics (age and gender), underlying diseases, duration of intubation prior to the tracheostomy, history of gastroesophageal reflux disease, length of antibiotic use, level of consciousness, and presence of nasogastric tubes. RESULTS: At the time of the tracheostomy, 25 (46%) ears from 14 (52%) patients were classified as cases of OME, 17 (31%) ears and 7 (26%) patients as normal cases, and 12 (11%) ears from 6 (11%) patients as cases of negative pressure in the tympanic cavity. Seven days after the tracheostomy, OME was resolved in 17 (68%) ears and persisted in 6 (24%) ears, whereas negative pressure developed in 2 (8%) ears. Our data showed that the incidence of OME reduced from 46% to 22% after tracheostomy was performed on the patients. CONCLUSION: The incidence of OME in adult ICU patients who were intubated for more than 14 days was found to reduce after tracheostomy. Notably, the rate of improvement in the conscious patients was significantly higher than that in the unconscious patients.

High resolution computed tomography analysis of the temporal bone.

Detailed radiological assessment by high resolution computed tomography (HRCT) of temporal bone is demanded before any temporal bone or skull base surgery. The aim of this study was to measure the relations between the anatomical landmarks of the temporal bone and to assist the otolaryngologist in establishing accurate preoperative evaluation. We enrolled 43 patients who underwent temporal bone HRCT between February 2004 and May 2004. Contiguous axial and coronal images at 1.0 mm thickness were obtained. Some landmarks such as the superior and inferior lips of the internal acoustic canal (IAC), the malleoincus joint, and the posterior semicircular canal were labeled in the coronal and axial views. Then we measured the distance between them. Average IAC diameter in the coronal and axial views was 5.33 mm and 6.92 mm. Average IAC length in the coronal and axial views was 12.29 mm and 11.09 mm. The thickness of the retrolabyrinthine bone was 3.78 mm. The incidence of thinning bone overlying the superior semicircular canal was 2.3%. Our data could be applied to normal distribution because there were no statistical differences between the measurements of normal ears and diseased ears. Several specific measurements can be applied to the preoperative evaluation of vestibular schwannoma including the retrosigmoid approach, the translabyrinthine approach and the middle fossa approach.