Perilymphatic fistula with characteristic findings of the inner ear by contrast-enhanced magnetic resonance imaging: a case report.

A perilymphatic fistula (PLF) presents with abnormal traffic in the otic capsule, causing cochlear and vestibular symptoms. However, the mechanisms underlying symptom recurrence remain controversial. Herein, we report the case of a 27-year-old female who complained of hearing disturbance in her right ear and recurrent vertigo after sudden onset of hearing loss with vertigo. The caloric test revealed unilateral weakness in the right ear, and the video head impulse test (vHIT) showed decreased vestibulo-ocular reflex (VOR) gain. Contrast-enhanced magnetic resonance imaging (MRI) using hybrid of reversed image of positive endolymph signal and negative image of perilymph signal (HYDROPS) indicated a collapsed endolymphatic space. As the vestibular symptoms did not improve, an exploratory tympanotomy was performed on the right ear. Although perilymph leakage was not noted in the oval or round windows, both windows were sealed with connective tissue. The patient's vestibular symptoms rapidly improved after surgery, and postoperative contrast-enhanced MRI showed improvement in the collapsed endolymphatic space. Although the caloric test revealed unilateral weakness, the VOR gain on the vHIT improved to normal on the right side. Thus, these findings indicated that recurrent symptoms caused by PLF are associated with a collapsed endolymphatic space. We speculate that the collapsed endolymphatic space was due to a ruptured Reissner's membrane. We hypothesized that sealing the fistula would promote normalization of perilymph pressure. The ruptured Reissner's membrane may have been gradually repaired as vestibular symptoms improved. This case adds to the existing literature on the occurrence of the "double-membrane break syndrome". Collapse of the endolymph due to a ruptured Reissner's membrane may be the cause of PLF symptoms.

Case report: Perilymphatic fistula from a round window microfissure.

A microfissure near the round window niche is an anatomical structure that communicates between middle ear and the ampulla of the posterior semicircular canal. It has been suggested that the microfissure can cause inner ear symptoms; however, the etiology has not yet been confirmed clinically. We report, to our knowledge, the first case of microfissure with complaint of hearing loss and vertigo and improvement in hearing after surgical sealing of the microfissure. A 50-year-old man complained of hearing disturbance, tinnitus with flowing-water sound in the left ear, and a floating sensation upon pushing the left tragus. He had moderate sensorineural hearing loss (43.3 dB) in the left ear for 3 days. His hearing worsened and he complained of severe vertigo. An exploratory tympanotomy was performed 8 days after onset. A microfissure and accumulation of clear fluid in the floor of the round window niche were detected, and leakage point was packed with connective tissue. One month after surgery, his hearing (20.0 dB) and disequilibrium had improved. The inner ear symptoms improved after the surgery in this case, suggesting that the microfissure might have caused the symptoms.

Primary Liposarcoma with Cholesteatoma in Mastoid.

Liposarcoma is a soft tissue neoplasm that commonly develops in the lower extremities and rarely in the head and neck region. Herein, we report the case of a patient with primary liposarcoma that was detected in the mastoid antrum during staged tympanoplasty for cholesteatoma. The tumor adjacent to the attic cholesteatoma was resected completely, and the pathological diagnosis was that of myxoid-type liposarcoma. Because positron emission tomography after the surgery showed no signs of tumor remnants or systemic metastasis, a second-stage surgery was performed 8 months after the first surgery. After confirming that there was no recurrence, tympanoplasty type III with interposition between the stapes and malleus and canal reconstruction was performed. No recurrence was observed for 5 years, and to date, good hearing has been maintained. This is the first report on long-term follow-up of a patient with liposarcoma in the mastoid antrum.

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.

Vestibule-Middle Ear Dehiscence Tested With Perilymph-Specific Protein Cochlin-Tomoprotein (CTP) Detection Test.

An 8-year-old boy was referred to the ENT department for further evaluation of right-sided conductive hearing loss. A small cyst anterior to the oval window and fixation of the stapes footplate were observed during an exploratory tympanotomy. The concentration of a perilymph-specific protein, cochlin-tomoprotein (CTP), in the middle ear lavage fluid was measured with an ELISA-based CTP detection kit. The level of CTP in the middle ear lavage fluid before fenestration of the cyst was 0.26 ng/ml (negative), and its level after fenestration was 2.98 ng/ml (positive), confirming the presence of perilymph in the cyst. A small bone dehiscence, considered to be the fissula ante fenestram, was observed anterior to the stapes footplate after removal of the cyst. The CTP detection test results allowed us to confirm that the small bone dehiscence was connected to the inner ear.

The prevalence of vestibular schwannoma among patients treated as sudden sensorineural hearing loss.

OBJECTIVE: To assess the prevalence of vestibular schwannoma (VS) in patients with sudden sensorineural hearing loss (SSNHL). METHODS: This is a retrospective chart review of 861 patients who were diagnosed with or treated for SSHNL between January 2008 and February 2017 at our department in a tertiary academic center. We retrospectively analyzed the medical charts and MRI findings of 499 patients who had undergone MRI. RESULTS: Fifteen (3.0%) of the 499 patients exhibited tumors at the cerebellopontine angle on the same side affected by SSNHL. In one patient, a tumor was incidentally detected in the contralateral ear. The 15 VS lesions were graded using the Koos acoustic neuroma grading system as follows: grade I (intracanalicular tumor), n=8; grade II (up to 2cm), n=6; and grade III (up to 3cm), n=1. Koos grade IV tumors, which are large tumors that displace the trunk or cranial nerves, were not found. CONCLUSION: The prevalence of VS in patients with SSNHL was 3.0% in the present study. Considering this high prevalence, clinicians should consider detailed examinations in addition to audiometry for patients with SSNHL.

Intractable persistent direction-changing geotropic nystagmus improved by lateral semicircular canal plugging.

Antigravitational deviation of the cupula of the lateral semicircular canal, which is also called light cupula, evokes persistent direction-changing geotropic nystagmus with a neutral point. No intractable cases of this condition have been reported. In our case, a 67-year-old man complained of positional vertigo 3 months after developing idiopathic sudden hearing loss in the right ear with vertigo. He showed a persistent direction-changing geotropic nystagmus with a leftward beating nystagmus in the supine position. The nystagmus resolved when his head was turned approximately 30° to the right. He was diagnosed with light cupula of the right lateral semicircular canal and was subsequently treated with an antivertiginous agent. However, his symptoms and positional nystagmus did not improve, so the right lateral semicircular canal was plugged by surgery. One month after surgery, his positional vertigo and nystagmus were completely resolved. We speculated that the cause of the patient's intractable light cupula was an enlarged cupula caused by his idiopathic sudden hearing loss.

LECT2 functions as a hepatokine that links obesity to skeletal muscle insulin resistance.

Recent articles have reported an association between fatty liver disease and systemic insulin resistance in humans, but the causal relationship remains unclear. The liver may contribute to muscle insulin resistance by releasing secretory proteins called hepatokines. Here we demonstrate that leukocyte cell-derived chemotaxin 2 (LECT2), an energy-sensing hepatokine, is a link between obesity and skeletal muscle insulin resistance. Circulating LECT2 positively correlated with the severity of both obesity and insulin resistance in humans. LECT2 expression was negatively regulated by starvation-sensing kinase adenosine monophosphate-activated protein kinase in H4IIEC hepatocytes. Genetic deletion of LECT2 in mice increased insulin sensitivity in the skeletal muscle. Treatment with recombinant LECT2 protein impaired insulin signaling via phosphorylation of Jun NH2-terminal kinase in C2C12 myocytes. These results demonstrate the involvement of LECT2 in glucose metabolism and suggest that LECT2 may be a therapeutic target for obesity-associated insulin resistance.

Hearing and vestibular functions after plugging surgery for the posterior semicircular canal.

CONCLUSIONS: Results of audiometry, caloric testing and vestibular evoked myogenic potential (VEMP) testing were hardly influenced by plugging surgery. OBJECTIVE: To evaluate the influence of surgical plugging of the posterior semicircular canal on inner ear function in patients with benign paroxysmal positional vertigo (BPPV). SUBJECTS AND METHODS: The subjects were five consecutive patients with intractable BPPV who underwent plugging surgery. The following functions of the inner ear were examined before and 6 months after surgery. Cochlea function was evaluated by the average hearing level of three frequencies (500, 1000 and 2000 Hz), that of the semicircular canal by canal paresis percent (CP%) in caloric testing and that of the otolith by the left-right difference ratio on VEMP testing. RESULTS: Positional vertigo was resolved in all patients. One subject was completely deaf before and after surgery. The average hearing level did not change more than 10 dB after surgery in the other four cases. CP% did not worsen more than 10% in any case. The VEMP results after surgery did not change more than 10% from before surgery in any case.

Activation of sodium-glucose cotransporter 1 ameliorates hyperglycemia by mediating incretin secretion in mice.

Glucose ingestion stimulates the secretion of the incretin hormones, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1). Despite the critical role of incretins in glucose homeostasis, the mechanism of glucose-induced incretin secretion has not been established. We investigated the underlying mechanism of glucose-induced incretin secretion in vivo in mice. Injection of glucose at 1 g/kg in the upper intestine significantly increased plasma GIP and GLP-1 levels, whereas injection of glucose in the colon did not increase GIP or GLP-1 levels. This finding indicates that the glucose sensor for glucose-induced incretin secretion is in the upper intestine. Coadministration of a sodium-glucose cotransporter-1 (SGLT1) inhibitor, phloridzin, with glucose in the upper intestine blocked glucose absorption and glucose-induced incretin secretion. alpha-methyl-d-glucopyranoside (MDG), an SGLT1 substrate that is a nonmetabolizable sugar, significantly increased plasma GIP and GLP-1 levels, whereas phloridzin blocked these increases, indicating that concomitant transport of sodium ions and glucose (substrate) via SGLT1 itself triggers incretin secretion without the need for subsequent glucose metabolism. Interestingly, oral administration of MDG significantly increased plasma GIP, GLP-1, and insulin levels and reduced blood glucose levels during an intraperitoneal glucose tolerance test. Furthermore, chronic MDG treatment in drinking water (3%) for 13 days reduced blood glucose levels after a 2-h fast and in an oral glucose tolerance test in diabetic db/db mice. Our findings indicate that SGLT1 serves as the intestinal glucose sensor for glucose-induced incretin secretion and that a noncalorigenic SGLT1 substrate ameliorates hyperglycemia by stimulating incretin secretion.

Role of MGAT2 and DGAT1 in the release of gut peptides after triglyceride ingestion.

Triglyceride ingestion releases gut peptides from enteroendocrine cells located in the intestinal epithelia and provides feedback regulations of gastrointestinal function. The precise mechanisms sensing lipids in the intestinal wall, however, are not well characterized. In the current study, we investigated the release of gut peptides following oral triglyceride loading in mice deficient for monoacylglycerol acyltransferase 2 (MGAT2KO) and diacylglycerol acyltransferase 1 (DGAT1KO), enzymes that sequentially re-synthesize triglyceride to secrete as chylomicron at the small intestine. In wild-type (Wt) mice, oral triglyceride loading resulted in hypertriglycemia. In addition, plasma glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) were significantly increased 30 min after triglyceride loading, before decaying in 2h. In MGAT2KO and DGAT1KO mice, oral triglyceride loading did not result in hypertriglycemia and the increase in GIP was significantly suppressed in both KO mouse strains. In contrast, the increases in plasma GLP-1 and PYY in both KO mouse strains were comparable to Wt mice 30 min after triglyceride loading, however, they remained elevated in DGAT1KO mice even 2h after triglyceride loading. In parallel to the changes in GLP-1 and PYY, gastric emptying was delayed after oral triglyceride loading in MGAT2KO mice comparably to Wt type mice and was further delayed in DGAT1KO mice. STC-1 and GLUTag, GLP-1-producing intestinal endocrine L-cell lines, displayed a significant level of DGAT1 activity but not MGAT activity. These findings suggest that synthesis and/or secretion of triglyceride-rich lipoproteins play an important role in the release of GIP. Moreover, DGAT1 may directly regulate the release of GLP-1 and PYY in L-cells.

Identification of a stable chemerin analog with potent activity toward ChemR23.

Chemerin is a novel peptide that was identified as a natural ligand for ChemR23. As it has been reported to be involved in the regulation of immune responses and adipogenesis, chemerin may have a variety of physiological functions. Chemerin is synthesized as a precursor (prochemerin) and is proteolytically activated and inactivated in sequential steps, which control its physiological roles in a coordinated manner. Chemerin-9 (chemerin148-156) was previously identified as the smallest peptide with low nanomolar potency. However, like mature chemerin, chemerin-9 is rapidly degraded and inactivated in plasma, which has limited the use of chemerin-9 in in vivo experiments. In order to identify stable chemerin analogs that facilitate in vivo studies, we synthesized a series of chemerin-9 analogs and examined intrinsic activity and metabolic stability. We identified an agonistic and metabolically stable chemerin-9 analog (d-Tyr(147)-[d-Ser(151), d-Ala(154), Tic(155)]chemerin148-156) that shows enhanced plasma exposure with prolonged half-life in mice upon intraperitoneal administration. Improvement of metabolic stability resulted in a reduction in the plasma free fatty acid levels in fasted mice, which cannot be accomplished by unstable-mouse chemerin-9. This reduction in plasma free fatty acids reflects the anti-lipolysis activity of chemerin-9 and analogs in mouse primary adipocytes. The discovery of a metabolically stable chemerin analog will facilitate investigation of the pharmacological roles of chemerin in vivo. Moreover, this stable chemerin analog might provide new therapeutic approaches to inflammatory diseases such as asthma and metabolic disorders such as obesity and diabetes where ChemR23 activation may be of benefit.

A case of Churg-Strauss syndrome with refractory otitis media.

OBJECTIVE: Churg-Strauss syndrome (CSS) is known as autoimmune vasculitis with peripheral eosinophilia after bronchial asthma and rarely has otological findings. We present a case of CSS with refractory otitis media and discuss the relationship between otological symptoms of CSS and eosinophilic otitis media. CASE REPORT: A 60-year-old woman had suffered from recurrent sinusitis for 8 years, and also otitis media with effusion for 4 months. Eruption with peripheral eosinophilia was found in the lower legs; therefore, she was diagnosed with CSS. She was treated with systemic administration of prednisolone, intratympanic injection of betamethasone, and betamethasone nasal spray; thereafter, eosinophilia, otitis media and sinusitis rapidly improved. CONCLUSION: The features of eosinophilic otitis media are similar to the otological symptoms of CSS. It should be considered whether patients with eosinophilic otitis media have early phase CSS.

Liposarcoma of temporal bone: a case report.

This is the third case report of liposarcoma of the temporal bone. A 69-year-old man complained of left otalgia, left otorrhea, and dizziness for several months, with a past history of tympanoplasty for cholesteatoma 28 years previously. Otoscopy revealed debris in the attic. We performed tympanoplasty for recurrent cholesteatoma. The postoperative pathological diagnosis was well-differentiated liposarcoma. Palliative resection of liposarcoma was performed 3 months after the first surgery. Neither local recurrence nor distant metastasis has been detected for 24 months after the first surgery. The favorable outcome in this patient was probably due to the histological type of his liposarcoma.

Triglycerides in fish oil affect the blood clearance of lipid emulsions containing long- and medium-chain triglycerides in mice.

Lipid emulsions containing long-chain triglycerides (LCT) and medium chain triglycerides (MCT) are widely used in parenteral nutrition. Recently, fish oil (FO) triglyceride (TG)-derived emulsions are considered therapeutic because of their many beneficial biological modulatory actions. We investigated in mice whether adding 10% FO to an intravenous lipid emulsion with MCT and LCT (MCT:LCT:FO -50:40:10% by wt) would affect particle blood clearance and tissue targeting in comparison to LCT (100% by wt) and MCT:LCT (50:50% by wt) emulsions. The 3 emulsions were labeled with [3H] cholesteryl oleoyl ether and administered by bolus injection (400 microg TG/mouse) to C57BL/6J mice. Contributions of LDL receptor (LDL-R) and LDL-R-related protein to emulsion catabolism were assessed using LDL-R-deficient mice and preinjection of lactoferrin, and the effects of lipoprotein lipase (LPL) were determined by preinjection of heparin and Triton WR 1339. Although fractional catabolic rates did not differ among the 3 emulsions, blood removal at each time point after injection was greater for MCT:LCT:FO particles due to their higher initial margination volume. Compared with MCT:LCT and LCT emulsions, patterns of tissue uptake of the MCT:LCT:FO emulsions were different, e.g. MCT:LCT:FO emulsion particle uptake was lower in heart, adipose tissue, and muscle, and higher in lung, and the removal of MCT:LCT:FO emulsion particles was less dependent on LPL, LDL-R, and lactoferrin-sensitive pathways. These data suggest that the addition of a low percentage of FO to MCT:LCT emulsions substantially changes their particle clearance and tissue uptake mechanisms.

[Case of toxic shock-like syndrome affecting the neck].

Toxic shock-like syndrome (TSLS) is a form of rapidly progressing septic shock that can lead to multiple organ failure and has a high mortality rate of 30%. We report a rare case of TSLS affecting the head and neck. A 40-year-old man complained of redness and swelling of the neck with vomiting and diarrhea. His blood pressure dropped, and multiple organ failure occurred. Streptcoccus pyogenes, Group A, was identified in a blood culture, and he was diagnosed as having TSLS. He was treated with high-dose carbapenem, clindamysin, and gamma globulin. Continuous hemodiafiltration (CHDF) and PMX-DHP was applied to prevent sepsis and multiple organ failure. Debridement of the neck was performed on day 16. He recovered gradually and was discharged from hospital on day 45. A total resection is required to treat TSLS, but such a procedure is difficult to perform in the head and neck region. Our case improved without resection but after debridement and general control. TSLS should be first treated by medication and then by surgery, consisting of either debridement or resection.

n-3 fatty acids and gene expression.

Accumulating evidence in both humans and animal models clearly indicates that a group of very-long-chain polyunsaturated fatty acids, the n-3 fatty acids (or omega-3), have distinct and important bioactive properties compared with other groups of fatty acids. n-3 Fatty acids are known to reduce many risk factors associated with several diseases, such as cardiovascular diseases, diabetes, and cancer. The mechanisms whereby n-3 fatty acids affect gene expression are complex and involve multiple processes. As examples, n-3 fatty acids regulate 2 groups of transcription factors, such as sterol-regulatory-element binding proteins and peroxisome proliferator-activated receptors, that are critical for modulating the expression of genes controlling both systemic and tissue-specific lipid homeostasis. Modulation of specific genes by n-3 fatty acids and cross-talk between these genes are responsible for many effects of n-3 fatty acids.

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.