Low-dose dexamethasone with fosaprepitant and palonosetron to prevent cisplatin-induced nausea and vomiting in head and neck cancer patients.

OBJECTIVE: To determine if a lower dose of dexamethasone can be used in combination with fosaprepitant and palonosetron for cisplatin-induced nausea and vomiting in head and neck cancer patients, we conducted a single-center, two-arm, cross-over comparison study. METHODS: Patients were randomly assigned to either standard dose dexamethasone group: intravenous 9.9 mg on day 1 and 6.6 mg on days 2-4 or low-dose dexamethasone group: intravenous 3.3 mg on days 1-4 for the first course and crossed over to the other treatment for the second course. The primary endpoint was complete response (CR) in the overall period. RESULTS: Twenty-five patients were screened for the study and 22 were evaluable. Eleven patients were randomly assigned to the standard dose dexamethasone group and 12 patients to the low-dose dexamethasone group. The CR rate in the overall period was 86% in the standard dose group and 73% in the low-dose group, showing no significant difference (p = .61). CONCLUSION: The efficacy of low-dose dexamethasone with fosaprepitant and palonosetron was not inferior to that of the standard dose dexamethasone in the highly emetogenic cisplatin-based treatment for head and neck cancer patients.

Influence of pneumococcal conjugate vaccines on acute otitis media in Japan.

OBJECTIVE: This study investigated: (i) changes in the incidence of acute otitis media (AOM) following introduction of public funding for free inoculation with 7- and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13, respectively) and (ii) changes in the rate of myringotomies for AOM (MyfA) in children 1year following the publication of the first edition of the clinical practice guidelines for the diagnosis and management of AOM in children in Japan. METHODS: PCV7 was launched on the Japanese market in 2010 and gained public funding in 2011. PCV7 was replaced with PCV13 in November 2013. Using the Japan Medical Data Center Claims Database, an 11-year study conducted between January 2005 and December 2015 investigated the decline in the incidence of visits to medical institutions (VtMI) due to all-cause AOM in children <15years. The rate of MyfA from January 2007 to December 2015was also investigated and changes before and after introduction of public funding for PCV7 (pfPCV7) and PCV13 (pfPCV13) for children were examined. Statistical data for the age group between 10 years and <15years served as the control. An analysis was conducted to examine changes for each age group, from infants that had received PCVs to children <5years. Statistical analysis was performed using the chi-square test and Ryan's multiple comparison tests. Ryan's multiple comparison tests were applied at a 5% level of significance. Due to significant changes in the guidelines on the indications for myringotomy introduced in 2013, statistical analysis of the rate of MyfA was limited to the pre- and post-PCV7 period. RESULTS: After introduction of pfPCV7 and pfPCV13, no significant suppression of the incidence of VtMI was observed in any age group. There was a gradual decline in the rate of MyfA after 2011. Compared to the control group, significant differences in all age groups from infants to children <5years were observed (p<0.009, chi-square test). Within 2 years after the introduction of PCV7, a significant decline in the rate of MyfA was observed in 1- and 5-year-olds using Ryan's multiple comparison tests at a 5% level of significance. CONCLUSION: The preventative effect of PCVs on AOM was not established in this study. There was, however, a significant decline in the rate of MyfA among 1- and 5-year-olds. Taking into consideration past studies, PCV7 may play a role in preventing the aggravation of AOM in 1-year-olds. When evaluating the effectiveness of PCVs, measures to evaluate severity may be as important as evaluating disease prevention.

Effects of Cerebral Blood Flow and Vessel Conditions on Speech Recognition in Patients With Postlingual Adult Cochlear Implant: Predictable Factors for the Efficacy of Cochlear Implant.

OBJECTIVES: Cochlear implantation (CI) has been the most successful procedure for restoring hearing in a patient with severe and profound hearing loss. However, possibly owing to the variable brain functions of each patient, its performance and the associated patient satisfaction are widely variable. The authors hypothesize that peripheral and cerebral circulation can be assessed by noninvasive and globally available methods, yielding superior presurgical predictive factors of the performance of CI in adult patients with postlingual hearing loss who are scheduled to undergo CI. DESIGN: Twenty-two adult patients with cochlear implants for postlingual hearing loss were evaluated using Doppler sonography measurement of the cervical arteries (reflecting cerebral blood flow), flow-mediated dilation (FMD; reflecting the condition of cerebral arteries), and their pre-/post-CI best score on a monosyllabic discrimination test (pre-/post-CI best monosyllabic discrimination [BMD] score). Correlations between post-CI BMD score and the other factors were examined using univariate analysis and stepwise multiple linear regression analysis. The prediction factors were calculated by examining the receiver-operating characteristic curve between post-CI BMD score and the significantly positively correlated factors. RESULTS: Age and duration of deafness had a moderately negative correlation. The mean velocity of the internal carotid arteries and FMD had a moderate-to-strong positive correlation with the post-CI BMD score in univariate analysis. Stepwise multiple linear regression analysis revealed that only FMD was significantly positively correlated with post-CI BMD score. Analysis of the receiver-operating characteristic curve showed that a FMD cutoff score of 1.8 significantly predicted post-CI BMD score. CONCLUSIONS: These data suggest that FMD is a convenient, noninvasive, and widely available tool for predicting the efficacy of cochlear implants. An FMD cutoff score of 1.8 could be a good index for determining whether patients will hear well with cochlear implants. It could also be used to predict whether cochlear implants will provide good speech recognition benefits to candidates, even if their speech discrimination is poor. This FMD index could become a useful predictive tool for candidates with poor speech discrimination to determine the efficacy of CI before surgery.

Extraskeletal osteosarcoma in the parotid gland: A case report.

Extraskeletal osteosarcoma is a very rare tumor and accounts for 4-5% of all osteosarcomas. We describe a 47-year-old Japanese man who presented with a right parotid tumor. The patient underwent total resection with postoperative radiotherapy; however, the tumor recurred in the lung, whereupon he underwent chemotherapy and partial lung resection. After surgery, a hemorrhagic brain metastasis appeared; this tumor was extirpated to prevent bleeding into the brain, after which additional chemotherapy was administered. Nevertheless, the patient developed additional metastases and died 17 months after the total parotidectomy. This tumor was unique in that it arose in the parotid gland; this case provides an instructional example of an extremely rare manifestation of this type of tumor.

Clinical outcomes of concurrent chemoradiotherapy with volumetric modulated arc therapy in patients with locally advanced nasopharyngeal carcinoma.

PURPOSE: The purpose of this study was to analyze the clinical results of concurrent chemoradiotherapy (CCRT) with volumetric modulated arc therapy (VMAT) for nasopharyngeal carcinoma (NPC) patients. MATERIALS AND METHODS: Patients with stage II-IVB NPC who received CCRT with VMAT between 2010 and 2014 were included in this study. The planned dose was 70 Gy in 35 fractions. RESULTS: Twenty patients aged between 28 and 85 years (median 60 years) were assessed. With a median follow-up time of 47 months, the 3-year overall survival and progression-free survival rates were 85 and 65%, respectively. The 3-year local, regional and distant control rates were 78, 88 and 79%, respectively. At 0, 3, 6 and 12 months from CCRT, 19, 6, 3, and 1 patients had grade 2 dry mouth, respectively. No cases of grade 3 or worse dry mouth were observed. The severity of dry mouth was downgraded from grade 2 to grade 0 or 1 significantly earlier in younger patients (<70 years, p = 0.02) or patients in whom the mean dose to one parotid gland was lower (<26 Gy, p = 0.04). CONCLUSIONS: Our clinical results regarding CCRT with VMAT for NPC patients showed favorable survival rates while maintaining organ function.

IL-5 and IL-6 are increased in the frontal recess of eosinophilic chronic rhinosinusitis patients.

BACKGROUND: Eosinophilic chronic frontal sinusitis is difficult to treat compared with non-eosinophilic sinusitis because of recurring inflammation and polyp formation in the frontal recess after the post-operative follow-up period. Studying inflammatory mediators in the frontal recess of eosinophilic chronic rhinosinusitis (ECRS) patients and non-eosinophilic chronic rhinosinusitis (non-ECRS) patients may lead to a better understanding of the pathogenesis of chronic frontal sinusitis. METHODS: Homogenates of sinonasal mucosa from 20 non-ECRS patients and 36 ECRS patients were measured for levels of transforming growth factor (TGF)-ß, interleukin (IL)-5, IL-6, and inducible nitric oxide synthase (iNOS) using real-time RT-PCR and TaqMan gene expression assays. Sinonasal mucosal specimens were obtained from the frontal recess, ethmoid sinus, and nasal polyp separately. RESULTS: The expression of IL-5 was significantly elevated in all sinonasal regions tested in the ECRS group, but absent in non-ECRS patients. Furthermore, the ECRS patients showed significantly increased levels of IL-5 in the frontal recess mucosa compared with ethmoid sinus mucosa. IL-6 was also significantly increased in the frontal recess mucosa compared with ethmoid sinus mucosa and nasal polyps in these patients. There were no significant differences in the levels of TGF-ß or iNOS between the ECRS and non-ECRS groups in any sinonasal region tested. CONCLUSIONS: This study is the first to characterize the cytokine milieu in the frontal recess of ECRS patients. We should keep these cytokine profiles in mind when we treat ECRS patients with frontal sinusitis.

Management of Intractable Nasal Hyperreactivity by Selective Resection of Posterior Nasal Nerve Branches.

The posterior nasal nerves emerge from the sphenopalatine foramen and contain sensory and autonomic nerve components. Posterior nasal neurectomy is an effective method to remove pathological neural networks surrounding the inferior turbinate that cause unregulated nasal hypersensitivity with excess secretion in patients with severe allergic rhinitis (AR). We describe the sophisticated endoscopic surgical procedure that allows feasible access to the confined area and selective resection of the nerve branches with the preservation of the sphenopalatine artery (SPA). We retrospectively analyzed the cases of 23 symptomatic severe AR patients who failed to respond to standard medical treatment and underwent surgery. There have been no major complications after surgery including nasal bleeding or transient numbness of the upper teeth. The mean total nasal symptom scores (TNSS) were decreased by 70.2% at 12 months after the procedure. Our comparison of the clinical effectiveness based on the number of severed nerve branches revealed that the improvement of the TNSS was significantly higher in patients with >2 branches. We conclude that this minimally invasive technique that preserves the SPA is clinically useful and decreases the rate of postoperative complications. This trial is registered with UMIN000029025.

The role of nasal fractional exhaled nitric oxide as an objective parameter independent of nasal airflow resistance in the diagnosis of allergic rhinitis.

OBJECTIVE: Patients with allergic rhinitis (AR) show augmented activity of nitric oxide (NO) metabolism, similar to those in bronchial asthma (BA). We hypothesized that measurements of nasal fractional exhaled NO (FeNO) could be used as an objective marker to detect the presence of AR. Our objective was to clarify the influence of nasal airflow resistance (NAR) on nasal FeNO levels through an exhalation maneuver in symptomatic AR patients. We also examined the diagnostic test validity of the mean nasal FeNO level for disease discrimination by means of a receiver operating characteristic (ROC) curve analysis. METHODS: Fifty-nine untreated perennial AR patients without BA and 60 healthy controls were enrolled in this retrospective cross-sectional study. The subjective symptoms were recorded and the disease severity was classified according to the Japanese guideline for AR. The oral and nasal FeNO measurements were carried out using a handheld electrochemical analyzer according to the ATS/ERS guidelines. NAR was measured using a rhinomanometer by the anterior method. RESULTS: The patients in the moderate-to-most severe AR group showed significantly higher levels of oral FeNO compared to the controls. The AR patients in both the mild (n=25) and the moderate-to-most severe (n=34) groups showed significantly higher levels of nasal FeNO compared to the controls (44.1ppb, 54.5ppb, and 26.5ppb, respectively). There was no significant difference in total NAR between the AR patients and the controls. The results of our comparison of nasal FeNO and NAR values of the ipsilateral nasal cavity for each individual indicated no significant correlation between the two-paired parameters. The optimal cut-off point of the mean nasal FeNO level was calculated as 38.5ppb (with 71% sensitivity and 86% specificity) to discriminate the presence of AR. CONCLUSION: Nasal FeNO measurements can be an objective parameter for the diagnosis and classification of perennial AR in Japanese individuals. Nasal FeNO and NAR appear to be two independent measures that can be used to objectively evaluate nasal functions.

Influence of Pneumococcal Conjugate Vaccine on Acute Otitis Media with Severe Middle Ear Inflammation: A Retrospective Multicenter Study.

The Japanese guidelines for acute otitis media in children recommend classifying acute otitis media by age, manifestations and local findings, and also recommend myringotomy for moderate-grade cases with severe local findings, severe-grade cases, and treatment-resistant cases. The heptavalent pneumococcal conjugate vaccine was released in Japan in February 2010. In Hiroshima City, public funding allowing free inoculation with this vaccine was initiated from January 2011, and the number of vaccinated individuals has since increased dramatically. This study investigated changes in the number of myringotomies performed to treat acute otitis media during the 5-year period from January 2008 to December 2012 at two hospitals and five clinics in the Asa Area of Hiroshima City, Japan. A total of 3,165 myringotomies for acute otitis media were performed. The rate of procedures per child-year performed in <5-year-old children decreased by 29.1% in 2011 and by 25.2% in 2012 compared to the mean rate performed in the 3 years prior to the introduction of public funding. A total of 895 myringotomies were performed for 1-year-old infants. The rate of myringotomies per child-year performed for acute otitis media in 1-year-old infants decreased significantly in the 2 years after the introduction of public funding for heptavalent pneumococcal conjugate vaccine compared to all years before introduction (p<0.000001). Our results suggest a benefit of heptavalent pneumococcal conjugate vaccine for acute otitis media in reducing the financial burden of myringotomy. In addition, this vaccine may help prevent acute otitis media with severe middle ear inflammation in 1-year-old infants.

Novel NOG mutation in Japanese patients with stapes ankylosis with broad thumbs and toes.

Human noggin (NOG) gene mutation causes multiple bony disorders showing up as stapes ankylosis with broad thumbs and toes (SABTT), proximal symphalangism (SYM1), multiple synostoses syndrome 1 (SYNS1), tarsal-carpal coalition syndrome (TCC) and brachydactyly type B2 (BDB2). These phenotypes are defined as NOG-related syndromes with the same mutation. Some of these syndromes feature stapes ankylosis as one of the several bony symptoms. Here, we report a Japanese family with conductive hearing loss due to congenital stapes ankylosis. This family showed multiple features and was diagnosed with SABTT. We performed analysis of the NOG in the family by direct sequence analysis, and found a novel NOG mutation: c.682 T> G (p.C228G). Our results and a review of previous cases with NOG protein conformation suggest that this mutated NOG protein lead to a change in antagonist activity in BMPs and/or a haploinsufficiency that likely impaired finger 2 structure.

Frontal recess anatomy in Japanese subjects and its effect on the development of frontal sinusitis: computed tomography analysis.

BACKGROUND: Comprehensive understanding of frontal recess anatomy is essential for the successful treatment of patients with frontal sinus disease. This study was designed to determine the prevalence of specific frontal recess cells in Japanese subjects and the association of these cells with the development of frontal sinusitis. METHODS: Frontal recess anatomy was analyzed using high-resolution spiral computed tomography images of paranasal sinuses from December 2008 through September 2011. The distribution of various frontal recess cells in patients with and without frontal sinusitis was compared by logistic regression analysis. RESULTS: A total of 150 patients met the criteria, and 300 sides were analyzed. Agger nasi cells were present in 88.0 % of sides; frontal cell types 1 (FC1), 2 (FC2), 3 (FC3), and 4 (FC4) were present in 37.0 %, 6.3 %, 4.3 %, and 1.3 %, respectively; supraorbital ethmoid cells in 6.0 %, suprabullar cells in 37.0 %, frontal bullar cells (FBC) in 7.0 %, and interfrontal sinus septal cells in 8.6 %. Multiple logistic regression analysis showed that the presence of FBCs was significantly associated with the development of frontal sinusitis (p = 0.043). CONCLUSIONS: The frequencies of frontal recess cells in Japanese adult patients were similar to those reported for other East Asian adult populations, including Chinese, Korean, and Taiwanese. Anatomically, FBCs may show a greater association with the development of frontal sinusitis than other frontal recess cells.

Long-term administration of vasopressin can cause Ménière's disease in mice.

CONCLUSION: A new murine model of Ménière's disease has been developed, based on long-term administration of vasopressin. Induction of vestibular dysfunction in the present animal model can cause additional stress, by reducing inner ear blood flow. Latanoprost, a selective agonist for the FP prostanoid receptor, may become a new remedy for Ménière's disease. OBJECTIVE: The purpose of this study was to develop a more suitable animal model, with a closer resemblance to the pathophysiological process in Ménière's disease. METHODS: Adult CBA/J or ICR mice were treated by subcutaneous injection of vasopressin for 5 days up to 8 weeks. Morphological analyses were performed of the cochlea, vestibular end organs and endolymphatic sac. The effect of latanoprost on the development of endolymphatic hydrops was also examined. RESULTS: All experimental animals showed mild to moderate endolymphatic hydrops, increasing in severity as the vasopressin treatment was prolonged. Animals treated with vasopressin for 8 weeks showed severe endolymphatic hydrops with partial loss of outer hair cells and spiral ganglion cells. These animals also had a reversible vestibular dysfunction following intratympanic injection of epinephrine. Latanoprost inhibited the development of endolymphatic hydrops caused by vasopressin.

Comparison of nasal nitric oxide levels between the inferior turbinate surface and the middle meatus in patients with symptomatic allergic rhinitis.

BACKGROUND: Because of the anatomical complexity and the high output of the human nose, it has been unclear whether nasal nitric oxide (NO) serves as a reliable marker of allergic rhinitis (AR). We examined whether nasal NO levels in the inferior turbinate (IT) surface and the middle meatus (MM) differ in symptomatic AR patients. METHODS: We measured fractional exhaled NO (FeNO) and nasal NO in normal subjects (n = 50) and AR patients with mild symptoms (n = 16) or moderate or severe symptoms (n = 27). Nasal NO measurements were obtained using an electrochemical analyzer connected to a catheter and an air-suction pump (flow rate 50mL/sec). RESULTS: Compared to the normal subjects, the AR patients showed significantly higher nasal FeNO and nasal NO levels in the IT area. No significant difference in the MM area was observed among the three groups. The MM area showed higher NO levels than the IT area in all three groups. The ratio of nasal NO levels of the MM area to the IT area (MM/IT ratio) was significantly lower in the AR groups. The moderate/severe AR patients showed significantly higher nasal NO in the IT area (104.4 vs. 66.2ppb) and lower MM/IT ratios than those in the mild AR patients. The analysis of nasal brushing cells revealed significantly higher eosinophil cationic protein and nitrotyrosine levels in the AR groups. CONCLUSIONS: Nasal NO assessment in the IT area directly reflects persistent eosinophilic inflammation and may be a valid marker to estimate the severity of AR.

Comparison of Nasal Nitric Oxide Levels between the Inferior Turbinate Surface the Middle Meatus in Patients with Symptomatic Allergic Rhinitis.

BACKGROUND: Because of the anatomical complexity and the high output of the human nose, it has been unclear whether nasal nitric oxide (NO) serves as a reliable marker of allergic rhinitis (AR). We examined whether nasal NO levels in the inferior turbinate (IT) surface and the middle meatus (MM) differ in symptomatic AR patients. METHODS: We measured fractional exhaled NO (FeNO) and nasal NO in normal subjects (n = 50) and AR patients with mild symptoms (n = 16) or moderate or severe symptoms (n = 27). Nasal NO measurements were obtained using an electrochemical analyzer connected to a catheter and an air-suction pump (flow rate 50 mL/ sec). RESULTS: Compared to the normal subjects, the AR patients showed significantly higher nasal FeNO and nasal NO levels in the IT area. No significant difference in the MM area was observed among the three groups. The MM area showed higher NO levels than the IT area in all three groups. The ratio of nasal NO levels of the MM area to the IT area (MM/IT ratio) was significantly lower in the AR groups. The moderate/severe AR patients showed significantly higher nasal NO in the IT area (104.4 vs. 66.2 ppb) and lower MM/IT ratios than those in the mild AR patients. The analysis of nasal brushing cells revealed significantly higher eosinophil cationic protein and nitrotyrosine levels in the AR groups. CONCLUSIONS: Nasal NO assessment in the IT area directly reflects persistent eosinophilic inflammation and may be a valid marker to estimate the severity of AR.

Expression of RANKL and proliferation abilities of cultured human middle ear cholesteatoma epithelial cells.

One of the most distinct characteristics of middle ear cholesteatomas is their capacity for bone destruction during the growth process. In this study, we examined the relationship between inflammatory mechanisms and both bone absorption and the proliferation of epithelial cholesteatoma cells. Cultured cholesteatoma epithelial cells were stimulated by lipopolysaccharide (LPS) and dexamethasone (Dex). We found that the expression of receptor activator of NF-kappaB ligand (RANKL) and Ki-67 in cultured cholesteatoma cells was increased by LPS stimulation, indicating that LPS promotes not only bone destruction but also the proliferative activities of these cells. The constitutive expression of RANKL and Ki-67 and the production of IL-6 and IL-8 were significantly inhibited by Dex treatment. Further, Dex significantly suppressed the stimulatory effects of LPS on RANKL and Ki-67 expression and on IL-6 and IL-8 production. Based on results so far, Dex likely exerts a beneficial action against acute inflammation. However, further studies might be required to assess its clinical features.

Increased exhaled nitric oxide and its oxidation metabolism in eosinophilic chronic rhinosinusitis.

OBJECTIVE: Monitoring of fractional concentrations of exhaled nitric oxide (FeNO) has become a reliable marker of inflammation in human nose and paranasal sinuses. However, it is still unknown to what extent nasal NO levels contribute to the pathology of chronic rhinosinusitis (CRS). In the present study, we aimed to examine FeNO levels and the underlying mechanism of NO production and metabolism in patients with eosinophilic chronic rhinosinusitis (ECRS) and non-ECRS. METHODS: Thirty-three untreated ECRS patients, 16 non-ECRS patients, and 38 normal subjects were enrolled in this cross-sectional study of FeNO levels. Oral and nasal FeNO levels were measured before treatment using an electrochemical NO analyzer (NObreath(®)) with a nose adaptor. The mRNA expression of three nitric oxide synthase (NOS) isoforms, interleukin-5 (IL-5), and transforming growth factor-beta (TGF-ß) in the ethmoid sinus mucosa and nasal polyps were analyzed by real-time PCR. Immunohistological localization of inducible NOS (iNOS) and nitrotyrosine (NT), a marker for oxidized NO metabolites, was also examined. RESULTS: ECRS patients showed significantly higher oral FeNO levels compared to non-ECRS patients and normal subjects (mean values, 47.6, 13.5, and 15.3ppb, respectively). Nasal FeNO levels of the non-ECRS patients (30.5ppb) were significantly lower than those of the ECRS patients (53.9ppb) and normal subjects (45.5ppb). Positive correlations existed between the blood eosinophil percentage and FeNO levels in ECRS patients. Histologically, ECRS patients showed higher eosinophil accumulation in the ethmoid mucosa than non-ECRS patients (103.1 vs. 16.3cells/HPF). Real-time PCR analysis showed significant upregulation of iNOS and IL-5 mRNA expression in the ethmoid mucosa of the ECRS patients compared to those of non-ECRS patients. Positive iNOS immunoreactivity was observed in ciliated epithelial cells, submucosal glands and associated inflammatory cells in both groups. NT immunoreactivity was detected in the epithelium and around inflammatory cells. Intense NT staining was co-localized with eosinophil accumulation and ECRS patients showed significantly higher rates of NT-positive cells than non-ECRS patients. CONCLUSION: A combination of oral and nasal FeNO measurement is a valid marker for the classification and definition of different CRS subtypes in Japan. Higher levels of oral and nasal FeNO in ECRS patients may reflect the persistence of eosinophilic inflammation in sinus mucosa with concomitant iNOS upregulation and accompanying deposition of oxidized NO metabolites.

Expression of prostanoid receptors (EP1, 2, 3, and 4) in normal and methimazole-treated mouse olfactory epithelium.

CONCLUSION: Prostanoid receptors (EP1, EP2, EP3, and EP4) are expressed in the olfactory epithelium (OE), and the EP4 prostanoid receptor may play an important role in the OE. OBJECTIVE: The purpose of the present study was to investigate the expression and localization of the four types of prostanoid receptors (EP1, EP2, EP3, and EP4) in the OE of normal and methimazole-treated mice to gain more complete knowledge about the functional significance of the prostanoid receptors in OE. METHODS: CBA/J mice were used in this study. The localization of the prostanoid receptors (EP1, EP2, EP3, and EP4) in the OE was investigated by immunohistochemistry. The changes in expression of prostanoid receptors were studied in methimazole-treated mice. Furthermore, the effect of EP agonists on the methimazole-induced degeneration of OE was assessed by morphological analysis and by assessment of apoptosis. RESULTS: All four types of EP receptors were recognized in mouse OE. Expression of EP4 in the OE was significantly reduced after methimazole treatment. In the methimazole-treated mice, an EP4 agonist reduced OE damage and apoptosis.