mocetinostat and Otitis-Media

Immunoglobulin G4-related disease (IgG4-RD) and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) have different clinical and pathological features. However, differentiation between these 2 disorders is sometimes difficult.. To report a case involving a patient with characteristics of both IgG4-RD and AAV.. Case report with literature review.. We report a case of myeloperoxidase-ANCA-positive otitis media and rhinosinusitis with pathological features of IgG4-RD in a 73-year-old man. The patient was first clinically suspected to have granulomatosis with polyangiitis. All of the main characteristic pathological features of IgG4-RD were present: dense lymphoplasmacytic infiltration, increased numbers of IgG4-positive plasma cells, storiform-type fibrosis, and obliterative phlebitis.. The simultaneous presence of the characteristics of both IgG4-RD and AAV makes diagnosis and treatment difficult.

Topics: Aged; Antibodies, Antineutrophil Cytoplasmic; Audiometry, Pure-Tone; Autoantibodies; Autoimmune Diseases; Glomerulonephritis, Membranoproliferative; Humans; Immunoglobulin G; Male; Nasal Septal Perforation; Otitis Media; Peroxidase; Rhinitis; Sinusitis; Tomography, X-Ray Computed

Otitis media is one of the common organ injuries that appear during the course of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We experienced four patients with myeloperoxidase (MPO)-ANCA-positive AAV with otitis media. All were elderly Japanese women. MPO-ANCA in our patients was reminiscent of microscopic polyangiitis (MPA), although chest computed tomography (CT) scans revealed characteristics of both granulomatosis with polyangiitis (GPA), showing bronchial lesions and nodule formation, and MPA, showing interstitial changes. Whether our cases should be classified as GPA or MPA is a matter of discussion. We detail their profiles, and review previous literature on MPO-ANCA-positive AAV with otitis media.

Topics: Aged, 80 and over; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Female; Humans; Immunosuppressive Agents; Middle Aged; Otitis Media; Peroxidase; Ribonucleosides; Treatment Outcome

Several case reports have indicated that nontuberculous mycobacterial pulmonary disease is associated with anti-neutrophil cytoplasmic antibody-associated vasculitides. However, the effect of the treatment for nontuberculous mycobacterial pulmonary disease on anti-neutrophil cytoplasmic antibody-associated vasculitides remains unclear. An asymptomatic 80-year-old woman presented with nodular bronchiectasis. After 1 year, she developed a productive cough. Mycobacterial culture of the respiratory specimen revealed Mycobacterium avium. She was diagnosed with nontuberculous mycobacterial pulmonary disease based on the criteria proposed by the American Thoracic Society. Concurrently, she had hearing loss, tinnitus, and weight loss. A blood test showed an elevated level of myeloperoxidase-anti-neutrophil cytoplasmic antibody (107 IU/mL, normal level: <3.5 IU/mL). Bilateral otitis media with anti-neutrophil cytoplasmic antibody-associated vasculitis was diagnosed based on the diagnostic criteria proposed by the Japan Otological Society. After starting antimicrobial agents for the nontuberculous mycobacterial pulmonary disease, her pulmonary symptoms and hearing loss improved, and the level of myeloperoxidase-anti-neutrophil cytoplasmic antibody normalized. No immunosuppressive treatment was administered. The present case suggests that nontuberculous mycobacterial pulmonary disease can cause otitis media with anti-neutrophil cytoplasmic antibody-associated vasculitides, and antimicrobial treatment for the nontuberculous mycobacterial pulmonary disease may resolve otitis media with anti-neutrophil cytoplasmic antibody-associated vasculitides.

Topics: Aged, 80 and over; Anti-Infective Agents; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Female; Hearing Loss; Humans; Lung Diseases; Mycobacterium Infections, Nontuberculous; Otitis Media; Peroxidase

Otitis media with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV) is a new category of otitis media in which cases of otitis media due to ANCA-associated vasculitis (AAV) are classified, regardless of ANCA variant or ANCA serotype. We aimed to describe the clinical features and course of patients with OMAAV and identify factors associated with hearing outcomes.. We retrospectively analysed 30 patients with OMAAV, classified based on the criteria proposed by the Japan Otological Society in 2016.. Single-positive myeloperoxidase-ANCA, single-positive proteinase 3-ANCA, double-positive ANCA, and double-negative ANCA were identified in 47%, 33%, 7%, and 13% of the patients, respectively. All patients subjected to audiometry showed hearing impairments, and 85% were affected bilaterally. Mixed- and sensorineural-type hearing impairments were identified in 80% and 20% of impaired ears, respectively. Hypertrophic pachymeningitis (HPM) was identified in 37% of the patients. Immunosuppressive therapy was administered to 93% of patients, and the median air conduction hearing levels at pre- and post-treatment were 66.1 dB and 43.4 dB, respectively, indicating significant hearing improvements. HPM and a long interval between disease onset and treatment initiation were significantly correlated with poor hearing prognosis.. OMAAV develops under any type of ANCA-serology and typically causes mixed or sensorineural bilateral hearing loss. The early initiation of immunosuppressive therapy and the absence of HPM were associated with good hearing outcomes.

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Humans; Meningitis; Myeloblastin; Otitis Media; Peroxidase; Retrospective Studies

The concept of otitis media with ANCA-associated vasculitis (OMAAV) was recently proposed by the study group of the Japan Otological Society. However, little is known about the effect of ear involvement on the clinical features and prognosis of AAV. We investigate this issue in this study.. We retrospectively examined 36 patients diagnosed with OMAAV and 44 patients diagnosed with AAV without ear involvement (non-OMAAV) at Ehime University Hospital from 2013 to 2018. We collected serological findings including ANCA type and titer, C-reactive protein (CRP), serum creatinine level, organ involved at initial diagnosis, treatment, remission, disease relapse, and mortality from medical records. We investigated whether clinical features and outcomes differed between the OMAAV and non-OMAAV groups.. Age, ANCA titer, and CRP at initial diagnosis were not significantly different between the two groups, and the rate of intravenous cyclophosphamide (IVCY) use also did not differ. The proportions of patients with concurrent eye involvement, facial palsy (FP), and hypertrophic pachymeningitis (HCP) were significantly higher in the OMAAV than in the non-OMAAV group (p = 0.005, 0.005 and 0.049, respectively), while both renal and peripheral nerve involvement were significantly less common in OMAAV patients (p = 0.04). Among the 30 patients with renal involvement, serum creatinine level at diagnosis was significantly lower in the OMAAV group (p = 0.04). The mortality rate was 8.3% in OMAAV and 6.8% in non-OMAAV cases, but this difference was not significant. The rate of relapse was 33.3% in OMAAV and 13.6% in non-OMAAV cases; this difference was significant (p = 0.04).. Serological measurements of disease activity did not differ between the groups. Eye involvement, FP, and HCP, however, were significantly more common in AAV with ear involvement. In addition, renal involvement was less common and renal impairment was milder in AAV with ear involvement. These findings can be considered clinical features. The relapse rate was significantly higher in AAV with ear involvement.

Topics: Aged; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; C-Reactive Protein; Cyclophosphamide; Eye Diseases; Facial Paralysis; Female; Glucocorticoids; Humans; Immunologic Factors; Immunosuppressive Agents; Kidney Diseases; Lung Diseases, Interstitial; Male; Meningitis; Methylprednisolone; Myeloblastin; Otitis Media; Peripheral Nervous System Diseases; Peroxidase; Prognosis; Rituximab

To investigate treatment outcomes, hearing outcomes, and adverse effects of rituximab (RTX) for intractable otitis media with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV).. Twenty-three patients who met the criteria proposed by the OMAAV study group were included. RTX was used for patients who had difficulty achieving induction of remission using glucocorticoids (GC) and intravenous cyclophosphamide (IVCY).. Six patients were treated with RTX (RTX group), while 17 patients did not require RTX for induction of remission (non-RTX group). All six patients in the RTX group achieved remission. Age, sex, and months from onset to diagnosis did not differ significantly between the groups. The air-conduction hearing thresholds at diagnosis and remission were 71.7±6.3dB and 50.1±5.1dB in the RTX group, and 56.8±4.8dB and 35.8±4.8dB in the non-RTX group, respectively. Hearing level at remission was significantly better in the non-RTX group (p<0.05), while hearing gain did not differ significantly between the groups. Infectious complications were similar between the groups.. Our findings suggest that RTX is effective and safe for intractable OMAAV patients who have a poor response to GC and IVCY.

Topics: Adult; Aged; Aged, 80 and over; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Female; Hearing; Humans; Immunologic Factors; Male; Middle Aged; Myeloblastin; Otitis Media; Peroxidase; Rituximab; Treatment Outcome

This prospective study aimed to evaluate the diagnostic and clinical utility of the myeloperoxidase (MPO)-DNA complex as a NETosis-derived product in the middle ear fluid of patients with otitis media with antineutrophil cytoplasmic antibody-associated vasculitis (OMAAV).. Prospective study.. Tertiary referral center.. Twenty-two patients diagnosed with OMAAV.. Collection of the fluid samples from middle ear.. The levels of the MPO-DNA complex in the fluid samples were quantified using an enzyme-linked immunosorbent assay.. Patients with both systemic and localized forms of OMAAV showed significantly higher levels of the MPO-DNA complex compared to the controls (p < 0.001 and p = 0.002, respectively). In particular, they showed significantly higher levels of MPO-DNA complex compared to the controls, regardless of serum antineutrophil cytoplasmic antibody status (p < 0.001 and p < 0.001, respectively) or immunosuppressive therapy (p < 0.001 and p < 0.001, respectively) at the time of sampling. An optical density cutoff value of 0.16 at 405 nm according to the receiver operating characteristic curve showed a sensitivity of 86.4%, specificity of 95.5%, positive predictive value of 95.0% and negative predictive value of 87.5% for the diagnosis of OMAAV. Significant positive correlations were observed between the levels of MPO-DNA complex and the values for air conduction - (r = 0.49, p = 0.022) and bone conduction - pure tone average thresholds (r = 0.45, p = 0.035).. The detection and quantification of the MPO-DNA complex in the otitis media fluid may aid in providing a definite diagnosis as well as predicting the activity and severity of OMAAV.

Topics: Adult; Aged; Aged, 80 and over; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Biomarkers; Body Fluids; DNA; Enzyme-Linked Immunosorbent Assay; Extracellular Traps; Female; Humans; Male; Middle Aged; Otitis Media; Peroxidase; Prospective Studies

The aim of this study was to investigate the effect of oxidative stress and antioxidant situation on chronic otitis media with effusions (COME) and acute otitis media (AOM) in children.. A total of 107 children aged 2 to 13 years were examined. The study included 31 patients with AOM, 39 with COME, and 37 as control subjects. Venous blood samples were collected from all patients and control group. Myeloperoxidase (MPO), glutathione peroxidase (GPx), catalase (CAT), nitric oxide (NO), malondialdehyde (MDA), and superoxide dismutase (SOD) activities were investigated in the blood samples.. The mean age was found as 7.3 ± 3.3 in the AOM group, 6.2 ± 3.0 in the COME group, and 6 ± 2.4 in the control group. MPO, NO, and CAT were found to be significantly higher in the AOM and COME groups than the control groups (P = 0.040, P = 0.001, and P = 0.044).. In this study, we observed activity of antioxidant and oxidative stress in children with COME and AOM. These results may be important in the diagnosis of these diseases and may affect the theurapeutic approach to the patients with COME and AOM.

Topics: Acute Disease; Adolescent; Antioxidants; Catalase; Child; Child, Preschool; Chronic Disease; Female; Glutathione Peroxidase; Humans; Male; Malondialdehyde; Nitric Oxide; Otitis Media; Otitis Media with Effusion; Oxidative Stress; Peroxidase; Superoxide Dismutase

We have recently reported that neutrophils play a pivotal role in innate defense against Streptococcus pneumoniae ( Spn) during mouse acute otitis media (AOM). However, the underlying mechanism remains unclear. By constructing models of pneumococcal AOM in C57BL/6 mice and using a specific inhibitor in vivo, we investigated the role of myeloperoxidase (MPO), one of the most important protein components of neutrophils. Experiment results showed a significant increase in MPO production of the recruited neutrophils in Spn-infected mice. Neutrophils killed Spn in a MPO-dependent manner. MPO facilitated the generation of reactive oxygen species (ROS), and consequently promoted Spn clearance at an early stage and exacerbated tissue damage. Moreover, MPO induced neutrophil apoptosis and necrosis, which, in turn, worsened tissue damage. In summary, our study demonstrates that neutrophil MPO plays a paradoxical role in bacterial clearance and tissue damage in pneumococcal AOM.

Topics: Animals; Apoptosis; Bacteriolysis; Disease Models, Animal; Female; Humans; Immunity, Innate; Male; Mice; Mice, Inbred C57BL; Necrosis; Neutrophils; Otitis Media; Peroxidase; Pneumococcal Infections; Reactive Oxygen Species; Streptococcus pneumoniae

Acute otitis media (AOM) is one of the most common bacterial infectious diseases in children aged 2 to 7 years worldwide. We previously demonstrated that interleukin-17A (IL-17A) promotes an acute inflammatory response characterized by the influx of neutrophils into the middle ear cavity during

Topics: Animals; Disease Models, Animal; Ear, Middle; Interleukin-17; MAP Kinase Signaling System; Mice; Mice, Knockout; Neutrophils; Otitis Media; p38 Mitogen-Activated Protein Kinases; Peroxidase; Receptors, Interleukin-17; Streptococcal Infections; Streptococcus pneumoniae

A previously healthy 77-year-old Japanese man presented with a 2-week history of daily fevers peaking at 38°C, chills, hearing loss, and almost 10 kg of unintentional weight loss over 2 months. Pure tone audiometry showed mixed conductive-sensorineural hearing loss: right, 63.6 dB, left, 80.0 dB. Blood tests after admission showed a high myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) level (>300 U/mL), so we suspected ANCA-related vasculitis. The Japanese Otorhinolaryngology Society has recently been advocating the concept of otitis media with ANCA-associated vasculitis (OMAAV). Our case met the criteria proposed, leading to our diagnosis.

Topics: Aged; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Hearing Loss; Humans; Male; Otitis Media; Peroxidase

We aimed to analyze clinical features and treatment outcomes of otitis media caused by antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), i.e. otitis media with AAV (OMAAV).. This survey was performed between December 2013 and February 2014. The study began with a preliminary survey to 123 otolaryngology institutions in Japan to inquire about their experiences with OMAAV patients during the past 10 years, and was followed by a questionnaire survey to investigate clinical and laboratory findings. OMAAV was defined using the criteria described in the text.. Two hundred and thirty-five patients classified as OMAAV were enrolled in this study. They were characterized as follows: (1) disease onset with initial signs/symptoms due to intractable otitis media with effusion or granulation, which did not respond to ordinary treatments such as antibiotics and insertion of tympanic ventilation tubes, followed by progressive hearing loss; (2) predominantly female (73%) and older (median age: 68 years); (3) predominantly myeloperoxidase (MPO)-ANCA-positive (60%), followed by proteinase 3 (PR3)-ANCA-positive (19%) and both ANCAs-negative (16%); (4) frequently observed accompanying facial palsy (36%) and hypertrophic pachymeningitis (28%); and (5) disease often involving lung (35%) and kidney (26%) lesions. Four factors associated with OMAAV were found to be related to an unfavorable clinical course threatening the patient's hearing and/or lives, namely facial palsy, hypertrophic pachymeningitis, both ANCAs-negative phenotype, and disease relapse. The occurrence of hypertrophic pachymeningitis was associated with facial palsy (p < 0.05), both ANCAs-negative phenotype (p < 0.001), and headache (p < 0.001). The administration of corticosteroid together with an immunosuppressant was an independent predicting factor for lack of disease relapse (odds ratio [OR] = 1.90, p = 0.03) and an improvement in hearing loss (OR =2.58, p = 0.0002).. Since OMAAV has novel clinical features, the disease may be categorized as a subentity for the classification of AAV.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Autoantibodies; Female; Health Surveys; Humans; Japan; Male; Middle Aged; Myeloblastin; Otitis Media; Peroxidase; Retrospective Studies; Sex Factors; Treatment Outcome

We studied the clinico-pathological differences among PR3-ANCA-positive granulomatosis with polyangiitis (PR3-GPA), MPO-ANCA-positive GPA (MPO-GPA) and microscopic polyangiitis (MPA). ANCA-associated vasculitis (AAV) was classified using the European Medicines Agency classification. We retrospectively analyzed 38 patients with GPA and 41 with MPA treated in eight hospitals in Japan. Of the patients with GPA, 17 were positive for MPO-ANCA, and 15 for PR3-ANCA. All patients with MPA were MPO-ANCA positive. The mean ages of those with MPO-GPA were 69.6 years old, 10 years older than those with PR3-GPA. The majority (82 %) of patients with MPO-GPA were woman, a significantly greater proportion than for PR3-GPA. We also found that ear, nose and throat (ENT), nervous system involvement were significantly more common in MPO-GPA, but renal function was less impaired than those with MPA. Both PR3-GPA and MPO-GPA relapsed more frequently than MPA, but overall survival was significantly better (P < 0.01 and P < 0.05, respectively). Univariate analysis identified the following factors as predictors of a poor prognosis: MPA (P < 0.01), pulmonary UIP pattern (P < 0.005) Cr ≥ 1.7 mg/dl (P < 0.01) and absence of ENT involvement (P < 0.05), which were characteristics of MPA. In our cohort, MPO-GPA was most likely to affect older women and was associated with otitis media, nervous system involvement, mild renal impairment and more favorable outcome. It is clinically useful to differentiate MPO-GPA from MPA and PR3-GPA in patients with AAV.

Topics: Age Factors; Aged; Antibodies, Antineutrophil Cytoplasmic; Female; Granulomatosis with Polyangiitis; Humans; Japan; Lung Diseases, Interstitial; Male; Middle Aged; Myeloblastin; Otitis Media; Peroxidase; Recurrence; Retrospective Studies; Sex Factors; Vasculitis, Central Nervous System

Otitis media (OM) is well known as a common feature of proteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA)-related Wegener granulomatosis, but is a very rare condition in myeloperoxidase ANCA (MPO-ANCA)-related vasculitis. In addition, there have been a few reports showing an association of MPO-ANCA-positive OM with cranial polyneuropathy. In this report, we describe 2 patients with bilateral facial nerve palsy due to MPO-ANCA-related OM. One patient also had bilateral trigeminal neuropathy, pachymeningitis and MPO-ANCA-related glomerulonephritis, whereas the other showed isolated bilateral facial nerve palsy with OM. In both the patients, treatment with prednisolone and immune-suppressant drugs resulted in an improvement of OM and cranial polyneuropathy. Physicians should be aware that MPO-ANCA-positive OM can cause bilateral facial nerve palsy.

Topics: Aged; Anti-Inflammatory Agents; Antibodies, Antineutrophil Cytoplasmic; Facial Paralysis; Female; Humans; Kidney; Male; Middle Aged; Otitis Media; Peroxidase; Prednisolone

It has been suggested that oxidative stress may play an important role in the pathogenesis of chronic otitis media (COM), but the role of oxidative stress in the pathogenesis of COM has not yet been fully explored. Therefore, the aim of this study was to investigate serum myeloperoxidase (MPO) activity, 4-hydroxynonenal (4-HNE), malondialdehyde (MDA), total antioxidant capacity (TAC) and nitric oxide (NO) in patients with COM. Sixty-one patients with COM and 30 controls were enrolled in the present study. Patients were divided into two groups according to the presence (n = 21) or absence (n = 40) of cholesteatoma. Serum MPO activity and 4-HNE, MDA and NO levels were significantly higher in patients with COM than controls (for all, p < 0.001), while TAC levels were significantly lower (for all, p < 0.001). Serum MPO activity and MDA, 4-HNE and NO levels were significantly higher in patients with cholesteatoma than in those without cholesteatoma, while TAC levels were significantly lower; but the difference between groups was not statistically significant (p > 0.05). Increased oxidative stress seems to be associated with decreased antioxidant levels in patients with COM. Thus, increased oxidative stress may play a role in the pathogenesis of COM. It is believed that the administration of antioxidant vitamins such as A, C and E may be useful in preventing and treating COM.

Topics: Adolescent; Adult; Aldehydes; Antioxidants; Case-Control Studies; Child; Chronic Disease; Female; Humans; Lipid Peroxidation; Male; Nitric Oxide; Otitis Media; Oxidants; Oxidation-Reduction; Oxidative Stress; Peroxidase; Young Adult

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is characterized by systemic necrotizing vasculitis, and patients fall into 2 groups: those with proteinase 3-ANCA and those with myeloperoxidase-ANCA. As infections are a trigger of ANCA-associated vasculitis, this disease tends to localize in areas around the upper airway. In this study, the authors compared ear and nasal symptoms between patients with proteinase 3-ANCA and those with myeloperoxidase-ANCA. We undertook a retrospective case series study of 34 patients diagnosed with ANCA-associated vasculitis. The otologic symptoms were divided into 3 types: chronic otitis media, secretory otitis media, and sensorineural hearing loss. Chronic otitis media was more common in patients with proteinase 3-ANCA (P = .001), whereas secretory otitis media was more frequently found in patients with myeloperoxidase-ANCA (P = .007). Crust formation (P = .001), saddle nose (P = .024), and sinusitis (P = .001) were more common in patients with proteinase 3-ANCA than in those with myeloperoxidase-ANCA. Marked differences were observed in the disease spectrum between the 2 ANCA groups.

Topics: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Chronic Disease; Disease Progression; Follow-Up Studies; Hearing Loss, Sensorineural; Humans; Myeloblastin; Otitis Media; Peroxidase; Prognosis; Retrospective Studies

A 77-year-old Japanese man was referred to our hospital because of the progression of renal dysfunction. Two months prior to the admission he had been diagnosed with otitis media. Urinalysis showed proteinuria and microscopic hematuria. Blood examination revealed renal dysfunction, hepatitis C virus (HCV)infection and positive myeloperoxidase (MPO)-ANCA. A chest CT revealed small infiltrates in the right middle lobe. The renal biopsy demonstrated crescentic glomerulonephritis with tubulitis. He was diagnosed as having Wegener's granulomatosis according to the American College of Rheumatology classification criteria. Methylprednisolone pulse therapy followed by oral prednisolone improved all of the otitis media, lung infiltrates and renal function. Recently, a high prevalence of ANCA has been reported in patients with HCV. It has also been reported that the prevalence of HCV infection is high in patients with Wegener's granulomatosis. Therefore, our case points to the clinical significance of HCV infection in ANCA-associated systemic vasculitis including Wegener's granulomatosis.

Topics: Aged; Antibodies, Antinuclear; Glomerulonephritis; Granulomatosis with Polyangiitis; Hepatitis C; Humans; Male; Methylprednisolone; Otitis Media; Peroxidase; Prednisolone; Pulse Therapy, Drug; Treatment Outcome

We report two cases of otitis media positive for antimyeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) associated with facial palsy. Case 1: A 73-year-old man treated for 3 months for bilateral otitis media with effusion had left facial nerve palsy and deteriorated bone conduction hearing in both ears. Blood analysis showed elevated MPO-ANCA to 134 EU. Case 2: A 66-year-old woman treated for about one year for bilateral otitis media with effusion and fluctuating mixed hearing loss had bilateral facial nerve palsy and a blood test positive for MPO-ANCA at 67 EU. Both were diagnosed with otitis media caused by ANCA-related vasculitis. After prednisolone and cyclophosphamide administration for half a year, blood test results were negative for MPO-ANCA. Both recovered almost completely from facial nerve palsy and bone conductive hearing loss partially improved except in one hearing-impaired ear. ANCA-related vasculitis of the temporal bone should thus be considered in those with intractable otitis media and deteriorated bone conduction hearing before the occurrence of facial palsy.

Topics: Aged; Antibodies, Antineutrophil Cytoplasmic; Facial Paralysis; Female; Humans; Male; Otitis Media; Peroxidase

In this study, the effect of endotoxin on the guinea pig cochlea was examined by electrophysiology and immunohistochemistry. Bacterial lipopolysaccharide (LPS) was injected into the middle ear transtympanically. Electrocochleograms were measured immediately and 48 h after the injection with an electrode inserted into the facial canal. After the electrophysiological measurement, the animals were killed with an intracardiac perfusion of fixative and the temporal bones were removed and processed for immunohistochemistry with anti-myeloperoxidase (MPO) antibody. MPO could be detected after 48 h in the lateral wall and the organ of Corti. After injection of LPS, the threshold of the compound action potential worsened significantly at 48 h in the LPS group. These results suggest that MPO and reactive oxygen species are involved in cochlea dysfunction under inflammatory conditions.

Topics: Acute Disease; Animals; Audiometry, Evoked Response; Cochlea; Guinea Pigs; Hearing Loss, Sensorineural; Injections; Lipopolysaccharides; Otitis Media; Peroxidase; Reactive Oxygen Species

Platelet activating factor (PAF), a potent inflammatory mediator, is a biologically active phospholipid. Recent studies have shown that PAF may play an important role in the pathogenesis of otitis media (OM). WEB 2170 BS has been shown to be a PAF antagonist both in vitro and in vivo. In this study, the anti-inflammatory effects of WEB 2170 BS were investigated in a guinea pig model of OM induced by middle ear (ME) inoculation of killed Staphylococcus aureus. The outcome of treatment was determined by measurement of myeloperoxidase activity in the samples of ME mucosa, evaluation of temporal bone histopathology, and the presence of ME fluid. The myeloperoxidase activity in the WEB 2170 BS-treated group was found to be significantly lower than that in the control group. Histopathology of the temporal bones indicated decreased inflammation in the treated group as compared to the controls. In addition, ME fluid was absent in 16 of the 20 ears of the 10 treated animals. These results demonstrate that WEB 2170 BS can produce significant anti-inflammatory effects in this model of OM.

Topics: Animals; Azepines; Disease Models, Animal; Ear, Middle; Guinea Pigs; Otitis Media; Peroxidase; Platelet Aggregation Inhibitors; Platelet Membrane Glycoproteins; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Staphylococcal Infections; Temporal Bone; Triazoles

Moraxella catarrhalis is a normal resident of the human nasopharyngeal flora, but it is also isolated from middle ear fluid of acute otitis media and otitis media with effusion patients. To determine whether M. catarrhalis has direct pathogenicity in the middle ear, heat-killed M. catarrhalis was inoculated into the middle ear bullae of guinea pigs, and the inflammatory response was investigated. Middle ear mucosal histopathology observed in M. catarrhalis-inoculated ears included subepithelial edema, capillary dilatation, thickening of lamina propria mucosa, inflammatory cell and erythrocyte infiltration into the lamina propria mucosa. Inflammatory cell numbers, lysozyme and myeloperoxidase concentrations in the middle ear washing suspensions of M. catarrhalis-inoculated ears were significantly higher than control ears throughout the experiment. Therefore, nonviable M. catarrhalis induced middle ear inflammation and mucoperiosteal histopathology, which might be caused by direct injury of the nonviable bacteria (e.g. lipooligosaccharide or outer membrane proteins) and metabolic products of inflammatory cells.

Topics: Animals; Ear, Middle; Edema; Epithelium; Guinea Pigs; Moraxella catarrhalis; Muramidase; Otitis Media; Peroxidase

Allergy may play a role in the middle ear inflammation that leads to otitis media with effusion. The purpose of this study was to determine whether an elevated mediator correlated with the patient's disease and thus could be used to differentiate allergy vs. infection as the cause of the middle ear inflammation.. WE evaluated 57 individuals with otitis media with effusion, 32 with persistent effusion but no recent acute infection, 14 with recent infection and purulent otitis media with effusion, and II healthy subjects. The mediator activity of eosinophils and neutrophils in effusion was studied in patients characterized as having allergy by positive intradermal skin test results and positive radioallergosorbent test results. Eosinophils were characterized by measurement of eosinophil cationic protein in the effusion. Neutrophils were characterized by measurement of myeloperoxidase in the effusion. The levels of eosinophil cationic protein and myeloperoxidase in patients with and without allergy were correlated to patient history.. Significantly elevated levels of both eosinophil cationic protein and myeloperoxidase indicated that inflammation in the ear of patients with otitis media with effusion was characterized by a pronounced involvement of both eosinophils and neutrophils. Eighty-nine percent of all patients with disease had allergy. A higher ratio of myeloperoxidase to eosinophil cationic protein in patients with purulent otitis media with effusion indicated that in patients with a superimposed acute infection, neutrophil activity was increased even further. The level of eosinophil cationic protein was elevated only during the effusion of patients with allergies as compared with controls (p < 0.01). Among 29 cases of nonpurulent otitis media with effusion, 96.5% had allergic immune-mediated disease proved by skin testing, which was related clinically to their ear disease. Eighty-nine percent (89.6%) of these patients had eosinophil cationic protein levels greater than 10 microgram/L.. Middle ear eosinophil cationic protein may be used as a marker of related allergy.

Topics: Adolescent; Adult; Aged; Biomarkers; Blood Proteins; Child; Child, Preschool; Chronic Disease; Diagnosis, Differential; Eosinophil Granule Proteins; Eosinophils; Humans; Hypersensitivity, Immediate; Immunoglobulin E; Inflammation Mediators; Middle Aged; Neutrophils; Otitis Media; Otitis Media with Effusion; Otitis Media, Suppurative; Peroxidase; Radioallergosorbent Test; Ribonucleases; Sensitivity and Specificity; Skin Tests

Haemophilus influenzae is one of the most frequent pathogens of acute otitis media. To determine the middle ear response during the early stage of acute inflammation, a small amount of H. influenzae was inoculated into the bullae of guinea pigs through the tympanic membrane. The bullae were harvested at 6, 12, 24, 36, and 48 hours after H. influenzae inoculation and washed with phosphate-buffered saline (PBS). The number of viable H. influenzae and inflammatory cells, the concentrations of myeloperoxidase (MPO) and lysozyme in the washing suspensions were measured, and compared with those in PBS-inoculated control ears. The number of viable H. influenzae increased very rapidly from 6 to 12 hours after inoculation and remained stationary up to 48 hours. The number of inflammatory cells and the MPO concentration were significantly higher in the H. influenzae-inoculated ears than in the control ears from 12 to 48 hours after inoculation. The lysozyme concentration was already significantly higher at 6 hours in the H. influenzae-inoculated ears; the lysozyme was released in the middle ear before the accumulation of inflammatory cells and degranulation of MPO from inflammatory cells. The results indicated that inflammatory reactions were present already at 6 hours after bacterial inoculation, and were rapidly accelerated during the subsequent hours. Consequently, acute middle ear inflammatory responses were seen immediately following inoculation of viable bacteria, and these responses originated in direct responses of middle ear mucosa, and oxidative and non-oxidative neutrophil metabolic products, which may cause tissue injury.

Topics: Acute Disease; Animals; Ear, Middle; Guinea Pigs; Haemophilus influenzae; Muramidase; Otitis Media; Peroxidase; Time Factors

To determine whether oxidative metabolic products of phagocytic cells are present in the middle ear during experimental pneumococcal otitis media, we measured the concentration of myeloperoxidase (MPO) in middle ear fluid (MEF) and the capacity of neutrophils isolated from MEF and peripheral blood to produce MPO and superoxide anion (O2-) after in vitro stimulation. Free MPO in MEF was significantly increased 24 and 48 h after either viable or nonviable pneumococci were inoculated into the middle ear. In vitro-stimulated production of MPO and O2- from middle ear neutrophils was significantly less than that from peripheral blood neutrophils 24 h after nonviable pneumococci were inoculated but similar to it after 48 h. Twenty-four hours after viable pneumococci were inoculated, middle ear neutrophils stimulated in vitro produced less MPO but the same amount of O2- as did blood neutrophils. Oxidative metabolic products, therefore, are released from phagocytic cells into the MEF during pneumococcal otitis media, and future studies will need to define the contribution of these products to acute and chronic middle ear tissue injury.

Topics: Animals; Cell Degranulation; Chinchilla; Neutrophils; Otitis Media; Peroxidase; Pneumococcal Infections; Streptococcus pneumoniae; Superoxides; Time Factors

In 19 children with recurrent otitis media the phagocytic activity of blood granulocytes was studied and indirectly also their bactericidal capacity by means of the NBT test and myeloperoxidase activity. The mean value of granulocytes containing latex particles was 44.32% in the patients group, which differed significantly from the mean value established in controls: 66.54%. The mean phagocytic number in the patients group, 1.82 was also significantly diminished in comparison to controls: 2.41. The average number of nitroblue tetrazolium (NBT)-positive cells in patients, 86.74% as well the mean myeloperoxidase index, 2.52 did not differ from the mean control values, 92% and 2.42, respectively. In two patients a lower percentage of NBT-positive cells was determined. They are probably heterozygous carriers of an enzyme deficiency related to a depressed bactericidal activity of phagocytes. Patients with recurrent otitis media should be tested on possible phagocytic dysfunctions which may be helpful in understanding the pathogenesis of infections and also in identifying infants at particular risk of otitis media.

Topics: Child; Female; Granulocytes; Humans; Male; Microspheres; Neutrophils; Nitroblue Tetrazolium; Otitis Media; Otitis Media, Suppurative; Peroxidase; Phagocytosis; Recurrence