Clinical-pathological findings of otitis media and media-interna in calves and (clinical) evaluation of a standardized therapeutic protocol.

BACKGROUND: The aims of this field trial were to describe the clinical-pathologic findings in calves with otitis media (OM) and media-interna (OMI), to evaluate, through the development of a scoring system, the effectiveness of a standardized therapeutic protocol, and to identify the causative pathogens and their possible correlation with concurrent respiratory disease. All animals underwent physical and neurological examinations at three experimental time points: at diagnosis/beginning of treatment (T0), 1 week (T1) and 2 weeks (T2) after therapy was started, respectively. Follow-up telephone interviews with animal owners were conducted 1 month later. The therapeutic protocol consisted of tulathromycin (Draxxin®; Zoetis), oxytetracycline hydrochloride (Terramicina 100®; Zoetis), and carprofen (Rimadyl®; Zoetis). RESULTS: Twenty-two calves were enrolled. Physical and otoscopic examination at T0 revealed monolateral and bilateral otorrhea in 16 and 6 calves, respectively, with peripheral vestibular system involvement in calves presenting with neurological signs (n = 17; 77 %). A significant improvement of clinical and neurological scores was observed in 20 (90 %) calves, a full recovery in only 1 (5 %). One calf worsened between T0 and T1 and it was removed from the study. None of the other animals showed a worsening of clinical conditions and/or required further treatments at one month follow up. Mycoplasma bovis was isolated in 89 % of the affected ears either alone or together with P. multocida (n = 5), Streptococcus spp. (n = 1), Staphylococcus spp. (n = 1), and Pseudomonas spp. (n = 1). M. bovis either alone or together with these bacteria was also isolated from the upper and/or lower respiratory tract in 19 (86 %) calves. CONCLUSIONS: This is the first prospective study to evaluate the effectiveness of a standardized therapeutic protocol for the treatment of OM/OMI in calves. The therapy led to clinical improvement in the majority of the calves. Persistence of mild clinical-neurological signs did not compromise productive performance. The numerical scoring system for clinical and neurological signs permitted objective evaluation of response to therapy. M. bovis was the pathogen most often isolated. This finding should be considered in the treatment of OM/OMI in calves. Moreover, respiratory tract infection should not be underrated, since it is one of the major risk factors for the development of OM/OMI.

Bilateral Granulomatous and Fibrinoheterophilic Otitis Interna due to Pseudomonas aeruginosa in a Captive Little Bustard ( Tetrax tetrax ).

A captive juvenile little bustard ( Tetrax tetrax ) was presented for acute onset of right head tilt and right circling. The bird failed to respond to supportive care and systemic antibiotic therapy. A bilateral granulomatous and fibrinoheterophilic otitis interna due to Pseudomonas aeruginosa was diagnosed postmortem by histopathologic examination and bacterial culture. In bustards, Pseudomonas species have been documented in the normal bacterial flora of the oropharynx and are frequently reported in upper respiratory tract infections. This is the first report of a peripheral vestibular syndrome due to P aeruginosa otitis interna in a bustard species. Pseudomonas aeruginosa should be included as a possible cause of otitis and peripheral vestibular syndrome in bustards.

Oral penicillin prescribing for children in the UK: a comparison with BNF for Children age-band recommendations.

BACKGROUND: The British National Formulary for Children (BNFC) recommends dosing oral penicillins according to age-bands, weight-bands, or weight-based calculations. Because of the rising prevalence of childhood obesity, age-band-based prescribing could lead to subtherapeutic dosing. AIM: To investigate actual oral penicillin prescribing by GPs in the UK with reference to the current BNFC age-band recommendations. DESIGN AND SETTING: Descriptive analysis of UK prescriptions in the 2010 IMS Disease-Analyzer database (IMS-DA). METHOD: A detailed database analysis was undertaken of oral penicillin prescriptions for 0-18 year olds from the 2010 IMS-DA. The prescription analysis included all available data on formulation, strength (mg), prescription quantity unit, package size, prescribed quantity, and volume. RESULTS: Considering amoxicillin alone, no infants (aged <1 year) were prescribed the BNFC 2011 edition recommended unit dose (62.5 mg), while the majority received double the dose (125 mg); among children aged 1-5 years, 96% were prescribed the recommended unit dose (125 mg), but 40% of 6-12 year olds and 70% of 12-18 year olds were prescribed unit doses below the BNFC recommendations. For otitis media, only those children aged <1 year received the recommended dose of amoxicillin (40-90 mg/kg/day). Similar variations in dosing across age-bands were observed for phenoxymethylpenicillin and flucloxacillin. CONCLUSION: There is wide variation in the dosing of penicillins for children in UK primary care, with very few children being prescribed the current national recommended doses. There is an urgent need to review dosing guidelines, in relation to the weights of children today.

ALH-L1005 attenuates endotoxin induced inner ear damage.

OBJECTIVE: To assess whether this compound (ALH-L1005) is conceivably an effective agent in protecting against cochlear damage induced by LPS. MATERIALS AND METHODS: Tube formation using human umbilical vein endothelial cell (HUVEC) and matrix metalloproteinase (MMP)-9 inhibition assay was performed. 24 guinea pigs were randomly divided into three groups. Intratympanic instillation of LPS (n=8) as negative control, instillation of oxytetracycline 1h after LPS as positive control (n=8), and intratympanic instillation of ALH-L1005 (n=8) 1h after LPS were considered experimental group. Evaluation by auditory brainstem response (ABR) measurement, cochlear blood flow, and blood-labyrinth barrier (BLB) permeability were performed. Cochlear hair cells were observed by field emission-scanning electron microscopy (FE-SEM). MMP-9 activation was measured by gelatin zymography. RESULTS: For HUVEC, the tube formation was suppressed in a dose dependant manner. ALH-L1005 inhibited the MMP-9 activity prominently. It also attenuated the elevation of LPS-induced hearing threshold shift and recovery of CBF. By FE-SEM, cochlear hair cells could be preserved in experimental group. ALH-L1005 significantly reduced the BLB opening compared to LPS group. Active MMP-9 expression could be detected in the LPS group. In contrast to ALH-L1005 group, active MMP-9 expression was not detected. CONCLUSION: Our results conclude that ALH-L1005 showed a protective effect in the cochlear lateral wall damage induced by LPS.

Recent advances in viral inner ear disorders.

PURPOSE OF REVIEW: To highlight the recent advances in the understanding of the diagnosis and management of viral inner ear disorders. Congenital sensorineural hearing loss (cSNHL), sudden sensorineural hearing loss (SSNHL), Ménière's disease, and vestibular neuritis/viral labyrinthitis are discussed. RECENT FINDINGS: Cytomegalovirus infection during pregnancy is an under-recognized cause of hearing loss and central nervous system disease amongst the general population. Prevention of maternal infection and treatment of affected newborns with ganciclovir are promising interventions. Recent evidence in SSNHL patients has resulted in recommendations against viral serology or the use of antivirals. There appears to be an increased risk of SSNHL in patients with comorbid hypertension and diabetes. The viral hypothesis of Ménière's disease remains unproven. In patients with an acute episode of vestibular neuritis, there is presently not sufficient evidence to support the routine use of corticosteroids or antiviral medications. SUMMARY: cSNHL remains the most clearly defined of the viral inner ear disorders. The evidence for viral involvement in SSNHL, Ménière's disease, and vestibular neuritis is indirect and equivocal. This review highlights the recent advancements in the diagnosis and management of these disorders.

Effect of Ginkgo biloba extract on endotoxin-induced labyrinthitis.

OBJECTIVE: There are no reports on the therapeutic effect of Ginkgo biloba extract (GBE) on otitis media-induced labyrinthitis. The present study examined whether GBE can protect against cochlear damage induced by intratympanic instillation of lipopolysaccharide (LPS)-induced labyrinthitis. MATERIALS AND METHODS: Experiments were performed in 20 healthy young male guinea pigs. The control group (n=10) received an intratympanic instillation of LPS (20 µl, 3mg/ml). The experimental group (n=10) received intratympanic instillation of LPS immediately after instillation of GBE (10mg/kg) and then experimental groups received GBE (100mg/kg) by intraperitoneal injection every day for 3 days. Instillation of LPS or LPS immediately after GBE was done in the right ear; the untreated left ear was considered normal. Physiological and morphological changes were evaluated. RESULTS: Statistical analysis of treatment of GBE revealed significantly less hearing loss than LPS group (p<0.05). The ratio of the value of cochlear blood flow (CBF) compared to untreated left side was significantly higher in the GBE treated group than in the LPS-treated group (p<0.05). This result indicated the recovery of CBF in GBE treated group compared to LPS treated group. In the LPS group, scanning electron microscopy revealed hair cell damage with edema. Missing stereocilia in the third layer of the outer hair cell was revealed. However, both the inner hair cells and the outer hair cells had normal appearance in the GBE group. LPS group showed that cochlear Evans blue extravasation was increased strongly in the stria vascularis, spiral limbus, and in the spiral ligament compared with the GBE treated group. CONCLUSION: GBE significantly minimizes cochlear damage against LPS-induced otitis media with labyrinthitis in a guinea pig model. GBE has potential as an adjunctive therapy to antibiotics in the treatment of acute otitis media with complicated labyrinthitis.

Blockade of interleukin-6 signaling suppressed cochlear inflammatory response and improved hearing impairment in noise-damaged mice cochlea.

Hearing impairment can be the cause of serious socio-economic disadvantages. Recent studies have shown inflammatory responses in the inner ear co-occur with various damaging conditions including noise-induced hearing loss. We reported pro-inflammatory cytokine interleukin-6 (IL-6) was induced in the cochlea 6h after noise exposure, but the pathophysiological implications of this are still obscure. To address this issue, we investigated the effects of IL-6 inhibition using the anti-IL-6 receptor antibody (MR16-1). Noise-exposed mice were treated with MR16-1 and evaluated. Improved hearing at 4kHz as measured by auditory brainstem response (ABR) was noted in noise-exposed mice treated with MR16-1. Histological analysis revealed the decrease in spiral ganglion neurons was ameliorated in the MR16-1-treated group, while no significant change was observed in the organ of Corti. Immunohistochemistry for Iba1 and CD45 demonstrated a remarkable reduction of activated cochlear macrophages in spiral ganglions compared to the control group when treated with MR16-1. Thus, MR16-1 had protective effects both functionally and pathologically for the noise-damaged cochlea primarily due to suppression of neuronal loss and presumably through alleviation of inflammatory responses. Anti-inflammatory cytokine therapy including IL-6 blockade would be a feasible novel therapeutic strategy for acute sensory neural hearing loss.

Necrotizing otitis externa: a new trend? Report of 6 atypical cases.

Necrotizing otitis externa (OE) is traditionally seen in elderly diabetics and immunocompromised patients. During a 7-year period at our institution, we treated 6 patients with necrotizing OE who were not diabetic, who were not immunocompromised, and who were relatively young (age range: 27 to 65 yr; mean: 42.8). The necrotizing OE in these patients was less aggressive but just as severe as its usual presentation in older diabetic or immunocompromised patients. All 6 patients had evidence of bony erosion on computed tomography of the temporal bones, although 4 had negative findings on technetium-99m scintigraphy. Four of the 6 patients required mastoid exploration and fascia lata grafting, and the other 2 chose to undergo extensive daily microdebridements and intravenous antibiotics followed by 6 weeks of oral antibiotics. We recommend that a diagnosis of necrotizing OE be kept in mind when evaluating any patient who presents with severe otalgia, particularly in the presence of Pseudomonas aeruginosa infection of the external auditory canal, edema, granulation tissue, and bony erosion.

Medical and surgical management of otitis in captive bongo (Tragelaphus eurycerus).

Six cases of severe otitis media-interna, an uncommon problem in nondomestic ruminants, were diagnosed in five captive bongo (Tragelaphus eurycerus). The cases were geographically clustered at zoological facilities in Florida. A visible ear droop, head shaking, and otic discharge were common at clinical presentation. Medical management with prolonged systemic and topical antimicrobial therapy, combined with repeated manual removal of debris from the otic canal, was successful in resolving two cases and effectively controlled a third case. Two bongo with severe otitis did not respond to medical management and required surgical intervention. A bulla osteotomy and total ear canal ablation were performed on these animals (bilaterally in one bongo). Surgery was successful in providing complete clinical resolution of the otitis and is recommended for severe cases that fail to respond to less invasive management.

Does acute dysfunction of the saccular afferents affect the subjective visual horizontal in patients with vestibular neurolabyrinthitis?

CONCLUSIONS: The results of a series of studies including the present study suggest that acute dysfunction of the utricular afferents accompanied by acute dysfunction of the saccular afferents might require more time for the compensation of the otolith-ocular system than acute utricular dysfunction that was not accompanied by acute saccular dysfunction. Perhaps the inputs from the saccule also have some contribution to the subjective visual horizontal (SVH). OBJECTIVE: To clarify if acute dysfunction of the saccular afferents affects the SVH. PATIENTS AND METHODS: Twenty-six patients with vestibular neurolabyrinthitis (20 men and 6 women, 23-67 years of age) were enrolled in this study. They had undergone measurement of SVH at the early stage (within 1 month after the attack) and 3 months after the attack. For the measurement of SVH, we used a device that has a red bar of light-emitting diodes with a head fixing frame. They also underwent vestibular evoked myogenic potentials (VEMPs) testing. For the recording of VEMPs, 95 dBnHL clicks were presented. RESULTS: Patients with vestibular neurolabyrinthitis showed deviation of SVH toward the affected side-down at the early stage after the attack, irrespective of VEMP results. However, 3 months after the attack SVH was significantly more deviated toward the affected side-down in patients who showed absent VEMPs than those with VEMPs present (p<0.01 Mann-Whitney U test).

AM-111 reduces hearing loss in a guinea pig model of acute labyrinthitis.

OBJECTIVES/HYPOTHESIS: This study investigated the otoprotective properties of AM-111, an inhibitor of c-Jun N-terminal kinase-mediated apoptosis and inflammation. STUDY DESIGN: A controlled, prospective animal study using a guinea pig model of acute labyrinthitis. METHODS: Acute labyrinthitis was generated by injection of antigen into the scala tympani of sensitized guinea pigs. Treatment groups received 100 microL of AM-111 at concentrations of 100 micromol/L, 10 micromol/L, and 1 micromol/L in a hyaluronic acid gel formulation delivered over the round window niche within 1 hour of antigen challenge. Cochlear function was monitored over 21 days with serial auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) measurements followed by histologic analysis. RESULTS: The ABR results on day 21 demonstrated that untreated control ears for acute labyrinthitis had a mean hearing loss (HL) of 68 +/- 12 dB. In contrast, ears treated with AM-111 (100 micromol/L) had a mean HL of 39 +/- 31 dB. These two groups were statistically different (one-way analysis of variance, P = .03). Secondary outcomes, including DPOAE shift, inner hair cell survival, inflammatory cell counts, and spiral ganglion density, were also statistically significant in favor of an otoprotective effect of AM-111. Lower doses of AM-111 did not produce a statistically significant reduction in HL over controls. CONCLUSION: AM-111 delivered over the round window membrane in a 100 microL hyaluronic acid formulation at a 100 micromol/L concentration immediately after induction of acute labyrinthitis in the guinea pig cochlea protects hearing, reduces hair cell loss, and reduces the number of inflammatory cells at 21 days after treatment.

TNFalpha blockers do not improve the hearing recovery obtained with glucocorticoid therapy in an autoimmune experimental labyrinthitis.

The effectiveness of etanercept [tumour necrosis factor-alpha (TNFalpha) blocker] and corticoids in treating immuno-mediated inner ear disease (IMIED) was compared in an animal model of autoimmune labyrinthitis. IMIED is one of the few forms of sensorineural hearing loss that is reversible with proper medical treatment. While the effectiveness and usefulness of immunomodulating agents (corticosteroids) in treating IMIED have been demonstrated, TNFalpha antagonists, which inhibit granuloma formation in rheumatoid arthritis and other autoimmune diseases, have been considered as an alternative therapy. The efficacy of etanercept (anti-TNFalpha) was evaluated in a guinea pig model of experimental autoimmune labyrinthitis in which 25 guinea pigs were divided in a control group, which was used to document the rise in hearing thresholds following immunisation, and two experimental groups, which were treated with steroids (6-methylprednisolone) and anti-TNFalpha (etanercept), respectively, after the immunisation. Comparison of the auditory thresholds obtained by means of auditory brainstem response (ABR) revealed that the auditory thresholds of the two experimental groups were not statistically different (6-methylprednisolone: 41.5 dB, SD: 8.51; etanercept: 37.5 dB, SD: 7.91) and that both compared favourably with that of the control group (60 dB, SD: 7.91) at p=0.001. We therefore conclude that etanercept is as effective as glucocorticoids in an animal model of autoimmune labyrinthitis; however, the potential adverse effects and high price of the former advise against its use as an initial therapy for IMIED.

[Relapsing polychondritis -- a case report and review of the literature]. / Polychondritis recidivans et atrophicans - ein Fallbericht und Literaturübersicht.

PATIENT: A case of a 54-year-old woman with a three month history of recurrent bilateral chondritis of the auricles, cochlear and vestibular inner ear damage and conjunctivitis is described. The diagnosis was based only on clinical criteria (auricular chondritis, conjunctivitis, inner ear damage). Antinuclear antibodies, ANCA and HLA-DR 4 antigen were negative. The only laboratory abnormality was an elevated erythrocyte sedimentation rate. The patient has been treated successfully with Methotrexate 20 mg 1 x /week and Prednisone 15 mg/die for 4 month now. DISCUSSION: The relapsing polychondritis (RP) is a rare, multisystemic and potentially fatal disease. The pathogenesis and optimal therapeutic approach is poorly understood. The disease is characterized by episodic inflammation of cartilage such as auricular, nasal and laryngotracheal. Many other proteoglycan-rich structures like inner ear, eye, kidney and blood vessels, may be involved as well. RP has an equal sex prevalence. The majority of cases appear between 40 and 60 years. Auricular inflammation is the most common feature. Effectiveness of non-steroidal anti-inflammatory drugs, dapsone, immunosuppressive drugs and prednisone has been described. The overall survival rates were 74 % at 5 years and 55 % at 10 in one 1986 series. CONCLUSION: The most common clinical presentation of RP regularly involves ENT-structures. Therefore ENT-specialists should be familiar with this disease. A close interdisciplinary cooperation is essential for therapy and follow-up, because pulmonary and cardiac involvement are limiting prognostic factors.

Immune-mediated hearing loss: basic mechanisms and options for therapy.

Immune responses are an important component of the defense of the inner ear against infection. However, immunity appears to be restricted in the labyrinth, as the inflammation associated with immune responses can damage the delicate cellular structures that mediate hearing and balance. When immunoregulation is compromised, either experimentally or through disease, immune-mediated inner ear damage and hearing loss can result. Because there are few resident leukocytes within the labyrinth, immunity and inflammation are mediated primarily by cells that enter the inner ear following the activation of post-capillary venules, which in the cochlea are the spiral modiolar veins. Activated lymphocytes are an important component of the infiltrating leukocytes, and their interactions with antigen mediate inner ear immunity. While evidence of autoimmunity specific to the inner ear is incomplete, an autoimmune origin is often suspected in idiopathic, bilateral, rapidly progressive hearing loss. Systemic immunosuppressive drugs can be effective in reversing such hearing loss, although at the cost of occasionally severe side-effects. Experimental evidence suggests that local therapy may be effective in treating this condition, if it were to target the infiltration of leukocytes into the labyrinth.

Otitis interna as a result of Pasteurella multocida infection in a laboratory woodchuck.

A laboratory woodchuck presented clinically with left-sided torticollis and a purulent exudate within the external auditory meatus of the left ear. Bacterial culture of the exudate resulted in a heavy growth of Pasteurella multocida. Treatment was initiated with topical and systemic antimicrobial compounds. There was no clinical improvement after 72 h of treatment, and euthanasia was elected. Radiographs correlated well with necropsy findings, confirming a diagnosis of otitis media; otitis interna was not confirmed but was suggested by the clinical presentation. To the authors knowledge, this is the first description of otitis media/interna as a result of P. multocida infection in a laboratory woodchuck.