Is there a relationship between myeloperoxidase activity and conductive hearing loss in chronic otitis media complicated by cholesteatoma?

We conducted a prospective, controlled study of patients with chronic otitis media and cholesteatoma (1) to examine the expression of myeloperoxidase (MPO) using immunohistochemical staining techniques and (2) to investigate the relationship between MPO activity and the degree of conductive hearing loss in these patients. Our study population included 51 adults-26 men and 25 women, aged 18 to 58 years (mean: 37.5)-who had been diagnosed with chronic otitis media and cholesteatoma by physical examination and computed tomography (study group). Another 30 patients-13 men and 17 women, aged 18 to 52 years (mean: 32.7)-who had chronic otitis media without cholesteatoma served as the control group. Following audiometric evaluations, all patients underwent appropriate surgery. Postoperatively, cholesteatoma samples were analyzed by immunostaining for MPO positivity as a marker for acute inflammation. We found that MPO activity was present in all 51 study patients (100%) but in only 10 controls (33.3%); the difference was statistically significant (p< 0.01). In the study group, the degree of MPO activity was slight in 6 patients (11.8%), moderate in 24 patients (47.1%), and intense in 21 patients (41.2%), while in the control group, all 10 MPO-positive cases showed only a slight degree of activity. We also found a statistically significant association in the study group between the degree of MPO activity and the degree of conductive hearing loss (χ(2) = 13.518; p < 0.001). We encourage further study of all steps in the process of cholesteatoma formation.

Mature middle and inner ears express Chd7 and exhibit distinctive pathologies in a mouse model of CHARGE syndrome.

Heterozygous mutations in the gene encoding chromodomain-DNA-binding-protein 7 (CHD7) cause CHARGE syndrome, a multiple anomaly condition which includes vestibular dysfunction and hearing loss. Mice with heterozygous Chd7 mutations exhibit semicircular canal dysgenesis and abnormal inner ear neurogenesis, and are an excellent model of CHARGE syndrome. Here we characterized Chd7 expression in mature middle and inner ears, analyzed morphological features of mutant ears and tested whether Chd7 mutant mice have altered responses to noise exposure and correlated those responses to inner and middle ear structure. We found that Chd7 is highly expressed in mature inner and outer hair cells, spiral ganglion neurons, vestibular sensory epithelia and middle ear ossicles. There were no obvious defects in individual hair cell morphology by prestin immunostaining or scanning electron microscopy, and cochlear innervation appeared normal in Chd7(Gt)(/+) mice. Hearing thresholds by auditory brainstem response (ABR) testing were elevated at 4 and 16 kHz in Chd7(Gt)(/+) mice, and there were reduced distortion product otoacoustic emissions (DPOAE). Exposure of Chd7(Gt)(/+) mice to broadband noise resulted in variable degrees of hair cell loss which inversely correlated with severity of stapedial defects. The degrees of hair cell loss and threshold shifts after noise exposure were more severe in wild type mice than in mutants. Together, these data indicate that Chd7(Gt)(/+) mice have combined conductive and sensorineural hearing loss, correlating with changes in both middle and inner ears.

Cyclo-oxygenase enzyme in the perilymph of human inner ear.

CONCLUSIONS: Cyclo-oxygenase-2 (COX-2) enzyme would not appear to be constitutively expressed in human perilymph while it is always induced in the perilymph of patients affected by sensorineural hearing loss (SNHL). The COX-2 isoform may be involved in hearing loss and, therefore, pathological states of the inner ear should possibly be further analyzed to clarify the clinical relevance of prostaglandin and selective COX-2 antagonist therapy. OBJECTIVES: Perilymph samples from a group of patients with bilateral SNHL and another with conductive hearing loss were collected to evaluate the presence of the COX-2 enzyme. The possible correlation between different causes of deafness and the expression of COX-2 in the human ear was studied. METHODS: A prospective clinical study of 14 patients with severe or profound hearing loss who underwent cochlear implant surgery and 4 patients with conductive hearing loss who underwent stapes surgery was carried out. Western blot analysis of perilymph samples was performed with monoclonal anti-human COX-2 antibody. RESULTS: COX-2 enzyme was detected in all patients affected by SNHL and was absent in all those with conductive hearing loss due to otosclerosis.

Stapedius muscle fibre characterization in the noise exposed and auditory deprived rat.

In skeletal muscle, interventions that unload the muscle cause slow-to-fast myosin heavy chain (MHC) conversions, whereas fast-to-slow conversions are seen when the muscles are engaged in resistance training and endurance exercise. The stapedius muscle (SM) is reported to prevent cochlear damage by noise. This theory may be supported by showing comparable changes of muscle fibre composition when ears are exposed to longstanding noise (SM training). Comparable changes after sound deprivation (SM unloading) would suggest that the SM needs a certain degree of daily activity evoked by environmental sound to sustain its normal composition. We investigated the difference in myosin composition of SM fibres from rats exposed to noise, from auditory deprived rats and from rats exposed to low level ambient noise (control group). Consecutive complete SM cross-sections were processed by enzymehistochemistry to determine acid/alkali lability of myofibrillar adenosine triphosphatase (mATPase) and by immunohistochemistry using MHC antibodies. Fibres were assigned to mATPase type I, IIA, IIX or 'Miscellaneous' categories. Per mATPase category, the fibres were attributed to groups with specific MHC isoform compositions. Auditory deprivation lasting nine weeks was accomplished by closure of the external meatus at the age of three weeks. A slow-to-fast shift was seen in these rats when compared to the control group. The noise exposed group was exposed to 65-90dB sound pressure level during a period lasting nine weeks from the age of three weeks onwards. A shift from an overwhelming presence of type mATPase IIX, as seen in the control group, to type mATPase IIA occurred in the noise exposed group. Also, more MHC IIA/IIX hybrid fibres were found in the mATPase IIX category. An adaptive response to the acoustic environment in the characteristics of the fibres of the SM, comparable to the response in skeletal muscles on unloading and training activity, can be ascertained. This supports the theory that the SM plays an active role in modulating external acoustic energy on entry to the cochlea. Our results are also in favour of another postulated function of the SM, the unmasking of high-frequency signals in low-frequency background noise.

Conductive hearing loss results in changes in cytochrome oxidase activity in gerbil central auditory system.

Conductive hearing loss (CHL) restricts auditory input to an intact peripheral auditory system. Effects of deprivation on the central auditory system (CAS) have been debated, although a number of studies support the hypothesis that CHL can cause modification of CAS structure and function. The present study was designed to test the hypothesis that unilateral CHL results in a decrease in cytochrome oxidase (CO) activity in CAS nuclei that receive major afferent input from the affected ear. Gerbils at postnatal day 12 (P21) or 6-8 weeks underwent left unilateral CHL (malleus removal), cochlear ablation, or a sham surgical procedure. After a survival time of 48 hours or 3 weeks, animals were sacrificed and tissue was processed for cytochrome oxidase histochemistry. Optical density (OD) measurements were made from individual neurons in the anteroventral cochlear nucleus (AVCN) and from medial and lateral dendritic fields in the medial superior olivary nucleus (MSO), the lateral superior olivary nucleus, and the inferior colliculus. The width of the CO-stained neuropil in MSO was also measured as an estimate of dendritic length. OD measures were corrected to neutral areas of the brain. Cochlear ablation caused significant decreases in CO activity in left lower brainstem nuclei, particularly in adult animals. Following CHL, a significant decrease in CO activity was observed in the ipsilateral AVCN and a significant increase was observed in the contralateral AVCN. Cochlear ablation resulted in decreased width of MSO neuropil containing dendrites that receive primary input from the ablated ear. CHL resulted in a significant increase in the width of MSO neuropil on both sides of the brain in the P21 animals that survived 3 weeks but not in P21 animals that survived only 48 hours or in the adult animals. Unilateral CHL is associated with changes in CO activity in the AVCN and may affect MSO dendritic length in younger animals.

Leukocyte esterase activity in effusion fluid of patients with otitis media.

Fluid obtained during myringotomy and tube placement in 20 patients with middle ear effusions was assayed for leukocyte esterase activity using a quantitative spectrophotometric assay. This quantitative assay used the synthetic substrate, N-tosyl indoxyl alaninate. Seven of the 20 samples showed no measurable enzyme activity (8 U/ml or less). The remaining samples demonstrated activity ranging from 20 to 1600 units. Although enzyme activity did not correlate well with the physical appearance of the fluid, it did correlate with clinical history, suggesting the presence of a purulent exudate rather than serous effusion. Leukocyte esterase activity in the fluid appears to hold promise as an indicator for the presence of chronic middle ear infection. The enzyme can be assayed by a simple and fast diagnostic strip test, with results available almost immediately.