Effect of ciprofloxacin/dexamethasone versus ciprofloxacin/hydrocortisone on lipopolysaccharide-induced experimental otitis media.

OBJECTIVES: The purpose of this study is to compare the effect of topical ciprofloxacin/dexamethasone versus topical ciprofloxacin/hydrocortisone on the outcome of lipopolysaccharide (LPS)­induced otitis media with effusion in chinchillas. STUDY DESIGN: A randomized experimental animal study. SETTING: Jerry L. Pettis Veteran's Medical Center. SUBJECTS AND METHODS: Otitis media with effusion was induced in 5 groups of chinchillas, 6 per group, by injecting 0.3 mL (1 mg/mL) of Salmonella enteric LPS into the superior bullae of each chinchilla with a venting needle in place. Each group was treated with 0.2 mL of test substance at ­2, 24, 48, and 72 hours relative to the 0-hour LPS induction. Group 1 was treated with vehicle control. Groups 2 to 5 received 0.3% ciprofloxacin with either 0.1% dexamethasone (group 2), 1% dexamethasone (group 3), 0.1% hydrocortisone (group 4), or 1% hydrocortisone (group 5). The outcome of each treatment was measured by the amount of middle ear effusion present and mucosal thickness at 120 hours posttreatment. RESULTS: Ciprofloxacin/dexamethasone 1% significantly (P = .0150) reduced middle ear effusion compared with control. Ciprofloxacin/dexamethasone 1% significantly reduced the mucosal thickness when compared with vehicle control (P = .0005), ciprofloxacin/dexamethasone 0.1% (P = .0240), and ciprofloxacin/hydrocortisone 0.1% (P = 1.00). Results also showed a dose-response effect between the ciprofloxacin/dexamethasone concentrations. CONCLUSIONS: This study demonstrated that treatment with a combination of topical ciprofloxacin and corticosteroid decreased the middle ear effusion when compared with the control group and that ciprofloxacin/dexamethasone suspension reduced the severity of LPS-induced experimental otitis media more than ciprofloxacin/hydrocortisone did.

Effects of ciprofloxacin-dexamethasone on myringotomy wound healing.

OBJECTIVE: To evaluate the effects of the ciprofloxacin-dexamethasone (CDX) combination ototopical treatment after myringotomy on tympanic membrane (TM) healing in ears with eustachian tube obstruction (ETO) and unobstructed ears. STUDY DESIGN: Prospective, randomized, masked, controlled. METHODS: ETO was created in the left ear of 30 rats to induce a model of otitis media with effusion (OME). After 3 weeks, bilateral myringotomy was performed (day 0). Animals were randomized into three groups to receive no treatment or bilateral once daily ototopical treatment with balanced salt solution (BSS, vehicle) or CDX for 13 days. Bilateral otomicroscopy was performed on days 7, 14, and 28. On day 14, five randomly selected animals per group were humanely euthanized and the TM harvested for histology. Three additional rats provided normal negative control ears for histologic comparisons. RESULTS: On day 14, TM perforation healing rates were 100% in all ears of untreated and BSS-treated animals, 89% (8/9) in CDX-treated obstructed ears, and 30% (3/10) in CDX-treated unobstructed ears (P < .05 vs. BSS). On day 28, 100% (5/5) of the CDX-treated unobstructed ears and 80% (4/5) of the CDX-treated obstructed ears were healed. Histology showed initial TM thickening postmyringotomy in all ears but no significant qualitative differences between groups on day 28. CONCLUSION: Myringotomy healing was transiently modulated by treatment with CDX but proceeded normally after CDX discontinuation. This early modulation might enhance middle ear drainage and middle ear concentrations of CDX when tympanostomy tube surgery is performed in patients with active OME and ETO, thus potentially reducing otorrhea and preventing or treating infection. It would not be expected to increase the risk of premature tube extrusion or adversely affect normal healing of the TM after usual spontaneous extrusion.

Multifield coupled finite element analysis for sound transmission in otitis media with effusion.

In this paper, a newly constructed three-dimensional finite element (FE) model of the human ear based on histological sections of a left ear temporal bone is reported. The otitis media with effusion was simulated in the model with variable fluid levels in the middle ear. The interfaces among the air, structure, and fluid in the ear canal and middle ear cavity were identified and the acoustic-structure-fluid coupled FE analysis was conducted when the middle ear fluid level was varied from zero to full fill of the cavity. The results show how the displacements of the tympanic membrane and stapes footplate or the middle ear transfer function is affected by fluid in the cavity across the auditory frequencies. Comparison of model results with measured data in temporal bones indicates that this model has the capability to extend FE analysis into pathological ears such as otitis media with visualized fluid-air interfaces inside the middle ear structures.

Routine nasopharyngeal biopsy in adults presenting with isolated serous otitis media: is it justified?

Nasopharyngeal malignancy accounts for less than 2 per cent of all head and neck cancers. Serous otitis media (SOM) causing deafness is a recognized indicator of nasopharyngeal obstruction and the possibility of a nasopharyngeal malignancy must be considered in all adults. Examination under anaesthesia (EUA) and biopsy of the nasopharynx is routinely undertaken in many centres to rule out nasopharyngeal malignancy in adults with SOM. The purpose of this 10-year retrospective study was to evaluate the case records of all adult cases of SOM, including their presentation, clinical findings, management and nasopharyngeal biopsy results. Eighty-five patients were included in the study. Fifty-nine presented with unilateral SOM and 26 with bilateral SOM. The primary presenting complaint in all cases was hearing loss. A nasopharyngeal mass was documented in 55 patients (69 per cent). Four nasopharyngeal masses were noted to have irregular or exophytic mucosa on flexible nasendoscopy. All patients underwent a EUA of the ears and a nasopharyngeal biopsy. The four patients with suspicious-looking masses were all found to have malignancies (two squamous cell carcinomas, one B-cell non-Hodgkin lymphoma and one adenocarcinoma). Three of these patients presented with unilateral SOM and one with bilateral SOM. All other patients with masses were found to have benign lymphoid hyperplasia. In total, 4.7 per cent of the adults with conductive hearing loss secondary to SOM were found to have a malignancy on nasopharyngeal biopsy. We would advocate a high index of suspicion of a nasopharyngeal tumour in adults presenting with SOM. If a mass is found in the nasopharynx then it should be biopsied. If no mass is found then it is not necessary to biopsy; however, close follow up, with repeat fibre-optic nasendoscopy, is advised.

The role of soluble interleukin-4 receptor and interleukin-5 antibody in preventing late-phase allergy-induced eustachian tube dysfunction.

OBJECTIVES: We investigated the role of soluble interleukin (IL)-4 receptors (sIL-4R) and IL-5 antibodies (IL-5Ab) in preventing allergic eustachian tube dysfunction (ETD) and middle ear effusion (MEE). STUDY DESIGN: Brown-Norway rats were sensitized to ovalbumin (OVA) and challenged transtympanically. Two groups of rats received either IL-4R or IL-5Ab transtympanically 1 hour before challenge. Three additional groups were used as controls. Following the second transtympanic challenge, the ventilatory and clearance functions of the eustachian tube (ET) were assessed at 0, 2, and 8 hours. Histology was prepared using cut paraffin sections stained with hematoxylin and eosin. RESULTS: sIL-4R-pretreated rats showed no significant changes in ventilatory or clearance functions of the ET or inflammatory changes in ET mucosa, whereas IL-5Ab pretreatment showed significant late ventilatory and clearance dysfunction as well as inflammatory mucosal changes. CONCLUSION: These data demonstrate that the late-phase allergic inflammatory response that leads to subsequent formation of ETD and MEE is prevented by pretreatment with sIL-4R and, more modestly, with IL-5Ab.

Effects of Allergina on the treatment of otitis media with effusions.

The number of pediatric patients with recurrent otitis media with effusions (ROMEs) is increasing because of the frequency of recurrence. The herbal combination Allergina is used for inflammatory-disease treatment in the Republic of Korea; in our study, the patients with ROME were treated with either Allergina (11 ears) or antibiotics (13 ears). We analyzed the levels of cytokines in middle-ear effusions (MEEs) and compared these levels in the Allergina-treated patients with those in the antibiotics-treated patients. The mean levels of interleukin (IL)-2 and IL-4 in MEEs were significantly higher in the Allergina-treated patients than in the antibiotics-treated patients, whereas levels of IL-1beta, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha in MEEs were significantly lower in the Allergina-treated patients than in the antibiotics-treated patients. Clinical signs of ROME disappeared markedly after all the patients were given an oral administration of Allergina. Our experimental studies provide evidence that Allergina may be beneficial in the treatment of ROME by regulating cytokine production.

Nitric oxide contributes to control of effusion in experimental otitis media.

OBJECTIVES/HYPOTHESIS: Nitric oxide (NO) is a small, short-lived free radical involved in cellular signaling and known to play a role in inflammation. It is generated on demand by the enzyme nitric oxide synthase (NOS) on arginine. We have previously found that mRNA encoding NOS is produced in the middle ear during otitis media. The role of NO was therefore explored in an experimental model of immune-mediated otitis media. STUDY DESIGN AND METHODS: Guinea pigs were systemically immunized and later challenged in the middle ear with the same antigen. One ear of each animal was challenged with antigen alone. In the opposite ear, antigen was combined with a potent inhibitor of NOS, N(G)-amino-L-arginine (L-NAA). After survival for 24, 48, or 72 hours, the middle ears were evaluated for otitis media. RESULTS: Inhibition of NOS resulted in significantly increased middle ear effusion at all three time periods. This increase was blocked by the addition of excess 1-arginine, which bypasses the inhibitory effects of L-NAA. The infiltration of cells into the middle ear lumen and the hyperplasia of the middle ear mucosa were unaffected by L-NAA administration. CONCLUSIONS: The results suggest that NO is involved in regulating the permeability of the middle ear vascular, the transudation of serum into the middle ear mucosa, and/or the movement of extracellular fluid across the middle ear mucosal epithelium.

[Clinical and experimental study on treatment of acute catarrhal otitis media with eryanling oral liquid].

OBJECTIVE: To study the clinical effect and mechanism of Eryanling (EYL) oral liquid in treating acute catarrhal otitis media (ACOM). METHODS: Sixty-eight cases (89 ears) of ACOM in the treated group were treated with EYL and compared with 34 cases (44 ears) in the control group treated with cephalexinum. Experimental study of effect of EYL on immune function in mice and non-suppurative otitis guinea pig was also conducted. RESULTS: The total effective rate of the treated group and the control group was 91.0% and 84.1% respectively, and their rate of curing 80.9% and 70.5% respectively, though the effect in the former was better, statistic analysis showed no significance between them. The effect initiated obviously earlier in the treated group than that in the control group. Results of experimental study suggested that EYL could strengthen the nonspecific immune function, cellular immune function and humoral immune function in mice, and reduce the degree of inflammatory exudation and mucosa swollen in guinea pig. CONCLUSION: EYL has good therapeutic effect in treating ACOM.

Effects of capsaicin pre-treatment in experimentally-induced secretory otitis media.

Neurogenic inflammation may play a role in the aetiology of secretory otitis media (SOM). The strongest candidate that initiates the characteristic symptoms of neurogenic inflammation is supposed to be substance P. Capsaicin is a specific antagonist of substance P. The effects of capsaicin on middle ear mucosa have not been studied yet. In an attempt to investigate the effect of pre-treatment with capsaicin on the development of SOM an experimental study was performed. Fourteen Wistar rats were divided into two groups. Seven rats were pre-treated with capsaicin (Group 1) and the others were administered isotonic saline solution (Group 2). Seven days after the third injection rats were operated on and the right tympanal orifice of the Eustachian tube was obstructed. Animals were sacrificed seven days after the operation. Their bullas were excised bilaterally and were studied by light microscopic technique. In Group 1 there was no effusion except for one case. The subepithelial layer was thickened by fibroblast proliferation. Capillary proliferation and some glandular atrophy were observed. In Group 2 the middle ear lumens were filled with effusion. Oedema with dilatation in capillaries and medium-sized vessels of lamina propria was observed as a common feature of the group. Subepithelial fibrosis was found in one case. Capsaicin pre-treatment prevented the formation of effusion in the middle ear lumen in spite of tuba occlusion. The results of this preliminary study lead us to consider that an imbalance in the autonomic innervation of the mucosa of the middle ear may play a role in the aetiology of SOM as in vasomotor rhinitis, and capsaicin may be an alternative in the treatment.

The herbal medicine, sairei-to, prevents endotoxin-induced otitis media with effusion in the guinea pig.

With current pharmacotherapy, otitis media with effusion (OME) is often recurrent and even develops to become chronic. There is now considerable experimental and clinical evidence that the cilia in the tubotympanum play an important part in the prevention of OME. A herbal medicine, sairei-to, has been shown to stimulate the ciliary activity in vitro, and oral administration of the medicine also stimulated the ciliary activity in the tubotympanum rather than physiological states. This study was designed to investigate whether oral administration of sairei-to could prevent experimental OME in the guinea pig. A total of 120 guinea pigs were used. The control group was treated with intratympanic injection of 0.1 ml of physiologic saline solution. The saline-control group was treated with oral administration of physiologic saline solution for 14 successive days. The low-dosage group and the high-dosage group were treated with oral administration of 120 and 600 mg/kg of sairei-to for 14 successive days, respectively. The saline-control group, the low-dosage group and the high-dosage group were then treated with intratympanic injection of 0.1 ml of lipopolysaccharide solution (100 micrograms/ml) derived from Klebsiella pneumoniae. All 10 animals from the 4 groups were sacrificed 1, 3, and 7 days after the intratympanic injection, to examine ciliary activity, mucociliary clearance time, and mucosal pathology of the tubotympanum. The saline-control group exhibited middle ear effusions and pathologies similar to human OME. The incidence of middle ear effusions in the low-dosage and the high-dosage groups was somewhat reduced compared with the saline-control group. The ciliary activity in the tubotympanum was significantly reduced in the saline-control and low-dosage groups compared with the normal-control group. By contrast, the magnitude of reduction in ciliary activity was much smaller in the high-dosage group. The ciliary activity especially in the Eustachian tube and the middle ear close to the tympanic orifice at 3 and 7 days in the high-dosage group was not significantly different from that in the normal-control group. Mucociliary clearance time in the high-dosage group was not different from that in the normal-control group throughout the observation period. The groups treated with sairei-to, especially the high-dosage group, exhibited much milder pathological changes in the tubotympanum than did the saline-control group. In conclusion, clinical application of sairei-to could be an effective measure to prevent the occurrence of OME and also the recurrence of the disease, especially OME-prone individuals.

The role of allergy in the pathogenesis of otitis media with effusion.

To explain an allergic basis for the development of otitis media with effusion (OME), it was suggested that the middle ear mucosa can act as an allergic "shock organ." To evaluate this possibility, 16 juvenile rhesus monkeys were passively sensitized to pollen by intravenous injection of allergic human serum. All ears were then challenged by insufflation of pollen via the nose and eustachian tube (ET), twice daily, for four to five days. Daily tympanometry and otomicroscopy were performed, and on the last day of challenge, tympanocentesis was done to recover effusions. Five animals were killed and the middle ears were processed for histologic study. The results showed that none of the ears developed a middle ear effusion or OME. It is concluded that middle ear challenge with an appropriate pollen antigen in passively sensitized rhesus monkeys does not initiate an inflammatory reaction in the middle ear or induce OME.