Resorption rate and biocompatibility characteristics of two polyester ventilation tubes in a guinea pig model

OBJECTIVES: Determine the resorption rate and biocompatibility characteristics of 2 polyester ventilation tubes, and to determine whether soap and water exposure accelerates polyester tube degradation. STUDY DESIGN AND SETTING: 50/50 poly (D, L-lactide-co-glycolide; PLGA-50) and poly (L-lactide; PLA) polymers were placed into the tympanic membranes of Hartley pigmented guinea pigs. Integrity of the tubes was determined by weekly otoscopic examination. Biocompatibility was assessed by comparing auditory brainstem response (ABR) thresholds and by examining tympanic membrane changes following tube resorption. Shah minigrommet ventilation tubes were used as controls. In the second portion of this study, implanted PLGA-50 and PLA tubes were exposed weekly to a mixture of soap and water (1:5) until complete resorption was observed. Biocompatibility was assessed by periodic ABR testing and tympanic membrane examination. RESULTS: The PLA tubes remained in the tympanic membrane for a longer period (63.2 +/- 19.3 days) than the PLGA-50 (18.8 +/- 8.1 days). The tympanic membrane and resorbable tube interface demonstrated equivalent findings for auditory thresholds and tissue histopathology at the implant site compared to nonresorbable controls. The resorption behavior was not altered by exposure to soap and water. Tympanic membranes of all animals following tube degradation and soap water exposure were intact with minimal scarring and no signs of persistent foreign body response. The histological analysis showed that implantation of resorbable tubes was not accompanied by secondary infection with otorrhea through the tube, did not result in a permanent perforation or dislocation of the tube into the middle ear cavity, and was not followed by excess tympanosclerosis or localized or diffuse membrane atrophy. CONCLUSIONS AND SIGNIFICANCE: Resorbable polyester pressure equalization tubes demonstrate predictable resorption behavior and similar biocompatibility characteristics when compared with nonresorbable Shah minigrommet ventilation tubes. Exposure to soap water does not accelerate polyester tube degradation nor change the host tissue response during the indwelling period or after complete resorption. The data suggests that resorbable ventilation tubes are substantially equivalent to other FDA-approved tympanostomy devices with regard to safety and biocompatibility in the guinea pig model examined and may provide improved clinical performance by combining this approach with sustained release technology. EBM RATING: B-2.     

Ototoxic protection of sodium thiosulfate: daily vs constant infusion.

OBJECTIVE: Compare the effect of a daily dose of sodium thiosulfate (STS) to continuous infusion of STS on Hartley albino guinea pig (HAGP) on cisplatin (CP)-induced sensorineural hearing loss.Study design Prospective randomized pilot study comparing a single daily dose of STS to a constant controlled infusion of STS given the middle ear space (MES) with an ototoxic regimen of CP. The hearing thresholds will be obtained by auditory brainstem response (ABR) 1 week before and after treatment. Treatment effects on responses at 2, 8, and 16 kHz signals will be investigated by an analysis of variance with one between subjects' condition and two within subjects' conditions. SETTING: Basic science laboratory. RESULTS: STS protection resulted in significantly less hearing loss post-treatment for the protected ears. Guinea pigs with continuous infusion of STS demonstrated less loss in the protected ear than those who received the single daily dose. As expected, hearing loss at 2 kHz was less than that at 8 and 16 kHz. CONCLUSION: A continuous infusion of STS directly to the MES is better than a single daily dose of STS to the MES in reducing the ototoxicity of CP. SIGNIFICANCE: Any targeted protection, whether by continuous infusion or daily dose, is better than no protection against the sensorineural hearing loss of CP.     

External and middle ear effects on infant hearing screening test results.

This study investigated the relationship between external and middle ear factors and hearing screening results by automated auditory brain stem response (ABR) and transient-evoked otoacoustic emissions (EOAEs). The ears of 200 healthy newborns aged 5 to 48 hours underwent screening by ABR and EOAE, followed by otoscopic examination. The pass rates for ABR and EOAE were 91% and 58.5%, respectively. On otoscopic examination, 28% (112/400) ears had occluding vernix obscuring the view of the tympanic membrane. Cleaning of vernix was successfully performed in all but 2 ears that had occluding vernix. Cleaning of vernix significantly increased the pass rates of all 400 ears for ABR and EOAE to 96% and 69%. Decreased tympanic membrane mobility was found in 22.7% (90/396) of ears that were evaluated otoscopically. Decreased tympanic membrane mobility had a significant effect on EOAE screening; only 33.4% of ears passed EOAE testing. Decreased tympanic membrane mobility did not significantly affect pass rates for ABR screening; 95% of these ears passed the automated ABR screen. Implications for newborn hearing screening are discussed.     

Changes in otoacoustic emissions and auditory brain stem response after cis-platinum exposure in gerbils

Ototoxicity associated with cis -platinum administration commonly presents as hearing loss and tinnitus. The hearing loss is usually an irreversible, high-frequency sensorineural loss. Histologic studies in humans and animals suggest that the outer hair cells (OHCs) are most susceptible to cis -platinum. Evoked otoacoustic emissions (EOAE), as a measure of outer hair cell function, are potentially useful in following ototoxic insults involving OHCs. Distortion-product otoacoustic emission (DPOAE) test frequency-specific regions of the cochlea and therefore may be particularly well suited for monitoring ototoxic injuries. We measured distortion product otoacoustic emissions, at f2 = 2, 4, 6, 8, 10, and 12 kHz, in gerbils after a single large dose of cis -platinum. Animals treated with saline served as controls. The findings were compared to auditory brain stem evoked response (ABR) thresholds, using tone pipe of the same frequencies. The DPOAE and ABR thresholds were measured before treatment and again 2, 5, and 14 days after drug administration. The changes in DPOAE were compared with the changes in ABR. No treatment effect was noted in the 2-day group. Animals treated with cis -platinum demonstrated significant elevation of DPOAE and ABR thresholds compared with control animals at 5 and 14 days. There was no significant difference between the threshold changes in the 5-and 14-day groups. (Otolaryngol Head Neck Surg 1997; 116:585-92.)     

The use of gene-modified bone marrow mesenchymal stem cells for cochlear cell therapy

BackgroundThe aim of this study was to investigate the potential of using bone marrow mesenchymal stem cells (BMSCs) for treatment of inflammation and autoimmune sensorineural hearing loss.MethodsFifty-five immunized guinea pigs were divided into five groups. Group A received BMSCs expressing IL-4, group B received BMSCs expressing an empty carrier vector, group C received recombinant lentivirus expressing IL-4, group D received recombinant lentivirus expressing an empty carrier vector, and group E received phosphate-buffered saline. Auditory function was monitored using brain stem responses (ABRs) to evaluate the auditory changes. The distribution of implanted BMSCs in the inner ear was estimated using fluorescence microscopy. The distribution and expression of IL-4 gene products in the inner ear were detected via immunohistochemistry.ResultsAfter transplantation, the ABR III wave threshold decreased significantly in BMSCs expressing exogenous IL-4 group (group A), BMSCs expressing empty carrier vector group (group B), and recombinant lentivirus expressing IL-4 group (group C) (P < 0.001), which means the auditory functions of the experimental guinea pigs were improved. Further statistical analysis revealed that BMSCs expressing exogenous IL-4 group (group A) and BMSCs expressing empty carrier vector group (group B) were able to improve the auditory function more obviously (P < 0.05). Lentivirus-infected BMSCs were able to migrate to the inner ear. Fluorescence-positive BMSCs were scattered in the scala tympani and vestibule.ConclusionsThese results demonstrated that BMSCs expressing exogenous IL-4 successfully migrated into the inner ear in an in vitro study. BMSCs expressing exogenous IL-4 and BMSCs can be used to treat inflammatory injury in autoimmune inner ear diseases.     

Neonatal hearing screening with otoscopy, auditory brain stem response, and otoacoustic emissions

A study was performed to investigate the relationship between external and middle ear factors and hearing screening results by auditory brain stem response (ABR) and transient evoked otoacoustic emissions (EOAEs). The ears of 200 well newborns aged 5 hours to 48 hours underwent screening by ABR and EOAEs, followed by otoscopic examination. The pass rates for ABR and EOAE screening were 88.5% and 79%, respectively. On otoscopic examination, 13% (53 of 400) ears had occluding vernix obscuring the view of the tympanic membrane. Cleaning of vernix was attempted in ears that failed ABR or EOAE screening. Seventeen ears that failed ABR were cleaned, and 12 (71%) of them passed repeat ABR. Thirty-three ears that failed EOAE screening were cleaned, and 22 (67%) of them passed repeat emissions testing. Cleaning vernix increased the pass rates for ABR and EOAE screening to 91.5% and 84%, respectively. Decreased tympanic membrane mobility was found in 9% of ears that could be evaluated otoscopically. Increased failure rates for both ABR and EOAE screening were found in infant ears with decreased tympanic membrane mobility, but significance testing could not be performed because of inadequate sample size. Prevalence of occluding external canal vernix and middle ear effusion as a function of increasing infant age were studied. Implications for newborn hearing screening are discussed. (Otolaryngol Head Neck Surg 1997;116:597-603.)     

Evaluation of hydroxyapatite ossicular chain prostheses.

Hydroxyapatite (HA) middle ear prostheses have gained popularity as an alternative to human autografts and homografts. This study reports on 3 HA prostheses types: total ossicular chain prostheses, used for grafting the stapes footplate to the tympanic membrane; partial ossicular chain prostheses, used for grafting the stapes superstructure to the tympanic membrane; and Kartush incus struts (Smith & Nephew Richards Inc), used for grafting the stapes superstructure to the undersurface of the malleus. This single-surgeon study of 33 consecutive cases revealed a statistically significant difference in mean postoperative air-bone gap and airbone gap closure between incus struts (14/26 dB) or partial (22/11 dB) or total (25/10 dB) ossicular chain prostheses (t test: P<0.05). Prognostic risk factors graded by the Middle Ear Risk Index indicate a tendency for worse postoperative hearing with increasing Middle Ear Risk Index. This study supports the use of HA ossicular prostheses and, in particular, the use of the malleus for ossicular chain construction.     

Safety assessment of trans-tympanic photobiomodulation

We evaluated functional and morphological changes after trans-tympanic laser application using several different powers of photobiomodulation (PBM). The left (L) ears of 17 rats were irradiated for 30 min daily over 14 days using a power density of 909.1 (group A, 5040 J), 1136.4 (group B, 6300 J), and 1363.6 (group C, 7560 J) mW/cm². The right (N) ears served as controls. The safety of PBM was determined by endoscopic findings, auditory brainstem response (ABR) thresholds, and histological images of hair cells using confocal microscopy, and light microscopic images of the external auditory canal (EAC) and tympanic membrane (TM). Endoscopic findings revealed severe inflammation in the TM of C group; no other group showed damage in the TM. No significant difference in ABR threshold was found in the PBM-treated groups (excluding the group with TM damage). Confocal microscopy showed no histological difference between the AL and AN, or BL and BN groups. However, light microscopy showed more prominent edema, inflammation, and vascular congestion in the TM of BL ears. This study found a dose-response relationship between laser power parameters and TM changes. These results will be useful for defining future allowance criteria for trans-tympanic laser therapies.     

Ototoxicity of antimycotics

Neither otomycoses nor defects of the tympanic membrane are rare. In cases of fungal infection when the tympanic membrane is not intact, the possibility exists that antimycotic medication could enter the middle ear and diffuse into the cochlea via the round window. Five antimycotic preparations were tested for acute ototoxic potential in guinea pigs. Those containing acetic acid or propylene glycol caused appreciable elevation of brainstem response thresholds, while little or no impairment resulted from tolnaftate or clotrimazole solutions in polyethylene glycol 400.     

Alternative indications for laser-assisted tympanic membrane fenestration

BACKGROUND AND OBJECTIVE: To assess the utility of the CO(2) Flashscanner laser for treatment of selected middle ear diseases other than otitis media with effusion (OME) and acute otitis media (AOM). STUDY DESIGN/MATERIALS AND METHODS: A retrospective review of the records of 144 patients treated with the OtoLAM((R)) device, a Flashscanner laser, between July 1, 1998, and February 29, 2000. Patients treated for AOM or OME were excluded. RESULTS: Data are presented on 11 patients (17 ears). Four indications were identified: Elimination of middle ear fluid before auditory brainstem response with or without otoacoustic emission testing (ABR +/- OAE), barotrauma, eustachian tube obstruction, tympanocentesis when a culture of middle ear fluid was deemed necessary. All tympanic membranes (TM) healed. CONCLUSIONS: Fenestration of the TM can be accomplished for both diagnostic and therapeutic purposes. Laser assisted tympanic membrane fenestration seems to be effective in the management of middle ear fluid before ABR +/- OAE, barotrauma, eustachian tube dysfunction, and for tympanocentesis.     

Acquired atrophy of the long process of the incus.

Various lesions can cause conductive hearing loss in a patient with a normal tympanic membrane. These include congenital ossicular anomaly, otosclerosis, and congenital or acquired ossicular fixation and discontinuity. We had an experience with a patient who presented with a conductive hearing loss in both ears, in which small pieces of the long process of the incus were absent and had been replaced with fibrous tissues in both ears. No other abnormalities, such as postinflammatory changes or fixation of the ossicles, were found. Because the long process of the incus undergoes remodeling through resorption and rebuilding throughout life, failure of the remodeling or impaired vascular supply to the long process of the incus may have been the cause of the conductive hearing loss in this patient.     

Labyrinthine fenestration in the guinea pig.

OBJECTIVE: To evaluate the auditory effects of single, double, and triple semicircular canal fenestration procedures, with and without sealing the labyrinthine defect. BACKGROUND: Violation of the inner ear remains a feared complication in otologic surgery because it commonly leads to profound sensorineural hearing loss. It has been assumed that the natural history of labyrinthine injury in the guinea pig is similar to that in human beings; however, this assumption has not been rigorously studied. DESIGN: Prospective, randomized, and controlled animal study. SUBJECTS: Sixty pigmented guinea pigs. OUTCOME: Click-evoked electrocochleographic response, with same-ear prefenestration control. RESULTS: All of the fenestration groups had elevated auditory thresholds at 1 hour when compared with controls (P < 0.01); however, this difference lost statistical significance at 1 and 4 weeks. The degree of labyrinthine injury did not correlate with the degree of hearing loss or with the incidence of anacusis. Hearing remained stable during the study period. Sealing the fenestration had no significant audiologic effect (P > 0.40). CONCLUSIONS: The guinea pig model of labyrinthine fenestration may not be representative of the human condition.     

Hyperbaric compression in the guinea pig with perilymph fistula.

OBJECTIVE: The study goal was to evaluate the effects of hyperbaric therapy on the auditory and vestibular function of guinea pigs compromised by perilymph fistula (PLF). METHODS: Twenty-four pigmented guinea pigs underwent induction of bilateral eustachian tube dysfunction before the creation of a unilateral PLF. Half of the animals were randomly assigned to receive immediate hyperbaric compression treatment of 4 "dives" each. Hearing was tested electrocochleographically, and signs of vestibulopathy were recorded before and after compression. RESULTS: After accounting for the effects of PLF, compression was not associated with significant hearing loss (P = 0.5411). Vestibulopathy was seen only in ears with PLF, and its incidence was similar for compression and noncompression groups. CONCLUSION: Hyperbaric compression does not compromise auditory or vestibular function in guinea pig ears with experimental PLF. SIGNIFICANCE: Our observations support the relative safety of recompression in patients with PLF.     

Bisphosphonate Therapy Ameliorates Hearing Loss in Mice Lacking Osteoprotegerin

Three auditory ossicles including the malleus, incus, and stapes conduct sound in the middle ear from the tympanic membrane to the inner ear. Auditory ossicles are massively resorbed by osteoclasts in Opg^?/? mice, which lack osteoprotegerin (OPG), a soluble decoy receptor for the osteoclastogenic cytokine RANKL. Opg^?/? mice exhibit progressive hearing loss and are a model for juvenile Paget's disease. However, effects of antiresorptive treatment on auditory ossicles and on hearing function in Opg^?/? mice are unknown. We intraperitoneally injected Opg^?/? mice with bisphosphonate risedronate 5 d/wk for 9 wk. Morphology of auditory ossicles was examined microscopically, radiographically, and histologically. Hearing function was monitored by measuring the auditory brain stem response (ABR). Control Opg^?/? mice exhibited thinning of all three ossicles and tibia. In contrast, risedronate treatment significantly inhibited bone loss in auditory ossicles as well as in long bones of Opg^?/? mice. Bony fusion of the junction between the stapes and the otic capsule was reduced after treatment. Moreover, ABR measurement showed that hearing in Opg^?/? mice was significantly improved by risedronate treatment. These data suggest that hearing loss in pathologies characterized by excessive resorption of the auditory ossicles may be prevented by bisphosphonates.     

Clonidine as an analgesic adjuvant to continuous paravertebral bupivacaine for post-thoracotomy pain

We prospectively evaluated the effect of clonidine as an adjuvant to bupivacaine for continuous paravertebral intercostal nerve block, measuring pain and sedation scores and pulmonary function tests. Thirty patients scheduled to undergo thoracotomy were randomized to receive either a bolus of 0.125% bupivacaine 2 mg/kg (group BUP) or 0.125% bupivacaine 2 mg/kg with clonidine 2 microg/kg (group BUP+CLO), followed by an infusion of 0.125% bupivacaine at 0.5 mg/kg/h, or 0.125% bupivacaine at 0.5 mg/kg/h with clonidine at 2 microg/kg/h, in respective groups, through a paravertebral intercostal catheter. Haemodynamic parameters, pain and sedation scores and pulmonary function tests were recorded at 6, 12, 24 and 48 hours after arrival in postoperative care unit. There were significantly lower pain scores at rest and on coughing in group BUP+CLO compared with group BUP (P <0.01). Multiple comparisons revealed a significant reduction in pain score at each time point (P<0.01), except at 12h to 24h, in group BUP+CLO. Sedation scores were significantly higher in group BUP+CLO compared with group BUP at each time point (all P<0.01). There was a linear effect of time on sedation score in group BUP whereas in group BUP+CLO, the effect was quadratic. Patients in the clonidine group had a higher incidence of hypotension (P < 0.01). There was no significant difference in pulmonary function between the groups. We conclude that using clonidine as an adjunct to bupivacaine for continuous paravertebral intercostal nerve block improves pain relief after thoracotomy, but hypotension and sedation are adverse effects interfering with its clinical application.     

耳内镜下耳屏软骨-软骨膜修补术治疗鼓膜穿孔的临床效果

的 探究耳内镜下耳屏软骨-软骨膜治疗鼓膜穿孔的临床应用价值。方法 选取2020-2022年广 元市中心医院接诊的78例鼓膜穿孔患者为研究对象，采取随机数字表法分为对照组（n=39）和观察组 （n=39）。对照组接受显微镜管下颞肌筋膜鼓膜修补术，观察组接受耳内镜下耳屏软骨-软骨膜鼓膜修 补术，比较两组临床疗效和术后不良反应。结果 观察组治疗总有效率为94.87%，高于对照组的82.05% （P＜0.05）；观察组术后不良反应发生率为5.13%，低于对照组的17.95%（P＜0.05）。结论 耳内镜下耳 屏软骨-软骨膜治疗鼓膜穿孔可降低术后不良反应的发生率，取得较高的治疗有效率，值得临床应用。     

Protection from ototoxicity of intraperitoneal gentamicin in guinea pig

BACKGROUND: Aminoglycoside antibiotics are common to treat peritonitis and exit-site infections in patients on peritoneal dialysis. Ototoxicity (loss of hearing or balance) is a well-documented adverse effect of aminoglycosides, and severe ototoxic reactions have been noted in patients receiving these drugs by intraperitoneal lavage. We have proposed a free-radical hypothesis for the mechanism of aminoglycoside ototoxicity and suggested a therapeutic prevention by the concomitant administration of antioxidants or iron chelators. Here we investigate whether 2, 3-dihydroxybenzoate can prevent the ototoxicity of intraperitoneal gentamicin. METHODS: Two strains of pigmented guinea pigs received daily intraperitoneal injections of gentamicin. Both strains developed ototoxicity, although different dosages were needed to produce similar auditory deficits (120 mg gentamicin base/kg body weight daily for 19 days vs. 135 mg/kg for 14 days). Dihydroxybenzoate was administered intraperitoneally once or twice daily. Auditory thresholds were measured by evoked brain stem response. Pathology was assessed as a loss of sensory cells in surface preparations of the organ of Corti. RESULTS: The auditory threshold shifts and hair cell loss were similar to the pathology observed following subcutaneous injections of gentamicin. Animals sustained almost complete loss of outer hair cells in the basal cochlea and a progressive hearing loss with threshold shifts of 60 dB at 18 kHz. The concomitant administration of dihydroxybenzoate significantly attenuated the threshold shift to less than 30 dB and reduced the loss of hair cells. The treatment with dihydroxybenzoate did not affect serum gentamicin levels. CONCLUSIONS: Antioxidant therapy is a promising approach to prevent aminoglycoside-induced hearing loss following intraperitoneal application.     

七氟醚对豚鼠耳蜗外毛细胞Ca2+跨膜内流和内质网钙释放功能的影响

目的 观察七氟醚对豚鼠耳蜗外毛细胞Ca2+跨膜内流和内质网钙释放功能的影响,探讨其对听觉外周感受器(耳蜗)作用的可能机制.方法 第一部分成年豚鼠,雌雄不拘,迅速断头,取耳蜗,酶孵育后,机械分离法分离外毛细胞,30个活力良好的外毛细胞随机分为3组(n=10):对照组(C组),低浓度七氟醚组(S1组)和高浓度七氟醚组(S2组),用Fluo-3AM钙荧光指示剂染色后,分别给予纯氧、1.7%七氟醚、3.4%七氟醚处理20min,然后加入40mmol/L氯化钾,测定细胞内游离钙离子浓度([Ca2+];).第二部分以20 mmol/L 咖啡因代替氯化钾其余处理及分组同第一部分.结果 第一部分与基础值比较,各组给予七氟醚后[Ca2+];差异无统计学意义(P＞0.05),加入氯化钾后[Ca2+];升高(P＜0.01);S1组和S2组加入氯化钾后[Ca2+];低于C组,且S2组低于S1组(P＜0.05).第二部分与基础值比较,各组给予七氟醚后[Ca2+];差异无统计学意义(P＞0.05),加入咖啡因后[Ca2+];升高(P＜0.0);加入咖啡因后各组[Ca2+];差异无统计学意义(P＞0.05).结论 七氟醚可浓度依赖性地抑制豚鼠耳蜗外毛细胞电压依赖型Ca2+通道开放,而对内质网Ryanodine敏感性钙释放功能无影响.     

Usefulness of 1000 Hz tone-burst-evoked responses in the diagnosis of acoustic neuroma

The auditory brain stem response (ABR) has become widely recognized as a sensitive and cost-effective screening modality in neuro-otologic diagnosis. However, the audiometric characteristics of the test ear may obscure the interpretation of the click-evoked ABR, particularly in the face of high-frequency hearing loss. It is often unclear whether latency delays or absent responses are attributable to retrocochlear disease or simply to the magnitude of the patient's hearing loss. The acoustic click stimulus commonly used in ABR testing activates predominantly the basilar membrane in the 2000 to 4000 Hz range. Because many cochlear and retrocochlear processes are associated mainly with hearing loss in this range, we have found it helpful in selected cases to use 1000 Hz tone-burst stimuli to circumvent the effects of elevated hearing thresholds on the ABR. In this article, our experience with the use of 1000 Hz nonlinearly gated tonebursts in 17 patients with acoustic neuroma is presented.     

Type III cartilage “shield” tympanoplasty: An effective procedure for hearing improvement

OBJECTIVE: To report the hearing results following type III cartilage "shield" tympanoplasty. STUDY DESIGN: Retrospective chart review at a tertiary referral center. METHODS: Conchal cartilage, shaped as a shield, was used to replace the entire tympanic membrane and reconstruct the ossicular chain in patients with an absent incus and diminished space between the stapes superstructure and malleolar manubrium. RESULTS: Between January 1998 and June 2005, 52 patients were treated. The mean age was 32.4 years (range, 7 to 72 years). The mean follow-up was 24 months (range, 12 to 36 months). Graft take was successful in all patients. The average hearing improvement was 11.22 dB (P<0.0001). An air-bone gap of 25 dB or less was achieved in 41 (78.8%) patients. Speech discrimination scores remained unchanged. No complications were identified. CONCLUSION: Type III cartilage "shield" tympanoplasty is an effective technique for hearing improvement in selected patients with chronic otitis media. The results of this procedure are similar to those obtained with partial ossicular replacement prosthesis.