鼓室给药治疗难治性梅尼埃病的研究进展

梅尼埃病(Ménière's disease,MD)是以反复发作的眩晕、听觉障碍、耳鸣和耳胀满感为典型特征的突发性内耳疾病,膜迷路积水为基本的病理基础。膜迷路积水考虑与耳蜗微循环障碍、内淋巴液生成及吸收平衡失调等有关。虽然目前内耳药物代谢动力学研究的结果差异较大,经鼓室局部给药,使药物通过圆窗膜选择性的通透作用进入内耳,优于口服或其他胃肠外给药的效果,用药量较少,能在内耳局部达到较高的药物浓度,可避免全身用药可能引起的不良反应。     

耳后给药及鼓室给药外淋巴液药物浓度的实验观察

目的研究耳后皮下注射给药、鼓室内给药后外淋巴液中地塞米松磷酸钠的药物代谢动力学特征,探讨两种给药途径的药代动力学差异。方法以地塞米松磷酸钠(10mg/ml)为药物示踪剂,将豚鼠随机分为耳后注射(耳后组)和鼓室内给药(鼓室组)2组,耳后组给药量为1ml(10mg/ml),鼓室组给药量为0.1ml(10mg/ml),分别采集耳后组给药0.25、0.5、1、2.5、5、6、8小时外淋巴液及鼓室组给药后0.5、1、2、3、4、6、8小时外淋巴液,用高效液相色谱法分别检测其中的药物浓度。结果 1两种方式给药后,豚鼠外淋巴液中均可检测出地塞米松,且浓度均随时间的延长呈下降趋势;2鼓室组:给药后0.5~8h外淋巴液中均可检出有效药物成份地塞米松,3h达峰,其峰浓度(Cmax)最高为906.55mg/l,生物半衰期为1.27h。3耳后组:给药后0.25~8h可检出地塞米松,其达峰时间(Tmax)为0.25h,其峰浓度(Cmax)最高为18.83mg/l,生物半衰期为3.36h。4鼓室组给药量为0.1ml,耳后组给药量为1ml,外淋巴液中鼓室组地塞米松的浓度高于耳后组。5耳后组药物半衰期比鼓室给药组高。结论提示耳后皮下注射给药药物可能通过多种途径进入外淋巴,药物浓度相对鼓室给药低;鼓室给药组因避开血脑屏障及血迷路屏障故可较快进入外淋巴,保持较高药物浓度;结合临床我们可推测激素在外淋巴中可能低浓度即可起效。     

糖皮质激素鼓室给药治疗突发性聋的现况分析

突发性聋是耳鼻喉科常见的急症,目前临床上全身使用糖皮质激素治疗突发性聋获得较为肯定的疗效,但全身使用糖皮质激素的禁忌症及可能引起严重的不良反应,使得糖皮质激素鼓室给药治疗突发性聋逐渐得到应用并成为广泛关注的热点。本文将对糖皮质激素鼓室给药的疗效进行评估,以及对其临床运用的现况进行阐述。     

经鼻给药对鼻粘膜结构的影响

目的 研究药物经鼻吸收对鼻粘膜结构的影响。方法 使用硫酸庆大霉素及胰岛素给家兔滴鼻,在用药后３、５、７ｄ和２周及停药后的１周及２周取鼻粘膜进行光不显微镜和透射显微镜观察。结果 用药后３￣７ｄ出现渐进性鼻粘膜损伤的改变,１周后部分区域上皮脱落,但基底膜完整。停药后１￣２周内上皮细胞及纤毛迅速修复。结论 鼻内给药是一种可行的有前途的给药途径。     

地塞米松纳米粒经鼓室给药的豚鼠体内分布及药动学研究

我们2006年1月至11月通过实验比较了鼓室和静脉注射醋酸地塞米松（dexamethasone acetate，DA）固体脂质纳米粒（solid lipid nanoparticle，SLN）后药物在豚鼠体内的分布及经时变化规律，分析了其药代动力学特性，探讨鼓室给药的规律和机理，为临床应用纳米粒治疗内耳疾病提供参考。     

甲强龙凝胶鼓室给药对噪声性聋大鼠内耳的保护作用

目的 通过鼓室注射甲强龙透明质酸水凝胶治疗噪声性聋大鼠,探讨鼓室给药对大鼠听觉功能的保护和治疗作用。方法 建立噪声性耳聋大鼠模型,按是否接受噪声刺激、鼓室注射甲强龙透明质酸水凝胶随机分成四组：对照组、鼓室给药组、噪声刺激组、噪声刺激鼓室给药组,检测各组大鼠的听性脑干诱发电位（ABR）听力阈值变化,取耳蜗基底膜铺片,荧光染色激光共聚焦显微镜下观察毛细胞的损伤情况。结果 噪声刺激鼓室给药组大鼠ABR阈值平均为（35.1±9.3）dB SPL,而噪声刺激组大鼠ABR阈值为（57.3±15.2）dB SPL,差异具有统计学意义（P<0.01）,噪声对耳蜗毛细胞形态会造成损伤,甲强龙鼓室给药对耳蜗毛细胞具有一定的保护作用。结论 甲强龙鼓室给药对耳蜗毛细胞具有一定的保护和治疗作用,为鼓室局部给药对内耳疾病的治疗提供理论依据。     

2020版梅尼埃病临床实践指南解读

梅尼埃病是一种病因不明的临床综合征.1861年,Ménière首先报道了内耳(膜迷路)病变可能是表现为发作性眩晕、耳鸣和听力损失的综合征的根源[1].目前有关梅尼埃病发病率和患病率的文献报道在不同国家、地区和人种之间均存在较大差异,2020年美国耳鼻咽喉头颈外科学会(American Academy of Otolar...     

碱性成纤维细胞生长因子鼓室给药治疗感音神经性聋的研究

目的:探讨碱性成纤维细胞生长因子治疗感音神经性聋的临床应用价值及鼓室局部给药的可行性。方法:随机选择本院1998～1999年收治的感音神经性聋患者40例(50耳),碱性成纤维细胞生长因子(bFGF)作鼓膜穿刺鼓室内给药。治疗前后进行纯音测听,定期随访,追踪观察bFGF的疗效。结果:经bFGF治疗后,患者语频、高频及0.25～4 kHz各频率的听阈平均值均有明显提高,分别与治疗前比较,差异有极显著性意义(P<0.01)。总有效率为96％,其中治愈率8％,显效率38％,好转率50％。除有轻度胀痛外,无其他不良反应。结论:鼓室局部应用bFGF治疗感音神经性聋疗效明显,方法可行。     

外耳道加压给药治疗分泌性中耳炎疗效观察

目的观察外耳道加压给药治疗分泌性中耳炎的疗效.方法共观察52例(76耳).治疗组在鼓膜穿刺抽液后行外耳道、鼓室加压给药 激光等治疗;对照组仅行鼓膜穿刺抽液、激光照射等治疗.结果外耳道、鼓室加压给药组疗效明显高于对照组(P＜0.05),差异有显著性意义,总有效率86.8%.结论外耳道、鼓室加压给药可提高分泌性中耳炎的疗效.     

鼓室局部给药后内耳药物代谢动力学研究进展

近年来,经鼓室局部给药已经成为治疗多种内耳疾病的新方法之一,该技术的主要理论依据是:药物与圆窗膜接触后,可不经过血-迷路屏障,直接经圆窗膜渗透进入内耳,并获得较全身用药更高的内耳药物浓度和持续时间[1～5],且可直接作用于患耳,避免全身用药的副作用.     

Impact of the pediatric tonsillectomy and polysomnography clinical practice guidelines

Objective

To evaluate the effect of the recently published guidelines on Tonsillectomy in Children and Polysomnography for Sleep-Disordered Breathing Prior to Tonsillectomy in Children on physician practice patterns.

Study design

Cross-sectional survey.

Method

Survey of members of the American Academy of Otolaryngology—Head and Neck Surgery.

Setting

Academic tertiary referral center.

Results

A total of 280 physicians completed the survey, with a response rate of 41.7%. 93% of respondents had read the clinical practice guidelines. Many respondents had completed a pediatric otolaryngology fellowship (46%). A large group of physicians (46%) continue to prescribe antibiotics within 24 h after surgery. One-third of respondents stopped prescribing antibiotics because of the guidelines. Discord between severity of symptoms and tonsil size was the most common reason cited for ordering a polysomnogram prior to tonsillectomy (76%). The most common reason cited for admission post-tonsillectomy was age less than 3 (40%). Less than half of physicians prescribe NSAIDs for pain control (43.8%) despite its safety profile, and only 23% reported that the guidelines influenced their use of NSAIDs postoperatively. Most respondents use intra-operative steroids (90%) as recommended.

Conclusion

The guidelines are intended to provide evidence based direction in tonsillectomy practices and improve referral patterns for polysomnography prior to tonsillectomy. The majority of the surveyed otolaryngologists reviewed these guidelines and some have changed their practice secondary to the guidelines. However, many physicians continue to prescribe post-operative antibiotics and do not use NSAIDs.     

A summary of the Clinical Practice Guideline for the Diagnosis and Management of Voice Disorders, 2018 in Japan

ObjectiveTo develop a summary of the first version of the Clinical Practice Guideline of Voice Disorders for Diagnosis, Management, and Treatment in Japan by the Clinical Practice Guideline Committee of the Japan Society of Logopedics and Phoniatrics and The Japan Laryngological Association. The 2018 recommendations, based on a review of the scientific literature, are intended to serve as clinical practice guidelines for the diagnosis, management, and treatment of voice disorders in Japan.MethodsA summary of the original version of the Clinical Practice Guideline of Voice Disorders for Diagnosis, Management, and Treatment in Japan was described. Recommendations for the diagnosis, management, and treatment of voice disorders were prepared. Twelve clinical questions (CQs) regarding the diagnosis, management, treatment, and effectiveness of therapy for voice disorders were also prepared.ResultsA summary of the first version of the clinical practice guidelines for the diagnosis, management, and therapy of voice disorders was prepared and is presented. Additionally, answers to the 12 CQs on the diagnosis, management, treatment, and effectiveness of voice disorder therapy were prepared, and include evidence-based recommendations.ConclusionThese guidelines present a summary of the standard approaches for the diagnosis and treatment of voice disorders and relevant CQs that consider the medical environments in Japan. We hope that the guidelines will assist physicians in clinical settings for patients with voice disorders.     

早期联合鼓室注射糖皮质激素治疗突发性聋效果分析

目的　探讨早期联合鼓室注射糖皮质激素治疗突发性聋的疗效。方法　178例突发性聋患者纳入研究,中低频下降型44例,高频下降型50例,平坦型44例,全聋型40例,随机分为两组,其中联合鼓室注射组（CT组）82例,全身口服激素组（OP组）96例,CT组在口服醋酸泼尼松片治疗同时给予鼓室注射甲泼尼龙琥珀酸钠,治疗后 8周复查纯音纯音听力阈值。结果　中低频突发性聋患者中,CT组纯音听力阈及其提高值分别为（26.14±14.91）dB、（41.23±12.61）dB,而OP组为（37.91±13.98）dB、（30.00±13.30）dB,两者差异均具有统计学意义（P 均＜0.05）,而两组在高频型、平坦型及全聋型的差异无统计学意义（P 均＞0.05）,CT组纯音听力阈提高值为（26.52±14.03）dB,高于OP组（22.06±11.17）dB（t =2.361,P ＜0.05）;中低频突发性聋患者中,CT组治愈16 例（72.73%）,OP组治愈9例（40.91%）,差异有统计学意义（χ2=4.539,P＜0.05）,有效、显效及总有效的比较结果显示,两组中低频型突发性聋的治疗效果差异无明显统计学意义,而在高频型、平坦型及全聋型的比较上,CT组与OP组无论是在治愈、有效、显效还是在总有效上,两组差异均无明显统计学意义,CT组共治愈33例（40.24%）,优于OP组的25例（26.04%）（χ2=4.061,P＜0.05）,而两组在显效、有效及总有效率上的差异未见明显统计学意义。结论  中低频型突聋患者,早期联合鼓室注射糖皮质激素会获得更好听力恢复及疗效,对高频型、平坦型及全聋型突聋患者,推荐全身激素用药。     

Outcomes research analysis of continuous intratympanic glucocorticoid delivery in patients with acute severe to profound hearing loss: Basis for planning randomized controlled trials

Conclusions. The data presented herein form the basis for conducting randomized placebo-controlled clinical trials evaluating the safety and efficacy of salvage treatment in patients with idiopathic sudden severe sensorineural hearing loss (but not anacusis) refractory to initial systemic therapy. Comparison of different application protocols and drug delivery systems will allow assessment of the value of continuous versus intermittent intratympanic glucocorticoid drug delivery. Objectives. To describe and critically evaluate the results of continuous intratympanic glucocorticoid delivery in patients with acute unilateral severe and profound sensorineural hearing loss refractory to initial systemic therapy and to compare the outcome with a historical control group. Material and methods. In a retrospective chart review, treatment results were analyzed in 23 patients with acute severe and profound hearing loss and failure of systemic standard therapy who received a continuous intratympanic delivery of glucocorticoids as a salvage treatment. Audiological results were compared within the local therapy group and with the results of an historical control group who did not receive salvage treatment. The study and control groups were matched with respect to hearing loss after initial systemic treatment failure. Results. The average pure-tone threshold after intratympanic salvage treatment showed a statistically significant improvement of 15?dB (95% CI?7–24 dB; p<0.001). After exclusion of patients with complete anacusis, i.e. a non-measurable hearing threshold, the local therapy group showed a significantly better improvement (mean 19?dB; 95%?CI?6–32 dB) than the historical control group (mean 5?dB;?95%?CI ??2–11 dB; p<0.05).     

Radiologic anatomy of the round window relevant to cochlear implantation and inner ear drug delivery

ObjectiveTo determine anatomic relationships and variation of the round window membrane to bony surgical landmarks on computed tomography.Study designRetrospective imaging review.Methods100 temporal bone images were evaluated. Direct measurements were obtained for membrane position. Vector distances and angulation from umbo and bony annulus were calculated from image viewer software coordinates.ResultsThe angle of round window membrane at junction with cochlear basal turn was (42.1 ± 8.6)°. The membrane''s position relative to plane of the facial nerve through facial recess was (14.7 ± 5.2)° posterior from a reference line drawn through facial recess to carotid canal. Regarding transtympanic drug delivery, the round window membrane was directed 4.1 mm superiorly from the inferior annulus and 5.4 mm anteriorly from the posterior annulus. The round window membrane on average was angled superiorly from the inferior annulus (77.1 ± 27.9)° and slightly anteriorly from the posterior annulus (19.1 ± 11.1°). The mean distance of round window membrane from umbo was 4 mm and posteriorly rotated 30° clockwise from a perpendicular drawn from umbo to inferior annulus towards posterior annulus. Together, these measurements approximate the round window membrane in the tympanic membrane''s posteroinferior quadrant.ConclusionsThese radiologic measurements demonstrate normal variations seen in round window anatomy relative to facial recess approach and bony tympanic annulus, providing a baseline to assess round window insertion for cochlear implantation and outlines anatomic factors affecting transtympanic drug delivery.     

A novel controlled local drug delivery system for inner ear disease

PURPOSE: Our goal is to develop a novel drug delivery system that can potentially improve clinical outcomes compared to current methods of dosing drugs such as dexamethasone or gentamicin. This system focuses on a single local application to the inner ear via the round window membrane. HYPOTHESIS: A chitosan-glycerophosphate (CGP)-hydrogel based drug delivery system can be engineered to provide local and sustained drug release to the inner ear. STUDY DESIGN: In vitro: drug release and (CGP)-hydrogel matrix degradation were characterized using dexamethasone as a model drug. In vivo: dexamethasone laden CGP-hydrogel was placed in the round window niche of mice. Perilymph samples were obtained from the oval window and analyzed for dexamethasone. The impact of CGP-hydrogel on auditory function was evaluated. RESULTS: In vitro: A CGP-hydrogel was designed to release 92% of the dexamethasone load over 4 consecutive days with concurrent degradation of the hydrogel matrix. In vivo: After surgical placement of CGP-hydrogel to the round window niche, we detected elevated levels of dexamethasone in perilymph for 5 days. Auditory function testing revealed a temporary hearing loss in the immediate postoperative period, which resolved by the 10th postoperative day. CONCLUSIONS: We report the development of CGP-hydrogel, a biodegradable matrix that achieves local, sustained delivery of dexamethasone to the inner ear. There were no significant complications resulting from the surgical procedure or the administration of CGP-hydrogel to our murine model.