Objective To study expression of adenoviral-mediated Hath1-EGFP gene in the guinea pig cochlea after transfer through intact round window membrane(RWM), and to assess its effects on hearing. Methods Twenty adult guine...Objective To study expression of adenoviral-mediated Hath1-EGFP gene in the guinea pig cochlea after transfer through intact round window membrane(RWM), and to assess its effects on hearing. Methods Twenty adult guinea pigs were used, of which: 12 were surgically inoculated with Ad-Hath1-EGFP in the bony groove of round window niche, and 8 with artificial perilymph. Auditory brainstem response(ABR) thresholds were determined in all animals before and 5 days after surgery. On post-surgery day 5 and day 14, animals were sacrificed and whole mounts of cochlea and frozen sections were examined. Results ABR tests showed no significant change of hearing after the surgery. Strong fluorescence staining in the cochleae was seen in Ad-Hath1-EGFP groups. The highest levels of gene expression were seen in the post-surgery day 5 group with little decrease on post-surgery day 14.The contralateral cochlea and those in the control groups were free of fluorescence staining. Conclusion The transgenic Hath1-EGFP can be effectively delivered into the inner ear through intact RWM, in an atraumatic manner.展开更多
According to the vibration characteristics of the round window, a mechani- cal model of a round window membrane is established. The Euler equation of the round window and the complementary boundary conditions are deri...According to the vibration characteristics of the round window, a mechani- cal model of a round window membrane is established. The Euler equation of the round window and the complementary boundary conditions are derived by the variational prin- ciple. Combined with the Bessel function, an analytical solution of the round window displacement is obtained by MATHEMATICA. Combined with clinical characteristics of round window membrane lesion, the effect of sound transmission due to thickening of the round window membrane caused by the otitis media, shrinkage of the round window membrane area caused by otosclerosis, and hardening of the round window membrane itself is analyzed. The results show that with thickening of the round window membrane, the displacement of the round window membrane is decreased. In the meantime, with hardening of the round window membrane and shrinkage of the membrane area, the max- imum displacement Of the round window membrane is gradually reduced, leading to a decrease in sound transmission. Thus, the analyticM analysis can avoid interference of environment and the technical level of personnel, and it can evaluate transmission per- formance of the round window membrane efficiently, providing a theoretical basis for the reverse excitation of artificial prosthesis.展开更多
We investigated the pharmacokinetics of caroverine in the perilymph,cerebrospinal fluid and plasma after systemic and local administrations in guinea pigs by using high-performance liquid chromatography.Auditory brain...We investigated the pharmacokinetics of caroverine in the perilymph,cerebrospinal fluid and plasma after systemic and local administrations in guinea pigs by using high-performance liquid chromatography.Auditory brainstem responses were measured to evaluate auditory functional effect.The results showed that local application was a both safe and efficient method.We further reviewed literature and pinpointed that the round window is effectively local drug delivery means for future inner ear treatment.展开更多
Background In recent years the interest of sustained drug delivery into inner ear is promising, at the same time a great deal of novel oral drugs using biodegradable vehicles have been produced to achieve sustained dr...Background In recent years the interest of sustained drug delivery into inner ear is promising, at the same time a great deal of novel oral drugs using biodegradable vehicles have been produced to achieve sustained drug release. The aim of this study was to use biodegradable vehicles to release dexamethasone in the round window membrane application. Methods Dexamethasone gels composed of alginate and chitin were prepared and the release-permeating profiles were studied using a reproducible in vitro apparatus. A longer-period time course was simulated using the parameters acquired in this study. The data obtained in this study was compared with those of other studies in intratympanic drug delivery, and an appropriate initial dosage was extrapolated. Results The combination of alginate and chitin could efficiently restrict dexamethasone diffusion and the time course suggested a sustained drug concentration within 24 hours. A higher initial dosage was estimated to achieve a stable therapeutic concentration in vivo. Conclusion The combination of alginate and chitin could be used as vehicle for sustained release of dexamethasone in intratympanic application.展开更多
Background Most patients with auditory neuropathy （AN） could receive good even the best effects after cochlear implantation. How to diagnose AN objectively and accurately is very important. In this study, we screene...Background Most patients with auditory neuropathy （AN） could receive good even the best effects after cochlear implantation. How to diagnose AN objectively and accurately is very important. In this study, we screened the patients with AN according to the presence or absence of compound action potential （CAP） of intraoperative round window electrocochleography （RW ECochG）. Methods Intraoperative RW ECochG was performed on 32 patients with profound sensorineural deafness, who had normal cochlea during cochlear implantation surgery under general anesthesia in the standard operating room. The cochlear microphonic （CM） and CAP of RW ECochG was observed and recorded. Results The presence of CM but the absence of CAP of RW ECochG occurred in 12 among the 32 patients. They were suspected to suffer from AN. The rest patients who had CM and CAP of RW ECochG were thought not to suffer from AN. Conclusion Application of intraoperative RW ECochG during the cochlear implantation surgery may objectively and accurately screen the patients with AN, and can give a meaningful clue for implanted device working.展开更多
Objective:To evaluate incidence of interscalar excursions between round window (RW) and cochleostomy approaches for cochlear implant (CI) insertion. Methods:This was a retrospective case-comparison. Flat-panel CT (FPC...Objective:To evaluate incidence of interscalar excursions between round window (RW) and cochleostomy approaches for cochlear implant (CI) insertion. Methods:This was a retrospective case-comparison. Flat-panel CT (FPCT) scans for 8 CI users with Med-El standard length electrode arrays were collected. Surgical technique was identified by a combination of operative notes and FPCT imaging. Four cochleae underwent round win-dow insertion and 4 cochleae underwent cochleostomy approaches anterior and inferior to the round window. Results:In our pilot study, cochleostomy approaches were associated with a higher likeli-hood of interscalar excursion. Within the cochleostomy group, we found 29% of electrode contacts (14 of 48 electrodes) to be outside the scala tympani. On the other hand, 8.5%of the electrode contacts (4 of 47 electrodes) in the round window insertion group were extra-scalar to the scala tympani. These displacements occurred at a mean angle of occur-rence of 364°±133°, near the apex of the cochlea. Round window electrode displacements tend to localize at angle of occurrences of 400? or greater. Cochleostomy electrodes occurred at an angle of occurrence of 19°e490°.展开更多
Objective:To determine anatomic relationships and variation of the round window membrane to bony surgical landmarks on computed tomography.Study design:Retrospective imaging review.Methods:100 temporal bone images wer...Objective:To determine anatomic relationships and variation of the round window membrane to bony surgical landmarks on computed tomography.Study design:Retrospective imaging review.Methods:100 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.Results:The 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.Conclusions:These 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.展开更多
目的研究腺病毒携带目的基因经完整圆窗膜途径耳蜗转导的可行性及安全性,为内耳基因治疗提供实验基础和理论依据。方法20只白色红目豚鼠,术前及术后分别行听性脑干反应(ABR)检查。实验组(12只)以重组腺病毒携带的增强型绿色荧光蛋白基因...目的研究腺病毒携带目的基因经完整圆窗膜途径耳蜗转导的可行性及安全性,为内耳基因治疗提供实验基础和理论依据。方法20只白色红目豚鼠,术前及术后分别行听性脑干反应(ABR)检查。实验组(12只)以重组腺病毒携带的增强型绿色荧光蛋白基因(enhanced green fluorescent protein,EGFP),对照组(8只)以人工外淋巴液注入豚鼠圆窗龛内。分别于术后5天、14天取双侧耳蜗标本做基底膜铺片,耳蜗冰冻切片观察。结果于圆窗龛内注入腺病毒携带目的基因的转导方法对听力无明显影响。转染耳蜗及对侧耳蜗内目的基因呈广泛表达。5天组表达产物最高,14天组逐渐降低。对照组耳蜗未见EPFP表达。结论于圆窗龛内注入腺病毒携带目的基因转导的方法对耳蜗无明显毒害作用,且能够将目的基因成功转导至双侧耳蜗组织并广泛表达。展开更多
目的研究腺病毒携带目的基因经小鼠耳后入路圆窗膜显微注射途径耳蜗转导的可行性,为以小鼠作为动物模型的内耳基因治疗提供实验基础和解剖学依据。方法12只C57BL/6J小鼠分为2组,实验组(8只)以重组腺病毒携带的增强型绿色荧光蛋白基因(en...目的研究腺病毒携带目的基因经小鼠耳后入路圆窗膜显微注射途径耳蜗转导的可行性,为以小鼠作为动物模型的内耳基因治疗提供实验基础和解剖学依据。方法12只C57BL/6J小鼠分为2组,实验组(8只)以重组腺病毒携带的增强型绿色荧光蛋白基因(enhanced green fluorescent protein,EGFP)、对照组(4只)以人工外淋巴液经耳后入路圆窗膜显微注射注入耳蜗内。分别于术后5、14天取双侧耳蜗标本做基底膜铺片,在激光共聚焦显微镜下观察GFP表达。结果术后动物存活10只(每组死亡1只)。实验组转染后耳蜗底回基底膜及螺旋神经节上目的基因有表达,14天组强于5天组。对照组耳蜗未见荧光表达。结论耳后入路操作简单、损伤小、易于暴露圆窗龛。耳后入路圆窗膜显微注射腺病毒携带目的基因转导的方法能够将目的基因成功转导至耳蜗组织并表达。展开更多
基金National NaturalScience Foundation grants No.30730040 and No.30628030.
文摘Objective To study expression of adenoviral-mediated Hath1-EGFP gene in the guinea pig cochlea after transfer through intact round window membrane(RWM), and to assess its effects on hearing. Methods Twenty adult guinea pigs were used, of which: 12 were surgically inoculated with Ad-Hath1-EGFP in the bony groove of round window niche, and 8 with artificial perilymph. Auditory brainstem response(ABR) thresholds were determined in all animals before and 5 days after surgery. On post-surgery day 5 and day 14, animals were sacrificed and whole mounts of cochlea and frozen sections were examined. Results ABR tests showed no significant change of hearing after the surgery. Strong fluorescence staining in the cochleae was seen in Ad-Hath1-EGFP groups. The highest levels of gene expression were seen in the post-surgery day 5 group with little decrease on post-surgery day 14.The contralateral cochlea and those in the control groups were free of fluorescence staining. Conclusion The transgenic Hath1-EGFP can be effectively delivered into the inner ear through intact RWM, in an atraumatic manner.
基金Project supported by the National Natural Science Foundation of China(Nos.11272200 and11572186)
文摘According to the vibration characteristics of the round window, a mechani- cal model of a round window membrane is established. The Euler equation of the round window and the complementary boundary conditions are derived by the variational prin- ciple. Combined with the Bessel function, an analytical solution of the round window displacement is obtained by MATHEMATICA. Combined with clinical characteristics of round window membrane lesion, the effect of sound transmission due to thickening of the round window membrane caused by the otitis media, shrinkage of the round window membrane area caused by otosclerosis, and hardening of the round window membrane itself is analyzed. The results show that with thickening of the round window membrane, the displacement of the round window membrane is decreased. In the meantime, with hardening of the round window membrane and shrinkage of the membrane area, the max- imum displacement Of the round window membrane is gradually reduced, leading to a decrease in sound transmission. Thus, the analyticM analysis can avoid interference of environment and the technical level of personnel, and it can evaluate transmission per- formance of the round window membrane efficiently, providing a theoretical basis for the reverse excitation of artificial prosthesis.
文摘We investigated the pharmacokinetics of caroverine in the perilymph,cerebrospinal fluid and plasma after systemic and local administrations in guinea pigs by using high-performance liquid chromatography.Auditory brainstem responses were measured to evaluate auditory functional effect.The results showed that local application was a both safe and efficient method.We further reviewed literature and pinpointed that the round window is effectively local drug delivery means for future inner ear treatment.
基金This work was supported by a grant from Beijing Medical Development Foundation(No.2002-2012)
文摘Background In recent years the interest of sustained drug delivery into inner ear is promising, at the same time a great deal of novel oral drugs using biodegradable vehicles have been produced to achieve sustained drug release. The aim of this study was to use biodegradable vehicles to release dexamethasone in the round window membrane application. Methods Dexamethasone gels composed of alginate and chitin were prepared and the release-permeating profiles were studied using a reproducible in vitro apparatus. A longer-period time course was simulated using the parameters acquired in this study. The data obtained in this study was compared with those of other studies in intratympanic drug delivery, and an appropriate initial dosage was extrapolated. Results The combination of alginate and chitin could efficiently restrict dexamethasone diffusion and the time course suggested a sustained drug concentration within 24 hours. A higher initial dosage was estimated to achieve a stable therapeutic concentration in vivo. Conclusion The combination of alginate and chitin could be used as vehicle for sustained release of dexamethasone in intratympanic application.
文摘Background Most patients with auditory neuropathy （AN） could receive good even the best effects after cochlear implantation. How to diagnose AN objectively and accurately is very important. In this study, we screened the patients with AN according to the presence or absence of compound action potential （CAP） of intraoperative round window electrocochleography （RW ECochG）. Methods Intraoperative RW ECochG was performed on 32 patients with profound sensorineural deafness, who had normal cochlea during cochlear implantation surgery under general anesthesia in the standard operating room. The cochlear microphonic （CM） and CAP of RW ECochG was observed and recorded. Results The presence of CM but the absence of CAP of RW ECochG occurred in 12 among the 32 patients. They were suspected to suffer from AN. The rest patients who had CM and CAP of RW ECochG were thought not to suffer from AN. Conclusion Application of intraoperative RW ECochG during the cochlear implantation surgery may objectively and accurately screen the patients with AN, and can give a meaningful clue for implanted device working.
文摘Objective:To evaluate incidence of interscalar excursions between round window (RW) and cochleostomy approaches for cochlear implant (CI) insertion. Methods:This was a retrospective case-comparison. Flat-panel CT (FPCT) scans for 8 CI users with Med-El standard length electrode arrays were collected. Surgical technique was identified by a combination of operative notes and FPCT imaging. Four cochleae underwent round win-dow insertion and 4 cochleae underwent cochleostomy approaches anterior and inferior to the round window. Results:In our pilot study, cochleostomy approaches were associated with a higher likeli-hood of interscalar excursion. Within the cochleostomy group, we found 29% of electrode contacts (14 of 48 electrodes) to be outside the scala tympani. On the other hand, 8.5%of the electrode contacts (4 of 47 electrodes) in the round window insertion group were extra-scalar to the scala tympani. These displacements occurred at a mean angle of occur-rence of 364°±133°, near the apex of the cochlea. Round window electrode displacements tend to localize at angle of occurrences of 400? or greater. Cochleostomy electrodes occurred at an angle of occurrence of 19°e490°.
文摘Objective:To determine anatomic relationships and variation of the round window membrane to bony surgical landmarks on computed tomography.Study design:Retrospective imaging review.Methods:100 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.Results:The 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.Conclusions:These 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.
文摘目的研究腺病毒携带目的基因经完整圆窗膜途径耳蜗转导的可行性及安全性,为内耳基因治疗提供实验基础和理论依据。方法20只白色红目豚鼠,术前及术后分别行听性脑干反应(ABR)检查。实验组(12只)以重组腺病毒携带的增强型绿色荧光蛋白基因(enhanced green fluorescent protein,EGFP),对照组(8只)以人工外淋巴液注入豚鼠圆窗龛内。分别于术后5天、14天取双侧耳蜗标本做基底膜铺片,耳蜗冰冻切片观察。结果于圆窗龛内注入腺病毒携带目的基因的转导方法对听力无明显影响。转染耳蜗及对侧耳蜗内目的基因呈广泛表达。5天组表达产物最高,14天组逐渐降低。对照组耳蜗未见EPFP表达。结论于圆窗龛内注入腺病毒携带目的基因转导的方法对耳蜗无明显毒害作用,且能够将目的基因成功转导至双侧耳蜗组织并广泛表达。
文摘目的研究腺病毒携带目的基因经小鼠耳后入路圆窗膜显微注射途径耳蜗转导的可行性,为以小鼠作为动物模型的内耳基因治疗提供实验基础和解剖学依据。方法12只C57BL/6J小鼠分为2组,实验组(8只)以重组腺病毒携带的增强型绿色荧光蛋白基因(enhanced green fluorescent protein,EGFP)、对照组(4只)以人工外淋巴液经耳后入路圆窗膜显微注射注入耳蜗内。分别于术后5、14天取双侧耳蜗标本做基底膜铺片,在激光共聚焦显微镜下观察GFP表达。结果术后动物存活10只(每组死亡1只)。实验组转染后耳蜗底回基底膜及螺旋神经节上目的基因有表达,14天组强于5天组。对照组耳蜗未见荧光表达。结论耳后入路操作简单、损伤小、易于暴露圆窗龛。耳后入路圆窗膜显微注射腺病毒携带目的基因转导的方法能够将目的基因成功转导至耳蜗组织并表达。
