两种仿生双相陶瓷生物骨修复节段性骨缺损的实验研究

摘要 目的：。将仿生双相陶瓷生物骨和仿生双相陶瓷生物活性骨移植于兔桡骨缺损处,确定双相陶瓷支架材料修复节段骨缺损的可能性。 方法: 实验于2004-10/2005-10在第四军医大学全军骨科研究所及青岛医学院中心实验室完成。选择成年健康日本大耳兔48只,随机数字表法分为生物活性骨组,生物骨组及空白组,每组16只。将仿生双相陶瓷生物活性骨和仿生双相陶瓷生物骨分别植入生物活性骨组和生物骨组兔桡骨缺损处, 将空白组兔双侧桡骨造成15 mm缺损不做移植修复,作为空白对照,分别于术后第2,4,8,12周取材, 进行植入材料的大体观察,组织切片分别做苏木精-伊红染色、Masson染色。 结果：纳入兔48只,均进入结果分析。①大体观察：生物活性骨组和生物骨组术后2周时无明显差别,材料与骨床间为纤维组织连接。4周及8周可见生物活性骨组断端周围新生骨痂较多,将材料包绕,12周时可见材料部分吸收新生骨长入,修复段塑型较好,基本接近宿主骨外形。12周时,生物骨组仅在骨折端有少量骨痂连接。空白组骨折端为纤维结蒂组织,骨缺损不能修复。②骨组织染色观察：生物活性骨组和生物骨组术后2周时无明显差别,材料与骨床间为纤维组织连接。术后4周8周,生物活性骨组有更多的血管和纤维组织长人材料,新骨形成逐渐增多,材料与骨床间为骨性连接。生物骨组材料与骨床间两端被新生的纤维组织和少量幼稚骨包绕,新生幼稚骨组织逐渐从缺损两端向材料内部长入。术后12周生物活性骨组材料降解增多,新生骨组织与两端骨床融合成一体,有骨髓样结构形成。术后12周生物骨组材料与骨床间两端为骨性连接,骨长入较少。空白组2周时骨折端为纤维结蒂组织,断端较整齐。12周时骨折端吸收,硬化,封闭。 结论：仿生双相陶瓷生物活性骨有较好的骨传导性和骨诱导性,又有一定的可吸收性,植入动物体内后未见明显免疫反应,修复节段骨缺损作用明显,应用双相陶瓷支架材料修复骨缺损具有较好的前景     

β-磷酸三钙/聚磷酸钙纤维/聚左旋乳酸支架复合骨髓基质细胞修复节段性骨缺损

背景：组织工程β-磷酸三钙/聚磷酸钙纤维/聚左旋乳酸支架材料具有良好的生物相容性。 目的：评估骨髓基质细胞与β-磷酸三钙/聚磷酸钙纤维/聚左旋乳酸复合体修复兔桡骨大段骨缺损成骨的效果。 方法：取新西兰大白兔40只,建立桡骨双侧大段骨缺损模型,其中35只右侧植入自体骨髓基质细胞与β-磷酸三钙/聚磷酸钙纤维/聚左旋乳酸复合物作为实验组,左侧植入β-磷酸三钙/聚磷酸钙纤维/聚左旋乳酸支架材料作为对照组;另5只作为空白对照不作任何处理。植入后4,8,12,16周拍摄X射线片观察骨缺损修复情况。 结果与结论：实验组术后2周可见缺损处有散在的、少量模糊状骨痂生成,术后4周可见明显骨生成影像,成云雾状,均匀分布在骨缺损区,术后8周整个缺损区均可见骨痂生成,成骨现象更加明显,部分髓腔已通,术后12~16周,缺损区已完全被新生骨组织充填,骨髓腔已完全再通,修复区较正常桡骨细,骨缺损修复效果明显优于对照组与空白对照组(P < 0.01)。说明自体骨髓基质细胞与β-磷酸三钙/聚磷酸钙纤维/聚左旋乳酸复合移植可较完全修复大节段骨缺损。     

新型硼酸盐生物玻璃修复节段性骨缺损

背景：硼酸盐生物玻璃是一种新型骨替代材料,体外实验显示具有良好的生物降解性能以及生物活性。 目的:体内实验评价新型硼酸盐生物玻璃材料修复节段性骨缺损的成骨作用。 设计、时间及地点：随机对照动物实验,于2008-04/10在上海市第六人民医院动物中心实验室完成。 材料：实验所用D-Alk-1B玻璃按泡沫浸渍法加工成多孔支架。β-磷酸三钙材料由上海贝奥路生物材料有限公司提供。 方法：36只新西兰大白兔随机分为D-Alk-1B组、D-Alk-1B+富血小板血浆组、β-磷酸三钙组、空白对照组,每组9 只。双侧桡骨中段制成15 mm 节段性骨缺损,分别植入D-Alk-1B材料、D-Alk-1B材料+富血小板血浆、β-磷酸三钙材料。空白对照组不进行任何处理。 主要观察指标：于术后4,8,12周取材,通过X 射线摄片和病理组织切片检测,评价新型硼酸盐生物玻璃的成骨作用。 结果：D-Alk-1B组材料植入体内4周时材料密度较宿主骨密度高,和宿主骨分界清楚;可见骨痂生长,材料两端和骨结合。8 周时由于材料降解密度降低,材料两端和骨基本融合。12周时骨塑形基本完成。D-Alk-1B +富血小板血浆组和D-Alk-1B组有相似的表现,材料周围骨痂生长较D-Alk-1B组明显,成骨表现比单纯D-Alk-1B材料好。β-磷酸三钙组骨痂生长较慢,材料降解比较慢。空白对照组骨缺损处从两个断端和尺侧生长骨痂,至12周有硬化表现,断端缺损仍然很明显。 结论：新型硼酸盐生物玻璃材料具有很好的成骨作用,和富血小板血浆结合有协同作用。与β-磷酸三钙相比,可控降解性的优点明显。     

生物衍生骨与骨髓间充质干细胞复合修复兔桡骨大段缺损

背景：生物衍生支架材料具备与自身骨相似的结构和微环境,具有较好的应用前景。 目的：探讨生物衍生骨复合成骨诱导的骨髓间充质干细胞修复兔桡骨的节段性骨缺损的可行性,并与单纯生物衍生骨进行比较。 设计、时间及地点：随机对照动物实验,于2007-01/2008-01在南华大学生命科学院实验室完成。 材料：同种异体骨经脱脂、脱蛋白、部分脱钙和冻干等方法处理后制备生物衍生骨支架材料,与自体骨髓间充质干细胞复合制备组织工程骨支架材料。 方法：25只健康成年新西兰大白兔双侧桡骨制备中段15 mm的骨缺损,随机取其中20只兔右侧桡骨为实验组植入组织工程骨,左侧为对照组植入单纯生物衍生骨,不做内外固定;另5只兔双侧骨缺损处不植入任何材料作为空白组。 主要观察指标：应用X射线放射学检查及组织学观察比较3组骨缺损修复的能力。 结果：X射线显示随时间延长骨折处骨痂逐渐增多, 实验组8周基本愈合,12周塑形完成;对照组骨痂少,愈合时间推迟;空白组术后12周骨缺损未见骨性修复,最后形成骨不连。术后2,4,8,12周实验组放射学检查评价新骨生成优于对照组 (P < 0.05)。组织学检查显示实验组术后4周时材料开始吸收,8周基本降解吸收被新生骨取代,12周完全修复;对照组明显推迟,新骨生成速度、生成量低于实验组(P < 0.05);空白组各时点均无新骨形成,最后缺损由纤维组织充填。 结论：成骨诱导的间充质干细胞／生物衍生骨复合构建组织工程化骨植入修复兔桡骨缺损能够加速新骨形成,其修复能力明显优于单纯生物衍生骨。     

双相陶瓷样生物骨修复骨缺损

背景：已有研究表明课题组制备的双相陶瓷样生物骨符合骨组织工程支架或直接作为植骨材料的要求。实验将材料植入兔桡骨节段性骨缺损，以进一步了解双相陶瓷样生物骨修复骨缺损的能力。 目的：用双相陶瓷样生物骨来修复兔桡骨骨缺损，评价双相陶瓷样生物骨的成骨作用。 设计、时间及地点：随机对照动物实验，于2008-03/09在昆明医学院动物实验中心完成。 材料：将猪椎骨煮沸12 h，经系列乙醇脱水后于800 ℃条件下煅烧6 h后制得陶瓷化骨，完全去除有机成分，再将陶瓷化骨与适当浓度的焦磷酸钠溶液复合后于800 ℃煅烧1 h，经缓慢冷却后制得双相陶瓷样生物骨。 方法：成年日本大耳白兔36只随机分为3组：双相陶瓷样生物骨组、自体髂骨组、空白对照组，每组12只。在兔双侧桡骨造成1.0 cm骨缺损后分别植入双相陶瓷样生物骨材料、自体髂骨，空白对照组不做任何处理直接缝合切口。 主要观察指标：术后4，8，12，24周取出双侧尺、桡骨后摄X射线片，了解移植物的X射线变化情况。制备组织切片，光镜下观察移植物的组织形态特征及新骨形成情况。 结果：X射线片：双相陶瓷样生物骨组在术后4周可见材料密度较宿主骨高，与宿主骨分界清楚，8周后材料与宿主骨分界模糊，12周后大部分材料呈高密度影，24周后材料仍有部分高密度影。自体髂骨组在术后4周可见髂骨与宿主骨分界模糊，24周后植骨部位密度与宿主骨一致。组织学形态观察：双相陶瓷样生物骨组发现有新骨贴附材料生长，材料随着时间的推移逐渐降解吸收，新骨形成增多。24周后新骨形成明显增多，仍可见部分残余材料；自体髂骨组在12周后髓腔完全再通，24周后植骨部位与宿主骨结构没有差别；空白对照组未见骨连接或髓腔再通，随着时间的推移缺损两端逐渐封闭并硬化。 结论：实验初步表明双相陶瓷样生物骨可用于桡骨骨缺损的修复。     

58S 生物玻璃/壳聚糖复合多孔支架材料的制备

背景：在前期研究的基础上用壳聚糖溶液与纯的58S生物玻璃支架进行复合,通过体外测试考察其生物活性,以确定是否符合组织工程对支架材料的要求。 目的：观察58S 生物玻璃/壳聚糖复合多孔支架的生物矿化特性及其与鼠骨髓间充质干细胞之间的体外相容性。 设计、时间及地点：观察性实验,于2008-03/10 在华南理工大学材料科学与工程学院生物材料研究所完成。 材料：选用58S 生物活性玻璃粉体为原料,利用预先处理过的聚氨酯泡沫作为模板,通过浸渍法制备58S 生物玻璃支架基体,与壳聚糖复合后制成生物玻璃/壳聚糖复合支架。 方法：①将试样放置于37 ℃恒温静态的100 mL模拟生理溶液中,分别浸泡1,3,7,15 d后取出样品,测试备用。②将第6代的小鼠骨髓间充质干细胞悬液以2×105/每个材料的密度接种到12 孔培养板中的支架材料上复合培养。 主要观察指标：采用X 射线衍射分析和红外光谱分析方法对支架矿化不同时间表面生成的矿物进行分析和表征;利用扫描电子显微镜观察支架表面矿物生成情况和小鼠骨髓间充质干细胞在多孔支架材料上的生长情况。 结果：①X 射线衍射分析结果显示支架在模拟生理溶液中矿化7 d后即出现标志羟基磷灰石形成的弱衍射峰,矿化15 d后这些衍射峰变得更强,说明材料表面形成了低结晶度的羟基磷灰石。②红外光谱分析测试结果显示支架在矿化7 d后即出现了标志羟基磷灰石形成的特征峰。③扫描电镜观察支架表面在矿化1 d后有颗粒状的矿物生成,矿化15 d后所形成的矿物成绒毛状,几乎覆盖整个支架表面。④小鼠骨髓间充质干细胞在支架材料上培养5 d后黏附生长良好,进一步表明此支架材料具有较高的生物矿化特性和细胞相容性。 结论：制备的58S/壳聚糖复合生物玻璃多孔支架具有较高的生物活性、与鼠骨髓间充质干细胞相容性良好。     

以部分脱钙冻干骨材料为支架组织工程骨移植早期兔外周血T淋巴细胞亚群的变化

背景：骨衍生材料中冻干骨异抗原去除不充分，免疫原性强烈；脱蛋白骨和完全脱钙骨基质抗原性较弱，但前者无成骨诱导能力，后者生物力学性能很差，临床应用受到限制。 目的：观察以部分脱钙冻干骨材料为支架的组织工程骨移植后兔外周血T细胞亚群的变化及移植组织的组织学变化。 设计、时间及地点：随机分组设计、动物对照观察，于2006-06/2007-06在四川大学华西医院，生物治疗国家重点实验室与干细胞与组织工程研究室完成。 材料：组织工程骨以兔骨膜来源的成骨细胞为种子细胞，经抗原自消化、部分脱钙、冻干后的异体骨为支架材料于体外构建。 方法：将48只兔按随机数字表法分为4组，每组12只。分别用部分脱钙冻干骨、组织工程骨、自体骨、同种异体骨植入兔桡骨1 cm节段性缺损处。 主要观察指标：流式细胞仪检测4组植入前及植入后1，2，4周移植早期外周血Ｔ淋巴细胞亚群变化，并通过组织学检测观察植入后2，4，8，12周时4种材料的成骨作用。 结果：①部分脱钙冻干骨组、组织工程骨组植入后1，2周外周血CD4+和CD8+ T细胞较植入前明显升高(P < 0.05)。植入后4周CD4+ T细胞较植入前偏高不显著(P > 0.05)。自体骨组植入后CD4+和CD8+ T细胞升高不明显(P > 0.05)。同种异体骨组植入后1，2，4周外周血CD4+和CD8+ T细胞较植入前及其他各组同期均明显增高(P < 0.05)。②组织工程骨组植入后2周与材料孔隙内有成骨细胞和成软骨细胞，可见骨及软骨混合性新生物形成，周边分布有破骨细胞，部分网架呈蚕食状被破坏吸收。植入后4周，形成的新生骨过渡为编织骨。植入后8周，形成板层骨，部分脱钙冻干骨支架材料已被完全降解﹑吸收。植入后12周，植入物均已完全被板层样骨所替代，髓腔再通。 结论：部分脱钙冻干骨为支架材料构建的细胞-材料复合体移植后外周血T淋巴细胞增高，但不影响其良好的修复骨缺损能力。     

400001/纳米羟基磷灰石纤维蛋白凝胶/重组人成骨蛋白-1复合人工骨的实验研究（加急11月）

目的：纳米级的羟基磷灰石纤维蛋白凝胶材料与人体内组织成分更为相似,具有更佳的生物性能。探讨纳米羟基磷灰石纤维蛋白凝胶/重组人成骨蛋白-1复合人工骨（Nano-Hydroxyapatite /Fibrin glue / Recombination Human Osteogenic protein-1,Nano-HA/FG/ rhOP-1）的骨缺损修复能力,为应用于临床骨缺损修复提供依据。 方法：实验于2008年10到2009年10月在深圳市第二人民医院组织工程实验室完成。①实验材料:：多孔纳米羟基磷灰石人工骨/纤维蛋白凝胶,重组人成骨蛋白-1。②实验动物:雄性新西兰大白兔45只,随机分为植入Nano-HA/FG/ rhOP-1复合材料组、植入Nano-HA/FG材料组、空白对照组,每组15只。实验过程中对动物处置符合动物伦理学要求。③实验方法:制备双侧桡骨骨缺损动物模型,然后用2种人工骨材料植入骨缺损处进行修复,空白对照组不植入任何材料。④实验评估:术后4,8和12周分别行大体标本观察、X线、扫描电镜（SEM）、放射性核素骨扫描（ECT）及生物力学测试,比较各组材料修复骨缺损的能力。 结果 实验动物均进入结果分析。 ①X射线片检查结果:术后4周、8周、12周,植入Nano-HA/FG/ rhOP-1复合材料组X射线评分高于植入Nano-HA/FG材料组,差异有显著性意义(P<0.05)。②扫描电镜观察结果:植入Nano-HA/FG/ rhOP-1复合材料组成骨效果明显优于植入Nano-HA/FG组和空白对照组。③放射性核素骨扫描( ECT)检测结果：术后4周、8周、12周,植入Nano-HA/FG/ rhOP-1复合材料组放射性聚集强度高于Nano-HA/FG材料组。④生物力学检测结果:术后4周、8周、12周,植入Nano-HA/FG/ rhOP-1复合材料组生物力学强度高于Nano-HA/FG材料组,差异有显著性意义(P<0.05)。 结论 Nano-HA/FG/ rhOP-1复合材料组具有良好的骨缺损修复能力,可望成为一种理想的骨缺损修复材料。     

猪松质骨支架/骨髓基质干细胞复合体兔体内成骨☆

目的：生物衍生骨具有天然骨组织的三维立体孔隙-网架结构，有利于种子细胞的黏附、增殖。观察猪松质骨支架/骨髓基质干细胞复合体在兔体内成骨及支架的降解。 方法：实验于2005-03/2006-12在中南大学湘雅医院中心实验室完成。选择健康家兔16只，3月龄左右，其中1只提供骨髓，另15只作组织工程骨植入，分4，8，12周3个时间点，每个时间点5只。采用Ficoll密度梯度离心法得到兔骨髓基质干细胞并诱导培养；采用物理化学方法对猪松质骨进行处理得到猪松质骨支架，与经诱导培养的骨髓基质干细胞体外复合培养后植入机体内，同时植入单纯猪松质骨支架做自身对照。 结果：纳入动物15只，均进入结果分析。采用X射线、苏木精-伊红染色、Masson三色染色及图像分析观察猪松质骨支架/骨髓基质干细胞复合体在兔体内成骨及支架的降解。①X射线观察：猪松质骨支架/骨髓基质干细胞复合体移植术后4周移植区周围可见少量散在分布的中密度影，8，12周时中高密度影逐渐向中心区增大。单纯猪松质骨支架移植术后各时间点移植区内均呈低密度影。②组织学观察：猪松质骨支架/骨髓基质干细胞复合体植入后4周开始有新骨生成，支架开始降解；8周时新骨的形成及支架的降解都明显增加；12周时新骨继续增加，逐渐向成熟骨组织转变，可见少量哈佛系统，但骨小梁尚不典型，毛细血管增生明显，少量支架残留，未见炎症细胞。单纯猪松质骨支架植入后各时间点无新骨形成。③图像分析表明：猪松质骨支架/骨髓基质干细胞复合体植入后新骨组织随时间延长而增加，而材料组织随时间延长而减少，但新生骨组织增加与支架材料组织减少无明显直线相关（P > 0.05）。 结论：猪松质骨支架与骨髓基质干细胞复合移植后新骨逐渐形成，支架逐渐降解，是一种较理想的骨组织工程支架材料。     

纳米羟基磷灰石-聚羟基丁酸戊酯/聚乙二醇人工骨对骨缺损修复的作用*

背景：为改善羟基磷灰石强度低、韧性差的缺点，尝试将具有良好机械性能的聚羟基丁酸戊酯和高亲水性材料聚乙二醇与之共混制备复合材料。 目的：评价纳米羟基磷灰石-聚羟基丁酸戊酯/聚乙二醇（Nano-HA-PHBV/PEG）人工骨对骨缺损的修复作用，并与单纯纳米羟基磷灰石人工骨相比较。 设计、时间及地点：对比分析，体内动物实验，于2007-06/2008-05在南方医科大学珠江医院中心实验室及生物力学实验室完成。 材料：自制纳米羟基磷灰石人工骨和Nano-HA-PHBV/PEG人工骨。 方法：将30只新西兰兔双侧桡骨中段制成15 mm节段性骨缺损，左侧植入Nano-HA-PHBV/PEG人工骨为实验组，右侧植入纳米羟基磷灰石人工骨为对照组。 主要观察指标：X射线片观察骨缺损修复及材料降解情况；术后2，4，8，16，24周分别处死6只兔子取材，用骨密度测量仪测量缺损修复区骨密度；术后4，8，16，24周在骨密度测试结束后切取完整桡骨标本，行三点抗弯试验测量弯曲强度。 结果：X射线显示4周后两组骨缺损处植入材料均有不同程度的降解，骨缺损处均有新骨形成；实验组新骨密度在材料植入8周后开始高于对照组(P < 0.05)；16，24周时实验组桡骨弯曲强度高于对照组(P < 0.05)。 结论：Nano-HA-PHBV/PEG人工骨具有良好的成骨能力和生物相容性，其成骨能力优于单纯纳米羟基磷灰石人工骨。     

Tongue/palate contact for the production of /s/ and /z/

Productions of /s/ and /z/ by ten adult speakers were investigated using the electropalatograph (EPG). The participants, ten speech researchers who spoke English as their first language, recorded productions of /s/ and /z/ in nonsense and real words. The maximum contact frame was used as the point of reference to compare tongue/palate contact for each production. Each speaker had alveolar contact, lateral bracing and most had a midline groove for both /s/ and /z/; however, the array of contacted electrodes was unique for each speaker. The groove widths and lengths ranged from 0–3 electrodes. There was significantly greater alveolar tongue/palate contact for /z/ compared to /s/ in word‐initial position, but not in word‐final position for the following measures: alveolar palatal contact, medial groove width, medial groove length. However, when measures of total palate contact and centre of gravity were considered, there was a complex interaction between the phonemes /s/ and /z/, coarticulation with the vowel, word position, and word context (real and nonsense words).     

Electropalatographic specification of Croatian fricatives /s/ and /z/

Electropalatographic specification of alveolar fricatives in Croatian is aimed at providing speech therapists with normative data about the range of acceptable productions of /s/ and /z/ in adult speakers of Croatian. Four variables were analysed: place of articulation, total contact, groove width and hold phase duration. Intra- and inter-speaker variability for each variable was analysed. Lingual palatal cues for voicing difference were also quantified and discussed. Results show that Croatian /s/ and /z/ are alveolar and not dental as previously reported. The comparison between the voiced and the voiceless fricative shows that durational measures provide the best differentiation. The voiceless counterpart is significantly longer. The difference between voiced and voiceless is also found in the total contact, with /z/ having more contact in the anterior four rows of electrodes, while /s/ has more contact in the posterior four rows of electrodes. This difference is also reflected in the anterior and the posterior groove widths. Possibilities of using these results as normative data for the diagnosis and treatment of atypical articulation of /s/ and /z/ are discussed.     

Tongue/palate contact for the production of /s/ and /z/

Productions of /s/ and /z/ by ten adult speakers were investigated using the electropalatograph (EPG). The participants, ten speech researchers who spoke English as their first language, recorded productions of /s/ and /z/ in nonsense and real words. The maximum contact frame was used as the point of reference to compare tongue/palate contact for each production. Each speaker had alveolar contact, lateral bracing and most had a midline groove for both /s/ and /z/; however, the array of contacted electrodes was unique for each speaker. The groove widths and lengths ranged from 0-3 electrodes. There was significantly greater alveolar tongue/palate contact for /z/ compared to /s/ in word-initial position, but not in word-final position for the following measures: alveolar palatal contact, medial groove width, medial groove length. However, when measures of total palate contact and centre of gravity were considered, there was a complex interaction between the phonemes /s/ and /z/, coarticulation with the vowel, word position, and word context (real and nonsense words).     

A comparative study of contractile responses in diaphragm muscles of normal and dystrophic (C57BL6Jdy2Jdy2J) mice

Potassium and caffeine contractures of isolated small bundles (100 to 200 μm diameter) of muscle fibers isolated from the diaphragm of normal and dystrophic ($\text{C57BL}\text{6J}\text{dy}{}^{\mathrm{2J}}\text{dy}{}^{\mathrm{2J}}$) mice were compared. In diaphragms of pathologic mice (3 to 5 months old) the resting potential, the characteristics of the twitch, and some histological examinations were typical of dystrophic muscles. The slopes of the relationships between the steady membrane potential and log [K]₀ were similar for the two types of cells. In 110 mM and 146 mM K there were no significant differences in the time course of the contractures and reduction in [Ca]₀ decreased the time to peak and the time constant of relaxation to the same extent; the relative efficiency of [Mg]₀ compared with [Ca]₀ was equivalent. Repriming of K contractures at different external calcium concentrations indicated that the normal diaphragm did not have any special advantage. The exposure of isolated strips to a solution containing caffeine resulted in a similar increase of the strength of the regularly evoked twitch responses. However, the contractures elicited by 1.25 to 20 mM caffeine showed a subsensitivity of the dystrophic diaphragm (K_mDys = 9.3 K_mN) and the rate of relaxation was significantly slower than in normal muscle (in 20 mM caffeine, 50% decay time for normal muscle was 25.2 ± 7.6 s and for dystrophic muscle 54.8 ± 11.2 s. THese results suggest an absence of major alterations in the mechanism of excitation-contraction coupling associated with dystrophy, except for a change in the specific element of the sarcoplasmic reticulum where caffeine acts.     

Pharmacology of vertigo/nystagmus/oscillopsia

PURPOSE OF REVIEW: To describe recent developments in the pharmacological treatment of vertigo and nystagmus while focusing on vestibular neuritis, Meniere's disease, downbeat nystagmus, periodic alternating nystagmus, acquired pendular nystagmus, and superior oblique myokymia. RECENT FINDINGS: In the last 2 years several studies have been published on possible pharmacological treatment options for nystagmus and oscillopsia. In the treatment of vestibular neuritis two studies showed that cortisone treatment was effective for restoring labyrinthine function. This benefit seems more likely if treatment is started within the first 2 days of onset. For recurrent vertigo attacks due to Meniere's disease, the titration technique with daily or weekly doses of intratympanic gentamicin until onset of vestibular symptoms, change in vertigo or hearing loss rated best for complete vertigo control. A new pharmacological treatment option for downbeat nystagmus is the administration of potassium channel blockers (e.g. 4-aminopyridine). They are thought to reinforce the inhibitory action of cerebellar Purkinje cells. Several case reports have proven the beneficial effect of baclofen on periodic alternating nystagmus, of gabapentin and memantine on acquired pendular nystagmus, and of carbamazepine and gabapentin on superior oblique myokymia. SUMMARY: There have been several new developments in the treatment of nystagmus and vertigo over the last 2 years. These include potassium channel blockers for the treatment of downbeat nystagmus, early cortisone treatment to improve recovery of the labyrinth function in vestibular neuritis, and intratympanic gentamicin treatment for Meniere's disease. Other pharmacological treatment options are baclofen for periodic alternating nystagmus, gabapentin and memantine for acquired pendular nystagmus, and carbamazepine for superior oblique myokymia.     

Rate and extent of functional reinnervation in fast-twitch and slow-twitch muscles of the dystrophic mouse (C57Bl6Jdy2jdy2j)

The extent of functional reinnervation of fast-twitch extensor digitorum longus muscle in dystrophic and normal mice was determined at various times after nerve transection. Functional reinnervation was assessed by measuring the twitch tension evoked by stimulation of the nerve central to the site of transection. In control mice aged 4 to 6 weeks at the time of denervation, complete reinnervation was observed after 6 weeks. In dystrophic mice of the same age reinnervation was clearly impaired. The ratio of functional innervation of the operated leg to that of the contralateral unoperated leg was only 0.62 after 6 weeks. In older dystrophic mice (4 to 6 months at the time of nerve transection) the reinnervation ratio was even lower, 0.43 after 12 weeks. Reinnervation of slow-twitch soleus muscle was assessed 8 weeks after denervation and was also found to be reduced in the older dystrophic animals. The extent of reinnervation was reflected in the measured values of muscle weight, twitch tension per unit wet weight, and twitch time course. The impairment of reinnervation of dystrophic muscle is consistent with, but not proof of, a neurogenic defect in murine muscular dystrophy.     

Statistical analysis of word-initial /k/ and /t/ produced by normal and phonologically disordered children

The acoustic characteristics of voiceless velar and alveolar stop consonants were investigated for normally articulating and phonologically disordered children using spectral moments. All the disordered children were perceived to produce /t/ for /k/, with /k/ being absent from their phonetic inventories. Approximately 82% of the normally articulating children's consonants were classified correctly by discriminant function analysis, on the basis of the mean (first moment), skewness (third moment) and kurtosis (fourth moment) derived from the first 40 ms of the VOT interval. When the discriminant function developed for the normally articulating children was applied to the speech of the phonologically disordered group of children, no distinction was made between the velar and alveolar stops. Application of the model to the speech of individual children in the disordered group revealed that one child produced distinct markings to the velar-alveolar contrast. Variability measures of target /t/ and /k/ utterances indicated greater variability in this disordered child's productions compared with the normally articulating children. Phonological analysis of this child's speech after treatment, in which the velar-alveolar contrast was not treated, revealed target appropriate productions of both /t/ and /k/. By contrast, the other three phonologically disordered children, for whom no acoustic distinction was found between target /t/ and target /k/, did not evidence any knowledge of the contrast after treatment with other target phonemes.