X射线照射诱导鼻咽癌细胞mdrl和p53基因的表达及临床意义

目的:探讨X射线照射后鼻咽癌CNE-1细胞产生多药耐药的机制。方法:采用RT-PCR和Westernblot方法,检测X射线照射后CNE-1细胞mdr1和p53基因的表达。结果:照射后细胞mdrlmRNA和P-gp表达均增强,p53蛋白的表达也增强,并与P-gp表达呈正相关性(P<0.05)。结论:X射线照射可诱导CNE-1细胞mdr1和p53基因的表达,两者的相互协调作用可能是照射后肿瘤细胞产生多药耐药的重要机制之一。     

胸骨前钢架内固定治疗漏斗胸

目的 介绍肋软骨链甲式切断，胸骨前置钢架抬举胸骨术治疗漏斗胸的方法及经验与体会。方法 自行设计制作钢架，用肋软骨链甲式切断，胸骨前置钢架抬举胸骨术治疗漏斗胸58例。结果 本术式具有手术损伤小，恢复时间快，无并发症，术后经过6个月～10年的随访疗效满意。结论 本术式对先天性漏斗胸是一种好的手术方法，特别适应小儿的生理解剖特性。     

Vestibular destruction by slow infusion of gentamicin into semicircular canals

Intratympanic or round window application of gentamicin is often used to alleviate disabling vertigo arising from unilateral Meniere's disease; however, treatment is often accompanied by hearing loss because the drug initially enters the cochlea before diffusing to the vestibular system. In order to enhance vestibular damage and reduce the risk of hearing loss, gentamicin was infused directly into the vestibular system. An osmotic pump containing 50, 100, 200 or 400 microg/ml of gentamicin was infused into the superior semicircular canal of the chinchilla for 7 days. Afterwards, vestibular damage was evaluated by measuring the decline in hair cell density in the utricle, saccule and superior semicircular canals. Auditory damage was assessed with distortion product otoacoustic emissions (DPOAE) and outer hair cell (OHC) and inner hair cell (IHC) loss. Infusion with the two lowest gentamicin concentrations resulted in significant hair cell loss and reduced duration of the nystagmus response, but had little or no effect on OHC or DPOAE. Higher doses of gentamicin damaged cochlear hair cells and reduced the DPOAE. In conclusion, slow infusion of a low dose of gentamicin into the semicircular canals mainly damages the vestibular hair cells and inactivates the nystagmus response without damaging cochlear hair cells or DPOAE.     

Time course of efferent fiber and spiral ganglion cell degeneration following complete hair cell loss in the chinchilla

Ethacrynic acid (EA) is known to interact with aminoglycoside antibiotics such as gentamicin (GM). In the chinchilla, co-administration of GM and EA can produce hair cell lesions ranging from a small loss of outer hair cells (OHCs) in the base of the cochlea to complete destruction of all hair cells, depending on dosing parameters. Although hair cell loss has been characterized, little is known about the fate of efferent fibers or spiral ganglion neurons (SGNs) in this model. To study the time course of efferent fiber and SGN loss, chinchillas were injected with GM (125 mg/kg IM) followed immediately by EA (40 mg/kg IV). Estimates of efferent fiber loss and density changes were made after 3 days or 1, 2, 3, or 4 weeks of survival. Estimates of SGN loss and density changes were made after 15 days or 1, 2, 4, or 6 months of survival. Cochlear function was rapidly abolished and all cochlear hair cells were missing within 24 h after treatment. Inner hair cells (IHCs) in the middle turn of the cochlea died earlier than cells in the apex or base, and OHCs in Rows 1 and 2 died earlier than OHCs in Row 3. Degeneration of efferent nerve fibers began 3-7 days post-injection, versus 15-30 days for SGNs, and the loss of efferent fibers was essentially complete within 1 month, versus 2-4 months for SGNs. The rapid time course of efferent fiber and SGN loss in the chinchilla may make it a practical model for studying mechanisms of neural loss and survival in the mammalian inner ear.     

Chinchilla models of selective cochlear hair cell loss

Although it is well known that ethacrynic acid (EA) can enhance gentamicin (GM) ototoxicity, there has been no systematic study of the relationship between dosing parameters and inner ear pathology. We examined the effects of two parameters, GM dose and time delay between GM and EA administration, on cochlear and vestibular hair cell loss in chinchillas. 'No delay' groups received one injection of GM (125, 40, 20, or 10 mg/kg i.m.) followed immediately by EA (40 mg/kg i.v.); 'delay' groups received GM (10 mg/kg i.m.) followed by EA 1 or 1.5 h later. Animals were sacrificed 7 days later for evaluation of hair cell loss in the cochlea and vestibular end organs (cristae, saccule and utricle). Vestibular function was assessed prior to sacrifice by measuring the duration of nystagmus induced by cold caloric stimulation. No delay groups had approximately 100% loss of outer hair cells and dose-dependent losses of inner hair cells, ranging from approximately 100% to 58%. In 1 and 1.5 h delay groups, inner hair cell losses were approximately 19% and 0%, outer hair cell losses were approximately 74% and 47%, and outer hair cell loss followed a typical base to apex gradient. Two results were remarkable. First, the three groups with partial inner hair cell loss showed an atypical lesion pattern in which losses were substantially greater in the apical half than in the basal half of the cochlea. Second, there was no vestibular pathology in any group. The results establish dosing parameters that can be used to produce animal models with defined patterns and magnitudes of cochlear hair cell damage, but normal vestibular function and morphology.     

M40403, a superoxide dismutase mimetic,protects cochlear hair cells from gentamicin,but not cisplatin toxicity

Gentamicin, an aminoglycoside antibiotic, and cisplatin, a platinum-based anticancer drug, are two commonly used clinical drugs with ototoxic side effects. The ototoxicity of gentamicin and cisplatin has been linked to the production of reactive oxygen species (ROS), although the specific ROS pathways have not been identified. One ROS that might play a role in ototoxicity is the superoxide radical, which is enzymatically dismutated to molecular oxygen and hydrogen peroxide by endogenous superoxide dismutase (SOD) enzymes. M40403, a manganese-based nonpeptidyl molecule that mimics the activity of SOD, was tested for its ability to protect against gentamicin and cisplatin toxicity in cochlear organotypic cultures from neonatal C57BL/10J mice. Cultures were treated with gentamicin or cisplatin alone or in combination with M40403. M40403 alone had no effect on outer hair cell (OHC) or inner hair cell (IHC) survival at doses of 1, 5, and 10 microM, but a high dose of 30 microM reduced hair cell numbers by approximately 30%. Gentamicin alone and cisplatin alone killed OHCs and IHCs in a dose-dependent manner. The addition of M40403 to gentamicin-treated cultures significantly increased OHC and IHC survival in a dose-dependent manner, whereas M40403 failed to protect hair cells in cisplatin-treated cultures at any dose. The results suggest that the toxicity of gentamicin and cisplatin to cochlear hair cells are mediated by different pathways. Clinically, increased levels of SOD or SOD mimetics might provide significant protection against aminoglycoside ototoxicity.     

军事飞行员心理创伤后应激反应与心理干预效果

目的　研究心理治疗干预对飞行员群体心理创伤后应激障碍及应激反应的矫治效果 ,为航空卫生保障提供依据。　方法　采用飞行人员心理健康量表 (CHI)、症状自评量表 (SCL- 90 )和心理创伤后应激症状调查表 (PTSD问卷 )对在疗养前一个月发生机毁人亡一等飞行事故部队的 44名飞行员进行评定 ,在此基础上采用认知疗法、生物反馈疗法和咨询教育法进行心理治疗干预 ,并观察和对比疗效。　结果　干预组与对照组在躯体化 (3.42 0 )、焦虑 (2 .312 )、人际敏感 (3.42 9)、抑郁(2 .0 37)等情绪应激因子上有显著性差异 (P<0 .0 5 ) ;症状学调查发现 :干预组应激反应症状 ,以持续的警觉性增加为主 ,与对照组比有非常显著性差异 (t=3.5 3,P<0 .0 1) ;Ridit分析显示 :不同疗法的治疗效果不同 (R=16 .43,P<0 .0 1) ,其中以认知治疗组为最好 (R=0 .35 18)。　结论　飞行员心理创伤后应激反应 ,以持续警觉性增高的临床症状及负性情绪为主 ,并与应激者的人格特征有关。应激状态下心理干预应首选认知疗法。     

温针灸治疗糖尿病性膀胱病变43例临床观察

运用温针灸治疗糖尿病性膀胱病变 4 3例 ,设对照组 4 3例 ,共治疗 30天。分别于治疗前后观察每日排尿次数、每次尿量、B超膀胱残余尿量。观察结果表明温针灸疗法能够减少每日排尿次数 ,提高每次尿量 ,减少B超膀胱残余尿量 ,同治疗前相比差异显著 (P >0 .0 5 )。     

Calpain在噪声损害毛细胞中的角色

目的：了解Calpain在噪声损害耳蜗毛细胞中所扮演的角色。方法观察Calpain免疫细胞化学反应产物在噪声损害中的变化。结果正常对照耳蜗样品中未见Calpain活性显示,但噪声损害耳蜗样品中可见外毛细胞底部及其神经末梢区域出现大量的Calpain。结论噪声引起的耳蜗毛细胞破坏可能与Calpain的激活及其降解功能有关。