CFTR基因在先天性双侧输精管缺如中的研究进展北大核心CSCD

先天性双侧输精管缺如(congenital bilateral absence of the vas deferens,CBAVD)目前认为主要由囊性纤维化跨膜转导子(cystic fibrosis transmembrane conductance regulator,CFTR)基因变异导致,在欧美国家CFTR基因变异检测已经用于胚胎植入前遗传学诊断,以避免子代发生CBAVD或携带CFTR变异基因。但是该基因变异类型繁多,与种族密切相关,差异巨大。现将CFTR基因在CBAVD中的研究进展综述如下。     

CFTR在生殖系统中的作用及其机制

囊性纤维化跨膜传导调节因子(CFTR)是一种cAMP依赖的氯离子通道蛋白,广泛表达于各组织的上皮细胞,介导离子和水分在上皮细胞的分泌和转运.CFTR基因突变会导致囊性纤维症的发生,对生殖的影响主要表现在男性先天性输精管缺如和精子发生缺陷,女性囊性纤维症患者的生育能力下降.CFTR在雌性和雄性生殖道的上皮细胞广泛表达,并...     

先天性输精管缺如性无精子症患者诊治分析

目的 分析与诊断先天性输精管缺如性无精子症,经附睾穿刺取精后行ICSI助育,探讨其助育结果.方法 结合查体,精液检查,超声检查,内分泌检查,精浆生化,必要时输精管造影.确诊为先天性双侧输精管缺如患者57例行附睾穿刺,倒置显微镜下观察发现有活动精子者行ICSI助育.结果 在双方完善相关检查后行ICSI助育,57例患者有30例于新鲜周期妻子妊娠(妊娠率52.63%),15例冷冻周期妻子妊娠,9例冷冻周期失败,行第2周期治疗,6例妊娠,3例失败,3例无冷冻胚胎,拟第3次治疗.结论 先天性双侧输精管缺如是由于CFTR基因突变所致的发育畸形,正确的临床诊断和采取合理的辅助生殖技术是目前该类患者治疗的较好方案.     

先天性双侧输精管缺如伴生精功能障碍一例

先天性双侧输精管缺如（congenital bilateral absence of vas deferens,CBAVD）是梗阻性无精子症的常见原因之一,睾丸生精功能一般正常,除了常见的囊性纤维化穿膜传导调节蛋白（cystic fibrosis transmembrane conductance regulator,CFTR）基因突变外,黏附G蛋白耦联受体G2（adhesion G protein-coupled receptor G2,ADGRG2）基因突变以及拷贝数变异也被认为是CBAVD的发病机制。本文报告1例CBAVD伴生精功能障碍的病例,睾丸组织病理学提示唯支持细胞综合征。全外显子组测序未发现该患者CFTR、ADGRG2以及无精子症相关基因存在致病变异,拷贝数变异分析也未发现有意义的拷贝数变异。该病例的确切遗传学病因尚未可知。CBAVD与生精功能障碍并存的临床现象,提示无精子症遗传病因的复杂性。     

肺囊性纤维化感染与细菌生物被膜的免疫逃逸

肺囊性纤维化 (cysticfibrosis,CF)为遗传性疾病 ,又名粘液物质阻塞症[1] 。主要表现为内、外分泌腺的功能紊乱 ,粘液腺增生 ,分泌液粘稠 ,汗液氯化钠含量增高 ,肺脏、气道、胰腺、肠道、胆道、输精管等的腺管被粘稠分泌物堵塞所引起的一系列症状 ,以肺部病症最为严重而多见。该病白种人发病率高 ,东方人及其他人种中罕见 ,婴幼儿期发病 ,主要发生于儿童 ,死亡率高。肺囊性纤维化内、外分泌腺功能障碍的发病机理还不十分清楚。但粘液分泌物中酸性蛋白含量较高 ,改变了粘液流变学的特性 ,可能是分泌物变粘稠的原因[2 ] 。发病粘稠分泌物堵塞…     

快速活化精子治疗先天性输精管缺如性不孕的临床研究

目的:探讨快速活化精子输精管缺如不孕的效果。方法:先天性输精管缺如患者20例在行手术诊治时,15例用自体睾丸精索鞘膜制成人工精池囊,5例在囊内放置用微涤纶制成的异质管。结果:术中抽吸10例附睾内精子快速活化,其中5例活化成功,行人工授精,2例怀孕,1例已生育一女孩。结论:不孕症是有生育可能的,但需要解决3个问题:①采用显微外科技术在附睾内取出一定数量的活精;②选配好快速活化剂使精子快速活动成功;③用患者的精浆培养自己的精子。建议对梗阻性无精症在手术疏通的同时,采用快速活化精子技术进行人工授精,以提高生育的效果。     

囊性纤维化跨膜转导调节因子基因多态性与男性先天性双侧输精管缺如的相关性研究

目的研究囊性纤维化转运调节因子(cystic fibrosis transmembrane conductance regulator,CFTR)基因多态性与男性先天性输精管缺如(congenital bilateral absence of vas deferens,CBAVD)的相关性。方法选择30例CBAVD患者和30例健康捐精者,提取其基因组DNA。CFTR基因的DNA片段采用PCR的方法进行扩增。多聚T(poly-T)TG、重复序列和M470V突变直接用自动测序仪进行测定。进行基因多态性分析。结果 CBAVD患者CFTR基因poly-T、TG重复有8种类型,健康捐精者有5种。CFTR基因poly-T、TG重复序列,M470V多态性单位点分析表明,3T、(TG)12、(TG)13差异有统计学意义,M470V等位基因分布频率差异无统计学意义(P0.05)。双位点联合分析,(TG)13T3差异有统计学意义(P0.05);三位点联合分析,T5-TG13-M差异有统计学意义(P0.05)。结论 CFTR单倍型3T,(TG)12、(TG)13(TG)13T3、T5-TG13-M与CBAVD有明显的相关性。     

ICSI治疗男性不育的有效性和安全性

胞浆内单精子注射技术(ICSI)是治疗多种原因所致男性不育的最有效手段,如部分无精症、严重少弱精症和中等程度少弱精症等。同时,ICSI技术存在一定的遗传学风险,为了减少这些风险,应进行严格的遗传学检测,主要有染色体核型分析、囊性纤维化病基因突变分析和Y染色体微缺失的分子检测等方面,再结合种植前遗传学检测和产前诊断,ICSI技术可以认为是安全的。     

胞浆内单精子注射技术的安全性

胞浆内单精子注射(ICSI)技术的安全性一直备受关注,可以概括为两个方面的问题:ICSI非操作技术相关性问题和ICSI操作技术相关性问题.前者包括使用遗传异常的精子,如染色体异常、囊性纤维化跨膜传导调节基因(CFTR)突变、Y染色体微缺失、雄激素受体(AR)基因三核苷酸重复等,和精子线粒体DNA(mtDNA)遗传;后者则主要指ICSI操作本身可能引起的机械和化学影响、外源性物质的导入及印迹基因的改变.针对这两方面的问题,应积极发展相关遗传学检测,规范ICSI操作及进行技术设备改良.     

ICSI治疗男性不育的有效性和安全性

胞浆内单精子注射技术(ICSI)是治疗多种原因所致男性不育的最有效手段,如部分无精症、严重少弱精症和中等程度少弱精症等.同时,ICSI技术存在一定的遗传学风险,为了减少这些风险,应进行严格的遗传学检测,主要有染色体核型分析、囊性纤维化病基因突变分析和Y染色体微缺失的分子检测等方面,再结合种植前遗传学检测和产前诊断,ICSI技术可以认为是安全的.     

Microbiologic data overview of Italian cystic fibrosis patients

The aim of our study was to determine the frequency of microbiological culturing and prevalence of colonization by principal pathogens of the respiratory tract of Italian cystic fibrosis patients. Data on all Italian cystic fibrosis patients were collected using a questionnaire sent to all Italian CF Centers. Results were obtained of microbiological cultures from 2,521 patients. Information was gained regarding the method of gathering biological samples, the percentage of patients undergoing microbiological culturing regularly, the procedures used to isolate bacteria and types of culture media used which were selective for Burkholderia cepacia. Ninety-four percent of Italian CF patients are regularly tested microbiologically. Sputum and pharyngeal cultures are most often carried out. 49% of Italian patients are colonized by Staphylococcus aureus, 5.4% by Haemophilus influenzae, 48.9% by Pseudomonas aeruginosa and 3.8% by Burkholderia cepacia. In Italy there is a high prevalence of CF patients colonized by Staphylococcus aureus and a low prevalence of patients colonized by Haemophilus influenzae. The prevalence of Burkholderia cepacia and Pseudomonas aeruginosa does not differ significantly from other countries examined.     

Cost-benefit analysis of a national screening programme for cystic fibrosis in an israeli population

The recently acquired ability to identify 97% of CF carriers in an Israeli Ashkenazi population, prompts an evaluation of a nationwide screening programme. In 1993, the programme would first screen and counsel 9,261 parents, then 396 spouses of carrier parents and finally screen 16.5 fetuses where both parents are carriers. Assuming 92% of screened parents choose abortion of fetus screened positive, 2.33 cases of CF will be prevented in 1993 at a direct cost of $781,000. The $326,000 direct costs of preventing a CF case, exceed the lifetime excess direct costs per case of $297,000. However, benefits of screening also accrue to subsequent pregnancies, resulting in a direct benefit ($14.45 million) to cost ($10.39 million) ratio of 1.39/1 for the period 1993–2032. When benefits and costs resulting from mortality changes, work absences and transport costs are included, the benefit ($15.95 million) to cost ($13.88 million) ratio falls to 1.15/1. Benefit-cost ratios are lower for other ethnic groups in Israel, due to lower carrier rates and lower mutation detection abilities. A CF screening programme will increase the freedom of individuals choice, but should be carried out carefully in order to minimize stigmatization and even discrimination against CF carriers.     

胰腺外分泌不足病人的胰酶替代治疗

胰酶主要用于胰腺外分泌功能不足的病人,如囊性纤维化、胰切除术后、全胃切除术后以及慢性胰腺炎.该文作者就胰酶的替代治疗作如下综述,主要包括胰腺外分泌功能的评估,胰腺外分泌不足的发病机制,胰酶制剂的多种形式及其疗效,胰酶使用的剂量,肠内营养与胰酶替代治疗的关系以及使用胰酶的不良反应等.     

Transition program from pediatric to adult care for Cystic Fibrosis patients

A survey of adolescents and young adults with cystic fibrosis (CF) attending an adult CF center was conducted to evaluate a transition program as a means of transferring care from pediatric to adult setting. A total of 40 patients completed a self-administered questionnaire of whom 13 (32.5%) went through the transition program, and 21 (52.5%) received their care at the University of Michigan Cystic Fibrosis Center. Fourteen patients (35.0%) were cared for at other pediatric CF centers, and five (12.5%) were first diagnosed as adults. All those in the transition program approved of having the visit with the internal medicine physician in the pediatric clinic. Most thought that the transition program made the change from pediatric to adult care easier. All patients were comfortable leaving the pediatric clinic after the transition period. Of the 40 patients, 17 (42%) recommended that other patients go through the transition program, although 9 of these 17 patients did not themselves go through the transition program. Twenty-six patients (65%) preferred the adult program. These findings suggest that adolescents with CF should be encouraged to transfer their medical care to an adult CF Center once they have reached an agreedupon age. This process should be smooth and should occur as part of the regular CF care. This is possible through a well-structured and well-organized transition program with committed pediatric and adult staff.     

A Baffling Hyperpyrexia

Thanks to the medical revolutions of the past half century, we have attained a remarkable understanding of health and disease, of diagnosis and therapy. Future generations will undoubtedly be intensely interested in the men and women whose work produced these revolutions. The ability to record their thought processes through the techniques of “oral history” can provide invaluable insights. It is in this belief that HOSPITAL PRACTICE is presenting a series of interviews conducted by cardiologist Allen B. Weisse, Professor of Medicine at the University of Medicine and Dentistry of New Jersey-New Jersey Medical School. They were originally published in 1984 as Conversations in Medicine: The Story of Twentieth-Century American Medicine in the Words of Those Who Created It (New York University Press, Washington Square, New York). Following is the interview with surgeon Owen H. Wangensteen, conducted in the fall of 1980.     

The revised German Cystic Fibrosis Questionnaire: Validation of a disease-specific health-related quality of life instrument

Background: The assessment of health related quality of life (HRQOL) has increasingly been recognized as an important adjunct to medical outcome parameters in the monitoring of cystic fibrosis (CF) patients and in clinical studies. The Cystic Fibrosis Questionnaire (CFQ) is a disease-specific HRQOL instrument for CF patients developed in France. Translations are currently being validated in four different countries. The aim of the present study was to validate the German adaptation of the CFQ-14+. Method: On the basis of results from a first dataset (n = 197 CF adolescent and adult patients), revisions were made and retested in a second sample of 103 patients. Results: The final revised version showed good construct validity. The same nine HRQOL domains as in the French original CFQ-14+ emerged from the analyses as structurally robust scales. The internal consistencies of the HRQOL scales ranged from 0.71 to 0.94. The instrument's clinical validity was supported by severely ill patients reporting lower HRQOL than less severely ill patients on most scales. Conclusion: We conclude that the evidence supports the validity and reliability of the instrument. An important future area of application is the use in comparative multi-center international studies.     

Probiotics: A new way to fight bacterial pulmonary infections?

Antibiotics, of which Fleming has identified the first representative, penicillin, in 1928, allowed dramatical improvement of the treatment of patients presenting with infectious diseases. However, once an antibiotic is used, resistance may develop more or less rapidly in some bacteria. It is thus necessary to develop therapeutic alternatives, such as the use of probiotics, defined by the World Health Organization (WHO) as “micro-organisms which, administered live and in adequate amounts, confer a benefit to the health of the host”. The scope of these micro-organisms is broad, concerning many areas including that of infectious diseases, especially respiratory infections. We describe the rational use of probiotics in respiratory tract infections and detail the results of various clinical studies describing the use of probiotics in the management of respiratory infections such as nosocomial or community acquired pneumonia, or on specific grounds such as cystic fibrosis. The results are sometimes contradictory, but the therapeutic potential of probiotics seems promising. Implementing research to understand their mechanisms of action is critical to conduct therapeutic tests based on a specific rational for the strains to be used, the dose, as well as the chosen mode and rhythm of administration.     

CT诊断成年囊性纤维化非结核性分枝杆菌感染的临床研究

目的 分析高分辨CT对成年囊性纤维化非结核性分枝杆菌(NTM)感染的诊断价值,以提高成年囊性纤维化非结核性分枝杆菌感染的临床诊治水平.方法 对医院2009年1月-2012年12月收治的100例成年囊性纤维化NTM感染患者进行高分辨CT检查与X线检查,比较CT检查结果与X线结果的异同,评价高分辨CT对成年囊性纤维化NTM感染的诊断价值;87例免疫功能正常患者根据病变部位将其分为典型组46例与非典型组41例,两组患者除发热外其他临床表现差异均无统计学意义.结果 共调查3976例就诊患者,其中100例患者确诊为囊性纤维化NTM感染,感染率为2.52％;64例患者病变位于双侧肺部,73例位于右上叶,55例位于左上叶,36例位于右中叶,23例位于左舌叶,50例位于右下叶者,53例位于左下叶者;85例患者可见肺部空洞,内壁较粗糙,空洞直径为1～5 cm;部分患者可见肺气肿,纤维条索状阴影以及纵隔淋巴结肿大;54例患者出现肺部支气管扩张;CT比X线多检出13例,且空洞与结节检出数量多于X线平片;此外,CT还检出24例支气管扩张,19例树芽征.结论 在疑似肺结核或痰液分枝杆菌检查阳性的患者中,若长期给予抗结核治疗无效或出现反复发作应考虑肺结核分枝杆菌感染,对此类患者给予高分辨CT检查能显著提高非结核分枝杆菌感染的临床检出率,提高诊断准确性,对患者临床治疗具有重要的临床意义.