Atypical genital nevi. A clinicopathologic analysis of 56 cases

Atypical genital nevi are rare melanocytic lesions that most commonly arise on the vulva of young women. They are currently regarded as nevi of special sites, in that despite histologically worrisome features, their clinical behavior is reportedly benign. However, only few studies with limited follow-up data are available. To better characterize the clinical presentation and behavior of these lesions and to further delineate their histologic features, we retrieved 56 atypical genital nevi arising in the lower female genital tract from our departmental and consultation files. The 56 lesions arose in 55 female patients with a median age of 26 years (range, 6 to 54 y). The dominant histologic feature was a lentiginous and nested junctional component composed of prominent round or fusiform nests, which often showed retraction artifact and/or cellular dyscohesion. Cytologic atypia was mild in 11 cases (20%), moderate in 34 (60%), and severe in 11 (20%). Ten cases (18%) showed focal pagetoid spread, with extension to the granular layer and stratum corneum in 1 case. The atypical junctional melanocytic proliferation was associated with a large common dermal nevus component that dominated the lesion in 26 cases (46%). Adnexal spread (46%) and nuclear atypia of melanocytes situated in the superficial dermis (39%) were relatively common, but dermal mitoses (7%) were uncommon and maturation was present in all cases. A broad zone of dense eosinophilic fibrosis within the superficial dermis was a frequent finding (41%). Clinical follow-up was available in 45 cases (80%) with a median follow-up period of 3.5 years (range, 1 to 16 y). Only 1 lesion recurred, 1.5 years after the initial excision. The original nevus in this patient had only mild cytologic atypia and was present at the margins of excision. The recurrent/persistent nevus was reexcised, and there was no further clinical recurrence in 11.5 additional years of follow-up. Our data support the hypothesis that atypical genital nevi have a benign clinical course despite their occasionally striking cytologic and architectural atypia. Awareness and recognition of this group of melanocytic lesions is important to avoid over diagnosis as melanoma with subsequent wide excision and possibly sentinel lymph node biopsy.     

Comparative bioavailability study with two amiodarone tablet formulations administered with and without food in healthy subjects

OBJECTIVE: The aim was to assess the comparative bioavailability of two formulations (200 mg tablet) of amiodarone (CAS 19774-82-4) in healthy volunteers of both sexes, with and without food. METHODS: The study was conducted using an open, randomized, two-period crossover design with a 3-week washout interval, in two groups, with and without food. Plasma samples were obtained for up to 240 h post dose. Plasma amiodarone concentrations were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) with positive ion electrospray ionization using multiple reactions monitoring (MRM). From the amiodarone plasma concentration vs. time curves, the following pharmacokinetic parameters were obtained, with and without food: AUC(last), AUC(inf), AUC(0-240h), AUC(0-72h) and C(max). RESULTS: The limit of quantification was 1 ng/mL for plasma amiodarone analysis. The geometric mean and 90% confidence interval CI of Test/Reference percent ratios were, without and with food, respectively: 107.61 (92.73-124.89) and 100.6 (94.1-107.5) for C(max), 107.05 (95.88-119.51) and 100.2 (96.0-104.7) for AUC(last), 107.27 (95.78-120.15) and 100.8 (97.0-104.8) for AUC(0-72h), 106.76 (95.84-118.94) and 100.2 (96.0-104.7) for AUC(0-240h) and AUC(inf) 105.15 (94.18-117.41) and 100.7 (96.6-105.0). CONCLUSION: Since the 90% CI for AUC(0-72) and C(max) ratios were within the 80-125% interval proposed by the US FDA, it was concluded that the amiodarone 200 mg tablet (test formulation) with and without food was bioequivalent to the reference 200 mg tablet for both the rate and extent of absorption.     

脐血干细胞和胎盘间充质干细胞在妇产科应用中的前景

目的:介绍脐血干细胞和胎盘间充质干细胞的研究进展,以及干细胞在妇产科中的应用前景。资料来源:应用计算机检索Medline1996-01/2006-12与脐血干细胞和胎盘间充质干细胞、以及干细胞在妇产科中的应用相关的文章,检索词为“human cord blood,mesenchy malstem cell,placenta,gene therapy in the uterus”,限定文献语种为“English”;同时检索万方数据库2000-01/2006-12相关文章,检索词为“脐血,间充质干细胞,胎盘,宫内治疗,卵巢癌,子宫癌”,限定文献语种为中文。资料选择:共检索到相关文献500余条,进一步查找全文,优先选择与临床应用靠近的文章,无论观察对象是人还是动物均纳入,筛除干细胞的提取、分化或培养等基础类研究,明显重复和综述文献也排除,最后纳入31条文献进行综述。资料提炼:31条文献中论述脐血干细胞和胎盘间充质干细胞的特点及应用文章有26篇,关于宫内移植干细胞治疗的文章有2篇,其他为研究干细胞在妇产科中应用的文章。资料综合:①大量实验证明脐血是骨髓、外周血后的第3种非常有潜力的造血干细胞资源。目前应用脐血移植治疗的疾病有急(慢)性白血病、恶性淋巴瘤、多发性骨髓瘤、再生障碍性贫血、严重免疫缺陷症等,而且已经有一定疗效。②胎盘作为胚胎发育中维系母体和胎儿氧气及营养物质交换的重要暂时性器官,无论从解剖结构还是在发育行为上,都包含了较为幼稚的胚胎及趋于成熟的成体干细胞成分,而且胎盘不会涉及伦理道德问题,目前已成为寻找人类间充质干细胞新来源及提高临床应用效果的研究热点。③干细胞宫内移植为先天性疾病治疗开辟了一条新途径。另外干细胞在器官再造、男性不育治疗和保存生育能力等生殖医学领域的研究也取得了重大进展,在妇科肿瘤方面,如以化疗保护为目标的基因治疗已逐步应用于临床。结论:脐血和胎盘取材方便、安全,还能避免免疫排斥和伦理问题,已成为人类间充质干细胞新来源。干细胞在宫内治疗、生殖疾病和妇科肿瘤方面也有广泛的临床应用前景。     

人T-bet基因的体外扩增及克隆和鉴定

目的:克隆人T-bet基因,构建其真核表达载体pEGFP-C1-T-bet。方法:实验于2005-07/2006-07在北京大学深圳医院中心实验室完成。①根据Genebank的人T-bet基因的全长cDNA序列,设计合成一对附加BglⅡ和SalⅠ两个限制性内切酶酶切位点的特异性引物。②分离人外周血单个核细胞,提取RNA,用反转录-聚合酶链反应方法将T-bet的编码序列cDNA扩增,装入pMD18-T载体并送去测序。③BglⅡ SalⅠ双酶切质粒pMD18-T-bet,经琼脂糖电泳切胶回收T-bet片段,将T-bet插入载体pEGFP-C1构建成重组真核表达载体pEGFP-C1-T-bet。④用双酶切和聚合酶链反应对插入片段进行分析和验证。结果:①反转录-聚合酶链反应产物经琼脂糖电泳结果显示在预期位置有相对分子质量为1608bp的特异性扩增带。②测序结果证实,T-bet的编码序列和Genbank中T-bet mRNA序列相同。③双酶切和聚合酶链反应结果证实插入片段序列正确。结论:实验成功扩增出人T-bet基因,构建了基因重组真核表达载体pEGFP-C1-T-bet,为探索T-bet基因对免疫细胞的调节作用和肿瘤基因治疗奠定了基础。     

Comparative bioavailability study with two gemfibrozil tablet formulations in healthy volunteers

OBJECTIVE: To assess the bioequivalence of gemfibrozil (CAS 25812-30-0) 900 mg tablet formulation from EMS Farmaceutica as test formulation versus a 900 mg tablet formulation as reference in 36 healthy volunteers of both sexes. METHODS: The study was conducted using an open, randomized, two-period crossover design with a 1-week washout interval. Plasma samples were obtained over a 24-h period. Plasma gemfibrozil concentrations were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) with negative ion electrospray ionization using multiple reaction monitoring (MRM). From the gemfibrozil plasma concentration vs time curves, the following pharmacokinetic parameters were obtained: AUClast, AUC(0-inf) and Cmax. RESULTS: The limit of quantification was 0.05 microg/mL for plasma gemfibrozil analysis. The geometric mean and respective 90% confidence interval (CI) of Test/Reference percent ratios were 90.29 (81.39-100.17) for Cmax, 96.26 (90.33-102.59) for AUClast, 96.04 (90.21-102.23) for AUC(0-24 h) and 96.62 (90.82-102.78) for AUC(0-infinity). CONCLUSION: Since the 90% CI for AUClast, AUC(0-inf) and Cmax, ratios were within the 80-125% interval proposed by the U.S. FDA, it was concluded that gemfibrozil 900 mg tablet (test formulation) was bioequivalent to the 900 mg tablet reference formulation for both rate and extent of absorption.     

Comparative bioavailability of 4 amoxicillin formulations in healthy human volunteers after a single dose administration

OBJECTIVE: To compare the bioavailability of two amoxicillin oral suspension (250 mg/5 ml) formulations and two amoxicillin capsule (500 mg) formulations (Amoxicilina from Medley S/A Indústria Farmace?tica, Brazil, as test formulations and Amoxil from SmithKline Beecham Laboratórios Ltda., Brazil, as reference formulations) in 48 volunteers of both sexes. MATERIAL AND METHODS: The study was conducted open with a randomized two-period crossover design and a one-week washout period. Plasma samples were obtained over a 12-hour interval. Amoxicillin concentrations were analyzed by combined reversed phase liquid chromatography and tandem mass spectrometry (LC-MS-MS) with positive ion electrospray ionization using the selected ion monitoring method. From the amoxicillin plasma concentration vs. time curves the following pharmacokinetic parameters were obtained: AUC(last), AUC(0-infinity) and Cmax. RESULTS: Geometric mean of Amoxicilina/Amoxil 250 mg/5 ml individual percent ratio was 103.70% for AUC(last), 103.15% for AUC(0-infinity) and 106.79% for Cmax. The 90% confidence intervals were 97.82-109.94%, 97.40 to 109.24%, and 96.38-118.33%, respectively. Geometric mean of Amoxicilina/Amoxil 500 mg capsule individual percent ratio was 93.26% for AUC(last), 93.27% for AUC(0-infinity) and 90.74% for Cmax. The 90% confidence intervals were 85.0-102.33%, 85.12-102.31%, and 80.14-102.73%, respectively. CONCLUSION: Since the 90% CI for both Cmax, AUC(last) and AUC(0-inifnity) were within the 80-125% interval proposed by the Food and Drug Administration, it was concluded that Amoxicilina 250 mg/5 ml oral suspension and Amoxicilina 500 mg capsule were bioequivalent to Amoxil 250 mg/5 ml oral suspension and to Amoxil capsule 500 mg, respectively, with regard to both the rate and extent of absorption.     

Approximate entropy analysis across electroencephalographic rhythmic frequency bands during physiological aging of human brain

GeroScience - Aging is the inevitable biological process that results in a progressive structural and functional decline associated with alterations in the resting/task-related brain activity,...