Genetic correction of PSA values using sequence variants associated with PSA levels

Measuring serum levels of the prostate-specific antigen (PSA) is the most common screening method for prostate cancer. However, PSA levels are affected by a number of factors apart from neoplasia. Notably, around 40% of the variability of PSA levels in the general population is accounted for by inherited factors, suggesting that it may be possible to improve both sensitivity and specificity by adjusting test results for genetic effects. To search for sequence variants that associate with PSA levels, we performed a genome-wide association study and follow-up analysis using PSA information from 15,757 Icelandic and 454 British men not diagnosed with prostate cancer. Overall, we detected a genome-wide significant association between PSA levels and single-nucleotide polymorphisms (SNPs) at six loci: 5p15.33 (rs2736098), 10q11 (rs10993994), 10q26 (rs10788160), 12q24 (rs11067228), 17q12 (rs4430796), and 19q13.33 [rs17632542 (KLK3: I179T)], each with P(combined) <3 × 10(-10). Among 3834 men who underwent a biopsy of the prostate, the 10q26, 12q24, and 19q13.33 alleles that associate with high PSA levels are associated with higher probability of a negative biopsy (odds ratio between 1.15 and 1.27). Assessment of association between the six loci and prostate cancer risk in 5325 cases and 41,417 controls from Iceland, the Netherlands, Spain, Romania, and the United States showed that the SNPs at 10q26 and 12q24 were exclusively associated with PSA levels, whereas the other four loci also were associated with prostate cancer risk. We propose that a personalized PSA cutoff value, based on genotype, should be used when deciding to perform a prostate biopsy.     

Training and career development for comparative effectiveness research workforce development: CTSA Consortium Strategic Goal Committee on comparative effectiveness research workgroup on workforce development

As comparative effectiveness research (CER) increasingly becomes a national priority, there are increased needs for training and workforce development in this area. Particularly important CER competencies include clinical epidemiology, biomedical informatics, economic analyses, systematic reviews, clinical practice guideline development, use of large databases and electronic health records for research, practice-based research, implementation and dissemination, health services research, and decision analysis. Institutions funded by Clinical and Translational Science Awards (CTSAs) should be one of the central stakeholders in providing training and career development in CER. Survey results regarding the current CER capacity and needs of CTSAs are presented, and recommendations are provided. Volume 5: 258-262.     

US Food and Drug Administration documents can provide unpublished evidence relevant to systematic reviews

ObjectivesA key systematic review (SR) methodology is comprehensive searching. The Drug Effectiveness Review Project (DERP) SRs search US Food and Drug Administration (FDA) documents to identify unpublished evidence. This study evaluates the success of those efforts.Study Design and SettingWe examined DERP reports published since 2003 for the use of FDA preapproval and postmarketing documents. We categorized evidence as (1) unique unpublished studies, (2) supplemental unpublished data, or (3) FDA postmarketing data analysis. Three reviewers independently assigned predetermined impact categories (e.g., qualitative or quantitative usage, fills gaps, confirms findings, and alters conclusions), resolving disagreements through consensus.ResultsAmong 114 DERP reports, 19% included unpublished studies and/or supplemental data and 10% included postmarketing analyses. From 175 preapproval documents, 14% provided eligible unpublished studies and 4.0% supplemental unpublished data that helped confirm previous findings, identify important harms, and fill gaps in knowledge about understudied subpopulations, outcomes, and comparisons. Report conclusion statements changed in 9 of 33 instances of premarketing documents compared with 4 of 12 postmarketing analyses.ConclusionsThe FDA documents can provide important unpublished evidence for SRs, although in a small proportion of cases. Future research should identify attributes that predict which reviews may benefit most from review of FDA documents.     

妥卡尼对豚鼠心室肌细胞钙电流和钾电流的抑制作用

利用酶分散的成年豚鼠心室肌细胞和全细胞电压钳技术,研究了妥卡尼(tocainide)对心室肌细胞钙电流(I_ca)、延迟整流钾电流(I_k)和ATP敏感性钾电流(Ik,ATP)的作用。结果表明,妥卡尼对I_ca和I_k均显示浓度相关的抑制作用,妥卡尼50umol·L^-1对I_ca和I_k的抑制率分别为16%和3%。这可能是妥卡尼有效抑制室上性心动过速和缩短心肌动作电位平台期的重要机制。     

回春液补肾助阳药效学的实验研究

回春液由人参、鹿茸、貂鞭等名贵中药组成。有补肾助阳,填精益气等功效。药效学研究证实,该药有促进幼鼠发育及增加去势大鼠前列腺——精液囊的重量,亦显著增加小鼠血红蛋白的含量,表明回春液有雄性激素样作用。     

Results of percutaneous epididymal sperm aspiration and intracytoplasmic sperm injection in two major groups of patients with obstructive azoospermia

Percutaneous epididymal sperm aspiration (PESA) and intracytoplasmic sperm injection (ICSI) were carried out in patients with congenital bilateral absence of the vas deferens (CBAVD) and men with failed reversal of vasectomy (FRV). PESA was successful in 55 out of 62 patients with CBAVD (89%) and in 57 out of 60 men with FRV (95%). The fertilization rates after ICSI (53 and 55%), cleavage rates (70 and 76%) and pregnancy rates (36 and 32%) did not differ significantly between the two respective groups (CBAVD and FRV). PESA and ICSI are effective both in patients with CBAVD and in those with FRV.      

Imiquimod 5% cream is an acceptable treatment option for external anogenital warts in uncircumcised males

OBJECTIVES: To determine the safety and efficacy of imiquimod (Aldara) 5% cream in the treatment of prepuce-associated warts in uncircumcised males. METHODS: An open-label study in six UK medical centres with 35 uncircumcised males with prepuce-associated warts treated with imiquimod 5% cream three times per week for up to 16 weeks. Other anogenital warts were also treated. RESULTS: Three times weekly application of imiquimod was found to be safe, with erythema as the most commonly reported local skin reaction. Forty per cent of patients had complete clearance of anogenital warts within 16 weeks. CONCLUSIONS: Imiquimod cream at a dosing regimen of three times per week, is effective and has an acceptable safety profile in the treatment of prepuce associated warts and other external anogenital warts in uncircumcised males.