Diagnostic value of RASSF1A hypermethylation in colorectal cancer: a meta-analysis

Purpose

Ras association domain family 1 isoform A (RASSF1A), a member of Ras association domain family, plays an important role in tumorigenesis. The goal of our meta-analysis was to assess the diagnostic value of RASSF1A hypermethylation in colorectal cancer (CRC).

Reduced (+/-)-3,4-methylenedioxymethamphetamine ("Ecstasy") metabolism with cytochrome P450 2D6 inhibitors and pharmacogenetic variants in vitro

"Ecstasy" [(+/-)-3,4-methylenedioxymethamphetamine or MDMA] is a CNS stimulant, whose use is increasing despite evidence of long-term neurotoxicity. In vitro, the majority of MDMA is demethylenated to (+/-)-3,4-dihydroxymethamphetamine (DHMA) by the polymorphic cytochrome P450 2D6 (CYP2D6). We investigated the demethylenation of MDMA and dextromethorphan (DEX), as a comparison drug, in reconstituted microsomes expressing the variant CYP2D6 alleles (*)2, (*)10, and (*)17, all of which have been linked to decreased enzyme activity. With MDMA, intrinsic clearances (V(max)/K(m)) in CYP2D6.2, CYP2D6.17, and CYP2D6.10 were reduced 15-, 13-, and 135-fold, respectively, compared with wild-type CYP2D6.1. With DEX, intrinsic clearances were reduced by 37-, 51-, and 164-fold, respectively. It was evident that CYP2D6.17 displayed substrate-specific changes in drug affinity (K(m)). Compounds potentially used with MDMA [fluoxetine, paroxetine, (-)-cocaine] demonstrated significant inhibition of MDMA metabolism in both human liver and CYP2D6.1-expressing microsomes. These data demonstrate that individuals possessing the CYP2D6(*)2, (*)17, and, particularly, (*)10 alleles may show significantly reduced MDMA metabolism. These individuals, and those taking CYP2D6 inhibitors, may demonstrate altered acute and/or long-term MDMA-related toxicity.     

Preliminary diagnostic guidelines for macrophage activation syndrome complicating systemic juvenile idiopathic arthritis

OBJECTIVE: To develop diagnostic guidelines for macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (S-JIA). STUDY DESIGN: We followed the classification criteria approach that is based on the comparison of patients with the index disease with patients with a "confusable" disease. The former group included 74 patients with S-JIA-associated MAS reported in the literature or seen by the authors; the latter group included 37 patients with S-JIA who had 51 instances of "high disease activity" seen by the authors. The relative power of clinical, laboratory, and histopathologic variables in discriminating patients with MAS from patients with high disease activity was evaluated by calculating the sensitivity rate, specificity rate, area under the receiver operating characteristic curve, and diagnostic odds ratio (DOR). The combinations of variables that led to best separation between patients and control subjects were identified through "the number of criteria present" method. RESULTS: The strongest clinical discriminators were hemorrhages (DOR = 67) and central nervous system dysfunction (DOR = 63); the strongest laboratory discriminators were decreased platelet count (DOR = 1092), increased aspartate aminotransferase (DOR = 247), leukopenia (DOR = 70), and hypofibrinogenemia (DOR = 165). The best separation between patients and control subjects occurred when any 2 or more laboratory criteria (DOR = 1309) were simultaneously present; the second best performance was provided by the presence of any 2, 3, or more clinical and/or laboratory criteria (DOR = 765 and 743, respectively). CONCLUSION: We identified preliminary diagnostic guidelines for MAS complicating S-JIA. These guidelines deserve prospective validation.     

Real-time elastography for the differentiation of benign and malignant superficial lymph nodes: a meta-analysis

Background

Real-time elastography (RTE), as a non-invasive method, is used for the classification of benign and malignant lymph nodes (LNs) and developed as an alternative to biopsy. Elasticity score (ES) and strain ratio (SR) are used for the interpretation of RTE. We studied the performance of RTE for diagnosis of malignant LNs using meta-analysis.

Methods

PubMed, the Cochrane Library, ISI Web of Knowledge, China National Knowledge Infrastructure were searched. The studies published in English or Chinese relating to the diagnostic value of RTE for superficial LNs were collected. Hierarchical summary receiver operating characteristic (HSROC) curve was used to examine the RTE accuracy. Clinical utility of RTE for LNs was evaluated by Fagan plot analysis.

Results

A total of 9 studies which included 835 LNs were analyzed. The summary sensitivity and specificity for the diagnosis of malignant LNs were 0.74 (95% confidence interval (CI), 0.66–0.81) and 0.90 (95% CI, 0.82–0.94) for ES, and 0.88 (95% CI, 0.79–0.93) and 0.81 (95% CI, 0.49–0.95) for SR, respectively. Compared to ES, SR obviously improved the diagnostic sensitivity value. The HSROCs were 0.88 for ES and 0.91 for SR, respectively. After RTE results over the cut-off value for malignant LNs (“positive” result), the corresponding post-test probability for the presence (if pre-test probability was 50%) was 88% for ES and 82% for SR, respectively; while, in “negative” measurement, the post-test probability was 22% and 13%, respectively.

Conclusion

RTE has a high accuracy in the classification of superficial LNs and can potentially help to select suspicious LNs for biopsy.     

芬吗通联合坤泰胶囊对卵巢储备功能低下性不孕的预处理及促排治疗

目的：探讨芬吗通联合坤泰胶囊治疗卵巢功能低下（decreasing ovarian reserve,DOR）的临床效果及促排卵后的受孕情况。方法选取2012年1月～2013年7月收治的57例DOR患者,芬吗通联合坤泰胶囊治疗3个月,检测卵泡刺激素（FSH）、促黄体生成素（LH）、雌二醇（E 2）、抗苗勒管激素（AMH）、窦卵泡数、卵巢体积、动脉收缩期峰值流速（PSV）。治疗前后采用自身对照。结果 FSH、LH水平较治疗前下降,E 2、AMH、窦卵泡数、PSV水平较治疗前上升,差异有统计学意义（P＜0.05）,卵巢体积较治疗前增加,但差异无统计学意义。联合治疗后给予来曲唑促排卵受孕率提高。结论芬吗通联合坤泰胶囊治疗卵巢功能低下,可有效改善卵巢储备,加以促排卵治疗,提高DOR患者的受孕成功率。     

Receptor–receptor interactions: A novel concept in brain integration

A brief historical presentation of the hypothesis on receptor–receptor interactions as an important integrative mechanism taking place at plasma membrane level is given. Some concepts derived from this integrative mechanism especially the possible assemblage of receptors in receptor mosaics (high-order receptor oligomers) and their relevance for the molecular networks associated with the plasma membrane are discussed. In particular, the Rodbell's disaggregation theory for G-proteins is revisited in the frame of receptor mosaic model.     

黄体期使用生长激素在高龄卵巢储备功能减退患者中的临床应用

目的探讨黄体期使用生长激素(GH)对高龄卵巢储备功能减退(DOR)患者超促排卵治疗的影响。方法选择接受体外受精/卵胞质内单精子显微注射-胚胎移植(IVF/ICSI-ET)且高龄(年龄≥35岁)DOR不孕患者156例为研究对象,均采用拮抗剂方案,分为研究组(加用GH)和对照组(不加用GH)。分析GH对促性腺激素(G n)使用总量、G n使用时间、获卵数、移植前内膜厚度、双原核(2 P N)率、优质胚胎率、着床率的影响。结果 Gn使用时间、Gn使用总量、移植前内膜厚度组间有统计学差异(P0.05)。h CG注射日E 2水平、获卵数、2 P N受精率、优质胚胎率、着床率、临床妊娠率及累积妊娠率组间无统计学差异(P0.05)。研究组临床妊娠率为28.0%、对照组为19.4%,研究组累积妊娠率为33.3%、对照组为20.0%,组间均无统计学差异(P0.05),但研究组临床妊娠率及累积妊娠率有上升趋势。结论 GH对年龄≥35岁DOR患者可明显降低Gn的使用总量及使用时间,增加子宫内膜的厚度,临床妊娠率及累积妊娠率有提高的趋势。