EMA对药用辅料右旋糖酐新的安全性评价

欧洲药品局（EMA）于2018年11月发布了"人用药品辅料右旋糖酐的包装说明书资料"，该文件引用大量文献全面评价了右旋糖酐的安全性，特别指出含有右旋糖酐辅料的注射和吸入制剂的疫苗与药品，应在说明书中描述有关其过敏反应信息的新要求。介绍该文件的主要内容，期望对我国这类药品说明书的撰写和监管有所帮助。     

Using arterial spin labeling blood flow and its histogram analysis to distinguish early-stage nasopharyngeal carcinoma from lymphoid hyperplasia

To investigate the feasibility of arterial spin labeling (ASL) blood flow (BF) and its histogram analysis to distinguish early-stage nasopharyngeal carcinoma (NPC) from nasopharyngeal lymphoid hyperplasia (NPLH).Sixty-three stage T1 NPC patients and benign NPLH patients underwent ASL on a 3.0-T magnetic resonance imaging system. BF histogram parameters were derived automatically, including the mean, median, maximum, minimum, kurtosis, skewness, and variance. Absolute values were obtained for skewness and kurtosis (absolute value of skewness [AVS] and absolute value of kurtosis [AVK], respectively). The Mann–Whitney U test, receiver operating characteristic curve, and multiple logistic regression models were used for statistical analysis.The mean, maximum, and variance of ASL BF values were significantly higher in early-stage NPC than in NPLH (all P < 0.0001), while the median and AVK values of early-stage NPC were also significantly higher than those of NPLH (all P < 0.001). No significant difference was found between the minimum and AVS values in early-stage NPC compared with NPLH (P = 0.125 and P = 0.084, respectively). The area under the curve (AUC) of the maximum was significantly higher than those of the mean and median (P < 0.05). The AUC of variance was significantly higher than those of the other parameters (all P < 0.05). Multivariate analysis showed that variance was the only independent predictor of outcome (P < 0.05).ASL BF and its histogram analysis could distinguish early-stage NPC from NPLH, and the variance value was a unique independent predictor.     

Prenatal Sonography in Suspected Proximal Gastrointestinal Obstructions: Diagnostic Accuracy and Neonatal Outcomes

BackgroundThe purpose of this study was to assess diagnostic accuracy and neonatal outcomes in fetuses with a suspected proximal gastrointestinal obstruction (GIO).MethodsAfter IRB approval, a retrospective chart review was conducted on prenatally suspected and/or postnatally confirmed cases of proximal GIO at a tertiary care facility (2012–2022). Maternal-fetal records were queried for presence of a double bubble ± polyhydramnios, and neonatal outcomes were assessed to calculate the diagnostic accuracy of fetal sonography.ResultsAmong 56 confirmed cases, the median birthweight and gestational age at birth were 2550 g [interquartile range (IQR) 2028–3012] and 37 weeks (IQR 34–38), respectively. There was one (2%) false-positive and three (6%) false-negatives by ultrasound. Double bubble had a sensitivity, specificity, positive predictive value, and negative predictive value for proximal GIO of 85%, 98%, 98%, and 83%, respectively. Pathologies included 49 (88%) with duodenal obstruction/annular pancreas, three (5%) with malrotation, and three (5%) with jejunal atresia. The median postoperative length of stay was 27 days (IQR 19–42). Cardiac anomalies were associated with significantly higher complications (45% vs 17%, p = 0.030).ConclusionsIn this contemporary series, fetal sonography has high diagnostic accuracy for detecting proximal gastrointestinal obstruction. These data are informative for pediatric surgeons in prenatal counseling and preoperative discussions with families.Level of EvidenceDiagnostic Study, Level III.     

Development and function of tissue resident macrophages in mice

Macrophages are important for tissue development, homeostasis as well as immune response upon injury or infection. For a long time they were only seen as one uniform group of phagocytes with a common origin and similar functions. However, this view has been challenged in the last decade and revealed a complex diversity of tissue resident macrophages. Here, we want to present the current view on macrophage development and tissue specification and we will discuss differences as well as common patterns between heterogeneous macrophage subpopulations.     

Carboxylesterase catalyzed 18O-labeling of carboxylic acid and its potential application in LC-MS/MS based quantification of drug metabolites

LC-MS quantification of drug metabolites is sometimes impeded by the availability of internal standards that often requires customized synthesis and/or extensive purification. Although isotopically labeled internal standards are considered ideal for LC-MS/MS based quantification, de novo synthesis using costly isotope-enriched starting materials makes it impractical for early stage of drug discovery. Therefore, quick access to these isotope-enriched compounds without chemical derivatization and purification will greatly facilitate LC-MS/MS based quantification. Herein, we report a novel ¹⁸O-labeling technique using metabolizing enzyme carboxylesterase (CES) and its potential application in metabolites quantification study. Substrates of CES typically undergo a two-step oxygen exchange with H₂¹⁸O in the presence of the enzyme, generating singly- and doubly-¹⁸O-labeled carboxylic acids; however, unexpected hydrolytic behavior was observed for three of the test compounds – indomethacin, piperacillin and clopidogrel. These unusual observations led to the discovery of several novel hydrolytic mechanisms. Finally, when used as internal standard for LC-MS/MS based quantification, these in situ labeled compounds generated accurate quantitation comparable to the conventional standard curve method. The preliminary results suggest that this method has potential to eliminate laborious chemical synthesis of isotope-labeled internal standards for carboxylic acid-containing compounds, and can be developed to facilitate quantitative analysis in early-stage drug discovery.     

微小切口双重荷包缝合法矫正重度乳头内陷

目的 介绍一种疗效确切,创伤小,矫正重度乳头内陷的新术式.方法 设计切口位于乳晕第四象限,方向斜向外下方,呈放射状切口,长约1.5 cm,松解乳头基底部,切断牵拉的纤维条索,上提乳头,在距乳头0.8cm和1.5cm处,双重荷包缝合固定.结果 12例乳头内陷患者术后随访1个月至4年,均获得满意疗效.乳头横径、纵径、高度及外观明显改善.结论 该术式矫正乳头内陷具有切口小、创伤轻微、操作简单易行、效果确切、不易复发和并发症少等优点.     

幕上星形细胞肿瘤Ki-67抗原表达及其预后作用

目的 探讨Ki-67抗原在幕上星形细胞肿瘤中的表达及其预后作用。方法 使用S-P免疫组化方法检测82例原发性幕上星形细胞肿瘤标本中Ki-67抗原的表达。单因素使用Kaplan-Meier法,多因素分析使用COX比例风险模型进行预后分析。结果Ki-67 指数在组织学分级GradeⅡ、Ⅲ、Ⅳ中分别为2.86%±1.57%,6.72%±3.95%,8.16%±3.92%(P<0.01)。单因素及多因素分析均提示Ki-67指数是独立的预后因素。在GradeⅡ中,Ki-67指数>2.5%与Grade Ⅲ中Ki-67指数≤2.5%的患者生存期差异无显著性(P>0.05);在GradeⅣ中,Ki-67指数≤2.5%与>2.5%的患者生存期有显著性差异(P<0.01)。结论 Ki-67指数随着各病理级别增高而增高;Ki-67指数>2.5%提示预后较差。在同一病理级别中,Ki-67指数不同,其预后有显著性差异。而部分不同病理级别的患者,随着Ki-67指数的不同,其生存期却无显著差异。联合组织病理检查及Ki-67指数检测有助于更精确地判断预后。     

胃癌大肠转移的X线钡灌肠表现

目的:分析胃癌大肠转移的X线钡灌肠表现。方法:104例胃癌入院术前检查发现结肠转移或胃癌术后转移入院治疗的病例。分析钡灌肠初次发现大肠转移征象的年龄、发现胃癌原发病变距初次发现大肠转移的间隔时间、转移病变的发生部位和病变造成的X线钡灌肠图像上的肠管变形和粘膜面的改变。结果:104例胃癌结肠转移,男67例,女37例。胃癌术前检查中发现结肠转移者32例,术后发现的大肠转移中,多数转移发生在手术后3年内(占91.3%)。胃癌原发灶的肉眼形态BorrmannⅢ型(28例)和BorrmannⅣ型(65例)者占89.4%,组织学中以低分化腺癌和印戒细胞癌为主要成分者占91.3%。X线钡灌肠检查显示大肠转移的好发部位为横结肠(80),其次为直肠(50)。转移灶可累及多节段肠管,其中横结肠中1/3段(47),横结肠左1/3(44),横结肠右1/3(39)和直肠腹膜返折之上(39)。X线显示肠管单侧变形者227处,双侧变形者96处。黏膜面表现为梳齿状黏膜纹聚集改变253处,颗粒结节状改变23处,外压性改变20处,弥漫性改变62处。结论:胃癌大肠转移的好发部位为横结肠和直肠,结肠黏膜面的梳齿状黏膜纹聚集为胃癌大肠转移的主要X线钡剂灌肠表现。     

用DIG标记的寡核苷酸基因探针杂交技术进行人轮状病毒VP7G血清型鉴定

目的：建立用地高辛（Ｄｉｇｏｘｉｇｅｎｉｎ，ＤＩＧ）标记的寡核苷酸基因探针鉴定Ａ群轮状病毒ＶＰ７Ｇ血清型的分子杂交技术，并应用该技术研究河南Ａ群轮状病毒的Ｇ血清型分布。方法：根据轮状病毒编码糖蛋白ＶＰ７的基因核苷酸序列，选择该基因高保守区序列中与ＶＰ７Ｇ血清型高度相关的核苷酸片段，人工合成，并用ＤＩＧ标记。在优选的杂交条件下进行杂交：结果：①Ｇ１、Ｇ２、Ｇ３和Ｇ４四种Ｇ血清型特异性寡核苷酸探针只与同血清型的轮状病毒参考毒株杂交，无交叉杂交现象。灵敏度和特异性达到放射性同位素３２Ｐ标记的水平。②１８８份经ＰＡＧＥ确定的轮状病毒阳性标本中，７９份（４２．０％）、３５份（１８．６％）、１５份（７．９％）分别与Ｇ１、Ｇ２或Ｇ３型探针杂交；未检出Ｇ４型；５６份（２９．８％）未能分型；３份分型特殊。结论：该Ｇ血清型分型技术具有高度特异性和灵敏度     

Spectrum of looping disturbances in stage 34 chicken hearts after retinoic acid treatment

Background: In a recently developed chick model the teratogen retinoic acid has appeared to induce a spectrum of double outlet right ventricle, which needs further detailed evaluation. It is known that retionic acid is able to induce cardiac malformations. Although the exact mechanism is not known, an interaction with neural crest cell function is thought to exist. Methods: After treatment with 1 μg all-trans retinoic acid at Hamburger and Hamilton stage 15 and reincubation until stage 34 of development 41 chicken embryos were evaluated macroscopically and microscopically, supported by graphic reconstructions. These retinoic acid treated embryos were compared with a control group (n = 8). Results: The retinoic acid treated embryos could be divided in three groups. Group 1 (23/41) had an intact septum, group 2 (11/41) had an isolated ventricular septal defect (VSD), and group 3 (7/41) had a double outlet right ventricle (DORV). Besides, in the group with an intact septum 11 hearts showed an abnormal course of the subaortic outflow tract. In the group with DORV a straddling tricuspid orifice (7/8) and a double inlet left ventricle (1/8) could be distinguished. Considering the external contour, the hearts in the DORV group all showed a dextroposed arterial pole. Malformed pharyngeal arch arteries were found in all three groups (11/41) and with a great diversity. Conclusions: The present cardiac malformations in the chicken as a result of retinoic acid treatment are part of a continuous spectrum, varying from hearts with an intact ventricular septum and a normal course of the subaortic outflow tract to a double outlet right ventricle with a straddling tricuspid orifice or even a double inlet left ventricle. A remarkable observation in this spectrum concerns the correlation of malformations of the inflow and outflow tracts, which is explained as a cardiac looping disturbance. The disturbance of the looping process seems to lead to malalignment of septal components, although, in the chick, retinoic acid does not in general interfere with the formation of these septal components themselves. © 1995 Wiley-Liss, Inc.