Patch testing and cross sensitivity study of adverse cutaneous drug reactions due to anticonvulsants: A preliminary report

AIM To evaluate the utility of patch test and cross-sensitivity patterns in patients with adverse cutaneous drug reactions(ACDR) from common anticonvulsants. METHODS Twenty-four(M:F = 13:11) patients aged 18-75 years with ACDR from anticonvulsants were patch tested 3-27 mo after complete recovery using carbamazepine, phenytoin, phenobarbitone, lamotrigine, and sodium valproate in 10%, 20% and 30% conc. in pet. after informed consent. Positive reactions persisting on D3 and D4 were considered significant. RESULTS Clinical patterns were exanthematous drug rash with or without systemic involvement(DRESS) in 18(75%), Stevens-Johnsons syndrome/toxic epidermal necrolysis(SJS/TEN) overlap and TEN in 2(8.3%) patients each, SJS and lichenoid drug eruption in 1(4.2%) patient each, respectively. The implicated drugs were phenytoin in 14(58.3%), carbamazepine in 9(37.5%), phenobarbitone in 2(8.3%), and lamotrigine in 1(4.7%) patients,respectively. Twelve(50%) patients elicited positive reactions to implicated drugs; carbamazepine in 6(50%), phenytoin alone in 4(33.3%), phenobarbitone alone in 1(8.3%), and both phenytoin and phenobarbitone in 1(8.33%) patients, respectively. Cross-reactions occurred in 11(92%) patients. Six patients with carbamazepine positive patch test reaction showed cross sensitivity with phenobarbitone, sodium valproate and/or lamotrigine. Three(75%) patients among positive phenytoin patch test reactions had cross reactions with phenobarbitone, lamotrigine, and/or valproate. CONCLUSION Carbamazepine remains the commonest anticonvulsant causing ACDRs and cross-reactions with other anticonvulsants are possible. Drug patch testing appears useful in DRESS for drug imputability and cross-reactions established clinically.

Chinese Expert Consensus on Clinical Application of Patch Test (Revised 2020)

Allergic contact dermatitis is a common clinical allergic disease.The patch test is the gold standard for finding and clarifying contact allergens.With the deepening understanding of the epidemiology,pathogenesis,and clinical manifestations of contact dermatitis,as well as the increased requirements for the standardized application of patch tests,the relevant consensus needs to be continuously updated.This consensus is updated on the basis of the version issued in 2015.In this revised version,it refines the selection of clinical indications,improves the judgment end interpretation of results,adds delayed detection and patient education,and so on,which aims to further standardize clinical applications and improve the value of patch test.

Enhanced patch test of finite element methods

Theoretically, the constant stress patch test is not rigorous. Also, either the patch test of non-zero constant shear for Mindlin plate problem or non-zero strain gradient curvature of the microstructures cannot be performed. To improve the theory of the patch test, in this paper, based on the variational principle with relaxed continuity requirement of nonconforming element for homogeneous differential equations, the author proposed the individual element condition for passing the patch test and the convergence condition of the element: besides passing the patch test, the element function should include the rigid body modes and constant strain modes and satisfy the weak continuity condition, and no extra zero energy modes occur. Moreover, the author further established a variational principle with relaxed continuity requirement of nonconforming element for inhomogene-ous differential equations, the enhanced patch test condition and the individual element condition. To assure the convergence of the element that should pass the enhanced patch test, the element function should include the rigid body modes and non-zero strain modes which satisfied the equilibrium equations, and no spurious zero energy modes occur and should satisfy new weak continuity condition. The theory of the enhanced patch test pro-posed in this paper can be applied to both homogeneous and inhomogeneous differential equations. Based on this theory, the patch test of the non-zero constant shear stress for Mindlin plate and the C0-1 patch test of the non-zero constant curvature for the couple stress/strain gradient theory were established.

Functions for patch test in finite element analysis of the Mindlin plate and the thin cylindrical shell

Current patch test for Mindlin plate element only satisfies the zero shear deformation condition.The patch test of non-zero constant shear for Mindlin plate problem cannot be performed.For shell element, the patch test does not even exist.Based on the theory of enhanced patch test proposed by Chen W J (2006),the authors proposed the enhanced patch test function for Mindlin plate and thin cylindrical shell elements.This enhanced patch test function can be used to assess the convergence of the Mindlin plate and cylindrical thin shell elements.

The Patch Test Condition in Curvilinear Coordinate System——Formulation and Application

The constant stress patch test condition has widely been studied in terms of Cartesian coordinates. However, such kind of conditions cannot be used for curvilinear coordinates. In this paper, certain forms of the patch test are established in terms of the general and the orthogonal curvilinear systems respectively. For the axisymmetric problem, the related patch test condition is formulated and used to construct an axisymmetric incompatible element. In addition, some new approaches to avoid spurious shear stress are presented.

Patch test function for axisymmetric element of conventional and couple stress theory

The enhanced patch test proposed by Chen W J(2006) can be used to assess the convergence of the problem with non-homogeneous differential equations.Based on this theory,we establish the patch test function for axisymmetric elements of conventional and couple stress theories,and reach an important conclusion that the patch test function for axisymmetric elements cannot contain non-zero constant shear.

C^0 and C^1 theories and test functions for FEM patch test in microstructures

Among many theories and categories in microstructures,rotation-displacement used as "independent" or "dependent" variables,is a noticeable topic. In FEM,it is called C0 and C1 theory. The convergence criteria of finite elements for microstructures are less mature than those for the conventional thin plate bending problem. In this paper,the patch test functions for assessing convergence of the C0 and C1 finite elements in microstructures is established based on the enhanced patch test theory. The author has further explored the C0 and C1 finite element theories and investigated the difference and correlation between their finite element formulations. Newly proposed finite element theories for microstructures are as follows:(1) the displacement-rotation dependent C1 element that requires the element function satisfying both C0 and C1 continuity;(2) the displacement-rotation independent C0 element which requires new convergence criteria,such as non-zero constant shear stress patch test and zero constant shear stress patch test for approximating C1 element.

超协调元

该文提出一类超协调的单元理论。不同于在普通协调元中采用的线位移协调插值格式,超协调元的单元插值函数首先引入转角自由度等线位移导数的高阶协调假设,并通过积分推导,进而获得超协调的线位移模型。基于超协调元理论,该文构造了一类新型的三结点三角形平板壳元SCT。数值算例表明:与其他类型单元相比,基于超协调元理论的单元具有计算精度高和计算效率好的优势。该文所提出单元理论构造简单,超协调元理论可以成为构造高性能数值算法的一种新的通用理论。

93例女性玫瑰痤疮患者化妆品斑贴试验结果分析

目的:检测女性玫瑰痤疮患者化妆品接触性过敏原情况。方法:对2018年1月—2021年12月在我院皮肤科就诊的93例女性玫瑰痤疮患者进行化妆品变应原斑贴试验。结果:93例患者中有68例(73.12%)呈阳性反应,其中阳性率排前4位的变应原种类分别是金属盐类(41例)、表面活性剂类(37例)、防腐剂类(30例)和芳香剂类(24例),阳性率排前9位的具体变应原成分分别是氯化镍(36例)、氯化钴(23例)、十二烷基硫酸钠(16例)、戊基肉桂醇(14例)、烷基醇聚氧乙烯醚(12例)、硫酸镍(12例)、硫柳汞(11例)、硫酸钠(11例)和橡苔浸膏(10例)。结论:化妆品接触性过敏原可能与玫瑰痤疮的发病和复发有关,金属盐类、表面活性剂类、防腐剂类和芳香剂类是最常见的化妆品变应原种类。

透皮贴剂特性质量研究方法及控制标准

作为非侵入型药物递送系统,透皮贴剂可通过皮肤以固定剂量和可调节的速率递送药物,从而产生全身或局部的治疗作用。本文聚焦透皮贴剂关键质量属性,阐述其检测方法及试验中的关键点,同时参考国内外药典及现行政策法规,简述部分其他特性质量的检测方法及控制标准,以期为企业及相关部门完善质量检测体系及控制标准提供参考。

基于斑贴及稳定性试验剖析含烟酰胺化妆品皮肤刺激性成因

为探究含烟酰胺化妆品可能引起人体皮肤刺激性反应的主要原因,开展了健康志愿者烟酸、烟酰胺斑贴试验及含烟酰胺化妆品稳定性试验研究。首先选取含烟酰胺化妆品进行斑贴试验,同时测定烟酸、烟酰胺含量水平;随后进行了不同含量烟酸溶液(0.000 5%,0.001%,0.01%,0.025%)和3%烟酰胺溶液斑贴试验,并开展了含烟酰胺化妆品稳定性试验。结果发现:45个含烟酰胺化妆品中,17个会引起皮肤反应(占总数的37.8%),41个检出烟酸(占总数的91.1%),含量为0.000 15%~0.026 6%;采用自建皮肤反应评分方法进行评分,皮肤反应评分总和与烟酸含量正相关具有统计学意义(r=0.406,P=0.006),与烟酰胺含量相关无统计学意义(r=0.099,P=0.517)。0.000 5%烟酸、0.001%烟酸、3%烟酰胺溶液对皮肤刺激性与阴性对照的差异无统计学意义(P>0.05);0.025%烟酸、0.01%烟酸对皮肤刺激性与阴性对照的差异具有统计学意义(P<0.05)。含烟酰胺化妆品在25℃放置8周烟酸含量稳定,在55℃放置8周烟酸含量呈现逐渐增加趋势。

阿戈美拉汀离子液体贴片的制备及体外透皮研究

目的制备阿戈美拉汀离子液体透皮贴片并对其进行质量评价。方法通过药物析晶、体外释放和渗透情况选择处方所用辅料;通过离子交换反应制备阿戈美拉汀-多库酯离子液体,并采用傅里叶变换红外光谱和磁共振波谱对其进行表征;通过溶剂蒸发法制备透皮贴片,对离子液体贴片的含量均匀性、体外释放及体外渗透性能进行质量评价。结果阿戈美拉汀离子液体贴片制备后,表面光滑透明,重量面积比为167 g·m^(-2),单位面积含药量为2.5 mg·cm^(-2);含量均匀度符合药典标准;体外释放速率为(478.31±0.87)μg/(cm^(2)·h^(1/2));体外渗透速率为(24.38±3.93)μg/(cm^(2)·h);24 h的累计透过量为(545.86±93.08)μg·cm^(-2),透过率为(21.78±3.85)%。结论阿戈美拉汀离子液体通过增大贴片的载药量,显著提高贴片的透皮效果,使得透皮贴剂有望成为阿戈美拉汀的新型给药制剂。

口罩伴侣清凉提神水凝胶贴片的制备工艺研究

(目的)制备一款载薄荷油的凝胶贴片,贴附于口罩内壁,对口罩佩戴时间过久产生的心情烦闷、精神疲倦、有臭气等问题进行优化。(方法)以聚乙烯醇(PVA)和壳聚糖(CS)为原料,采用循环冷冻/解冻法制备薄荷油/PVA/CS复合水凝胶贴片,在单因素试验基础上以响应面法优化出最佳制备工艺,并采用单盲法测试出薄荷油最佳载药量。(结果)水凝胶贴片的最佳制备工艺条件为:PVA溶液与CS溶液质量比5.3∶1、冷冻时长12.5 h、冷冻次数4次,载薄荷油量0.5%~0.6%。(结论)运用响应面法制备得到的水凝胶贴片具有黏性好、使用方便、体积较小、芳香气味持续时间久、安全无毒、无刺激等优点,表明优化水载薄荷油的凝胶贴片的制备工艺合理、可行。

瑞敏系列和TURE TEST系列斑贴试剂检测结果比较

目的分析瑞敏系列(R)和TURE TEST系列(T)斑贴试剂检测结果及一致性。方法分别用这两个系列斑贴试剂检测196例慢性湿疹和接触性皮炎患者,对其检测结果进行比较。结果瑞敏系列和TURE TEST系列斑贴试剂对各变应原检测阳性率不完全相同,它们检测常见变应原种类均与国内已有报道类似;两个系列中相同的16种变应原的检测反应强度一致性较好,检测的阳性率差异无统计学意义(P>0.05)。结论两个系列斑贴试剂的一致性较好,临床上可根据患者情况选择应用。

1084例接触性皮炎斑贴试验结果分析

目的了解接触性皮炎患者常见变应原。方法对1084例接触性皮炎患者进行斑贴试验,并对实验结果进行统计分析。结果1084例接触性皮炎患者斑贴变应原呈阳性反应者787例,阳性率反应较高的变应原是硫柳汞、硫酸镍。硫酸镍、硫柳汞、对苯二胺是引起二、三级过敏反应的主要变应原;男性患者对橡胶、对苯二胺、重酪酸钾、三乙醇胺更易过敏,女性患者对硫酸镍更易过敏;汉族更易对硫柳汞过敏,维吾尔族更易对硫酸镍过敏。年轻患者更易对硫柳汞过敏,中年患者更易对硫酸镍过敏,老年患者更易对对苯二胺和重络酸钾过敏。结论硫柳汞、硫酸镍是本地接触性皮炎的常见过敏原,硫柳汞、硫酸镍、对苯二胺更容易引起高级别过敏反应。男性应提防职业接触导致的过敏反应,女性患者更应该注重金属首饰引起的过敏,老年患者对染发过敏要更加重视。斑贴试验是确定接触性皮炎患者变应原的一个较为安全、简单、可靠的方法,为预防和治疗该类疾病提供理论依据。

应用斑贴试验检测过敏原在皮炎和湿疹诊断中的临床价值分析

目的探讨氯化钴等20种过敏原在皮炎、湿疹发生发展中的作用及其检测对临床诊疗的应用价值。方法选取2016年至2020年来广州市皮肤病防治所就诊且临床诊疗资料基本齐备的248例皮炎、湿疹患者作为分析对象,其中皮炎患者144例(男17例、女127例),年龄4~75岁;湿疹患者95例(男27例、女68例),年龄2~78岁。对其氯化钴、疏基化合物、咪唑烷基脲、对苯二胺、N-环已基硫酞内酯、夸特15等20种过敏原斑贴试验的72 h观察结果进行回顾性分析研究。统计学方法采用χ^(2)检验。结果在皮炎、湿疹患者中,硫酸镍、氯化钴、芳香混合物Ⅰ3种过敏原阳性率均居前3位,其阳性率分别为29.17%(42/144)、19.44%(28/144)、9.72%(14/144)和21.05%(20/95)、16.84%(16/95)、11.58(11/95)。在皮炎患者中,男女比例为1.00:7.47,过敏原阳性检出率分别为47.06%(8/17)、66.93%(85/127);少年、青年、中年、老年比例为1.00:23.00:3.80:1.00,其过敏原阳性检出率分别为20.00%(1/5)、66.09%(76/115)、57.89%(11/19)、100%(5/5),各年龄组间差异有统计学意义(χ^(2)=9.02,P<0.05);1种、2种与3种及以上过敏原阳性患者百分率为29.17%(42/144)、19.44%(28/144)、15.97%(23/144),三者间差异有统计学意义(χ^(2)=7.98,P<0.05)。在湿疹患者中,男女比例为1.00:2.52,过敏原阳性检出率分别为51.85%(14/27)、64.71%(44/68);少年、青年、中年、老年比例为1.00:14.25:5.75:2.75,其过敏原阳性检出率分别为25.00%(1/4)、63.16%(36/57)、52.17%(12/23)、81.82%(9/11);1种、2种与3种及以上过敏原阳性患者百分率分别为36.84%(35/95)、8.42%(8/95)、15.79%(15/95),三者间差异有统计学意义(χ^(2)=25.50,P<0.05)。结论硫酸镍、氯化钴、芳香混合物Ⅰ3种过敏原为皮炎、湿疹的高发诱因,然而对于所有过敏原而言,性别、年龄、不同数量的过敏原阳性检出率之间则存在不同差异性的特点,因此,应用斑贴试验检测过敏原有助于皮炎和湿疹的诊断与鉴别诊断。

溶剂型冷补沥青制备及其黏附性能评价

为制备高性能沥青路面修补材料,研制了9种不同配比的冷补沥青。测量冷补沥青的接触角并通过表面自由能理论计算内聚功、黏附功、剥落功和能量比,结合定量的黏附性测试手段对理论计算的结果进行验证。结果表明,60℃旋转黏度、改进水煮法、光电比色法以及黏结强度测试所得最佳配比与表面自由能计算所得一致,且3种黏附性测试方法所反映的结果无显著差异。冷补沥青最佳配合比为m(沥青)∶m(柴油)∶m(SBS)∶m(增黏树脂)∶m(抗剥落剂)=100∶30∶3∶5∶0.5,可直接采用光电比色法和接触角测试相结合或黏结强度测试与接触角测试相结合的方法量化评价其黏附性。

不正确程序修复补丁识别

程序自动修复技术是保证软件质量、提高开发效率的有效手段.目前,大多数自动修复工具使用测试用例作为补丁正确性验证的最终方法,有限的测试用例难以对程序进行充分的测试,因此自动修复工具生成的补丁集合包含大量的不正确补丁.为了识别不正确补丁,我们采用对比缺陷修复前后成功测试的执行路径以及生成测试用例的方法来识别修复补丁的有效性,以解决自动修复工具精度低的问题.我们的方法评估了来自6个经典的自动修复工具生成的132个补丁,并成功地排除了80个不正确的补丁并且没有排除正确的补丁,这表明我们的方法可以有效地排除不正确补丁,并且提高自动修复工具的精度.

端羧基丁腈橡胶/环氧树脂冷补沥青研发及其混合料性能

为研究端羧基液体丁腈橡胶(CTBN)/环氧树脂E51冷补沥青及其混合料性能,基于正交试验,以60℃旋转黏度和1d质量损失率为指标,确定CTBN/E51冷补沥青各组分最佳掺量为稀释剂18%,环氧树脂14%,固化剂4.7%,增韧剂3%和抗剥落剂4%。通过水煮法、动态剪切流变试验(DSR)、弯曲梁流变试验(BBR)评价冷补沥青的黏附性、高温性能和低温性能。采用LB-10级配,6.2%的油石比制备CTBN/E51冷补沥青混合料,与市面上常用的GR牌和GJY牌冷补料进行强度试验、车辙试验、低温劈裂试验、浸水马歇尔试验、施工和易性试验和容留时间试验,结果表明:CTBN/E51冷补料具有较好的路用性能且容留时间为3h。

基于数据流分析的过拟合补丁识别

自动程序修复技术可实现对软件缺陷的自动修复,并使用测试套件评估修复补丁.然而因为测试套件不充分,通过测试套件的补丁可能并未正确修复缺陷,甚至引入新的缺陷并产生波及效应,导致自动程序修复生成大量过拟合补丁.针对这个问题,本文提出了一种基于数据流分析的过拟合补丁识别方法,首先将补丁对程序的修改分解为对变量的操作,然后采用数据流分析方法识别补丁影响域,并根据补丁影响域选择针对性覆盖准则来识别目标覆盖元素,进而选取测试路径并生成测试用例实现对修复程序的充分测试,避免修复副作用的影响.本文在两个数据集上进行了评估,实验结果表明,基于数据流分析的过拟合补丁识别方法可有效提升自动程序修复的正确性.