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1.
《European journal of medical genetics》2021,64(12):104345
BackgroundEpidermolysis bullosa (EB) is a genodermatosis characterized by skin fragility and blisters with variable severity. Patients with Dystrophic EB (DEB) or Junctional EB (JEB) mainly present to clinic due to greater functional impairment. Pathogenic sequence variations in COL7A1 are implicated in DEB.ObjectiveWe have tried to decipher the molecular spectrum and genotype phenotype correlation of 21 Indian patients with EB.MethodsNext generation sequencing (NGS) was performed to determine the pathogenic variants. Sanger sequencing was also done for validation of the variants in eleven individuals.ResultsPathogenic variants were detected in 20 individuals (diagnostic yield of 95%). Majority of them (90%) had sequence variation in COL7A1 while two had pathogenic variants in ITGB4 and KRT14 respectively. Out of the 18 patients confirmed to have DEB, 3 had Dominant DEB (DDEB) whereas 15 patients had Recessive DEB (RDEB). Amongst 23 sequence variations identified, 12 were found to be novel (3 were missense, 5 were premature termination codon variants while 4 were splice-site changes).ConclusionGenotype phenotype correlation was noted with milder manifestations in those with dominant inheritance types. Exact molecular diagnosis can be ascertained by NGS in majority of cases. 相似文献
2.
《Value in health》2022,25(12):1958-1966
ObjectivesNational health technology assessments (HTAs) across Europe show differences in evidentiary requirements from assessments by the European Medicines Agency (EMA), affecting time to patient access for drugs after marketing authorization. This article analyzes the differences between EMA and HTA bodies’ evidentiary requirements for oncology drugs and provides recommendations on potential further alignment to minimize and optimally manage the remaining differences.MethodsInterviews were performed with representatives and drug assessment experts from EMA and HTA bodies to identify evidentiary requirements for several subdomains and collect recommendations for potentially more efficiently addressing differences. A comparative analysis of acceptability of the evidence by EMA and the HTA bodies and for potential further alignment between both authorities was conducted.ResultsAcceptability of available evidence was higher for EMA than HTA bodies. HTA bodies and EMA were aligned on evidentiary requirements in most cases. The subdomains showing notable differences concerned the acceptance of limitation of the target population and extrapolation of target populations, progression-free survival and (other) surrogate endpoints as outcomes, cross-over designs, short trial duration, and clinical relevance of the effect size. Recommendations for reducing or optimally managing differences included joint early dialogues, joint relative effectiveness assessments, and the use of managed entry agreements.ConclusionsDifferences between assessments of EMA and HTA bodies were identified in important areas of evidentiary requirements. Increased alignment between EMA and HTA bodies is suggested and recommendations for realization are discussed. 相似文献
3.
《Journal de gynecologie, obstetrique et biologie de la reproduction》2015,44(5):411-418
4.
胃癌雌激素受体表达及新一代抗受体药物在胃癌治疗中的探讨 总被引:3,自引:0,他引:3
目的 探讨胃癌雌激素受体 (ER)实际表达率 ,为临床使用新一代抗ER药物 (toremifene ,TOR)治疗胃癌提供临床病理依据。方法 用免疫组化法对 349例胃癌标本进行ER的检测 ,其中 2 99例用ABC(avidinbiotinperoxidasecomplex)法 ,5 0例用葡聚糖聚合物技术二步法进行检测。在检测ER的同时也检测 p5 3及PCNA的表达。结果 两种检测方法的ER阳性率分别为 2 .3% (7/ 2 99)及 0 % (0 / 5 0 ) ,p5 3阳性率 37.1% (111/ 2 99)及 4 6 %(2 3/ 5 0 ) ,PCNA 94 .3% (2 82 / 2 99)及 96 % (48/ 5 0 )。结论 胃癌细胞可表达ER但实际表达率很低 ,而且存在质和量的变化。tamoxifen (TAM )及TOR的抗胃癌效应需要进一步研究 相似文献
5.
本文报道242例高脂血症患者血小板(PLT)、平均血小板数(MPLT)及平均血小板体积(MPV)等参数的测定结果,其中高胆固醇并高甘油三酯患者,PLT、MPLT及巨大血小板比例(Macro-PLT)高于正常,MPV正常;而单纯高胆固醇或高甘油三酯患者,上述指标与正常人无显著性差异。提示高胆固醇并高甘油三酯患者,存在血小板生成动力学异常,其血小板的破坏增加,生成率加速、但处于一种高水平的动态平衡之中。这可能是高脂血症出现高凝状态的原因之一。同时表明此类患者使用抗血小板疗法具有一定的合理性和必要性。 相似文献
6.
阐述了节能建筑的特点,分析了建筑节能设计规程及标准的特点,并结合中国的资源状况和北京的能耗现状,论述了医院建筑电气专业的具体设计做法。 相似文献
7.
Harwant S. Gill Michael W. O'Boyle Julie Hathaway 《Cortex; a journal devoted to the study of the nervous system and behavior》1998,34(5):707-718
Alpha power (8–12 Hz) was monitored over the frontal, temporal, parietal and occipital lobes of the left and right cerebral hemispheres while participants mentally rotated three-dimensional shapes to match a specified target. By comparing the activational patterns generated during three experimental conditions, each designed to systematically isolate the involvement of the various subcomponents comprising this mental rotation task, it was suggested that the right frontal lobe mediates encoding and comparison/decision processes, while the left parietal and the left temporal region appear most involved in the generation of images and their mental rotation. A preliminary model describing the cooperative interaction of these cortical regions during mental rotation tasks is proposed. 相似文献
8.
Levodopa improves physical fatigue in Parkinson's disease: a double-blind, placebo-controlled, crossover study. 总被引:1,自引:0,他引:1
Jau-Shin Lou Greg Kearns Theodore Benice Barry Oken Gary Sexton John Nutt 《Movement disorders》2003,18(10):1108-1114
We quantitatively investigated the effect of carbidopa/levodopa (25/100) on physical fatigue during finger tapping and force generation in a double-blind, placebo-controlled crossover study. Parkinson's disease (PD) subjects were randomly assigned to carbidopa/levodopa or placebo for Visit 1 or 2 and participated in the following two studies: (1) Finger tapping. Twenty-five PD patients used their index fingers to strike two keys 20 cm apart on a musical instrument digital interface (MIDI) keyboard. The slopes of the regression line of dwell time and movement time were used to assess the rate of fatigue development. (2) Force generation. Twelve PD patients contracted the wrist extensors maximally to obtain a baseline maximum voluntary contraction (BMVC) force. Then they repetitively contracted the wrist extensors at 50% of the BMVC for 7 seconds and rested for 3 seconds. An interval maximum voluntary contraction (IMVC) was measured every three repetitions. Fatigue was defined as an IMVC of less than 60% of the BMVC. The slope of the regression line of IMVC was used to assess the rate of force decline. These two studies were repeated 1 hour after carbidopa/levodopa (25/100) or placebo. Subjects filled out the Multidimensional Fatigue Inventory (MFI) at the beginning of the first visit. Results showed that the slope of dwell time decreased with levodopa but not with placebo (P = 0.004). The rate of force decline also decreased with levodopa but not with placebo (P = 0.01). The subscores in the dimension of physical fatigue in the MFI did not correlate with the rate changes in dwell time or the rate changes in force decline. We concluded that (1) levodopa improves physical fatigue in finger tapping and force generation, (2) physical fatigue in Parkinson's disease is at least partially related to dopamine deficiency, and (3) the MFI measures different aspects of physical fatigue compared with those measured by finger tapping and force generation. 相似文献
9.
Biochemical and ultrastructural alterations produced by miconazole and econazole in Trypanosoma cruzi 总被引:6,自引:0,他引:6
R Docampo S N Moreno J F Turrens A M Katzin S M Gonzalez-Cappa A O Stoppani 《Molecular and biochemical parasitology》1981,3(3):169-180
Miconazole and econazole, two fungicide imidazole derivatives, completely inhibited growth of Trypanosoma cruzi (Tulahuen strain) at concentrations of about 20 muM. Culturing of T. cruzi in the presence of lower doses of imidazole derivatives produced: decrease of 5,7-diene sterol content in epimastigotes (including ergosterol); disappearance of the nuclear chromatin, vacuolization and decrease in the electron density of the cytoplasm; selective surface alterations as revealed by an increased response to wheat-germ- and phytohemagglutinin. At variance with the effect of miconazole on Candida (De Nollin et al. (1977) Antimicrobial. Agents Chemother. 11, 500-513), miconazole and econazole, under the experimental conditions used, did not increase the rate of hydrogen peroxide generation by T. cruzi. 相似文献
10.
Expression of receptors for plasminogen activators on endothelial cell surface depends on their origin 总被引:4,自引:0,他引:4
Summary. Receptors for plasminogen activators present on endothelial cell (EC) surface regulate local plasmin activity. Plasmin generation by human ECs, derived from cerebral cortex, skin and lung, iliac artery, iliac vein, aorta and coronary artery, was studied. The respective ECs were treated with recombinant tissue plasminogen activator (rt-PA) or with recombinant urokinase-type plasminogen activator (ru-PA), washed, plasminogen added and the plasmin generated then assayed. The largest amounts of plasmin were generated by cerebral ECs, under baseline conditions or after exposure to rt-PA or ru-PA ( P < 0.0001). Exposure to rt-PA also resulted in more plasmin generation than ru-PA in the cerebral ECs ( P < 0.0001) but not in the other ECs. Heparin enhanced plasmin generation by both rt-PA and ru-PA. Specific antibody against annexin II, a t-PA receptor, blocked plasmin generation by rt-PA. Western blotting showed higher amounts of annexin II on the cell membrane in cerebral ECs. This suggests that expression of annexin II in ECs depends on their location, being greatest in cerebral ECs. In contrast, expression of u-PA receptor was the same for all ECs. This has implications for higher risk of intracranial bleeding during thrombolytic therapy, and for a role of t-PA in neurological development and function. 相似文献