Salmeterol/fluticasone propionate in a Single Inhaler Device versus theophylline+fluticasone propionate in patients with COPD

STUDY OBJECTIVES: The aim of this study was to compare the relative efficacy in terms of improvement in symptoms and lung function of salmeterol/fluticasone propionate (SLM/FP) combination administered through the Diskus inhaler versus theophylline (THEO) added to FP Diskus in patients with stable chronic obstructive pulmonary disease (COPD). METHODS AND MEASUREMENTS: Eighty patients were randomized to receive 4 months of treatment in one of two treatment groups: (1) fixed combination of SLM 50 microg and FP 500 microg Diskus, 1 inhalation twice daily; or (2) FP Diskus 500 microg, 1 inhalation twice daily, plus oral titrated THEO twice daily. Patients attended the clinic before and after 4, 8, 12 and 16 weeks of treatment for evaluations of pulmonary function, and dyspnea, which was assessed using an analogic visual scale. Also the supplemental salbutamol use was measured. RESULTS:. Sixty-six patients completed the 4-month treatment period: 37 patients receiving SLM/FP and 29 patients receiving THEO+FP. Patients were withdrawn for various reasons, the most common of which were poor compliance with the protocol, exacerbation and GI events. A gradual increase in FEV(1) was observed with each treatment. Maximum significant increases in FEV(1) over baseline values that were observed after 4 months of treatment were as follows: SLM/FP 0.172 l (95% CI: 0.084-0.260) and THEO+FP 0.155 l (95% CI: 0.054-0.256). SLM/FP experienced significantly (p<0.05) greater improvements in dyspnea, and required significantly fewer supplemental salbutamol treatments than the THEO+FP group. CONCLUSIONS: Our results suggest that SLM/FP combination may provide substantial benefits in both physiologic and clinical outcomes in symptomatic patients with COPD. It also causes a more effective control than THEO+FP.     

TSH/cAMP up-regulate sarco/endoplasmic reticulum Ca2+-ATPases expression and activity in PC Cl3 thyroid cells

OBJECTIVE: We recently reported that the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) 2b is the SERCA form preferentially expressed in rat thyroid. Moreover, SERCA2b expression dramatically decreases in virally transformed, highly tumorigenic, PC Cl3 thyroid cells. These results suggest that, in the thyroid, SERCA2b, in addition to its housekeeping role, is linked to differentiation and is a regulated gene. We therefore sought to study the effect of TSH, the main regulator of thyroid function, on SERCA2b expression and activity. METHODS: PC Cl3 cells were hormone starved in low-serum medium and stimulated for long (48 h) or short (1, 2 and 4 h) times. SERCA2b expression and activity were evaluated by Northern and Western blots, Ca2+-ATPase activity and Ca2+ store content. RESULTS: In PC Cl3 cells, SERCA2b mRNA and protein were induced twofold by a 48-h long treatment with TSH. Long-term elevation (48 h) of intracellular cAMP levels, by forskolin or 8-Br-cAMP, had similar effects on SERCA2b mRNA and protein. We also measured Ca2+-ATPase activity and Ca2+ store content. Both long (48 h) and short (0.5-1 h) treatments with TSH, forskolin or 8-Br-cAMP induced a marked increase of SERCA2b activity. This effect was completely abolished by H89, a specific inhibitor of cAMP-dependent protein kinase A (PKA). TSH and 8-Br-cAMP increased Ca2+ store content after both long (48 h) and short (1-2 h) treatments. CONCLUSIONS: These data suggested that TSH/cAMP acts as an important regulator of both SERCA2b expression and activity in the thyroid system, through PKA activation.     

Crystal structure of a eukaryotic zinc-dependent histone deacetylase, human HDAC8, complexed with a hydroxamic acid inhibitor

Histone deacetylases (HDACs) are a family of enzymes involved in the regulation of gene expression, DNA repair, and stress response. These processes often are altered in tumors, and HDAC inhibitors have had pronounced antitumor activity with promising results in clinical trials. Here, we report the crystal structure of human HDAC8 in complex with a hydroxamic acid inhibitor. Such a structure of a eukaryotic zinc-dependent HDAC has not be described previously. Similar to bacterial HDAC-like protein, HDAC8 folds in a single alpha/beta domain. The inhibitor and the zinc-binding sites are similar in both proteins. However, significant differences are observed in the length and structure of the loops surrounding the active site, including the presence of two potassium ions in HDAC8 structure, one of which interacts with key catalytic residues. CD data suggest a direct role of potassium in the fold stabilization of HDAC8. Knockdown of HDAC8 by RNA interference inhibits growth of human lung, colon, and cervical cancer cell lines, highlighting the importance of this HDAC subtype for tumor cell proliferation. Our findings open the way for the design and development of selective inhibitors of HDAC8 as possible antitumor agents.     

Bovine pericardial bioprosthesis in mitral position. A ten-year follow-up

BACKGROUND: The pericardial bovine prosthesis Pericarbon should offer some advantages in comparison with the former generations, because its development is focused on solving previous problems and resulted in the variation of the pericardial fixation method, of valve structure and of stent coating. This hypothesis was evaluated through a retrospective follow-up. METHODS: Between 1985 and 1989, 78 Pericarbon prostheses O 29 were implanted in mitral position by the same surgeon. All patients received warfarin for the first three months to maintain an International Normalized Ratio between 2.5 and 3.5; after which they received antiaggregant therapy indefinitely. With an average follow-up period of 7.34 years for a total of 573 patient-years, we evaluated perioperative and late mortality, late morbidity (thromboembolic and haemorrhagic events, reoperations, primary tissue failures, endocarditic events) and patient clinical conditions. RESULTS: Perioperative mortality was 1.28% (1/78), late mortality was 11.6% (9/77) with 5 valve-related deaths. 5-year survival was 93% and 10-year survival 97%. Fifteen patients required reoperation for prosthetic replacement, fourteen for primary tissue failure. There were ten minor thromboembolic events, one major event, one haemorrhage and one prosthetic endocarditis (the last two with patient exitus). After 10 years (75% of patients were in New York Heart Association class I-II. CONCLUSIONS: Besides the known better haemodynamic performance, Pericarbon bioprosthesis seems to present a survival and redofreedom curve comparable to the best porcine prosthesis, with less incidence of endocarditis, thromboembolic events and prosthesis leakage.     

关于骨质疏松超声诊断仪器亟待厘清的若干基本概念

继双能X线吸收仪之后,定量超声测骨仪器逐渐从群体筛查发展为筛查兼诊断手段,从补充、辅助工具进化成为潜在的主力。然而,在骨质疏松和骨折问题的本质,超声测骨仪器的产品名称、检测参数、派生参数、声学特性参数与骨矿密度相关性、产品性能表征与检验等方面,国内外均存在严重误读。本文就所涉及的一系列基本概念作了系统厘清,以期推动该类产品的科学、健康发展。     

墨旱莲化学成分的分离鉴定

[目的] 对墨旱莲中的化学成分进行分离鉴定。[方法] 采用正相硅胶、反相ODS(十八烷基键合硅胶)、凝胶等柱色谱及制备型高效液相色谱(HPLC)法分离纯化, 并利用质谱分析(MS)、核磁共振波谱(NMR)等方法对化合物结构进行鉴定。[结果] 从墨旱莲体积分数为70%的乙醇提取物中分离鉴定了9个化合物, 分别鉴定为2,2';5', 2"-三联噻酚(1)、5-醛基-2,2';5', 2"-三联噻酚(2)、5-羟甲基-2,2';5', 2"-三联噻酚(3)、2,2';5', 2"-三联噻酚-5-羧酸(4)、5-醛基-5'-(3-丁烯-1-炔基)-2,2'-二联噻酚(5)和5-丁-1'-炔-3'-羟基-4'-氯-(2-戊-1", 3"二炔)-噻酚(6),二氢猕猴桃内酯(7),黑麦草内酯(8),原儿茶酸乙酯(9).[结论] 化合物6～9为首次从鳢肠属植物中分离得到。     

超声造影诊断壶腹部良恶性病变的临床价值

目的探讨超声造影对壶腹部良恶性病变鉴别诊断的临床价值。方法回顾性分析62例经手术病理组织检查或胆道镜检查证实的壶腹部病变患者,包括壶腹部癌16例、胆总管下段癌11例,十二指肠乳头癌6例,胰头癌5例,胆总管下段结石或胆泥21例,十二指肠乳头炎3例。比较常规超声与超声造影对壶腹部病变的显示能力及良恶性病变的诊断正确性,并分析其超声造影表现。结果超声造影对病变显示率98.4%(61/62)明显优于常规超声54.8%(34/62),其差异有统计学意义(P<0.001);常规超声与超声造影对壶腹部病变诊断的准确性、敏感性、特异性分别为50.0%、55.3%、41.7%与95.2%、97.4%、91.7%,两者比较均有统计学差异(P<0.001)。结论超声造影可提高壶腹部病变的显示能力,且有助于病变的良恶性鉴别诊断,对临床指导治疗具有重要价值。     

10例HIV/AIDS相关Burkitt淋巴瘤(BL)临床病理和免疫表型分析

 目的  探讨HIV/AIDS相关Burkitt淋巴瘤(Burkitt lymphoma,BL)的临床病理学形态、免疫表型特点、诊断及其鉴别诊断。方法  按照WHO(2008)造血与淋巴组织肿瘤病理学分类,应用HE染色、免疫组化EnVision法染色、荧光原位杂交(fluorescence in situ hybridization,FISH)及原位杂交并结合临床资料对2010年8月至2013年3月收集的10例HIV/AIDS相关BL进行综合分析。结果  10例患者中活检腋下肿块4例、颈部肿块3例、腹股沟肿块1例、腹部手术切除肿物2例。免疫组化染色瘤细胞均显示IgM、CD20、CD19、CD79a、CD10、Bcl 6阳性,CD5、CD21、CD30、EMA、Bcl 2、CD3、ALK-1、TdT阴性,Ki67增殖指数均＞90%,1例表达CD38及MUM-1,3例c-myc阳性,1例LMP-1阳性,突变型p53阳性表达5例。原位杂交EBER 示3例阳性;FISH示C-MYC基因断裂重组8例t(8;14)(q24;q32)。病理诊断:经典型BL 9例,浆细胞样分化BL 1例。结论  HIV-BL为高度恶性淋巴瘤,预后较差,光镜下易与弥漫大B细胞淋巴瘤和淋巴母细胞性淋巴瘤/白血病等相混淆,结合典型病理表现、免疫组化和FISH技术有助于临床病理诊断及其鉴别诊断。     

大黄贴敷联合复方聚乙二醇电解质散口服对便秘患者肠道准备给药时机的影响

目的探讨大黄贴敷神阙穴和天枢穴联合口服复方聚乙二醇电解质散(PGEP)在便秘患者肠道准备中的给药时机。方法选择行结肠镜检查的便秘患者300例,分3组,各100例。A组检查前1天晚上9点,行中药贴敷神阙穴和天枢穴,检查当天早上5~7点服完PGEP 139.12 g(2 000 ml);B组检查前1天晚上9点行中药贴敷神阙穴和天枢,检查当天上午10~12点服完相同剂量的PGEP;C组检查当天早上5点行中药贴敷神阙穴和天枢穴,早上5~7点服完相同剂量的PGEP。服药后4 h行结肠镜检查。应用Boston肠道准备量表(BBPS)评分,并对肠腔内气泡进行评分,比较3组患者肠道准备有效性、耐受性及安全性。结果 A组的肠镜检查时间(7.25±0.60)min明显短于B组(9.10±0.80)min和C组(10.50±0.55)min;A组的BBPS评分(8.50±0.35)分明显高于B组(7.35±1.25)分和C组(6.65±1.30)分;A组的肠腔内气泡评分(0.25±0.15)分明显低于B组(0.75±0.65)分和C组(0.55±0.50)分;A组肠道准备接受率、再次肠道准备接受率(96.00%、93.00%)明显高于B组(85.00%、70.00%)和C组(90.00%、88.00%);A组的总体不良反应评分(1.45±0.04)分明显低于B组(1.75±0.55)分和C组(1.60±0.25)分。差异均有统计学意义(P0.05)。结论检查前1天晚上9点大黄穴位贴敷联合检查当天早上5~7点口服PGEP对便秘患者行结肠镜检查肠道准备效果好。