• 【缺乏连接蛋白的小鼠没有静脉瓣37。】 复制标题 收藏 收藏
    DOI:10.1016/j.ydbio.2012.10.032 复制DOI
    作者列表:Munger SJ,Kanady JD,Simon AM
    BACKGROUND & AIMS: :Venous valves play a crucial role in blood circulation, promoting the one-way movement of blood from superficial and deep veins towards the heart. By preventing retrograde flow, venous valves spare capillaries and venules from being subjected to damaging elevations in pressure, especially during skeletal muscle contraction. Pathologically, valvular incompetence or absence of valves are common features of venous disorders such as chronic venous insufficiency and varicose veins. The underlying causes of these conditions are not well understood, but congenital venous valve aplasia or agenesis may play a role in some cases. Despite progress in the study of cardiac and lymphatic valve morphogenesis, the molecular mechanisms controlling the development and maintenance of venous valves remain poorly understood. Here, we show that in valved veins of the mouse, three gap junction proteins (Connexins, Cxs), Cx37, Cx43, and Cx47, are expressed exclusively in the valves in a highly polarized fashion, with Cx43 on the upstream side of the valve leaflet and Cx37 on the downstream side. Surprisingly, Cx43 expression is strongly induced in the non-valve venous endothelium in superficial veins following wounding of the overlying skin. Moreover, we show that in Cx37-deficient mice, venous valves are entirely absent. Thus, Cx37, a protein involved in cell-cell communication, is one of only a few proteins identified so far as critical for the development or maintenance of venous valves. Because Cxs are necessary for the development of valves in lymphatic vessels as well, our results support the notion of common molecular pathways controlling valve development in veins and lymphatic vessels.
    背景与目标: : 静脉瓣膜在血液循环中起着至关重要的作用,促进血液从浅静脉和深静脉向心脏的单向运动。通过防止逆行血流,静脉瓣膜备用毛细血管和小静脉不会受到破坏性的压力升高,尤其是在骨骼肌收缩期间。从病理上讲,瓣膜功能不全或瓣膜缺失是静脉疾病的常见特征,例如慢性静脉功能不全和静脉曲张。这些疾病的根本原因尚不清楚,但在某些情况下,先天性静脉瓣膜发育不全或发育不全可能起一定作用。尽管心脏和淋巴管瓣膜形态发生的研究取得了进展,但控制静脉瓣膜发育和维持的分子机制仍知之甚少。在这里,我们显示在小鼠的瓣膜静脉中,三种间隙连接蛋白 (Connexins,Cxs) Cx37,Cx43和Cx47仅在瓣膜中以高度极化的方式表达,其中Cx43位于瓣膜的上游侧小叶和Cx37位于下游侧。令人惊讶的是,上覆皮肤受伤后,在浅静脉的非瓣膜静脉内皮中强烈诱导Cx43表达。此外,我们显示在Cx37-deficient小鼠中,静脉瓣膜完全不存在。因此,Cx37是一种参与细胞-细胞通讯的蛋白质,是迄今为止确定的对静脉瓣膜的发育或维持至关重要的少数蛋白质之一。由于Cxs对于淋巴管中瓣膜的发育也是必需的,因此我们的结果支持控制静脉和淋巴管中瓣膜发育的常见分子途径的概念。
  • 【三级护理中心引发深静脉血栓形成的特征。】 复制标题 收藏 收藏
    DOI:10.1016/j.jvsv.2017.02.006 复制DOI
    作者列表:Brownson KE,Brahmandam A,Huynh N,Reynolds J,Fares WH,Lee AI,Dardik A,Ochoa Chaar CI
    BACKGROUND & AIMS: OBJECTIVE:Provoked deep venous thrombosis (DVT) is precipitated by a specific event. This paper compares the characteristics of provoked DVT in patients with transient risk (TR) factors and patients with continuous risk (CR) factors. METHODS:A retrospective review of records of all consecutive patients diagnosed with DVT between January 2013 and August 2014 was performed. Patients with provoked DVT were included in the TR group if the provoking event resolved in 2 weeks and they did not have ongoing risk of thrombosis. Patients in the CR group had a provoked DVT with ongoing risk of thrombosis due to individual factors deemed to be ongoing risks of thrombosis, such as cancer, hypercoagulable disorder, and prolonged immobilization. Demographics, risk factors, association with pulmonary embolism (PE) and its severity, risk of recurrent venous thromboembolism (VTE), and mortality were compared between the two groups. RESULTS:A total of 838 patients were diagnosed with DVT, and 50.7% (425) were provoked. There were 127 (29.9%) patients with TR and 298 (70.1%) with CR. TR patients were younger (60.4 ± 16.3 vs 65.9 ± 16.0; P = .001). TR was more likely to be provoked by surgery (70.9% vs 55.4%; P = .003), whereas CR was more likely to be provoked by immobilization (21.5% vs 12.6%; P = .032). CR patients were affected by cancer (48.7%) and hypercoagulable disorders (4.4%). TR patients were more likely to have calf DVTs (36.2% vs 26.2%; P = .047). There was a trend toward lower association with PE on presentation in TR (17.3% vs 21.1%; P = .072), but that did not reach statistical significance. However, TR factors were more likely to be associated with low-risk PE compared with CR factors (30.2% vs 54.6%; P = .040). After mean follow-up of 7.2 months, CR had higher risk of recurrent VTE (14.0% vs 6.8%; P = .045) and mortality (23.5% vs 7.1%; P < .0001). CONCLUSIONS:Provoked DVT with CR factors affects older patients and is associated with high recurrence of VTE and mortality compared with provoked DVT with TR factors.
    背景与目标:
  • 【小儿心脏手术后局部静脉血氧饱和度与混合静脉饱和度。】 复制标题 收藏 收藏
    DOI:10.1111/aas.12016 复制DOI
    作者列表:Moreno GE,Pilán ML,Manara C,Magliola R,Vassallo JC,Balestrini M,Lenz AM,Krynski M,Althabe M,Landry L
    BACKGROUND & AIMS: BACKGROUND:Central venous oxygen saturation (ScvO2) remains the gold standard surrogate for tissue oxygen extraction in paediatric cardiac surgery. Near-infrared spectroscopy (NIRS) has been developed as a non-invasive diagnostic tool for regional oxygen saturation. The aim was to compare regional oxygen saturation measured by NIRS with ScvO2 in postoperative paediatric cardiac patients. METHODS:In this prospective study, we included newborns and infants younger than 45 days undergoing heart surgery. We recorded continuous ScvO2 and NIRS regional saturation placed on the forehead (B) and right flank (S) for 48 h postoperatively. A Bland-Altman's analysis was used to assess the agreement between these measurements. RESULTS:A total of 23 patients were included with a median age of 12 days (2-46) and median weight of 3.1 kg (2.3-4.47). The mean difference (MD) ScvO2- B NIRS was 10.45% with limits of agreement (LOA) -17.23 to 38.13% and ScvO2- S NIRS MD 7.16% with LOA: -25.51 to 39.84%. The single ventricle ScvO2- S NIRS subgroup had MD within ± 5%; however, wide LOA was observed. The remaining subgroups showed MD nearly above ± 5%, with wide LOA. CONCLUSIONS:The regional oxygen saturation of brain and kidney did not match ScvO2 as estimation of global tissue perfusion. Nevertheless, NIRS may still provide information regarding regional circulation that may help in the management of neonatal cardiac surgery patients.
    背景与目标:
  • 【核苷 (酸) 类似物治疗对慢性乙型肝炎患者肝癌发生的影响: 倾向评分分析。】 复制标题 收藏 收藏
    DOI:10.1016/j.jhep.2012.10.025 复制DOI
    作者列表:Kumada T,Toyoda H,Tada T,Kiriyama S,Tanikawa M,Hisanaga Y,Kanamori A,Niinomi T,Yasuda S,Andou Y,Yamamoto K,Tanaka J
    BACKGROUND & AIMS: BACKGROUND & AIMS:Some patients with chronic hepatitis B virus (HBV) infection progress to hepatocellular carcinoma (HCC). However, the long-term effect of nucleos(t)ide analogue (NA) therapy on progression to HCC is unclear. METHODS:Therefore, we compared chronic hepatitis B patients who received NA therapy to those who did not, using a propensity analysis. RESULTS:Of 785 consecutive HBV carriers between 1998 and 2008, 117 patients who received NA therapy and 117 patients who did not, were selected by eligibility criteria and propensity score matching. Factors associated with the development of HCC were analyzed. In the follow-up period, HCC developed in 57 of 234 patients (24.4%). Factors significantly associated with the incidence of HCC, as determined by Cox proportional hazards models, include higher age (hazard ratio, 4.36 [95% confidence interval, 1.33-14.29], p=0.015), NA treatment (0.28 [0.13-0.62], p=0.002), basal core promoter (BCP) mutations (12.74 [1.74-93.11], p=0.012), high HBV core-related antigen (HBcrAg) (2.77 [1.07-7.17], p=0.036), and high gamma glutamyl transpeptidase levels (2.76 [1.49-5.12], p=0.001). CONCLUSIONS:NA therapy reduced the risk of HCC compared with untreated controls. Higher serum levels of HBcrAg and BCP mutations are associated with progression to HCC, independent of NA therapy.
    背景与目标:
  • 【内科患者静脉血栓栓塞的预防: 过多还是过少?】 复制标题 收藏 收藏
    DOI:10.2147/CLEP.S38304 复制DOI
    作者列表:Christiansen CF
    BACKGROUND & AIMS: :Venous thromboembolism (VTE) is a potentially serious complication occurring in 1%-2% of hospitalized medical patients. Despite this low absolute risk, as many as 82% of medical patients are considered to be at increased risk of developing VTE and are eligible for medical thromboprophylaxis. In this commentary, The author will discuss the main findings of a recent paper published in Clinical Epidemiology that questions the large proportion of individuals who are eligible for medical thromboprophylaxis, and also discuss the potential implications for the prevention of VTE. The recent paper demonstrated that when a population is divided into high- and low-risk groups, the maximum absolute risk depends on the inverse of the proportion of patients that is considered to be high risk. Consequently, even an effective treatment will only result in a small reduction in the absolute risk when the high-risk group comprises the largest proportion of this population. For medical thromboprophylaxis, this implies that even patients considered to be at high-risk for developing VTE have a maximum absolute VTE risk of 2% when the overall risk is 1.6%. Therefore, even an effective preventive initiative will only result in a small risk reduction. This small potential benefit should be weighed against potential harms associated with prophylaxis, mainly bleeding events. Still, there may be a reasonable overall balance between prevention of pulmonary embolism and major bleeding, mainly because major bleeding events are rare. Nonetheless, this discussion underscores that future risk prediction models should aim to predict the benefits and harms in individual patients in order to provide optimal care for the right patients.
    背景与目标: : 静脉血栓栓塞 (VTE) 是一种潜在的严重并发症,发生在住院患者的1% 2% 中。尽管绝对风险较低,但仍有多达82% 的医疗患者被认为患有VTE的风险增加,并且有资格进行医疗血栓预防。在这篇评论中,作者将讨论最近发表在《临床流行病学》上的一篇论文的主要发现,该论文质疑了有资格进行医疗血栓预防的大部分个体,并讨论了预防VTE的潜在影响。最近的论文表明,当人群分为高风险组和低风险组时,最大绝对风险取决于被认为是高风险的患者比例的倒数。因此,当高危人群占该人群的最大比例时,即使是有效的治疗也只能导致绝对风险的小幅降低。对于医疗血栓预防,这意味着即使被认为处于发生VTE的高风险的患者,当总体风险1.6% 时,也具有2% 的最大绝对VTE风险。因此,即使是有效的预防举措,也只会导致很小的风险降低。应权衡这种小的潜在益处与预防相关的潜在危害,主要是出血事件。尽管如此,预防肺栓塞和大出血之间可能存在合理的总体平衡,主要是因为大出血事件很少。尽管如此,该讨论强调了未来的风险预测模型应旨在预测单个患者的收益和危害,以便为合适的患者提供最佳护理。
  • 【MDMA (± 3,4-亚甲二氧基甲基苯丙胺) 辅助心理治疗治疗耐药性慢性创伤后应激障碍 (PTSD) 的随机对照试验研究。】 复制标题 收藏 收藏
    DOI:10.1177/0269881112464827 复制DOI
    作者列表:Oehen P,Traber R,Widmer V,Schnyder U
    BACKGROUND & AIMS: :Psychiatrists and psychotherapists in the US (1970s to 1985) and Switzerland (1988-1993) used MDMA legally as a prescription drug, to enhance the effectiveness of psychotherapy. Early reports suggest that it is useful in treating trauma-related disorders. Recently, the first completed pilot study of MDMA-assisted psychotherapy for PTSD yielded encouraging results. Designed to test the safety and efficacy of MDMA-assisted psychotherapy in patients with treatment-resistant PTSD; our randomized, double-blind, active-placebo controlled trial enrolled 12 patients for treatment with either low-dose (25 mg, plus 12.5 mg supplemental dose) or full-dose MDMA (125 mg, plus 62.5 mg supplemental dose). MDMA was administered during three experimental sessions, interspersed with weekly non-drug-based psychotherapy sessions. Outcome measures used were the Clinician-Administered PTSD Scale (CAPS) and the Posttraumatic Diagnostic Scale (PDS). Patients were assessed at baseline, three weeks after the second and third MDMA session (end of treatment), and at the 2-month and 1-year follow-ups. We found that MDMA-assisted psychotherapy can be safely administered in a clinical setting. No drug-related serious adverse events occurred. We did not see statistically significant reductions in CAPS scores (p = 0.066), although there was clinically and statistically significant self-reported (PDS) improvement (p = 0.014). CAPS scores improved further at the 1-year follow-up. In addition, three MDMA sessions were more effective than two (p = 0.016).
    背景与目标: : 美国 (20世纪70年代1985年) 和瑞士 (1988-1993) 的精神科医生和心理治疗师合法使用MDMA作为处方药,以提高心理治疗的有效性。早期报告表明,它在治疗创伤相关疾病中很有用。最近,第一个完成的MDMA辅助心理治疗PTSD的初步研究取得了令人鼓舞的结果。旨在测试MDMA辅助心理治疗在治疗耐药的PTSD患者中的安全性和有效性; 我们的随机,双盲,活性安慰剂对照试验招募了12名患者接受低剂量 (25 mg,加12.5 mg补充剂量) 或全剂量MDMA (125 mg,加62.5 mg补充剂量)。MDMA在三个实验课程中进行,并散布在每周的非基于药物的心理治疗课程中。使用的结果指标是临床医生管理的PTSD量表 (CAPS) 和创伤后诊断量表 (PDS)。在基线,第二次和第三次MDMA疗程 (治疗结束) 后三周以及2个月和1年随访时对患者进行评估。我们发现MDMA辅助心理治疗可以在临床环境中安全施用。未发生与药物相关的严重不良事件。尽管有临床和统计学上显着的自我报告 (PDS) 改善 (p = 0.066),但我们没有看到CAPS评分的统计学显着降低 (p = 0.014)。在1年的随访中,CAPS评分进一步提高。此外,三个MDMA会话比两个更有效 (p = 0.016)。
  • 【肺肺泡上皮II型细胞长期暴露于烟草特异性致癌物NNK导致恶性转化: 一种新的体外肺癌发生模型。】 复制标题 收藏 收藏
    DOI:10.1002/mc.21987 复制DOI
    作者列表:Mennecier G,Torres LN,Cogliati B,Sanches DS,Mori CM,Latorre AO,Chaible LM,Mackowiak II,Nagamine MK,Da Silva TC,Fukumasu H,Dagli ML
    BACKGROUND & AIMS: :Lung cancer is the leading cause of cancer-related mortality in both men and women throughout the world. This disease is strongly associated with tobacco smoking. The aim of this manuscript was to establish an in vitro model that mimics the chronic exposures of alveolar epithelial type II cells to the tobacco-specific nitrosamine carcinogen, NNK. Immortalized non-neoplastic alveolar epithelial cells type II, (E10 cells), from BALB/c mice were exposed to low concentration of NNK (100 pM) during 5, 10, 15, and 20 cycles of 48 h. NNK-transformed cells showed an increase of proliferation rate and motility. Moreover, these cells underwent epithelial-to-mesenchymal transition (EMT). Increased migratory capacity and EMT were correlated to the time of exposure to NNK. NNK-transformed cells were tested for their growth and metastatic capacity in vivo. Subcutaneous injection of cells exposed to NNK for 20 cycles (E10-NNK20 clone) into BALB/c mice led to the formation of subcutaneous tumors that arose after 40 ± 17 d in all animals, which died 95 ± 18 d after cell inoculation, with lymph nodes and lung metastasis. The morphological characteristics of tumors were compatible with metastatic undifferentiated carcinoma. Cells exposed to NNK for 5-10 cycles did not display metastatic capacity, while those exposed for 15 cycles displayed low capacity. Our results show that prolonged exposures to NNK led the cells to increasingly acquire malignant properties. The cellular model presented in this study is suitable for studying the molecular events involved in the different stages of malignant transformation.
    背景与目标: : 肺癌是全世界男性和女性癌症相关死亡率的主要原因。这种疾病与吸烟密切相关。本手稿的目的是建立一个体外模型,该模型模拟肺泡上皮II型细胞对烟草特异性亚硝胺致癌物NNK的慢性暴露。来自BALB/c小鼠的永生化的非肿瘤性II型肺泡上皮细胞 (E10细胞) 在48  h的5、10、15和20个周期中暴露于低浓度的NNK (100  pM)。NNK转化的细胞显示出增殖速率和运动能力的增加。此外,这些细胞经历了上皮-间质转化 (EMT)。迁移能力和EMT的增加与NNK暴露时间相关。测试NNK转化的细胞在体内的生长和转移能力。在BALB/c小鼠中皮下注射暴露于NNK 20个周期的细胞 (E10-NNK20克隆) 导致所有动物皮下肿瘤的形成,该肿瘤在40  ±   17 d后出现,在细胞接种后95  ±   18 d死亡,并伴有淋巴结和肺转移。肿瘤的形态特征与转移性未分化癌相容。暴露于NNK 5-10个周期的细胞未显示转移能力,而暴露于15个周期的细胞显示低容量。我们的结果表明,长时间暴露于NNK导致细胞越来越多地获得恶性特性。本研究中提出的细胞模型适用于研究恶性转化不同阶段涉及的分子事件。
  • 【外周静脉疾病与动脉内皮功能障碍的关系: 概念验证研究。】 复制标题 收藏 收藏
    DOI:10.1258/phleb.2012.012048 复制DOI
    作者列表:Moro L,Pedone C,Serino FM,Incalzi RA
    BACKGROUND & AIMS: :The objective of the study was to evaluate the association between peripheral venous disease (PVD) and arterial endothelial dysfunction (ED). Arterial and venous diseases have been always considered as two completely different entities, but the recent discovery of a relationship between arterial and venous thrombosis have challenged this assumption. ED, considered to be an early process in the pathophysiology of atherosclerotic disease, could represent a common pathogenetic background. We studied 39 healthy volunteers (median age: 34 years; men: 25.6%). PVD was diagnosed using ultrasound examination, arterial ED using flow-mediated dilation (FMD) and FMD normalized for the peak shear rate (nFMD). Compared with controls, participants with PVD had a lower FMD (15.2 versus 23.4%, P < 0.001) and nFMD (12.7 × 10(-3) versus 19 × 10(-3)/second, P < 0.001). People with the most clinically evident disease had the worst endothelial function. In conclusion, our findings, if confirmed in larger population, might corroborate the idea that venous and arterial disease could have common causes.
    背景与目标: : 该研究的目的是评估外周静脉疾病 (PVD) 与动脉内皮功能障碍 (ED) 之间的关系。动脉和静脉疾病一直被认为是两个完全不同的实体,但是最近发现动脉和静脉血栓形成之间的关系对这一假设提出了挑战。ED被认为是动脉粥样硬化疾病病理生理的早期过程,可能代表了共同的发病背景。我们研究了39名健康志愿者 (中位年龄: 34岁; 男性: 25.6%)。使用超声检查诊断PVD,使用血流介导的扩张 (FMD) 进行动脉ED,并针对峰值剪切速率 (nFMD) 标准化FMD。与对照组相比,PVD参与者的FMD (15.2 vs 23.4%,P <0.001) 和nFMD (12.7 × 10(-3) vs 19 × 10(-3)/秒,P <0.001) 较低。临床上最明显的疾病患者的内皮功能最差。总之,如果在更多人群中得到证实,我们的发现可能证实了静脉和动脉疾病可能具有共同原因的观点。
  • 【内镜注射硬化疗法治疗肝内和肝外门静脉阻塞儿童静脉曲张出血: 注射道栓塞的益处。】 复制标题 收藏 收藏
    DOI:10.7196/samj.6263 复制DOI
    作者列表:Bandika VL,Goddard EA,De Lacey RD,Brown RA
    BACKGROUND & AIMS: BACKGROUND:The outcome of sclerotherapy for bleeding oesophageal varices may be influenced by injection technique. In a previous study at our institution, sclerotherapy was associated with a high re-bleeding rate and oesophageal ulceration. Embolisation of the injection tract was introduced in an attempt to reduce injection-related complications. METHODS:To determine the outcome and effectiveness of injection tract embolisation in reducing injection-related complications, we retrospectively reviewed a series of 59 children who underwent injection sclerotherapy for oesophageal varices (29 for extrahepatic portal vein obstruction (EHPVO) and 30 for intrahepatic disease) in our centre. RESULTS:Sclerotherapy resulted in variceal eradication in only 11.8% of the children (mean follow-up duration: 38.4 months). Variceal eradication with sclerotherapy alone was achieved in 20.7% and 3.3% of EHPVO and intrahepatic disease patients, respectively. Injection tract embolisation was successful in reducing the number of complications and re-bleeding rates. Complications that arose included: transient pyrexia (16.7%); deep oesophageal ulcers (6.7%); stricture formation (3.3%); and re-bleeding before variceal sclerosis (23%). CONCLUSION:Injection sclerotherapy did not eradicate oesophageal varices in most children. Injection tract embolisation by sclerosant was associated with fewer complications and reduced re-bleeding rates.
    背景与目标:
  • 【以慢性护理为重点的医疗体系的途径: 来自西班牙的证据。】 复制标题 收藏 收藏
    DOI:10.1016/j.healthpol.2012.09.014 复制DOI
    作者列表:García-Goñi M,Hernández-Quevedo C,Nuño-Solinís R,Paolucci F
    BACKGROUND & AIMS: :Increasing healthcare expenditure is a matter of concern in many countries, particularly in relation to the underlying drivers of such escalation that include ageing, medical innovation, and changes in the burden of disease, such as the growing prevalence of chronic diseases. Most healthcare systems in developed countries have been designed to 'cure' acute episodes, rather than to 'manage' chronic conditions, and therefore they are not suitably or efficiently organized to respond to the changing needs and preferences of users. New models of chronic care provision have been developed to respond to the changing burden of disease and there is already considerable practical experience in several different countries showing their advantages but also the difficulties associated with their implementation. In this paper, we focus on the Spanish experience in terms of policy changes and pilot studies focused on testing the feasibility of moving towards chronic care models. In particular, we discuss a framework that identifies and analyses ten key prerequisites to achieving high performing chronic care-based healthcare systems and apply it to the current Spanish National Health System (NHS). We find that the design of the Spanish NHS already meets some of these pre-requisites. However, other features are still in their early stages of development or are being applied only in limited geographical and clinical contexts. We outline the policies that are being implemented and the pathway that the Spanish NHS is taking to address the crucial challenge of the transition towards an optimal health system focused on chronic care. Given the current evidence and trends, we expect that the pathway for developing a chronicity strategy being followed by the Spanish NHS will significantly transform its current healthcare delivery model in the next few years.
    背景与目标: : 在许多国家,医疗保健支出的增加是一个令人关注的问题,特别是在这种升级的潜在驱动因素方面,包括老龄化、医疗创新和疾病负担的变化,例如慢性病的日益流行。发达国家的大多数医疗保健系统旨在 “治愈” 急性发作,而不是 “管理” 慢性病,因此它们没有适当或有效地组织起来以应对用户不断变化的需求和偏好。已经开发了新的长期护理模式,以应对不断变化的疾病负担,几个不同国家已经有相当多的实践经验,显示了它们的优势,但也显示了与实施相关的困难。在本文中,我们着重于西班牙在政策变化方面的经验,并着重于测试转向慢性病模式的可行性的试点研究。特别是,我们讨论了一个框架,该框架确定并分析了实现高性能的基于慢性护理的医疗保健系统的十个关键先决条件,并将其应用于当前的西班牙国家卫生系统 (NHS)。我们发现西班牙NHS的设计已经满足了其中一些先决条件。但是,其他功能仍处于开发的早期阶段,或者仅在有限的地理和临床环境中应用。我们概述了正在实施的政策以及西班牙NHS为应对向以长期护理为重点的最佳卫生系统过渡的关键挑战而采取的途径。鉴于目前的证据和趋势,我们预计西班牙NHS遵循的制定慢性病策略的途径将在未来几年内显着改变其当前的医疗保健模式。
  • 【T细胞缺失骨髓移植后慢性粒细胞性白血病患者嵌合和白血病复发的细胞遗传学分析。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Offit K,Burns JP,Cunningham I,Jhanwar SC,Black P,Kernan NA,O'Reilly RJ,Chaganti RS
    BACKGROUND & AIMS: :Serial cytogenetic studies were performed on 64 patients with chronic myelogenous leukemia (CML) after T cell-depleted allogeneic bone marrow transplantation (BMT). Forty patients with CML in chronic phase (CP) received cytoreduction followed by BMT with HLA-matched T cell-depleted allogeneic marrow. The remaining 24 patients were transplanted in second chronic, accelerated, or blastic phase, or received T cell-depleted grafts with a dose of T cells added back. The Y chromosome and autosomal heteromorphisms were used to distinguish between donor and host cells. Mixed hematopoietic chimerism (presence of donor and host cells) was identified in 90% of patients in first CP. The Philadelphia (Ph) chromosome reappeared in 16 of the 40 first CP CML patients. As expected, patients who had detectable Ph chromosome positive cells at any time during the posttransplant period had a high likelihood of subsequent clinical relapse. Transient disappearance of the Ph positive clone was rarely observed, and was followed by reappearance of the Ph chromosome or clinical relapse. A subset of engrafted patients with greater than 25% host cells within 3 months post-BMT had a significantly shorter survival time free of cytogenetic or clinical relapse compared with other patients. In patients who had received donor T cells added to the T cell-depleted graft, there was a higher proportion of complete chimerism. Clonal progression of Ph positive as well as negative cells was observed and may be the result of radiation induced breakage. Serial cytogenetic studies of patients post-BMT can provide useful information regarding the biologic and clinical behavior of CML.
    背景与目标: : 在T细胞耗尽的同种异体骨髓移植 (BMT) 后,对64例慢性粒细胞性白血病 (CML) 患者进行了系列细胞遗传学研究。40例慢性期 (CP) 的CML患者接受了细胞减灭,然后接受了HLA匹配的T细胞耗尽的同种异体骨髓的BMT。其余24例患者被移植到第二个慢性,加速或母细胞期,或接受T细胞耗尽的移植物,并加回一定剂量的T细胞。Y染色体和常染色体异形被用来区分供体细胞和宿主细胞。在第一个CP的90% 患者中鉴定出混合的造血嵌合体 (供体和宿主细胞的存在)。费城染色体重新出现在40例第一批CP CML患者中的16例中。如预期的那样,在移植后的任何时候都具有可检测到的Ph染色体阳性细胞的患者随后临床复发的可能性很高。很少观察到Ph阳性克隆的瞬时消失,随后出现Ph染色体或临床复发。与其他患者相比,BMT后3个月内移植的宿主细胞大于25% 的患者亚群的无细胞遗传学或临床复发的生存时间明显更短。在接受T细胞耗尽移植物中添加了供体T细胞的患者中,完全嵌合的比例更高。观察到Ph阳性细胞和阴性细胞的克隆进程,这可能是辐射引起的破坏的结果。BMT后患者的一系列细胞遗传学研究可以提供有关CML生物学和临床行为的有用信息。
  • 【维生素d减少左心室肥厚和慢性肾脏疾病患者的左心房体积。】 复制标题 收藏 收藏
    DOI:10.1016/j.ahj.2012.09.018 复制DOI
    作者列表:
    BACKGROUND & AIMS: BACKGROUND:Left atrial enlargement, a sensitive integrator of left ventricular diastolic function, is associated with increased cardiovascular morbidity and mortality. Vitamin D is linked to lower cardiovascular morbidity, possibly modifying cardiac structure and function; however, firm evidence is lacking. We assessed the effect of an activated vitamin D analog on left atrial volume index (LAVi) in a post hoc analysis of the PRIMO trial (clinicaltrials.gov: NCT00497146). METHODS AND RESULTS:One hundred ninety-six patients with chronic kidney disease (estimated glomerular filtration rate 15-60 mL/min per 1.73 m(2)), mild to moderate left ventricular hypertrophy, and preserved ejection fraction were randomly assigned to 2 μg of oral paricalcitol or matching placebo for 48 weeks. Two-dimensional echocardiography was obtained at baseline and at 24 and 48 weeks after initiation of therapy. Over the study period, there was a significant decrease in LAVi (-2.79 mL/m(2), 95% CI -4.00 to -1.59 mL/m(2)) in the paricalcitol group compared with the placebo group (-0.70 mL/m(2) [95% CI -1.93 to 0.53 mL/m(2)], P = .002). Paricalcitol also attenuated the rise in levels of brain natriuretic peptide (10.8% in paricalcitol vs 21.3% in placebo, P = .02). For the entire population, the change in brain natriuretic peptide correlated with change in LAVi (r = 0.17, P = .03). CONCLUSIONS:Forty-eight weeks of therapy with an active vitamin D analog reduces LAVi and attenuates the rise of BNP. In a population where only few therapies alter cardiovascular related morbidity and mortality, these post hoc results warrant further confirmation.
    背景与目标:
  • 【慢性纳曲酮治疗可增加离散脑区域中前脑啡肽和前激肽mRNA的表达。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Tempel A,Kessler JA,Zukin RS
    BACKGROUND & AIMS: :Long-term blockade of brain opioid receptors by the opiate antagonist naltrexone increases methionine-enkephalin content in the striatum and nucleus accumbens (Tempel et al., 1984). To determine whether these changes in peptide levels reflect increased peptide synthesis, we examined preproenkephalin mRNA content in discrete brain regions of control (placebo-treated) and chronic naltrexone-treated animals by Northern analysis. Chronic naltrexone treatment (8 d) led to an approximately 12-fold increase in the striatal content of preproenkephalin mRNA relative to that of control animals. In contrast, no statistically significant change was observed in striatal mRNA for cyclophilin (1B15) or actin. Small increases in preproenkephalin mRNA content occurred in the hippocampus (+40%) and hypothalamus (+19%). No significant changes occurred in the frontal cortex. Increases in levels of the mRNA were seen as early as 24 hr after antagonist treatment. In contrast, changes in opioid receptor density required 3-4 d to reach half-maximal up-regulation after chronic antagonist treatment. Recent evidence has suggested that substance P is regulated by opioid peptides. To determine whether substance P synthesis is altered by chronic antagonist treatment, the mRNA corresponding to the precursor for substance P was examined using a probe for exon-7 of the preprotachykinin gene. Preprotachykinin mRNA content in the striatum was increased 6-fold after chronic antagonist treatment relative to that of control animals. Substance P content was increased 3-fold after chronic antagonist treatment. These data suggest that chronic blockade of brain opioid receptors leads to the increased synthesis of both enkephalin and substance P in the striatum and that these changes are relatively specific.(ABSTRACT TRUNCATED AT 250 WORDS)
    背景与目标: 鸦片拮抗剂纳曲酮对脑阿片受体的长期阻断增加纹状体和伏隔核中的蛋氨酸-脑啡肽含量 (Tempel等,1984)。为了确定肽水平的这些变化是否反映了肽合成的增加,我们通过Northern分析检查了对照组 (安慰剂治疗) 和慢性纳曲酮治疗动物的离散大脑区域中的前脑啡肽mRNA含量。与对照动物相比,慢性纳曲酮治疗 (8 d) 导致前脑啡肽前mRNA的纹状体含量增加了约12倍。相反,亲环蛋白 (1B15) 或肌动蛋白的纹状体mRNA未观察到统计学上的显着变化。前脑啡肽mRNA含量在海马 (+ 40%) 和下丘脑 (+ 19%) 中出现少量增加。额叶皮层无明显变化。早在拮抗剂治疗后24小时,就可以看到mRNA水平的升高。相比之下,慢性拮抗剂治疗后,阿片受体密度的变化需要3-4 d才能达到一半的最大上调。最近的证据表明,p物质受阿片肽调节。为了确定是否通过慢性拮抗剂治疗改变了p物质的合成,使用用于exon-7预速激肽基因的探针检查了对应于p物质前体的mRNA。与对照动物相比,慢性拮抗剂治疗后,纹状体中的促前激肽mRNA含量增加了6倍。慢性拮抗剂治疗后,p物质含量增加了3倍。这些数据表明,大脑阿片受体的慢性阻断导致纹状体中脑啡肽和p物质的合成增加,并且这些变化是相对特定的。(摘要截短于250字)
  • 【CD11c在慢性淋巴细胞白血病中的表达与并发症和生存有关。】 复制标题 收藏 收藏
    DOI:10.1111/ijlh.12695 复制DOI
    作者列表:Umit EG,Baysal M,Durmus Y,Demir AM
    BACKGROUND & AIMS: INTRODUCTION:Chronic lymphocytic leukemia (CLL) is a disorder of mature but dysfunctional monoclonal B cells. Microenvironment, antigenic stimulation and genetical mutations are demonstrated in etiopathogenesis. We aimed to evaluate the expression of CD11c in patients with CLL and its possible clinical significance. METHODS:Data of 259 patients with CLL between 2010 and 2016 in Trakya University Faculty of Medicine, including age at diagnosis, sex, whole blood count, stage, percentage of CLL cells in bone marrow, line of treatments, development of Richter's transformation and secondary tumors, autoimmune complications, IgG level, prognostic cytogenetic analysis, and length of survival were recorded from files. RESULTS:151 patients were male (58.3%) and 108 were male (41.7%). Mean age was 70 (21-92) years. CD11c was observed to be positive (>%20) in 103 patients (39.8%). Development of Richter's transformation, secondary tumors and ITP was significantly frequent in patients with CD11c positivity (P values .000, .003, .000 respectively). Also, IgG levels were significantly lower in this group (P = .000). Hemoglobin level, RAI stage and bone marrow CLL infiltration percentage were statistically related with CD11c (P values .036, .037, .000 respectively). Finally, CD11c was statistically related (in positive group 70 months, negative group 79 months, P = .001). CONCLUSION:CD11c, expressed not only in Hairy cell leukemia but also in dendritic cells, macrophages and monocytes is a differentiation marker for inflammation. Prolonged inflammation in the microenvironment of CLL cells may cause a susceptibility to autoimmune disorders and secondary tumors in CLL, in this way, an increase in mortality.
    背景与目标:
  • 【慢性边缘牙周炎患者牙髓变化的微观方面。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Caraivan O,Manolea H,Corlan Puşcu D,Fronie A,Bunget A,Mogoantă L
    BACKGROUND & AIMS: :Chronic periodontitis is one of the most frequent and severe diseases involving the tooth. Untreated, they can lead to tooth loss. Our study involved 67 patients with chronic marginal periodontitis who underwent tooth extraction, of which 29 had moderate periodontal lesions and 38 severe periodontal lesions. The microscopic study of the dental pulp revealed significant changes in all patients. In patients with moderate periodontitis the pulp tissue was found to be the site of an enhanced process of collagenous fibrosis associated with a moderate inflammatory infiltrate, dystrophic mineralization, reduced blood vascularization and arteriolosclerosis. The dental pulp of patients with severe periodontitis showed an abundant chronic inflammatory infiltrate associated with pulpal necrosis, vascular congestion, microhemorrhages, dentin demineralization and odontoblast impairment.
    背景与目标: : 慢性牙周炎是涉及牙齿的最常见和最严重的疾病之一。如果不治疗,它们会导致牙齿脱落。我们的研究涉及67例接受拔牙的慢性边缘牙周炎患者,其中29例患有中度牙周病变,38例患有严重牙周病变。牙髓的显微镜研究显示,所有患者均发生了显着变化。在中度牙周炎患者中,发现牙髓组织是胶原性纤维化过程增强的部位,与中度炎症浸润,营养不良矿化,血液血管化减少和动脉硬化相关。严重牙周炎患者的牙髓显示出大量的慢性炎症浸润,与牙髓坏死,血管充血,微出血,牙本质脱矿质和成牙本质损伤有关。

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