• 【晚期结直肠癌患者的黑色素瘤裂解物脉冲树突状细胞疫苗接种: 来自I期研究的报告。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Burgdorf SK,Fischer A,Claesson MH,Kirkin AF,Dzhandzhugazyan KN,Rosenberg J
    BACKGROUND & AIMS: :Immune therapy have shown new and exciting perspectives for cancer treatment. Aim of our study was to evaluate toxicity and possible adverse effects from vaccination of patients with advanced colorectal cancer with autologous dendritic cells (DC) pulsed with lysate from a newly developed melanoma cell line, DDM-1.13. Six patients were enrolled in the phase I trial. Autologous DCs were generated in vitro from peripheral blood monocytes in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). DCs were pulsed with melanoma cell lysate from a cloned and selected melanoma cell line enriched in expression of MAGE-A antigens and deficient in expression of melanoma differentiation antigens: tyrosinase, MART-1 and gp100. Vaccinations were administered intradermally on the proximal thigh with a total of five given vaccines at 2 weeks intervals. Each vaccine contained 3-5 x 10(6) DCs. Five of the six patients received all five vaccines. The treatment was well tolerated in all patients without any observed vaccine-correlated adverse effects. Treatment with this DC-based cancer vaccine proved safe and non-toxic.
    背景与目标: : 免疫疗法为癌症治疗展示了新的令人兴奋的观点。我们研究的目的是评估用新开发的黑色素瘤细胞系DDM-1.13的裂解液对自体树突状细胞 (DC) 进行疫苗接种的毒性和可能的不良反应。6名患者参加了I期试验。在存在粒细胞-巨噬细胞集落刺激因子 (gm-csf) 和interleukin-4 (IL-4) 的情况下,从外周血单核细胞体外产生自体dc。用来自克隆和选择的黑色素瘤细胞系的黑色素瘤细胞裂解液对dc进行脉冲,该细胞系富含MAGE-a抗原的表达,并且缺乏黑色素瘤分化抗原的表达: 酪氨酸酶,MART-1和gp100。在大腿近端皮内接种疫苗,每隔2周共接种5种疫苗。每种疫苗含有3-5x10(6) dc。六名患者中有五名接受了全部五种疫苗。所有患者的治疗耐受性良好,没有观察到任何与疫苗相关的不良反应。使用这种基于DC的癌症疫苗进行治疗被证明是安全且无毒的。
  • 【乳腺癌流行的局部治疗方案对对照临床试验以外生存的影响: 印度北部一家专业乳腺部门的经验。】 复制标题 收藏 收藏
    DOI:10.1007/s00268-006-0037-1 复制DOI
    作者列表:Tewari M,Pradhan S,Kumar M,Shukla HS
    BACKGROUND & AIMS: BACKGROUND:This study aimed at analyzing different treatments of breast cancer (BC) prevalent in the region, their effect on patients' survival, and discusses the most suitable method within available resources. METHODS:The study was set up at a tertiary care hospital in north India. We retrospectively reviewed data of 473 female BC patients who attended the departments of Surgical Oncology and Radiotherapy from January 1997 to December 1999. Patients with cTNM stage IV and inoperable stage III were included; those who defaulted or were lost to follow-up were excluded. Out of 473 patients, 372 were selected. The selected patients were divided into groups on the basis of place and type of local treatment they received: (1) local excision only, (2) standard breast conservation therapy (BCT), (3) total mastectomy (TM) + axillary lymph node dissection + radiotherapy (RT), and (4) modified radical mastectomy (MRM) + RT. Data regarding recurrence and survival were analyzed in December 2005. Minimum follow-up was 6 years. RESULTS:Overall recurrence rates were significantly higher in patients operated elsewhere (P <0.0001). Of 194 operated at our Breast Unit, 25 (14.6%) of 171 MRM patients and none of 23 BCT had recurrence. Of 178 patients operated elsewhere, 44 (100%), 6 (42.9%), 41 (41%), and 8 (40%) developed recurrence in groups 1, 2, 3, and 4 respectively. Overall survival was significantly better in patients with MRM at our unit versus TM outside (93.6% vs. 80%). CONCLUSIONS:Several types of treatment from improper local excision alone, BCT, TM, to a carefully done MRM are prevalent here. Properly done, MRM yields significant local control with survival benefit and appears to remain the gold standard in management of our BC patients.
    背景与目标:
  • 【代表性全科样本中晚年失眠的危险因素。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Morgan K,Clarke D
    BACKGROUND & AIMS: BACKGROUND:Insomnia is widely reported and widely treated in general practice, yet relatively little research has focused on the natural history of the condition in primary care settings. As a result, there is at present little information to enable clinicians to assess insomnia risk, or anticipate outcomes in older general practice populations.

    AIM:To estimate, using 8-year longitudinal data, the risk of insomnia onset associated with selected health and lifestyle factors.

    METHOD:Survivors from a nationally representative sample (n = 1042) of elderly people originally interviewed in 1985 were reassessed in 1989 (n = 690) and 1993 (n = 410). At the first follow up in 1989, 84 new cases of insomnia were identified (a weighted incidence rate per person per year at a risk of 3.1%; 95% CI = 2.7-3.5). In logistic regression analyses controlling for age and sex, the risk of insomnia onset was then assessed in relation to the selected factors.

    RESULTS:Three factors assessed in 1985 were significantly and independently related to incident insomnia: psychometric ratings consistent with depressed mood odds ratio (OR) = 4.41; 95% CI = 3.32-5.43); health index scores indicating lower physical health status (OR = 1.19; 95% CI = 1.06-1.31 per unit change in scale score); and moderate and low levels of physical activity (OR = 1.91 and 2.14; 95% CI = 1.91-3.62 and 2.14-3.64 respectively). However, although depressed mood represented a major risk factor, the most likely source of risk was physical rather than mental ill-health.

    CONCLUSIONS:Psychiatric, somatic and lifestyle factors significantly and independently increase the risk of insomnia in older general practice patients. In predicting incident sleep disturbance, these factors exceed in importance the age and sex of patients.

    背景与目标: 背景 : 失眠在一般实践中已被广泛报道和广泛治疗,但针对初级保健机构中该病的自然史的研究相对较少。因此,目前几乎没有信息可以使临床医生评估失眠风险,或预测老年全科医生的结果。
    目标 : 使用8年的纵向数据进行估计,失眠发作的风险与选定的健康和生活方式因素有关。
    方法 : 1989年 (n = 690) 和1993 (n = 410) 重新评估了来自1985年最初接受采访的具有全国代表性的老年人样本 (n = 1042) 的幸存者。在第一次随访1989年,发现了84例新的失眠病例 (每人每年加权发病率,风险为3.1%; 95% CI = 2.7-3.5)。在控制年龄和性别的逻辑回归分析中,然后根据所选因素评估失眠发作的风险。
    结果 : 1985年评估的三个因素与失眠事件显着且独立相关: 符合抑郁情绪优势比 (OR) = 4.41; 95% CI = 3.32-5.43); 健康指数得分表明较低的身体健康状况 (OR = 1.19; 95% CI = 1.06-1.31每单位变化的量表得分); 和中等和低水平的体育活动 (OR = 1.91和2.14; 95% CI分别 = 1.91-3.62和2.14-3.64)。但是,尽管情绪低落是主要的危险因素,但最可能的危险来源是身体健康而不是精神健康不良。
    结论 : 精神病学,躯体和生活方式因素显着且独立地增加了老年全科患者的失眠风险。在预测事件睡眠障碍时,这些因素的重要性超过了患者的年龄和性别。
  • 【晚期癌症患者对肿瘤基因组分析中次级种系发现的兴趣和态度。】 复制标题 收藏 收藏
    DOI:10.1200/JOP.2016.020057 复制DOI
    作者列表:Hamilton JG,Shuk E,Genoff MC,Rodríguez VM,Hay JL,Offit K,Robson ME
    BACKGROUND & AIMS: PURPOSE:Tumor genomic profiling (TGP) can reveal secondary findings about inherited disease risks in a patient with cancer. Little is known about how patients with advanced cancer, currently the primary users of TGP, perceive the benefits and harms of secondary germline findings. METHODS:We conducted semistructured interviews with 40 patients with advanced breast, bladder, colorectal, or lung cancer who had TGP. Qualitative interview data were evaluated by using a thematic content analysis approach. RESULTS:Most participants expressed interest in the prospect of learning their secondary germline findings (57%), although a minority was equivocal (29%) or disinterested (14%). Reasons for these preferences varied but were influenced by participants' perceptions of diverse benefits and harms of this information, which they regarded as relevant to themselves; their families; and other patients with cancer, medical science, and society. These attitudes were uniquely shaped by participants' personal disease experiences and health status. CONCLUSION:Many patients with advanced cancer are interested in learning secondary germline findings and hold optimistic and perhaps unrealistic beliefs about the potential health benefits. Patients also have important concerns about clinical and emotional implications of this information. These perceptions are necessary to address to ensure that patients make informed decisions about learning secondary germline findings.
    背景与目标:
  • 【腹腔镜胃癌全胃切除术: 我们92例的经验。】 复制标题 收藏 收藏
    DOI:10.3109/13645706.2012.743919 复制DOI
    作者列表:Corcione F,Pirozzi F,Cuccurullo D,Angelini P,Cimmino V,Settembre A
    BACKGROUND & AIMS: INTRODUCTION:Laparoscopic total gastrectomy (LTG) is seldom used for gastric cancer because the complex vascularization and lymphatic drainage makes lymphadenectomy and esophagojejunal anastomosis difficult and requires special skills. Our aim was to demonstrate the feasibility and accuracy of LTG in gastric cancer with D2 lymphadenectomy. MATERIAL AND METHODS:Eighty-eight LTG and four laparoscopic remnant gastrectomies (LRGs) were performed over >12 years. The median patient age was 64 years, and the male/female ratio was 1.49/1. Eighty-seven patients had a D2 and only five patients had a D1 lymphadenectomy. We propose the retrospective analysis of intra- and perioperative mortality and morbidity. RESULTS:In only four of 96 cases approached by laparoscopy, a conversion to laparotomy was needed. There were two (2.17%) perioperative deaths in 92 procedures and few complications. Histological data show 79 advanced gastric cancers (AGC), 11 early gastric cancers (EGC), and two gastric diffused lymphomas. The five-year Kaplan-Meier overall survival in patients with EGC and AGC was 100% and 58%, respectively. CONCLUSIONS:The results demonstrate the feasibility of an oncologically correct minimally invasive total gastrectomy. We would like to promote comparisons among different institutions to achieve better standardization of indications and techniques for a laparoscopic approach to gastric cancer.
    背景与目标:
  • 【贝伐单抗和厄洛替尼靶向治疗适合复发性胶质母细胞瘤患者的分子特征.初步经验。】 复制标题 收藏 收藏
    DOI:10.1007/s00701-012-1536-5 复制DOI
    作者列表:D'Alessandris QG,Montano N,Cenci T,Martini M,Lauretti L,Bianchi F,Larocca LM,Maira G,Fernandez E,Pallini R
    BACKGROUND & AIMS: BACKGROUND:Advances in comprehension of molecular biology of glioblastoma (GBM) have led to the development of targeted therapies. The aim of the present study was to evaluate the efficacy and safety of a targeted therapeutic approach in which administration of bevacizumab and erlotinib was tailored on the molecular profile of recurrent GBM. METHODS:We prospectively enrolled ten adult patients suffering from recurrent GBM who had undergone surgical resection and standard chemo-radiotherapy. Tumor tissue was assessed for the expression of EGFRvIII and MGMT promoter methylation by RT-PCR, and for PTEN and VEGF expression by immunohistochemistry. Normal PTEN status was required for inclusion. Patients with VEGF overexpressing tumors (10/10) were treated with bevacizumab (10 mg/kg iv every 2 weeks in 6-week cycles); patients whose tumor expressed EGFRvIII (4/10) added erlotinib (150 mg/day orally; 300 mg/day if on enzyme-inducing antiepileptic drugs). Therapy was continued until disease progression or unacceptable toxicity. Primary endpoints of the study were response rate (RR), 6-month progression-free survival (PFS-6), and safety profile. RESULTS:The RR and PFS-6 were 100 % (4/4) and 50 % (3/6) in patients treated with bevacizumab+erlotinib (n = 4) and bevacizumab (n = 6), respectively. In the whole cohort (n = 10), RR and PFS-6 were both 70 % (7/10); median PFS and overall survival (OS) were 8.0 (3.0-31.0) and 9.5 (5.0-31.0) months, respectively. No grade 3/4 adverse events were observed; three patients treated with bevacizumab+erlotinib displayed grade 1/2 rash not requiring dose reduction; one patient treated with bevacizumab developed intratumoral hemorrhage requiring treatment discontinuation. CONCLUSION:To our knowledge, this is the first study on recurrent GBM in which administration of bevacizumab and erlotinib was tailored on the molecular profile of the patient's tumor. Although we treated a limited number of patients, we obtained significantly higher RR and PFS-6 than those reported in a previous trial lacking molecular tumor analysis.
    背景与目标:
  • 【通过实践整合行动和大小感知。】 复制标题 收藏 收藏
    DOI:10.1177/0301006617715378 复制DOI
    作者列表:Coutte A,Camus T,Heurley L,Brouillet D
    BACKGROUND & AIMS: :Size perception is known to influence our usual interactions with environment. Numerous studies highlighted that during the visual presentation of an object, the properties of manual actions vary as a function of this object's size. In order to better understand the dynamic variations of relationships between size perception and action, we used an experimental paradigm consisting in two phases. During a previous implicit learning phase, a manual response (right or left) was specifically associated with the appearance of a large or small stimulus. During further test phase, participants were required to prepare a response while discriminating the color of a stimulus (GO/No GO task). We observed that the response execution was faster when the size of the stimulus was congruent with the size that had been associated to this response (during implicit learning phase). These results suggest that when a response usually co-occurs with visual stimuli characterized by a specific size pattern, the response and the size pattern become integrated. Any subsequent preparation and execution of this action are therefore influenced by the reactivation of this visual pattern. This result brings out new insights on how sensorimotor interactions may modulate the ability to anticipate perceptive size variations in the environment.
    背景与目标: : 众所周知,大小感知会影响我们通常与环境的互动。大量研究强调,在对象的视觉呈现过程中,手动动作的属性随对象大小的变化而变化。为了更好地理解大小感知和动作之间关系的动态变化,我们使用了一个由两个阶段组成的实验范例。在先前的内隐学习阶段,手动响应 (右或左) 与大或小刺激的出现特别相关。在进一步的测试阶段,要求参与者在区分刺激颜色的同时准备响应 (GO/No GO任务)。我们观察到,当刺激的大小与与该响应相关的大小一致时 (在隐式学习阶段),响应执行更快。这些结果表明,当响应通常与以特定大小模式为特征的视觉刺激同时发生时,响应和大小模式将成为一体。因此,此操作的任何后续准备和执行都受到此视觉模式重新激活的影响。该结果为感觉运动相互作用如何调节预测环境中感知大小变化的能力带来了新的见解。
  • 【患者咨询课程对一年级药学专业学生的沟通理解,结果期望和自我效能感的影响。】 复制标题 收藏 收藏
    DOI:10.5688/ajpe768152 复制DOI
    作者列表:Rogers ER,King SR
    BACKGROUND & AIMS: OBJECTIVES:To evaluate first-year doctor of pharmacy (PharmD) students' communication apprehension, outcome expectations, and self-efficacy for communication over the duration of a 15-week patient-counseling course. DESIGN:First-year PharmD students (n=94) were asked to complete a 47-item, self-administered questionnaire on 3 occasions over the duration of the Nonprescription Drugs/Patient-Counseling course during the fall 2009 and 2010 semesters. ASSESSMENT:Eighty-seven of 94 students completed the survey instrument across data collection periods. There were significant reductions in total communication apprehension scores and in the communication apprehension subscores for meetings and public speaking, and significant increases in self-efficacy over time. No differences were found for outcome expectations of communication scores or the subscores for interpersonal conversations and group discussion. CONCLUSIONS:Communication apprehension may be decreased and self-efficacy for communication increased in first-year PharmD students through a 15-week Nonprescription Drugs/Patient-Counseling course using small-group practice sessions, case studies, and role-play exercises in conjunction with classroom lectures.
    背景与目标:
  • 【接受乳腺癌手术的女性先进成像应用趋势。】 复制标题 收藏 收藏
    DOI:10.1002/cncr.27838 复制DOI
    作者列表:Breslin TM,Banerjee M,Gust C,Birkmeyer NJ
    BACKGROUND & AIMS: BACKGROUND:Evidence-based guidelines recommend limited perioperative diagnostic imaging for new breast cancer diagnoses. For patients aged >65 years, conventional imaging use (mammography, plain radiographs, and ultrasound) has remained stable, whereas advanced imaging (computed tomography [CT], nuclear medicine scans [positron emission tomography/bone scans], and magnetic resonance imaging [MRI]) use has increased. In this study, the authors evaluated traditional and advanced imaging use among younger patients (aged ≤ 65 years) undergoing breast cancer surgery. METHODS:The MarketScan Commercial Claims and Encounters Research Database from 2005 through 2008 was analyzed to evaluate the use of conventional and advanced diagnostic imaging associated with surgery for ductal carcinoma in situ (DCIS) or stage I through III invasive breast cancer. RESULTS:The study cohort included 52,202 women (13% with DCIS and 87% with stage I-III breast cancer). The proportion of patients undergoing conventional imaging remained stable, whereas the average number of conventional imaging tests per patient increased from 4.21 tests in 2005 to 4.79 tests per patient in 2008 (P < .0001). For advanced imaging, the proportion of women who underwent imaging increased from 48.8% in 2005 to 68.8% in 2008 (P < .0001), as did the number of tests per patient (from 1.53 tests in 2005 to 1.98 tests in 2008; P < .0001). MRI examinations accounted for nearly all of the increase in advanced imaging. Patients who underwent MRI examinations received significantly more traditional imaging tests compared with to those who did not, indicating that these tests are additive and are not replacing traditional imaging. CONCLUSIONS:The current results demonstrate that the use of perioperative breast MRI has increased among women aged <65 years. Further study is indicated to determine whether the benefits of this procedure justify increased use.
    背景与目标:
  • 【胆固醇目标的实现和更高成本的他汀类药物的处方: 一般实践中的横断面研究。】 复制标题 收藏 收藏
    DOI:10.3399/bjgp12X659286 复制DOI
    作者列表:Fleetcroft R,Schofield P,Duerden M,Ashworth M
    BACKGROUND & AIMS: BACKGROUND:There is conflicting evidence as to whether achievement of cholesterol targets at the population level is dependent on the choice and cost of statin. AIM:To investigate the practice-level relationship between cholesterol quality indicators in patients with heart disease, stroke, and diabetes and prescribing of low-cost statins. DESIGN AND SETTING:Correlations and linear regression modelling of retrospective cross-sectional practice-level data with potential explanatory variables in 7909 (96.4%) general practices in England in 2008-2009. METHOD:Quality indicator data were obtained from the Information Centre and prescribing data from the NHS Business Authority. A 'cholesterol quality indicator' score was constructed by dividing the numbers of patients achieving the target for cholesterol control of ≤5 mmol/l in stroke, diabetes, and heart disease by the numbers on each register. A 'low-cost statin' ratio score was constructed by dividing the numbers of defined daily doses of simvastatin and pravastatin by the total numbers of defined daily doses of statins. RESULTS:Simvastatin accounted for 83.3% (standard deviation [SD] = 15.7%) of low-cost statins prescribed and atorvastatin accounted for 85.7% (SD = 14.8%) of high-cost statins prescribed. The mean cholesterol score was 73.7% (SD = 6.0%). Practices using a higher proportion of the low-cost statins were less successful in achieving cholesterol targets. An increase of 10% in the prescribing of low-cost statins was associated with a decrease of 0.46% in the cholesterol quality indicator score (95% confidence interval = -0.54% to -0.38%, P<0.001). CONCLUSION:Greater use of low-cost statins was associated with a small reduction in cholesterol control.
    背景与目标:
  • 【抗pdgfr α 人单克隆抗体Olaratumab在晚期和/或转移性癌症患者中的群体药代动力学模型。】 复制标题 收藏 收藏
    DOI:10.1007/s40262-017-0562-0 复制DOI
    作者列表:Mo G,Baldwin JR,Luffer-Atlas D,Ilaria RL Jr,Conti I,Heathman M,Cronier DM
    BACKGROUND & AIMS: BACKGROUND AND OBJECTIVES:Olaratumab is a recombinant human monoclonal antibody that binds to platelet-derived growth factor receptor-α (PDGFRα). In a randomized phase II study, olaratumab plus doxorubicin met its predefined primary endpoint for progression-free survival and achieved a highly significant improvement in overall survival versus doxorubicin alone in patients with advanced or metastatic soft tissue sarcoma (STS). In this study, we characterize the pharmacokinetics (PKs) of olaratumab in a cancer patient population. METHODS:Olaratumab was tested at 15 or 20 mg/kg in four phase II studies (in patients with nonsmall cell lung cancer, glioblastoma multiforme, STS, and gastrointestinal stromal tumors) as a single agent or in combination with chemotherapy. PK sampling was performed to measure olaratumab serum levels. PK data were analyzed by nonlinear mixed-effect modeling techniques using NONMEM®. RESULTS:The PKs of olaratumab were best described by a two-compartment PK model with linear clearance (CL). Patient body weight was found to have a significant effect on both CL and central volume of distribution (V 1), whereas tumor size significantly affected CL. A small subset of patients developed treatment-emergent anti-drug antibodies (TE-ADAs); however, TE-ADAs did not have any effect on CL or PK time course of olaratumab. There was no difference in the PKs of olaratumab between patients who received olaratumab as a single agent or in combination with chemotherapy. CONCLUSION:The PKs of olaratumab were best described by a model with linear disposition. Patient body weight and tumor size were found to be significant covariates. The PKs of olaratumab were not affected by immunogenicity or chemotherapeutic agents.
    背景与目标:
  • 【在晚期前列腺癌的早期药物开发中检验生物学假设的新策略。】 复制标题 收藏 收藏
    DOI:10.1373/clinchem.2012.185157 复制DOI
    作者列表:Ferraldeschi R,Attard G,de Bono JS
    BACKGROUND & AIMS: BACKGROUND:Major advances in our understanding of the underlying biology of prostate cancer have helped to herald a new era in the treatment of castration-resistant prostate cancer (CRPC), with 5 new agents having shown a survival advantage in the last 3 years and an impressive number of promising novel agents now entering the clinic. CONTENT:We discuss the challenges facing drug development for CRPC and strategies to meet these challenges, with a focus not only on the development of predictive and intermediate endpoint biomarkers, but also on novel hypothesis-testing, biomarker-driven clinical trial designs. SUMMARY:With several promising agents now entering the clinic, there is increasing pressure to rethink drug development for CRPC to ensure that novel agents are appropriately evaluated and that patients and resources are appropriately allocated. We envision that biomarker-driven, reiterative clinical trials will have a major impact on CRPC treatment through the testing of robust scientific hypotheses with rationally designed drugs and drug combinations administered to selected patients.
    背景与目标:
  • 【产后前3周的产妇精神卫生: 护理人员支持的影响和分娩的主观体验-纵向路径模型。】 复制标题 收藏 收藏
    DOI:10.3109/0167482X.2012.730584 复制DOI
    作者列表:Gürber S,Bielinski-Blattmann D,Lemola S,Jaussi C,von Wyl A,Surbek D,Grob A,Stadlmayr W
    BACKGROUND & AIMS: OBJECTIVE:Acute stress reactions (ASR) and postpartum depressive symptoms (PDS) are frequent after childbirth. The present study addresses the change and overlap of ASR and PDS from the 1- to 3-week postpartum and examines the interplay of caregiver support and subjective birth experience with regard to the development of ASR/PDS within a longitudinal path model. METHOD:A total of 219 mothers completed questionnaires about caregiver support and subjective birth experience (Salmon's Item List) at 48-6-h postpartum. ASR and PDS were measured for 1- and 3-week postpartum. The Impact of Event Scale (IES) was used to assess ASR, and the Edinburgh Postnatal Depression Scale (EPDS) was used to assess PDS. RESULTS:ASR was frequent 1-week postpartum (44.7%) and declined till week 3 (24.8%, p <.001), while the prevalence of PDS was continuous (14.2% week 1; 12.6% week 3; p = .380). Favorable reports of caregiver support were related to better subjective childbirth experience, which was related to lower ASR and PDS (controlled for age, mode of delivery, parity, EDA and duration of childbirth). CONCLUSION:High quality of intrapartum care and positive birth experiences facilitate psychological adjustment in the first 3-week postpartum.
    背景与目标:
  • 【在CKD计划中参与初级保健: 英国的经验。】 复制标题 收藏 收藏
    DOI:10.1093/ndt/gfs103 复制DOI
    作者列表:Stevens PE,de Lusignan S,Farmer CK,Tomson CR
    BACKGROUND & AIMS: :Over the last decade, since the introduction of an international classification of chronic kidney disease (CKD) and the development of simple tools to detect people with CKD, primary care has had to adapt to a new paradigm of disease. Significantly, improved identification of CKD, and increased awareness and understanding of the potential associated adverse outcomes, has in turn required the development, implementation and integration of new policies, models and pathways of care. The UK health care system, including primary care, is uniquely positioned to respond to new initiatives. Despite early reservations, CKD has gone from an unheard of condition in primary care prior to 2006 to one where people with this condition are recorded in disease registers and increasingly managed in accordance with evidence-based guidance. National and local initiatives implemented together have contributed to the improved understanding and management of CKD in primary care in the UK and are showing signs of having made significant health gains in CKD.
    背景与目标: : 在过去的十年中,自从引入国际慢性肾脏病 (CKD) 分类和开发简单的工具来检测CKD患者以来,初级保健不得不适应新的疾病范式。值得注意的是,改善对CKD的识别,并提高对潜在相关不良后果的认识和理解,反过来又需要制定,实施和整合新的政策,模式和护理途径。包括初级保健在内的英国医疗保健系统在应对新举措方面处于独特的地位。尽管有早期的保留,但CKD已从2006年前初级保健中闻所未闻的状况转变为将患有这种状况的人记录在疾病登记册中,并根据循证指南进行越来越多的管理。共同实施的国家和地方举措有助于提高英国初级保健对CKD的理解和管理,并显示出在CKD中取得重大健康成就的迹象。
  • 【晚期糖基化终产物的受体: 混杂受体的复杂信号情景。】 复制标题 收藏 收藏
    DOI:10.1016/j.cellsig.2012.11.022 复制DOI
    作者列表:Rojas A,Delgado-López F,González I,Pérez-Castro R,Romero J,Rojas I
    BACKGROUND & AIMS: :Firstly described in 1992, the receptor for advanced glycation end-products has attracted increasing attention due to its diverse ligand repertoire and involvement in several pathophysiological processes associated with inflammation such as in diabetes, cancer, autoimmune diseases and neurodegenerative diseases. This receptor in addition to its binding capacity for advanced glycation end-products also recognizes some molecules classified as both, pathogen- and damage-associated molecular patterns and thus triggering the transcription of genes encoding inflammatory mediators. Some of these ligands are common for both, the receptor of advanced glycation end-products and members of the Toll-like receptor family, generating shared signaling cascades. Furthermore, these receptors may cooperate as essential partners through the recruitment and assembly of homo- and hetero-oligomers in order to strengthen the inflammatory response. The purpose of this review is to highlight the importance of some particular features of this multiligand receptor, its signaling cascade as well as the cross-talk with some members of the Toll-like receptor family.
    背景与目标: 首先,1992年描述,晚期糖基化终产物的受体由于其多样化的配体库和参与与炎症相关的多种病理生理过程,如糖尿病,癌症,自身免疫性疾病和神经退行性疾病,已引起越来越多的关注。该受体除了与高级糖基化终产物的结合能力外,还识别出某些分子,这些分子被归类为与病原体和损伤相关的分子模式,从而触发了编码炎症介质的基因的转录。这些配体中的一些对于晚期糖基化终产物的受体和Toll样受体家族的成员都是共同的,从而产生共享的信号级联。此外,这些受体可以通过招募和组装同质和异质寡聚体作为重要伴侣进行合作,以增强炎症反应。这篇综述的目的是强调这种多配体受体的某些特定特征的重要性,其信号级联以及与Toll样受体家族某些成员的串扰。

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