• 【表面上健康的男性和女性的组织因子血清水平和未来冠状动脉疾病的风险: EPIC-Norfolk前瞻性人群研究。】 复制标题 收藏 收藏
    DOI:10.1111/j.1538-7836.2006.02190.x 复制DOI
    作者列表:Keller TT,Choi D,Nagel C,Te Velthuis H,Gerdes VE,Wareham NJ,Bingham SA,Luben R,Hack CE,Reitsma PH,Levi M,Khaw KT,Boekholdt SM
    BACKGROUND & AIMS: INTRODUCTION:Tissue factor (TF) has been implicated in coronary artery disease (CAD). High levels of circulating TF are found in patients with acute atherothrombotic events. Whether high serum TF levels predict risk of future CAD independent of known risk factors remains unknown. METHODS:We conducted a prospective case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk population study. Cases (n=1037) were apparently healthy men and women, aged 45-79 years, who developed fatal or non-fatal CAD during follow-up. Controls (n=2005) were matched by age, sex, and enrolment time. Serum TF levels were measured using high-affinity antibodies. RESULTS:In men, median TF levels were not significant higher in cases than in controls (59.0 pg mL-1, range: 16.7-370.4 vs. 54.9 pg mL-1, range: 16.2-452.4). In women, median TF levels were not significant higher in controls than in cases (73.4 pg mL-1, range: 16.7-492.3 vs. 50.5 pg mL-1, range: 16.5-376.7). The incidence of smoking was about double in the lowest compared with the highest TF quartile. Correcting for sex, age, body mass index, smoking, diabetes, systolic blood pressure, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol and C-reactive protein levels, the risk of future CAD was 1.05 (95% CI: 0.81-1.36) for people in the highest TF quartile, compared with those in the lowest (P-value for linearity=0.8). CONCLUSION:High levels of serum TF were not independently associated with an increased risk of future CAD in apparently healthy individuals.
    背景与目标:
  • 【庞贝病骨骼肌自噬和治疗酶的误用。】 复制标题 收藏 收藏
    DOI:10.1016/j.ymthe.2006.08.009 复制DOI
    作者列表:Fukuda T,Ahearn M,Roberts A,Mattaliano RJ,Zaal K,Ralston E,Plotz PH,Raben N
    BACKGROUND & AIMS: :Enzyme replacement therapy (ERT) became a reality for patients with Pompe disease, a fatal cardiomyopathy and skeletal muscle myopathy caused by a deficiency of glycogen-degrading lysosomal enzyme acid alpha-glucosidase (GAA). The therapy, which relies on receptor-mediated endocytosis of recombinant human GAA (rhGAA), appears to be effective in cardiac muscle, but less so in skeletal muscle. We have previously shown a profound disturbance of the lysosomal degradative pathway (autophagy) in therapy-resistant muscle of GAA knockout mice (KO). Our findings here demonstrate a progressive age-dependent autophagic buildup in addition to enlargement of glycogen-filled lysosomes in multiple muscle groups in the KO. Trafficking and processing of the therapeutic enzyme along the endocytic pathway appear to be affected by the autophagy. Confocal microscopy of live single muscle fibers exposed to fluorescently labeled rhGAA indicates that a significant portion of the endocytosed enzyme in the KO was trapped as a partially processed form in the autophagic areas instead of reaching its target--the lysosomes. A fluid-phase endocytic marker was similarly mistargeted and accumulated in vesicular structures within the autophagic areas. These findings may explain why ERT often falls short of reversing the disease process and point toward new avenues for the development of pharmacological intervention.
    背景与目标: : 酶替代疗法 (ERT) 已成为Pompe病患者的现实,Pompe病是一种致命的心肌病和骨骼肌肌病,该病是由糖原降解溶酶体酶酸 α-葡萄糖苷酶 (GAA) 缺乏引起的。该疗法依赖于重组人GAA (rhGAA) 的受体介导的内吞作用,似乎对心肌有效,但对骨骼肌无效。我们以前已经显示出GAA基因敲除小鼠 (KO) 的抗药性肌肉中溶酶体降解途径 (自噬) 的严重干扰。我们在这里的发现表明,除了在KO的多个肌肉群中增加糖原填充的溶酶体外,还存在逐渐的年龄依赖性自噬积累。治疗酶沿内吞途径的运输和加工似乎受到自噬的影响。暴露于荧光标记的rhGAA的活的单根肌肉纤维的共聚焦显微镜显示,KO中很大一部分内吞酶被捕获为自噬区域中的部分加工形式,而不是达到其目标-溶酶体。类似地,液相内吞标记物被错误地捕获并积累在自噬区域内的囊泡结构中。这些发现可以解释为什么ERT经常无法逆转疾病过程,并为药物干预的发展指明了新的途径。
  • 【重组人可溶性肿瘤坏死因子受体融合蛋白治疗异基因造血干细胞移植后类固醇难治性移植物抗宿主病.】 复制标题 收藏 收藏
    DOI:10.1002/ajh.20752 复制DOI
    作者列表:Busca A,Locatelli F,Marmont F,Ceretto C,Falda M
    BACKGROUND & AIMS: :Etanercept is a recombinant human soluble tumor necrosis factor (TNF-alpha) receptor fusion protein that inhibits TNF-alpha, a major mediator in the pathogenesis of graft-versus-host disease (GVHD). The purpose of our study was to evaluate the safety and efficacy of etanercept therapy in 21 patients with steroid-refractory acute GVHD (aGVHD) (n = 13) and chronic GVHD (cGVHD) (n = 8). Etanercept 25 mg was given subcutaneously twice weekly for 4 weeks followed by 25 mg weekly for 4 weeks. At the time of initiation of etanercept, 14 patients had skin, 13 had gastro-intestinal, 5 had liver, 5 had pulmonary, and 4 had oral involvement. Twelve patients (57%) completed 12 doses of therapy. Overall, 11 of 21 patients (52%) responded to the treatment with etanercept, including 6 patients (46%) with aGVHD [n = 4 complete response (CR), n = 2 partial response (PR)] and 5 patients (62%) with cGVHD (n = 1 CR, n = 4 PR). Clinical responses were most commonly seen in patients with refractory gut aGVHD with 55% of the patients having a CR and 9% having a PR. CMV reactivation occurred in 48% of patients, bacterial infections in 14% of patients, and fungal infections in 19% of patients. Fourteen patients (67%) were alive after a median follow-up of 429 days (range 71-1007 days) since initiation of etanercept. Seven patients died, 3 of infections, 2 of refractory aGVHD, and 2 of disease progression. In conclusion, our preliminary data indicate that etanercept is well tolerated and can induce a high response rate in patients with steroid-refractory aGVHD and cGVHD, particularly in the setting of GI involvement.
    背景与目标: : 依那西普是一种重组人可溶性肿瘤坏死因子 (TNF-α) 受体融合蛋白,可抑制TNF-α,TNF-α 是移植物抗宿主病 (GVHD) 发病机理中的主要介质。我们研究的目的是评估依那西普治疗21例类固醇难治性急性GVHD (aGVHD) (n = 13) 和慢性GVHD (cGVHD) (n = 8) 患者的安全性和有效性。依那西普25 mg,每周皮下注射两次,持续4周,然后每周注射25 mg,持续4周。在开始使用依那西普时,14例患者有皮肤,13例有胃肠道,5例有肝脏,5例有肺部,4例有口腔受累。12名患者 (57%) 完成12剂治疗。总体而言,21例患者中有11例 (52%) 对依那西普治疗有反应,其中6例 (46% 例) aGVHD [n = 4完全缓解 (CR),n = 2部分缓解 (PR)] 和5例 (62%) cGVHD (n = 1 CR,n = 4 PR)。临床反应最常见于难治性肠道aGVHD患者,其中55% 患者具有CR,9% 患者具有PR。48% 患者发生CMV再激活,14% 患者发生细菌感染,19% 患者发生真菌感染。自依那西普开始以来,中位随访429天 (范围71-1007天) 后,有14名患者 (67%) 还活着。7例患者死亡,3例感染,2例难治性aGVHD,2例疾病进展。总之,我们的初步数据表明,依那西普具有良好的耐受性,并且可以在类固醇难治性aGVHD和cGVHD患者中诱导高反应率,尤其是在GI受累的情况下。
  • 【克罗恩病的Interleukin-12和Th1免疫反应: 发病相关性和治疗意义。】 复制标题 收藏 收藏
    DOI:10.3748/wjg.v12.i35.5606 复制DOI
    作者列表:Peluso I,Pallone F,Monteleone G
    BACKGROUND & AIMS: :Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory disorders of the gastrointestinal tract that share clinical and pathological characteristics. The most accredited hypothesis is that both CD and UC result from a deregulated mucosal immune response to normal constituents of the gut microflora. Evidence, however, indicates that the main pathological processes in these two diseases are distinct. In CD, the tissue-damaging inflammatory reaction is driven by activated type 1 helper T-cell (Th1), whereas a humoral response predominates in UC. Consistently, a marked accumulation of macrophages making interleukin (IL)-12, the major Th1-inducing factor, is seen in CD but not in UC mucosa. Preliminary studies also indicate that administration of a monoclonal antibody blocking the IL-12/p40 subunit can be useful to induce and maintain clinical remission in CD patients. Notably, the recently described IL-23 shares the p40 subunit with IL-12, raising the possibility that the clinical benefit of the anti-IL-12/p40 antibody in CD may also be due to the neutralization of IL-23 activity. This review summarizes the current information on the expression and functional role of IL-12 and IL-12-associated signaling pathways both in patients with CD and experimental models of colitis, thus emphasizing major differences between IL-12 and IL-23 activity on the development of intestinal inflammation.
    背景与目标: 克罗恩病 (CD) 和溃疡性结肠炎 (UC) 是胃肠道的慢性炎症性疾病,具有共同的临床和病理特征。最受认可的假设是,CD和UC都是由于对肠道微生物群落正常成分的粘膜免疫反应失调所致。然而,有证据表明,这两种疾病的主要病理过程是不同的。在CD中,破坏组织的炎症反应是由激活的1型辅助T细胞 (Th1) 驱动的,而在UC中,体液反应占主导地位。一致地,在CD中观察到产生主要Th1-inducing因子白介素 (IL)-12的巨噬细胞的明显积累,但在UC粘膜中未见。初步研究还表明,施用阻断IL-12/p40亚基的单克隆抗体可用于诱导和维持CD患者的临床缓解。值得注意的是,最近描述的IL-23与IL-12共享p40亚基,这增加了CD中anti-IL-12/p40抗体的临床益处也可能归因于IL-23活性的中和的可能性。这篇综述总结了有关CD患者和结肠炎实验模型中IL-12和IL-12-associated信号通路的表达和功能作用的最新信息,从而强调了IL-12和IL-23活性在肠道炎症发展中的主要差异。
  • 【MRI引导的阿尔茨海默病内侧颞叶血流的SPECT测量。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Julin P,Lindqvist J,Svensson L,Slomka P,Wahlund LO
    BACKGROUND & AIMS: UNLABELLED:In this study, we assessed the accuracy and reliability of MRI-guided SPECT measurements of medial temporal lobe blood flow in Alzheimer's disease (AD).

    METHODS:Interactively aligned three-dimensional MP-RAGE MRI and 99mTc-HMPAO SPECT images were used for MRI-guided measurement of medial temporal lobe CBF in eight control subjects and eight patients with probable AD. Intraoperator reliability was assessed by repeated alignment and measurement by one experienced operator. Accuracy was assessed by examining two subjects with fiducial markers.

    RESULTS:The alignment error was less than 1 SPECT pixel size (3.5 mm) and the coefficient of variation in repeated measures of medial temporal-to-cerebellar CBF ratios was 3.2%. The difference in mean medial temporal-to-cerebellar CBF ratios between eight control subjects and eight AD patients was 12%. Also by using three-dimensional seed-grow defined healthy brain reference regions, there were significant differences between control subjects and AD patients in medial temporal blood flow. Furthermore, the volumes of the MRI-defined medial temporal ROIs were smaller in the AD patients. The best separation between AD patients and control subjects was achieved by combining MRI measurements of atrophy and SPECT measurements of CBF.

    CONCLUSION:These data show that the accuracy and reliability of MRI-guided SPECT measurements of medial temporal CBF clearly allow the detection of changes in AD. Also, a direct comparison of structural and functional changes is possible by this methodology, which might improve the early diagnosis of AD.

    背景与目标: 未标记 : 在这项研究中,我们评估了MRI引导的SPECT测量阿尔茨海默氏病 (AD) 内侧颞叶血流的准确性和可靠性。
    方法 : 交互式对齐的三维MP-RAGE MRI和99mTc-HMPAO SPECT图像用于MRI引导的8名对照受试者和8名可能患有AD的患者的内侧颞叶CBF测量。一位经验丰富的操作员通过重复对准和测量来评估操作员内部的可靠性。通过检查两个具有基准标记的受试者来评估准确性。
    结果 : 对齐误差小于1 SPECT像素大小 (3.5毫米),并且重复测量的变异系数内侧颞-小脑CBF比3.2%。12% 了八名对照受试者和八名AD患者之间平均内侧颞与小脑CBF比率的差异。同样,通过使用三维种子生长定义的健康大脑参考区域,对照组和AD患者在内侧颞血流方面存在显着差异。此外,在AD患者中,MRI定义的内侧颞roi的体积较小。通过结合萎缩的MRI测量和CBF的SPECT测量,可以实现AD患者与对照组之间的最佳分离。
    结论 : 这些数据表明,MRI引导的内侧颞CBF SPECT测量的准确性和可靠性显然可以检测AD的变化。此外,通过这种方法可以直接比较结构和功能变化,这可能会改善AD的早期诊断。
  • 【氯氮平治疗帕金森氏病左旋多巴诱发的精神病: 回顾性研究。】 复制标题 收藏 收藏
    DOI:10.1177/089198879701000205 复制DOI
    作者列表:Widman LP,Burke WJ,Pfeiffer RF,McArthur-Campbell D
    BACKGROUND & AIMS: Levodopa-induced psychosis can complicate the treatment of Parkinson's disease (PD). In this retrospective, uncontrolled report, we describe our experience treating PD-related psychosis with clozapine, emphasizing those patients treated for longer than 1 year. Twenty-seven patients were treated, 14 for longer than 1 year. Most patients showed a rapid improvement from baseline within 1 month using the Clinical Global Impression and Global Psychosis Rating Scores. Five patients discontinued the drug due to side effects, but only two patients reported side effects after 6 months of treatment. Clozapine appears to be effective in treating PD related psychotic symptoms while not interfering with motor function.

    背景与目标: 左旋多巴引起的精神病会使帕金森氏病 (PD) 的治疗复杂化。在这份回顾性,不受控制的报告中,我们描述了我们用氯氮平治疗PD相关精神病的经验,强调了那些治疗时间超过1年的患者。27例患者接受了治疗,其中14例超过1年。使用临床总体印象和总体精神病评分,大多数患者在1个月内从基线显示出快速改善。五名患者因副作用而停药,但只有两名患者在治疗6个月后报告副作用。氯氮平似乎可有效治疗PD相关的精神病性症状,同时不干扰运动功能。
  • 【在其他健康的分枝杆菌疾病患者中发现新的STAT1等位基因。】 复制标题 收藏 收藏
    DOI:10.1371/journal.pgen.0020131 复制DOI
    作者列表:
    BACKGROUND & AIMS: :The transcription factor signal transducer and activator of transcription-1 (STAT1) plays a key role in immunity against mycobacterial and viral infections. Here, we characterize three human STAT1 germline alleles from otherwise healthy patients with mycobacterial disease. The previously reported L706S, like the novel Q463H and E320Q alleles, are intrinsically deleterious for both interferon gamma (IFNG)-induced gamma-activating factor-mediated immunity and interferon alpha (IFNA)-induced interferon-stimulated genes factor 3-mediated immunity, as shown in STAT1-deficient cells transfected with the corresponding alleles. Their phenotypic effects are however mediated by different molecular mechanisms, L706S affecting STAT1 phosphorylation and Q463H and E320Q affecting STAT1 DNA-binding activity. Heterozygous patients display specifically impaired IFNG-induced gamma-activating factor-mediated immunity, resulting in susceptibility to mycobacteria. Indeed, IFNA-induced interferon-stimulated genes factor 3-mediated immunity is not affected, and these patients are not particularly susceptible to viral disease, unlike patients homozygous for other, equally deleterious STAT1 mutations recessive for both phenotypes. The three STAT1 alleles are therefore dominant for IFNG-mediated antimycobacterial immunity but recessive for IFNA-mediated antiviral immunity at the cellular and clinical levels. These STAT1 alleles define two forms of dominant STAT1 deficiency, depending on whether the mutations impair STAT1 phosphorylation or DNA binding.
    背景与目标: 转录因子信号转导和转录激活因子-1 (STAT1) 在抵抗分枝杆菌和病毒感染的免疫中起关键作用。在这里,我们描述了来自其他健康的分枝杆菌疾病患者的三个人类STAT1种系等位基因。先前报道的L706S,如新型Q463H和E320Q等位基因,对干扰素 γ (IFNG) 诱导的 γ 激活因子介导的免疫和干扰素 α (IFNA) 诱导的干扰素刺激基因因子3介导的免疫具有内在的有害作用,如用相应等位基因转染的STAT1-deficient细胞所示。然而,它们的表型效应是由不同的分子机制介导的,L706S影响STAT1磷酸化,Q463H和E320Q影响STAT1 DNA结合活性。杂合子患者表现出特异性受损的IFNG诱导的 γ 激活因子介导的免疫力,导致对分枝杆菌的敏感性。实际上,IFNA诱导的干扰素刺激基因因子3介导的免疫不受影响,并且这些患者对病毒性疾病并不特别敏感,这与其他纯合的患者不同,同样有害的STAT1突变对两种表型均隐性。因此,三个STAT1等位基因在IFNG介导的抗分枝杆菌免疫中占主导地位,但在细胞和临床水平上对IFNA介导的抗病毒免疫具有隐性。这些STAT1等位基因定义了两种形式的显性STAT1缺陷,具体取决于突变是否损害STAT1磷酸化或DNA结合。
  • 【疾病机制: 2型糖尿病的肝脂肪变性-发病机制和临床意义。】 复制标题 收藏 收藏
    DOI:10.1038/ncpendmet0190 复制DOI
    作者列表:Roden M
    BACKGROUND & AIMS: :Hepatic steatosis is defined by an increased content of hepatocellular lipids (HCLs) and is frequently observed in insulin-resistant states including type 2 diabetes mellitus. A dietary excess of saturated fat contributes significantly to HCL accumulation. Elevated HCL levels mainly account for hepatic insulin resistance, which is probably mediated by partitioning of free fatty acids to the liver (fat overflow) and by an imbalance of adipocytokines (decreased adiponectin and/or increased proinflammatory cytokines). Both free fatty acids and adipocytokines activate inflammatory pathways that include protein kinase C, the transcription factor nuclear factor kappaB, and c-Jun N-terminal kinase 1 and can thereby accelerate the progression of hepatic steatosis to nonalcoholic steatohepatitis and cirrhosis. Proton magnetic resonance spectroscopy has made it possible to quantify HCL concentrations and to detect even small changes in these concentrations in clinical settings. Moderately hypocaloric, fat-reduced diets can decrease HCL levels by approximately 40-80% in parallel with loss of up to 8% of body weight. Treatment with thiazolidinediones (e.g. pioglitazone and rosiglitazone) reduces HCL levels by 30-50% by modulating insulin sensitivity and endocrine function of adipose tissue in type 2 diabetes. Metformin improves hepatic insulin action without affecting HCL levels, whereas insulin infusion for 67 h increases HCL levels by approximately 18%; furthermore, HCL levels positively correlate with the insulin dosage in insulin-treated type 2 diabetes. In conclusion, liver fat is a critical determinant of metabolic fluxes and inflammatory processes, thereby representing an important therapeutic target in insulin resistance and type 2 diabetes mellitus.
    背景与目标: : 肝脂肪变性是由肝细胞脂质 (HCLs) 含量增加定义的,在胰岛素抵抗状态 (包括2型糖尿病) 中经常观察到。饮食中过量的饱和脂肪会显着促进HCL的积累。HCL水平升高主要是导致肝胰岛素抵抗的原因,这可能是由游离脂肪酸分配到肝脏 (脂肪溢出) 和脂肪细胞因子失衡 (脂联素减少和/或促炎细胞因子增加) 介导的。游离脂肪酸和脂肪细胞因子都激活炎症途径,包括蛋白激酶C,转录因子核因子kappaB和c 6月N端激酶1,从而可以加速肝脂肪变性向非酒精性脂肪性肝炎和肝硬化的进展。质子磁共振波谱已使量化HCL浓度并在临床环境中检测到这些浓度的微小变化成为可能。中度低热量,减脂饮食可使HCL水平降低约40-80%,同时减少多达8% 的体重。噻唑烷二酮类药物 (例如吡格列酮和罗格列酮) 的治疗通过调节2型糖尿病中脂肪组织的胰岛素敏感性和内分泌功能,将HCL水平降低30-50%。二甲双胍改善肝胰岛素作用而不影响HCL水平,而胰岛素输注67小时可使HCL水平增加约18%; 此外,在胰岛素治疗的2型糖尿病中,HCL水平与胰岛素剂量呈正相关。总之,肝脏脂肪是代谢通量和炎症过程的关键决定因素,因此是胰岛素抵抗和2型糖尿病的重要治疗目标。
  • 【通过微孔过滤测量的外周血中性粒细胞流变学很好地反映了白塞氏病的活动。】 复制标题 收藏 收藏
    DOI:10.1016/s0923-1811(97)00599-9 复制DOI
    作者列表:Iijima S,Otsuka F
    BACKGROUND & AIMS: Activated neutrophils take a long time to pass through a narrow lumen like a micropore, and are supposed to play a deteriorating effect on microcirculation. Although the activation of neutrophils has been demonstrated in Behçet's disease, nobody analyzes the clinical activity of the disease by means of the rheological measure of neutrophils activity. Using a micropore (pore diameter 5 microns) filtration technique, we measured the filtration time of peripheral blood neutrophils, as a rheological measure of their activity, in order to determine the clinical activity of Behçet's disease. Twenty-one patients with Behçet's disease and 14 healthy control individuals were enrolled in the study. Symptoms and signs exhibited in the patients led us to distinguish the Behçet's disease into inactive and active cases. The latter were further differentiated into cases with absent symptoms and with present symptoms. Neutrophil filtration times were 11.5 +/- 4.8 s in the active cases with present symptoms, which were significantly (P < 0.05) larger than those (7.4 +/- 1.9 s) in the active cases with absent symptoms. The latter filtration times were further significantly (P < 0.001) larger than values (3.7 +/- 1.3 s) in the inactive cases and also those (4.8 +/- 1.2 s) in control subjects. Furthermore, increases in the filtration time obtained immediately after the exposure of cells to the chemotactic peptide formyl-methionyl-leucyl-phenylalanine (FMLP10 nM) were significantly (P < 0.01) larger in the active cases with present symptoms than those in the active cases with absent symptoms. The latter were also larger, but not significantly, than those in the inactive cases, and were significantly (P < 0.01) larger than those in control subjects. The present results demonstrate that the micropore filtration method reflects well the rheological activity of neutrophils as well as the clinical status of Behçet's disease. This method is much better than the measurement of O2 production to differentiate between active cases with absent symptoms and inactive patients or even control individuals. Furthermore, it is more sensitive and useful than laboratory data like the CRP value or the number of peripheral blood neutrophils.

    背景与目标: 活化的中性粒细胞需要很长时间才能通过像微孔一样的狭窄管腔,并且应该对微循环起到恶化的作用。尽管在beh ç et病中已经证明了中性粒细胞的激活,但没有人通过中性粒细胞活性的流变学测量来分析该疾病的临床活性。使用微孔 (孔径5微米) 过滤技术,我们测量了外周血中性粒细胞的过滤时间,作为其活性的流变学指标,以确定白塞氏病的临床活性。21名beh ç et病患者和14名健康对照者参加了这项研究。患者表现出的症状和体征使我们将白塞氏病区分为不活跃和活跃的病例。后者进一步分为无症状和现有症状的病例。有症状的活动病例的中性粒细胞过滤时间为11.5 +/- 4.8 s,显著 (P < 0.05) 大于无症状的活动病例的中性粒细胞过滤时间 (7.4 +/- 1.9 s)。后者的过滤时间进一步显著 (P < 0.001) 大于非活性情况下的值 (3.7 +/- 1.3 s),也大于对照受试者中的值 (4.8 +/- 1.2 s)。此外,在细胞暴露于趋化肽甲酰基-甲硫酰基-亮氨酸-苯丙氨酸 (fmlp10nm) 后立即获得的过滤时间的增加在存在症状的活动病例中比在不存在症状的活动病例中显着 (P < 0.01) 大。后者也比不活跃的情况更大,但不显著,并且显著 (P < 0.01) 大于对照组。目前的结果表明,微孔过滤方法很好地反映了嗜中性粒细胞的流变活性以及白塞病的临床状况。此方法比O2产生的测量要好得多,可以区分无症状的活跃病例和不活跃的患者甚至对照组。此外,它比CRP值或外周血中性粒细胞数量等实验室数据更敏感和有用。
  • 【慢性鼻-鼻窦炎伴哮喘的临床特点。】 复制标题 收藏 收藏
    DOI:10.1016/j.anl.2006.05.002 复制DOI
    作者列表:Kim HY,Dhong HJ,Chung SK,Chung YJ,Kim MG
    BACKGROUND & AIMS: OBJECTIVE:This study was directed at identifying clinical features of chronic rhinosinusitis with asthma, and examining the differences of the postoperative outcomes in asthmatics and nonasthmatics. STUDY DESIGN AND SETTING:Twenty-one asthmatic and 77 nonasthmatic patients who underwent functional endoscopic sinus surgery (FESS) were entered into the study. The following six parameters were determined in asthmatic and nonasthmatic groups; the presence of allergy, previous sinus surgery, severity of preoperative rhinosinusitis symptoms, improvements in postoperative rhinosinusitis symptoms, preoperative disease extent, and postoperative endoscopic outcomes. RESULTS:Symptom scores improved significantly in both asthmatics and nonasthmatics postoperatively, and asthmatics exhibited significantly worse postoperative endoscopic outcomes compared with nonasthmatics. No difference was found in other parameters between two groups. Multivariate analysis revealed asthma continues to be an independent predictor of success. CONCLUSIONS:The present study found that chronic rhinosinusitis in asthmatics showed worse postoperative outcomes than in nonasthmatics, and every attempt should be made for the improvement of surgical results in these patients.
    背景与目标:
  • 【过敏性眼病结膜上皮结构蛋白减少。】 复制标题 收藏 收藏
    DOI:10.1111/j.1398-9995.2006.01207.x 复制DOI
    作者列表:Hughes JL,Lackie PM,Wilson SJ,Church MK,McGill JI
    BACKGROUND & AIMS: AIMS:Allergic eye disease affects up to 20% of the population with varying severity. The conjunctival epithelium plays a key role in allergic eye disease. The purpose of this study was to determine whether the conjunctival epithelium is abnormal in allergic eye disease. METHODS:Conjunctival biopsy samples were taken from patients with seasonal allergic conjunctivitis (SAC) 'in' and 'out of season' and nonatopic control subjects. Specimens were fixed in glycol methacrylate, 2 microm serial sections cut and Image-J used to assess the sites and areas of immuno-staining. RESULTS:E-cadherin, CD44, keratins K5/6, K8, K13, K14, K18 and pan-keratin immuno-staining were all significantly lower in patients 'out of season' compared with normal controls. No structural differences in the epithelium were observed between the two groups. The epithelium of patients 'in season' was thicker and immuno-staining of the above markers similar to controls. CONCLUSIONS:The expression of a wide spectrum of epithelial cell adhesion proteins and cytoskeletal elements is downregulated in the conjunctiva of SAC patients 'out of season' compared with normal controls. We suggest that this could have an important impact on the ability of the epithelium to protect itself against allergen penetration, potentially influencing the development and course of allergic eye disease and offering a novel area for therapeutic control.
    背景与目标:
  • 【持续静脉和皮下吗啡治疗慢性癌症疼痛的前瞻性,患者内交叉研究。】 复制标题 收藏 收藏
    DOI:10.1016/s0885-3924(96)00329-6 复制DOI
    作者列表:Nelson KA,Glare PA,Walsh D,Groh ES
    BACKGROUND & AIMS: The dose, efficacy, and side effects of continuous intravenous infusion (CIVI) of morphine were compared with continuous subcutaneous infusion (CSCI) of morphine in patients with chronic cancer pain. Eligible patients were referred to the Palliative Care Program and were receiving a stable dose of CIVI of morphine. The design was a within-patient, one-way crossover; in which each patient provided data before and after a switch from CIVI to CSCI of morphine. "Rescue" doses were 50% of the hourly dose given every 2 hours as needed. Morphine was infused intravenously (i.v.) and subcutaneously (s.c.) via a McGaw/AccuPro Volumetric Infusion Pump. After baseline data, including side effects and pain assessment, were obtained, patients were evaluated twice daily for toxicity and analgesic efficacy. Those who had a stable CIVI dose for 48 consecutive hr were crossed over to the CSCI at the same dose as the intravenous (i.v.) phase. A stable dose was defined as no dose change, four or less rescue doses in the previous 24 hr, and a pain rating of none or mild. CIVI was considered equal to CSCI if these criteria were maintained for 96 consecutive hr. Fifty-seven patients were entered, and 40 were evaluable (15 women and 25 men). The median age was 67 (range 30-83 years). All 40 participants, after maintaining a stable dose throughout the i.v. phase, crossed to the s.c. phase and remained on s.c. for at least 48 hr. Thirty-two patients maintained a stable dose throughout the i.v. and s.c. phases. The mean stable i.v. dose (day 2) was 5.05 mg/hr, and the mean stable s.c. dose (day 4) was 5.7 mg/hr (P = 0.01). The mean number of rescue doses on day 2 was 0.83 per 24 hr versus 0.80 per 24 hours on day 4 (P = 0.6). The mean categorical pain score on day 2 was 0.83, and on day 4, 0.85 (P = 0.7). The mean visual analogue scale (VAS) on day 2 was 22.9 mm versus 17.6 mm on day 4 (P = 0.1). The mean incidence of side effects on day 2 was 1.7, and on day 4, 2.0 (P = 0.2). No patient was withdrawn or had a dose reduction due to unacceptable toxicity. There were two reports of local toxicity (mild erythema) at the SC needle insertion point, which required a site change. All of our 40 patients had adequate pain control with CIVI and CSCI morphine. Of the eight participants who were not maintained on the same i.v. and s.c. dose, all had adequate pain control and a similar side-effect profile on a higher s.c. morphine dose. These data suggest that the i.v. and s.c. routes are equianalgesic for most patients when administered as a continuous infusion. Pain control and side-effect profiles are quite similar and acceptable. s.c. morphine is an excellent alternative to i.v. morphine in both inpatients and outpatients requiring parenteral morphine for pain.

    背景与目标: 比较了慢性癌痛患者持续静脉输注 (CIVI) 吗啡与持续皮下输注 (CSCI) 吗啡的剂量,疗效和副作用。符合条件的患者被转诊到姑息治疗计划,并正在接受稳定剂量的CIVI吗啡。该设计是患者内部的单向交叉; 其中每个患者在吗啡从CIVI切换到CSCI之前和之后提供数据。“抢救” 剂量是根据需要每2小时给予的每小时剂量的50%。通过McGaw/AccuPro容积输液泵静脉内 (i.v.) 和皮下 (s.c.) 注入吗啡。获得包括副作用和疼痛评估在内的基线数据后,每天两次评估患者的毒性和镇痛效果。那些连续48小时稳定的CIVI剂量的人以与静脉 (i.v.) 阶段相同的剂量交叉到CSCI。稳定剂量定义为无剂量变化,在之前的24小时内有四个或更少的抢救剂量,并且疼痛等级为无或轻度。如果连续96个小时保持这些标准,CIVI被认为等于CSCI。进入了57名患者,其中40名可评估 (15名女性和25名男性)。中位年龄为67岁 (范围30-83岁)。所有40名参与者在整个静脉内保持稳定剂量后。阶段,越过s.C.阶段并保留在s.c.至少48小时。32名患者在整个静脉内保持稳定剂量。和南卡罗来纳州阶段。平均稳定的静脉注射。剂量 (第2天) 为5.05 mg/hr,平均稳定s.c.剂量 (第4天) 为5.7 mg/hr (P = 0.01)。第2天的平均抢救剂量为每24小时0.83次,而第4天的平均抢救剂量为每24小时0.80次 (P = 0.6)。第2天和第4天的平均分类疼痛评分为0.83,0.85 (P = 0.7)。第2天的平均视觉模拟量表 (VAS) 为22.9毫米,第4天为17.6毫米 (P = 0.1)。第2天和第4天的平均副作用发生率为1.7,2.0 (P = 0.2)。没有患者因不可接受的毒性而退出或剂量减少。有两份关于SC针插入点局部毒性 (轻度红斑) 的报告,需要改变部位。我们的40名患者均使用CIVI和CSCI吗啡进行了足够的疼痛控制。在没有保持相同i.v.的八名参与者中。和南卡罗来纳州剂量,都有足够的疼痛控制,并且在较高的s.C.上有相似的副作用。吗啡剂量。这些数据表明,静脉注射和南卡罗来纳州当作为连续输注给药时,大多数患者的途径是等镇痛。疼痛控制和副作用特征非常相似且可以接受。吗啡是静脉注射的绝佳替代品需要胃肠外吗啡治疗疼痛的住院患者和门诊患者的吗啡。
  • 【荷兰用英夫利昔单抗治疗克罗恩病指南。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Vermeire S
    BACKGROUND & AIMS: -2
    背景与目标: -2
  • 【比较基于相机的99mTc-MAG3和24小时肌酐清除率评估肾功能。】 复制标题 收藏 收藏
    DOI:10.2214/AJR.05.1025 复制DOI
    作者列表:Esteves FP,Halkar RK,Issa MM,Grant S,Taylor A
    BACKGROUND & AIMS: OBJECTIVE:The 24-hour creatinine clearance is the standard clinical technique for measuring kidney function; however, this measurement is cumbersome and inconvenient for patients. We hypothesized that a camera-based technetium-99m mercaptoacetyltriglycine (MAG3) clearance obtained simultaneously with a standard MAG3 scan would correlate well with the 24-hour creatinine clearance and could serve as a simple marker of kidney function. MATERIALS AND METHODS:Data were obtained from a retrospective analysis of 28 patients with varying degrees of kidney dysfunction and 85 subjects evaluated for kidney donation. The MAG3 clearance was calculated using a camera-based technique without blood or urine sampling. The creatinine clearance was measured using the plasma creatinine and a 24-hour urine collection. The MAG3 and creatinine clearances were corrected for body surface area, and clearance values in healthy subjects and patients were compared using the paired Student's t test. The linear association between the MAG3 and creatinine clearances was expressed by Pearson's correlation coefficient. RESULTS:The mean MAG3 clearance in the potential kidney donors was 321 +/- 95 mL/min/1.73 m2 (95% CI, 171-546 mL/min/1.73 m2), significantly higher than the mean creatinine clearance of 152 +/- 51 mL/min/1.73 m2 (79-278 mL/min/1.73 m2, p < 0.001). The mean MAG3 clearance in patients was 153 +/- 70 mL/min/1.73 m2 (32-316 mL/min/1.73 m2) and was also significantly higher than the mean creatinine clearance of 74 +/- 36 mL/min/1.73 m2 (21-138 mL/min/1.73 m2, p < 0.001). The ratio of the mean creatinine clearance to the mean MAG3 clearance was essentially the same for volunteers and patients, 0.47 and 0.48, respectively. The Pearson's correlation between the MAG3 and creatinine clearances was 0.80 (0.72-0.86). CONCLUSION:The camera-based 99mTc-MAG3 clearance correlates well with the 24-hour creatinine clearance and can provide a simple and convenient index of kidney function.
    背景与目标:
  • 【乳糜泻患者的小麦淀粉不耐受。】 复制标题 收藏 收藏
    DOI:10.1016/S0002-8223(97)00156-9 复制DOI
    作者列表:Chartrand LJ,Russo PA,Duhaime AG,Seidman EG
    BACKGROUND & AIMS: OBJECTIVE:Evaluate in patients with celiac disease the tolerance of prolonged consumption of small amounts of gliadin contained in products containing wheat starch.

    DESIGN:Open 1-year trial of the addition of wheat starch to a gluten-free diet in a cohort of adult patients with biopsy-proven celiac disease who had never consumed wheat starch. The control group consisted of patients with celiac disease who tolerated wheat starch.

    SUBJECTS:Seventeen patients with celiac disease and 14 control patients, all diagnosed according to criteria of the European Society of Pediatric Gastroenterology and Nutrition, were recruited from the Canadian Celiac Association and the Quebec Celiac Foundation.

    SETTING:The study was conducted in the outpatient clinic of the Gastroenterology and Nutrition Service of Ste Justine Hospital, Montreal, Quebec, Canada.

    INTERVENTIONS:Patients were asked to consume four to six portions daily of a wheat starch-containing product, mainly bread, for up to 1 year.

    MAIN OUTCOME MEASURES:The gliadin content of the wheat starch product used in this trial was quantified by enzyme-linked immunosorbent assay. Patient outcome measures included symptoms, nutritional parameters (anthropometric data, complete blood count, serum folate and iron levels), and immunologic parameters (antigliadin antibody and antiendomysium antibody titers).

    RESULTS:A quantifiable amount of immunoreactive gliadin (0.75 mg/100 g) was found in the wheat starch. The majority of the patients with celiac disease (11 of 17) who had never consumed wheat starch previously developed symptoms, which resolved within weeks of discontinuing the product. Relapse of skin lesions was seen in two of three patients with coexisting dermatitis herpetiformis. No weight loss or biochemical changes were observed. Despite the presence of symptoms, antigliadin antibody and antiendomysium antibody determinations were not useful to detect the clinical intolerance.

    APPLICATIONS:The innocuousness of the long-term ingestion of "gluten-free" products containing wheat starch is still unproven, and prolonged use of such products by patients with celiac disease cannot be recommended.

    背景与目标: 目标 : 评估乳糜泻患者对含有小麦淀粉的产品中含有的少量麦醇溶蛋白的长期食用的耐受性。
    设计 : 在从未食用过小麦淀粉的活检证实的乳糜泻成年患者队列中,将小麦淀粉添加到无麸质饮食中进行了为期1年的开放试验。对照组由耐受小麦淀粉的乳糜泻患者组成。
    受试者 : 17例乳糜泻患者和14例对照患者,均根据欧洲儿科胃肠病与营养学会的标准进行诊断,是从加拿大乳糜泻协会和魁北克乳糜泻基金会招募的。
    设置 : 该研究是在魁北克蒙特利尔Ste Justine医院胃肠病学和营养服务门诊进行的,加拿大。
    干预措施 : 要求患者每天食用四到六份含小麦淀粉的产品,主要是面包,长达1年。
    主要结果指标 : 通过酶联免疫吸附测定法对该试验中使用的小麦淀粉产品的麦醇溶蛋白含量进行了定量。患者结局指标包括症状,营养参数 (人体测量数据,全血细胞计数,血清叶酸和铁水平) 和免疫学参数 (抗麦醇溶蛋白抗体和抗肌内膜抗体滴度)。
    结果 : 在小麦淀粉中发现可定量的免疫反应性麦醇溶蛋白 (0.75 mg/100g)。以前从未食用过小麦淀粉的大多数乳糜泻患者 (17人中有11人) 出现症状,这些症状在停用该产品后的几周内得到缓解。在三名并存的疱疹样皮炎患者中,有两名发现了皮肤病变的复发。未观察到体重减轻或生化变化。尽管存在症状,但抗麦醇溶蛋白抗体和抗肌内膜抗体的测定对检测临床不耐受没有用。
    应用 : 长期摄入含有小麦淀粉的 “无麸质” 产品的无伤害性仍未得到证实,并且不建议乳糜泻患者长期使用此类产品。

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