• 【使用源自人脐带血的干细胞的潜在临床应用。】 复制标题 收藏 收藏
    DOI:10.1016/s1472-6483(10)60646-3 复制DOI
    作者列表:Ghen MJ,Roshan R,Roshan RO,Blyweiss DJ,Corso N,Khalili B,Zenga WT
    BACKGROUND & AIMS: :There is an abundance of clinical applications using human umbilical cord blood (HUCB) as a source for stem cell populations. Other than haematopoietic progenitors, there are mesenchymal, endothelial stem cells and neuronal precursors, in varying quantities, that are found in human umbilical cord blood. These may be useful in diseases such as immune deficiency and autoimmune disorders. Considering issues of safety, availability, transplant methodology, rejection and side effects, it is contended that a therapeutic stem cell transplant, utilizing stem cells from HUCB, provides a reliable repository of early precursor cells that can be useful in a great number of diverse conditions. Drawbacks of relatively smaller quantities of mononucleated cells in one unit of cord blood can be mitigated by in-vitro expansion procedures, improved in-vivo signalling, and augmentation of the cellular milieu, while simultaneously choosing the appropriate transplantation site and technique for introduction of the stem cell graft.
    背景与目标: :有大量的临床应用使用人类脐带血(HUCB)作为干细胞群体的来源。除造血祖细胞外,人类脐带血中还存在不同数量的间充质,内皮干细胞和神经元前体。这些可能对诸如免疫缺陷和自身免疫性疾病等疾病有用。考虑到安全性,可用性,移植方法,排斥反应和副作用等问题,可以认为,利用HUCB干细胞进行的治疗性干细胞移植可提供可靠的早期前体细胞库,该库可在多种条件下使用。可以通过体外扩增程序,改进的体内信号传导和细胞环境增强来缓解一单位脐带血中相对较少数量的单核细胞的缺点,同时选择合适的移植部位和技术引入干细胞移植。
  • 【太空飞行期间对便携式临床血液分析仪的评估。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Smith SM,Davis-Street JE,Fontenot TB,Lane HW
    BACKGROUND & AIMS: This study was designed to validate the utility of a commercial portable clinical blood analyzer (PCBA) in ground-based studies and on the space shuttle. Ionized calcium, pH, electrolytes, glucose, and hematocrit were determined. Results agreed well with those from traditional laboratory methods, and the PCBA demonstrated good between-day precision for all analytes. In-flight analysis of control samples revealed differences in one analyte (sodium). There were few changes in crew members' results during flight, and these were expected. Potassium increased in flight compared with before flight, and potassium, pH, and hematocrit decreased after flight. Ionized calcium was decreased in flight and on landing day. Changes during flight were likely related to sample collection technique. Postflight changes likely reflected the fluid redistribution that occurs after exposure to weightlessness. These data confirm that the PCBA is a reliable instrument for most analytes, and can provide important medical data in remote locations, such as orbiting spacecraft.

    背景与目标: 这项研究旨在验证商用便携式临床血液分析仪(PCBA)在地面研究和航天飞机上的实用性。测定了电离的钙,pH,电解质,葡萄糖和血细胞比容。结果与传统实验室方法的结果非常吻合,PCBA证明所有分析物的日间精度都很高。对照样品的飞行中分析揭示了一种分析物(钠)的差异。机组人员在飞行过程中的结果变化不大,这是可以预期的。与飞行前相比,飞行中钾增加,而飞行后钾,pH和血细胞比容下降。电离钙在飞行中和降落当天减少。飞行过程中的变化可能与样本采集技术有关。飞行后的变化很可能反映了失重后流体的重新分布。这些数据证实,PCBA是用于大多数分析物的可靠仪器,并且可以在诸如轨道飞行器之类的偏远地区提供重要的医学数据。

  • 【艾滋病患者的更昔洛韦耐药性巨细胞病毒(CMV)视网膜炎一例:CMV病毒载量和血室中病毒突变的纵向分子分析。】 复制标题 收藏 收藏
    影响因子 :
    发表时间:1997-06-01
    来源期刊:AIDS
    DOI:10.1097/00002030-199707000-00005 复制DOI
    作者列表:Boivin G,Gilbert C,Morissette M,Handfield J,Goyette N,Bergeron MG
    BACKGROUND & AIMS: OBJECTIVE:To study the temporal relationships between cytomegalovirus (CMV) viral load and specific UL97 mutations in polymorphonuclear leukocytes (PMNL) and plasma samples from a patient with AIDS who developed ganciclovir-resistant CMV retinitis.

    METHODS:Sequential PMNL and plasma samples were analysed for determination of the CMV viral load using non-molecular methods and a quantitative polymerase chain reaction (PCR) assay. Screening of the same samples for the most common mutations conferring ganciclovir resistance was performed using nested PCR and restriction enzyme analysis.

    RESULTS:At the time of progression of CMV retinitis (after 6 months of ganciclovir), a rapid increase in the CMV DNA load was found in both PMNL and plasma samples. This increase paralleled the emergence of a specific mutation (V594) in the same samples and recovery of ganciclovir-resistant blood isolates. In this patient, however, the only tests that substantially predicted the progression of CMV disease were the quantitative PCR assay using PMNL and to a lesser extent the pp65 antigenemia assay.

    CONCLUSIONS:Quantitative evaluation of the CMV viral load in PMNL using sensitive assays such as PCR appears to be a promising approach for monitoring antiviral therapy in subjects with AIDS. In addition, common mutations conferring ganciclovir resistance can be detected directly in PMNL and plasma samples.

    背景与目标: 目的:研究巨细胞病毒耐药性巨细胞病毒性视网膜炎的艾滋病患者的巨细胞病毒(CMV)病毒载量与多形核白细胞(PMNL)和血浆样品中特定UL97突变之间的时间关系。

    方法:使用非分子方法和定量聚合酶链反应(PCR)分析了连续的PMNL和血浆样品,以测定CMV病毒载量。使用巢式PCR和限制性内切酶分析对相同样品中最引起更昔洛韦耐药的突变进行筛查。

    结果:在CMV视网膜炎进展时(6个月后) (更昔洛韦)的检测,在PMNL和血浆样品中均发现CMV DNA载量迅速增加。这种增加与相同样品中特异突变(V594)的出现和更昔洛韦耐药血分离株的回收率平行。然而,在该患者中,唯一可以预测CMV疾病进展的检测方法是使用PMNL进行定量PCR检测,并在较小程度上使用pp65抗原血症检测。使用敏感的检测方法(如PCR)评估PMNL中CMV病毒载量似乎是监测艾滋病患者抗病毒治疗的一种有前途的方法。此外,可以在PMNL和血浆样品中直接检测到更昔洛韦耐药的常见突变。

  • 【在阿尔茨海默氏病中,MRI指导的SPECT测量颞叶内侧血流。】 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: UNLABELLED :在这项研究中,我们评估了MRI指导的SPECT测量中度颞叶血流在阿尔茨海默病(AD)中的准确性和可靠性。

    方法 strong>:交互式对准的三维MP-RAGE MRI和99mTc-HMPAO SPECT图像用于MRI指导的八名对照受试者和八名可能患有AD的患者的内侧颞叶CBF的测量。一位经验丰富的操作员通过反复对准和测量来评估操作员的可靠性。通过检查两个带有基准标记的受试者来评估准确性。

    结果:对准误差小于1个SPECT像素大小(3.5毫米),并且重复内侧测量的变异系数颞小脑CBF率为3.2%。八名对照受试者和八名AD患者之间的平均内侧颞小脑CBF比率的差异为12%。同样,通过使用定义的三维种子生长的健康大脑参考区域,对照受试者和AD患者之间的颞内侧血流存在显着差异。此外,在AD患者中,MRI定义的内侧颞部ROI的体积较小。通过将萎缩的MRI测量值和CBF的SPECT测量值相结合,可以使AD患者与对照组之间达到最佳分离。

    结论:这些数据表明,MRI指导的准确性和可靠性内侧颞CBF的SPECT测量清楚地允许检测AD的变化。同样,通过这种方法可以直接比较结构和功能的变化,这可能会改善AD的早期诊断。

  • 【患有肺囊性纤维化的患者,在呼气压力为正值且振荡的呼气压力为正值的情况下,进行胸部物理治疗时,血气压力立即变化。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Lagerkvist AL,Sten GM,Redfors SB,Lindblad AG,Hjalmarson O
    BACKGROUND & AIMS: OBJECTIVE:To assess and compare immediate effects of chest physiotherapy with positive expiratory pressure (PEP) versus oscillating PEP on transcutaneously measured blood-gas tensions in patients with cystic fibrosis. METHODS:Fifteen patients (mean age 12.5 y, range 6.9-21.5 y) participated. The treatments were randomized and performed on 2 separate occasions, 8 weeks apart. Spirometry was conducted before and after each treatment. We transcutaneously measured oxygen tension (P(tO2). RESULTS:There were no changes in spirometry values. During PEP, different trends in blood-gas tension were seen, and there were no consistent changes. During oscillating PEP, P(tO2) increased and P(tCO2) decreased. During oscillating PEP, P(tCO2) was lower and the intra-individual change in P(tCO2) was more pronounced than during PEP. The results obtained immediately after oscillating PEP showed a higher P(tO2) and a lower P(tCO2) than with PEP. CONCLUSION:PEP and oscillating PEP can both cause transitory effects on blood gases in patients with cystic fibrosis. However, oscillating PEP alters blood-gas tensions more than does PEP, and hyperventilation during oscillating PEP may reduce treatment time.
    背景与目标: 目的:评估和比较呼气正压(PEP)和振荡PEP对胸部物理治疗对囊性纤维化患者经皮测量的血气张力的即时效果。
    方法:15例患者(平均年龄12.5岁,范围6.9-21.5岁)参加了研究。治疗是随机的,分别在两个不同的场合进行,相隔8周。在每次治疗之前和之后进行肺活量测定。我们经皮测量了氧气张力(P(tO2)。
    结果:肺活量测定值没有变化。在PEP期间,观察到了血气紧张的不同趋势,并且没有一致的变化。在振荡PEP期间,P(tO2)增加而P(tCO2)减少。在振荡PEP期间,P(tCO2)较低,并且P(tCO2)的内部个体变化比PEP期间更为明显。振荡PEP后立即获得的结果显示,与PEP相比,P(tO2)更高,P(tCO2)更低。
    结论:PEP和振荡PEP均可对囊性纤维化患者的血气产生短暂影响。但是,与PEP相比,振荡PEP对血气压力的改变更大,并且在振荡PEP期间过度换气可能会减少治疗时间。
  • 【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贝塞特的疾病活动。】 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: 活化的嗜中性粒细胞需要很长时间才能通过像微孔一样的狭窄内腔,因此应该对微循环起恶化作用。尽管在白塞氏病中已证明嗜中性粒细胞的活化,但没有人通过流变学方法测量嗜中性粒细胞的活性来分析该疾病的临床活性。我们使用微孔(孔径为5微米)过滤技术,测量外周血中性粒细胞的过滤时间,作为其活性的流变学指标,以确定贝塞特氏病的临床活性。本研究招募了21名Behçet病患者和14名健康对照者。患者表现出的症状和体征使我们将Behçet病区分为非活跃和活跃病例。后者被进一步区分为无症状和有当前症状的病例。在有症状的活跃病例中,中性粒细胞过滤时间为11.5 /-4.8 s,比没有症状的活跃病例中的中性粒细胞过滤时间显着(P <0.05)大(P <0.05)。后者的过滤时间比不活动时的值(3.7 /-1.3 s)大得多(P <0.001),也比对照组的人(4.8 /-1.2 s)大。此外,在有症状的活动病例中,将细胞暴露于趋化肽甲酰基-甲硫酰基-亮氨酰-苯丙氨酸(FMLP10 nM)后立即获得的过滤时间增加明显大于活动病例(P <0.01)。没有症状。后者也比不活动者大,但不显着,并且比对照组大(P <0.01)。目前的结果表明,微孔过滤方法很好地反映了中性粒细胞的流变活性以及白塞氏病的临床状况。这种方法比测量氧气的产生要好得多,以区分没有症状的活动患者和无活动的患者,甚至是对照个体。此外,它比实验室数据(如CRP值或外周血中性粒细胞的数量)更为敏感和有用。

  • 【在全髋关节置换术中使用其他血液回输技术进行血液稀释。】 复制标题 收藏 收藏
    DOI:10.1097/00003086-199706000-00018 复制DOI
    作者列表:Oishi CS,D'Lima DD,Morris BA,Hardwick ME,Berkowitz SD,Colwell CW Jr
    BACKGROUND & AIMS: Acute normovolemic hemodilution has been reported to result in blood savings varying from 18% to 90%. Very few of these are randomized prospective studies. This study attempts to determine the blood transfusion savings if acute normovolemic hemodilution is used in combination with autologous predonated blood and cell saver. Thirty-three patients undergoing total hip arthroplasty were assigned randomly to one of two groups (control, n = 16; hemodilution, n = 17). Patients in both groups entered an autologous predonation program if cleared medically and were placed on Cell Saver intraoperatively and in the postanesthesia care unit. In addition, the hemodilution group underwent acute normovolemic hemodilution preoperatively. Only 41% of the patients in the hemodilution group required any autologous blood transfusion as compared with 75% of the control group. In addition, the hemodilution group required a mean lower quantity of autologous blood transfusion (41% of the estimated blood loss) as compared with the control group (71%). The net anesthesia time increased by an average of 11.4 minutes in the hemodilution group. Acute normovolemic hemodilution is a safe procedure even in an older patient population. Hemodilution resulted in fewer patients needing autologous predonated blood transfusions. The major benefit of hemodilution was seen when predonation was not possible.

    背景与目标: 据报道,急性降血常规血液稀释可节省18%至90%的血液。这些很少是随机的前瞻性研究。这项研究试图确定如果将急性等渗血液稀释与自体预先捐献的血液和细胞保护剂结合使用可节省的输血量。将接受全髋关节置换术的33例患者随机分为两组(对照组,n = 16;血液稀释,n = 17)。两组患者均在接受医学检查后进入了自体捐赠程序,并在术中和麻醉后监护病房接受了Cell Saver治疗。另外,血液稀释组术前进行了急性等渗血液稀释。血液稀释组中只有41%的患者需要自体输血,而对照组为75%。此外,血液稀释组与对照组(71%)相比平均需要较少量的自体输血(估计失血量的41%)。血液稀释组的净麻醉时间平均增加了11.4分钟。即使在年龄较大的患者中,急性降血常规血液稀释也是一种安全的方法。血液稀释导致更少的患者需要自体先验的输血。当无法进行预先捐赠时,可以看到血液稀释的主要好处。

  • 【正常成年大鼠的血脑屏障缺陷区域的免疫环境增强。】 复制标题 收藏 收藏
    DOI:10.1016/s0165-5728(97)00038-6 复制DOI
    作者列表:Pedersen EB,McNulty JA,Castro AJ,Fox LM,Zimmer J,Finsen B
    BACKGROUND & AIMS: The circumventricular organs (CVOs) in the brain are without a blood-brain barrier (BBB) and as such directly exposed to blood plasma constituents and blood-borne pathogens. In light of previous studies showing discrepancies regarding the immunocompetence of these organs, we initiated the present study to provide a comprehensive immunohistochemical analysis of the cellular expression of immune-associated antigens within the pineal gland, area postrema and the subfornical organ. In all CVOs, subpopulations of cells morphologically similar to complement receptor type 3 immunoreactive microglial/macrophage cells expressed major histocompatibility complex (MHC) class II antigen, leucocyte common antigen (LCA/CD45), as well as CD4 and ED1 antigen. Based on morphological criteria the MHC class II antigen expressing cells could be grouped into a major population of classical parenchymal and perivascular ramified microglial cells and a minor population presenting itself as scattered or small groups of rounded macrophage-like cells. CD4 and ED1 antigen were expressed by both cell types. CD45 was preferentially expressed by macrophage-like cells. MHC class I antigen was expressed by the vascular endothelium in both BBB-protected and BBB-deficient areas and was additionally present as a lattice-like network throughout the BBB-deficient parenchyma in all CVOs. The results suggest that the BBB-free areas of the brain besides being constantly surveyed by blood-borne macrophages, possess an intrinsic immune surveillance system based on resting and activated microglial cells, which may function as a non-endothelial, cellular barrier against blood-borne pathogens.

    背景与目标: 大脑中的室间隔器官(CVO)没有血脑屏障(BBB),因此直接暴露于血浆成分和血源性病原体。鉴于先前的研究表明这些器官的免疫能力存在差异,我们启动了本研究,以提供对松果体,视网膜后区域和分支下器官内免疫相关抗原的细胞表达的全面免疫组织化学分析。在所有CVO中,与补体受体3型免疫反应性小胶质细胞/巨噬细胞细胞形态相似的细胞亚群表达了主要的组织相容性复合物(MHC)II类抗原,白细胞常见抗原(LCA / CD45)以及CD4和ED1抗原。根据形态学标准,可以将表达MHC II类抗原的细胞分为经典的实质和血管周围分枝的小神经胶质细胞的主要群体,以及表现为散在的或成团的圆形巨噬细胞样细胞的少数群体。 CD4和ED1抗原通过两种细胞类型表达。 CD45优先由巨噬细胞样细胞表达。 MHC I类抗原在BBB保护区和BBB缺失区均由血管内皮表达,并在所有CVO中的整个BBB缺失实质中均呈格子状网络存在。结果表明,除了大脑中无血脑屏障的区域不断被血源性巨噬细胞检查外,还具有基于静止和活化的小胶质细胞的内在免疫监视系统,该系统可能起非内皮细胞屏障的作用。传播的病原体。

  • 【肝细胞癌患者中识别野生型p53衍生表位的CD8 T淋巴细胞频率增加与表位缺失肿瘤变体的存在相关。】 复制标题 收藏 收藏
    DOI:10.1002/ijc.22251 复制DOI
    作者列表:Cicinnati VR,Zhang X,Yu Z,Ferencik S,Schmitz KJ,Dworacki G,Kaczmarek E,Oldhafer K,Frilling A,Baba HA,Schmid KW,Grosse-Wilde H,Broelsch CE,DeLeo AB,Gerken G,Beckebaum S
    BACKGROUND & AIMS: :Wild-type (WT) sequence p53 peptides are attractive candidates for broadly applicable cancer vaccines. The aim of this study was to evaluate the potential of a WT p53-based immunotherapeutic approach for patients with hepatocellular carcinoma (HCC). Circulating CD8+ T cells specific for WT p53(149-157) and WT p53(264-272) HLA-A*0201 restricted epitopes were directly identified in the peripheral blood by the use of peptide/HLA-A2.1 tetramers in 24 HCC patients. Cytotoxic T lymphocyte (CTL) activity after WT p53 peptide-specific stimulation was assessed by analysis of granzyme B and interferon-gamma mRNA transcription, using a quantitative real-time polymerase chain reaction assay. Tumor immunophenotyping was performed to evaluate the p53 status, the expression of major histocompatibility complex (MHC) and costimulatory molecules in freshly isolated tumor cells. HCC patients exhibited significantly higher frequencies of WT p53-specific memory CD8+ T cells and stronger WT p53-specific CTL activity, when compared with healthy controls. Increased frequencies of p53-specific CD8+ T cells and their activity correlated with selective HLA-A2 allele loss and reduced costimulatory molecule expression of tumor cells. Moreover, augmented numbers of p53-specific T cells coincided with high MHC class II expression in tumor cells but were inversely related to the T status of the tumor node metastasis staging system. Our results indicate the existence of natural immunosurveillance and tumor immune evasion, involving a T cell response against WT p53 tumor antigen in patients with HCC. These findings may have important implications for the future development of cancer vaccines.
    背景与目标: :野生型(WT)序列p53肽是广泛应用的癌症疫苗的诱人候选物。这项研究的目的是评估肝细胞癌(HCC)患者基于WT p53的免疫治疗方法的潜力。通过在24 HCC中使用肽/HLA-A2.1四聚体直接在外周血中鉴定出对WT p53(149-157)和WT p53(264-272)HLA-A * 0201限制性表位具有特异性的循环CD8 T细胞耐心。 WT p53肽特异性刺激后的细胞毒性T淋巴细胞(CTL)活性通过使用实时定量聚合酶链反应测定的颗粒酶B和干扰素-γmRNA转录分析来评估。进行肿瘤免疫表型分析以评估新鲜分离的肿瘤细胞中p53的状态,主要组织相容性复合体(MHC)的表达和共刺激分子。与健康对照相比,HCC患者表现出明显更高的WT p53特异性记忆CD8 T细胞频率和更强的WT p53特异性CTL活性。 p53特异性CD8 T细胞的频率增加及其活性与选择性HLA-A2等位基因缺失和肿瘤细胞共刺激分子表达降低有关。此外,p53特异性T细胞数量的增加与肿瘤细胞中II类MHC的高表达相吻合,但与肿瘤淋巴结转移分期系统的T状态呈负相关。我们的结果表明,在肝癌患者中存在自然免疫监视和肿瘤免疫逃避,涉及针对WT p53肿瘤抗原的T细胞应答。这些发现可能对癌症疫苗的未来发展具有重要意义。
  • 【通过气管内施用编码人血小板生成素cDNA的腺病毒载体来提高血小板水平。】 复制标题 收藏 收藏
    DOI:10.1038/nbt0697-570 复制DOI
    作者列表:Cannizzo SJ,Frey BM,Raffi S,Moore MA,Eaton D,Suzuki M,Singh R,Mack CA,Crystal RG
    BACKGROUND & AIMS: :This study was designed to evaluate the hypothesis that administration of a replication-deficient, recombinant adenovirus vector to the epithelial surface of the respiratory tract can be used to deliver a recombinant protein to the systemic circulation in sufficient quantities to evoke a systemic response appropriate to the recombinant protein. We administered AdCMV.TPO-an adenovirus vector containing an expression cassette coding for the human thrombopoietin (TPO) cDNA-to the respiratory epithelium of immunocompetent Balb/c mice. Over the following week, serum human TPO levels were elevated, platelet levels increased more than sixfold, and megakaryocytosis was evident in bone marrow. This strategy may be a useful approach to the nonparenteral administration of a variety of therapeutic recombinant proteins, such as those relevant to clotting, endocrine function, and bone-marrow function.
    背景与目标: :这项研究旨在评估以下假设:向呼吸道上皮表面施用复制缺陷型重组腺病毒载体可将重组蛋白以足够的量递送至全身循环,以引起适当的全身反应。重组蛋白。我们将AdCMV.TPO-一种含有编码人血小板生成素(TPO)cDNA的表达盒的腺病毒载体施用于具有免疫功能的Balb / c小鼠的呼吸道上皮。在接下来的一周中,人的血清TPO水平升高,血小板水平升高了六倍以上,并且在骨髓中发现了巨核细胞增多。该策略可能是非胃肠道给药多种治疗性重组蛋白(例如与凝血,内分泌功能和骨髓功能相关的蛋白)的有用途径。
  • 【运动性脚趾和肌阵挛伴有遗传性神经病,伴有压力性麻痹(HNPP)。】 复制标题 收藏 收藏
    DOI:10.1002/(sici)1097-4598(199707)20:7<881::aid-mus13 复制DOI
    作者列表:Shaibani A,Gooch C,Harati Y
    BACKGROUND & AIMS: :A 22-year-old male awoke with right foot drop and numbness. Nerve conduction studies, sural nerve biopsy, and molecular genetic analysis were consistent with hereditary neuropathy with liability to pressure palsy (HNPP). Two months later he developed involuntary flexion/extension movements of the right toes with associated intermittent dystonic flexion of the right foot. Over the next 2 months these movements spread to the left foot and hand and myoclonus of the left trapezius and rhomboid appeared. This is the first case report of moving toes syndrome and segmental myoclonus in association with HNPP. The temporal and topographic patterns of spread of the abnormal movements suggest a central mechanism probably induced by peripheral pathology.
    背景与目标: :一名22岁的男性,醒来时右脚掉落且麻木。神经传导研究,腓肠神经活检和分子遗传学分析与遗传性神经病一致,伴有压力性麻痹(HNPP)。两个月后,他出现了右脚的不自主屈曲/伸展运动以及相关的右脚间歇性张力性屈曲。在接下来的两个月中,这些运动扩展到了左脚和手部,出现了左斜方肌和菱形肌阵挛。这是与HNPP相关的运动脚趾综合征和节段性肌阵挛的第一例报告。异常运动传播的时间和地形图表明了一种可能由周围病理引起的中心机制。
  • 【限压通气过程中连续气管内气体注入对急性肺损伤家兔肺表面活性物质的影响。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Zhu GF,Zhang W,Zong H,Liang Y
    BACKGROUND & AIMS: BACKGROUND:Pulmonary surfactant dysfunction may contribute to the development of ventilator induced lung injury (VILI). Tracheal gas insufflation (TGI) is a technique in which fresh gas is introduced into the trachea and augment ventilation by reducing the dead space of ventilatory system, reducing ventilatory pressures and tidal volume (V(T)) while maintaining constant partial arterial CO2 pressure (PaCO(2)). We hypothesised that TGI limited peak inspiratory pressure (PIP) and V(T) and would minimize conventional mechanical ventilation (CMV) induced pulmonary surfactant dysfunction and thereby attenuate VILI in rabbits with acute lung injury (ALI). METHODS:ALI was induced by intratracheal administration of lipopolysaccharide in anaesthetized, ventilated healthy adult rabbits randomly assigned to continuous TGI at 0.5 L/min (TGI group) or CMV group (n = 8 for each group), and subsequently ventilated with limited PIP and V(T) to maintain PaCO(2) within 35 to 45 mmHg for 4 hours. Physiological dead space to V(T) ratio (V(D)/V(T)), dynamic respiratory compliance (Cdyn) and partial arterial O(2) pressure (PaO(2)) were monitored. After ventilation, lungs were analysed for total phospholipids (TPL), total proteins (TP), pulmonary surfactant small to large aggregates ratio (SA/LA) in bronchoalveolar lavage fluid (BALF) and for determination of alveolar volume density (V(V)), myeloperoxidase and interleukin (IL)-8. RESULTS:TGI resulted in significant (P < 0.05 or P < 0.01) decrease in PIP [(22.4 +/- 1.8) cmH2O vs (29.5 +/- 1.1) cmH2O], V(T) [(6.9 +/- 1.3) ml/kg vs (9.8 +/- 1.11) ml/kg], V(D)/V(T) [(32 +/- 5)% vs (46 +/- 2)%], TP [(109 +/- 22) mg/kg vs (187 +/- 25) mg/kg], SA/LA (2.5 +/- 0.4 vs 5.4 +/- 0.7), myeloperoxidase [(6.2 +/- 0.5) U/g tissue vs (12.3 +/- 0.8) U/g tissue] and IL-8 [(987 +/- 106) ng/g tissue vs (24 +/- 3) mN/m] of BALF, and significant (P < 0.05) increase in Cdyn [(0.47 +/- 0.02) ml.cmH2O(-1).kg(-1) vs (0.31 +/- 0.02) ml.cmH2O(-1).kg(-1)], PaO(2) [(175 +/- 24) mmHg vs (135 +/- 26) mmHg], TPL/TP (52 +/- 8 vs 33 +/- 11) and Vv (0.65 +/- 0.05 vs 0.44 +/- 0.07) as compared with CMV. CONCLUSIONS:In this animal model of ALI, TGI decreased ventilatory requirements (PIP, V(T) and V(D)/V(T)), resulted in more favourable alveolar pulmonary surfactant composition and function and less severity of lung injury than CMV. TGI in combination with pressure limited ventilation may be a lung protective strategy for ALI.
    背景与目标: 背景:肺表面活性物质功能障碍可能导致呼吸机诱发的肺损伤(VILI)的发展。气管内注气(TGI)是一种将新鲜气体引入气管并通过减少通气系统的死腔,降低通气压力和潮气量(V(T))并保持恒定的局部动脉CO2压力来增强通气的技术( PaCO(2))。我们假设TGI限制了峰值吸气压力(PIP)和V(T),并且将传统机械通气(CMV)引起的肺表面活性剂功能异常减至最小,从而减轻了急性肺损伤(ALI)兔的VILI。
    方法:通过气管内脂多糖经气管内施用麻醉的,通气的健康成年兔,以0.5 L / min(TGI组)或CMV组(每组n = 8)随机分配为连续TGI,然后在有限的PIP和通气条件下通气,从而诱发ALI。 V(T)将PaCO(2)维持在35至45 mmHg的范围内4个小时。监测生理死区与V(T)的比率(V(D)/ V(T)),动态呼吸顺应性(Cdyn)和部分动脉O(2)压力(PaO(2))。通气后,对肺中的总磷脂(TPL),总蛋白(TP),支气管肺泡灌洗液(BALF)中的肺表面活性剂小到大聚集比(SA / LA)进行分析,并测定肺泡体积密度(V(V)) ),髓过氧化物酶和白介素(IL)-8。
    结果:TGI导致PIP显着降低(P <0.05或P <0.01)[(22.4 /-1.8)cmH2O与(29.5 /-1.1)cmH2O],V(T)[(6.9 /-1.3)ml / kg vs(9.8 /-1.11)ml / kg],V(D)/ V(T)[(32 /-5)%vs(46 /-2)%],TP [(109 /-22)mg / kg vs(187 /-25)mg / kg],SA / LA(2.5 /-0.4 vs 5.4 /-0.7),髓过氧化物酶[(6.2 /-0.5)U / g组织vs(12.3 /-0.8)U / g组织]和IL-8 [(987 /-106)ng / g组织vs(24 /-3)mN / m] BALF,Cdyn [(0.47 /-0.02)ml.cmH2O显着(P <0.05)增加(-1).kg(-1)vs(0.31 /-0.02)ml.cmH2O(-1).kg(-1)],PaO(2)[(175 /-24)mmHg vs(135 /-26 )mmHg],TPL / TP(52 /-8 vs 33 /-11)和Vv(0.65 /-0.05 vs 0.44 /-0.07)。
    结论:在这种ALI动物模型中,TGI降低了通气需求(PIP,V(T)和V(D)/ V(T)),与CMV相比,肺泡表面活性剂的肺泡表面活性剂组成和功能更佳,肺部损伤的严重程度更低。 TGI结合限压通气可能是ALI的肺保护策略。
  • 【硬皮病中的P波振幅和肺动脉压。】 复制标题 收藏 收藏
    DOI:10.1016/j.jelectrocard.2006.01.004 复制DOI
    作者列表:Wokhlu N,Hsu VM,Wilson A,Moreyra AE,Shindler D
    BACKGROUND & AIMS: BACKGROUND AND PURPOSE:Scleroderma is an immune-mediated disease characterized by excess deposition of collagen leading to microvascular occlusion. Morbidity and mortality are often secondary to pulmonary hypertension from injury to pulmonary microvasculature and interstitial lung disease. This study correlated P-wave findings on the 12-lead electrocardiogram (ECG) with mean pulmonary artery pressure (mPAP) measured by right heart catheterization in patients with scleroderma. METHODS:A retrospective review of 12-lead ECGs in 23 patients referred to a rheumatology clinic with the diagnosis of scleroderma was performed. Right heart catheterization was performed within 1 month of the resting ECG. RESULTS:Linear regression related P-wave amplitude in lead II with mPAP (r = 0.52, P = .011) This model was 73% sensitive and 67% specific for the presence or absence of elevated mPAP. CONCLUSIONS:P-wave amplitude analysis on the ECG may be helpful in the assessment of pulmonary hypertension in patients with scleroderma.
    背景与目标: 背景与目的:硬皮病是一种免疫介导的疾病,其特征是胶原蛋白的过度沉积导致微血管闭塞。发病率和死亡率通常是继发于肺动脉高压的疾病,从损伤到肺微脉管系统和间质性肺疾病。这项研究将硬皮病患者的12导联心电图(ECG)上的P波发现与右心导管检查测得的平均肺动脉压(mPAP)相关联。
    方法:回顾性分析23例转诊至风湿病诊所并诊断为硬皮病的患者的12导联心电图。静息ECG后1个月内进行右心导管检查。
    结果:与mPAP的铅II线性回归相关的P波振幅(r = 0.52,P = .011)该模型对存在或不存在mPAP升高的敏感性为73%,特异性为67%。
    结论:心电图的P波振幅分析可能有助于评估硬皮病患者的肺动脉高压。
  • 【使用MR数字减影血管造影评估儿童颅内病变的血液供应。】 复制标题 收藏 收藏
    DOI:10.1007/s00247-006-0268-1 复制DOI
    作者列表:Chooi WK,Connolly DJ,Coley SC,Griffiths PD
    BACKGROUND & AIMS: BACKGROUND:MR digital subtraction angiography (MR-DSA) is a contrast-enhanced MR angiographic sequence that enables time-resolved evaluation of the cerebral circulation. OBJECTIVE:We describe the feasibility and technical success of our attempts at MR-DSA for the assessment of intracranial pathology in children. MATERIALS AND METHODS:We performed MR-DSA in 15 children (age range 5 days to 16 years) referred for MR imaging because of known or suspected intracranial pathology that required a dynamic assessment of the cerebral vasculature. MR-DSA consisted of a thick (6-10 mm) slice-selective RF-spoiled fast gradient-echo sequence (RF-FAST) acquired before and during passage of an intravenously administered bolus of Gd-DTPA. The images were subtracted and viewed as a cine loop. RESULTS:MR-DSA was performed successfully in all patients. High-flow lesions were shown in four patients; these included vein of Galen aneurysmal malformation, dural fistula, and two partially treated arteriovenous malformations (AVMs). Low-flow lesions were seen in three patients, all of which were tumours. Normal flow was confirmed in eight patients including two with successfully treated AVMs, and in three patients with cavernomas. CONCLUSION:Our early experience suggests that MR-DSA is a realistic, non-invasive alternative to catheter angiography in certain clinical settings.
    背景与目标: 背景:MR数字减影血管造影(MR-DSA)是一种对比增强的MR血管造影序列,可对脑循环进行时间分辨评估。
    目的:我们描述了MR-DSA评估儿童颅内病理的尝试的可行性和技术成功。
    材料与方法:由于已知或怀疑颅内病理需要动态评估脑血管系统,我们对15例接受MR成像的儿童(年龄范围5天至16岁)进行了MR-DSA检查。 MR-DSA由厚的(6-10 mm)切片选择性RF破坏的快速梯度回波序列(RF-FAST)组成,在静脉内给予Gd-DTPA推注之前和期间均已获得。减去图像并将其视为电影循环。
    结果:所有患者均成功进行了MR-DSA检查。四名患者出现高流量病灶。其中包括Galen动脉瘤畸形静脉,硬脑膜瘘和两个经过部分治疗的动静脉畸形(AVM)。在三名患者中均发现了低流量病变,所有这些都是肿瘤。在八名患者中确认了正常血流,其中包括两名成功治疗过的AVM和三名患有海绵状瘤的患者。
    结论:我们的早期经验表明,在某些临床情况下,MR-DSA是导管血管造影术的一种现实的,非侵入性的替代方法。
  • 【基于人群的样本中肾血浆对血管紧张素II的血流反应与血压之间的关系。】 复制标题 收藏 收藏
    DOI:10.1097/00004872-199715050-00004 复制DOI
    作者列表:Turner ST,Kardia SL
    BACKGROUND & AIMS: OBJECTIVE:To assess whether interindividual variation in renal plasma flow or in its response to angiotensin II infusion is associated with interindividual differences in blood pressure in a population-based sample of 287 non-Hispanic whites (143 women and 144 men), aged 20-49.9 years.

    METHODS:After seven days of eating a high-sodium diet (260 mmol/day), the renal plasma flow was determined by measuring the clearance of p-aminohippurate before and after infusion of 3 ng/kg per min angiotensin II. Multiple linear regression methods were used to assess whether measures of the renal plasma flow and of its response to angiotensin II infusion were predictive of systolic or diastolic blood pressures measured prior to administration of the high-sodium diet, on day 6 of the high-sodium diet, or during the renal clearance procedure on day 7 prior to angiotensin II infusion.

    RESULTS:There was some evidence that measures of the renal plasma flow and of its response to angiotensin II infusion during the high-sodium diet were statistically significant predictors of measures of blood pressure in women; there was less evidence for this for blood pressures in men. Interindividual variation in measures of the renal plasma flow and of its response to angiotensin II infusion explained less than 10% of the interindividual variation in any measure of the blood pressure in both sexes.

    CONCLUSION:These results suggest that interindividual variation in renal plasma flow ad in its response to angiotensin II infusion during a high-sodium diet will be of limited utility in elucidating the basis for interindividual differences in blood pressure.

    背景与目标: 目标:在以人群为基础的287名非西班牙裔白人(143名女性和144名男性,年龄20-49.9岁。

    方法:进食高钠饮食(260 mmol /天)7天后,通过测量来确定肾脏血浆流量输注前后每分钟3 ng / kg血管紧张素II对对氨基马尿酸盐的清除率。使用多种线性回归方法评估在高钠饮食第6天测量肾血浆流量及其对血管紧张素II输注的反应是否预示着在服用高钠饮食之前测得的收缩压或舒张压饮食,或在输注血管紧张素II的第7天进行肾脏清除手术期间。

    结果:有证据表明,可以测量肾脏血浆流量及其对血管紧张素II的反应高钠饮食期间的输注是女性血压测量的统计学上显着的预测因子;男性血压下降的证据较少。肾血浆流量及其对血管紧张素II输注的反应的个体差异解释了在任何性别的血压测量中个体差异的不足10%。

    结论 >:这些结果表明,在高钠饮食期间,肾血浆流量的个体差异及其对血管紧张素II输注的反应在阐明个体间血压差异的依据方面将发挥有限的作用。

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