自体造血干细胞的体外净化

目的:综合分析自体造血干细胞体外净化的方法。资料来源:应用计算机检索Medline 1991-01/2003-12有关自体造血干细胞体外净化方法的文章,检索词“purging,HSCT”,并限定文章语言种类为English。同时计算机检索CNKI数据库1991-01/2003-12有关自体造血干细胞体外净化方法的文章,检索词“体外净化,PUVA”,并限定文章语言种类为中文。资料选择:对相关资料进行整理,选取同一领域、不同方面的文献,以近期发表或权威杂志的文章优先。资料提炼:共检索到42篇有关自体造血干细胞体外净化方法的文献,其中24篇文章符合要求。排除18篇,其中15篇系重复同一研究,3篇为Meta分析。资料综合:自体造血干细胞的体外净化方法很多,如物理方法、生物学方法、药物方法、免疫净化、基因净化等。每种净化方法都有其各自的优势和不足,如淋巴系统疾病可以采用免疫净化;慢性粒细胞白血病患者可考虑反义技术;大多数患者则均可以考虑药物净化的方法。结论:针对不同的疾病,可以选择不同的净化方法,还可以将几种净化方法联合起来,其效果和方法的改进也在不断的研究探索中。     

Fluoroscopic analysis of lumbar epidural contrast spread after lumbar interlaminar injection

Weil L, Frauwirth NH, Amirdelfan K, Grant D, Rosenberg JA. Fluoroscopic analysis of lumbar epidural contrast spread after lumbar interlaminar injection.

Objective

To describe and answer questions concerning the spread of contrast in patients receiving correctly placed lumbar epidural steroid injections (ESIs) under fluoroscopy.

Design

Prospective observational study.

Setting

An outpatient surgery center.

Participants

Consecutive patients (N=114) receiving ESIs under fluoroscopy who met inclusion criteria.

Interventions

Not applicable.

Main Outcome Measures

Spread of contrast in relation to variables, including unilateral versus bilateral, anterior versus posterior, and spread more than 1 level caudally versus less than 1 level. Variables were examined in relation to needle tip placement, level of injection, and male versus female patients. All data were collected with fluoroscopy images in lateral and anteroposterior views after injection of 5mL of fluid.

Results

Spread was greater than 1 segment caudally more than 75% of the time under all variables. Anterior versus posterior epidural spread on the lateral view was approximately even over all cases and anterior spread was found more often when the needle was within the width of the distal spinous process tip. Needle placement medial or lateral to the spinous process width also significantly affected whether the spread was unilateral versus bilateral. If the needle tip was lateral to the width of the spinous process, spread was unilateral 75% of the time, versus 45% of the time if the needle tip was medial.

Conclusions

Contrast spread is affected by needle placement, with other variables kept equal, in the performance of an interlaminar lumbar ESI. These data support the performance of interlaminar lumbar ESIs with fluoroscopic guidance and provide some parameters with which to guide the injectionist.     

Implementation of MR colonography

Background MR colonography (MRC) is a promising method of examining the colon, but is limited to a few specialist centres. The purpose of this article was to describe the implementation of MRC with fecal tagging. Materials and methods Patients referred for conventional colonoscopy (CC) were offered MRC with fecal tagging before CC. Two days before MRC patients ingested an oral contrast agent. Before and after MRC and CC a number of questions were addressed. MR images were rated by a blinded investigator. Results In 6 months, 30 consecutive patients were included. The median time in the MR suite was 44 min, 23 min for the MRC examination and 9 min for the evaluation. The median time for CC was 32 min. Sixty-six percent of the patients preferred MRC as the future method of examination, 10% preferred CC, 21% had no preferences. Of the oral contrast agents, barium sulphate with ferumoxsil was significantly better than barium sulphate alone. Conclusion The majority of the patients found MRC less unpleasant than CC and a majority would prefer MRC over CC as a future colon examination. MRC also appears to be less time consuming to the patients and medical personnel than CC with post-procedural monitoring.     

Informal stroke rehabilitation: what are the main reasons of Thai caregivers?

The aim of this study was to identify the reasons for the provision of informal rehabilitation services at home to stroke relatives by Thai caregivers. Twenty primary informal caregivers were individually interviewed at their homes by using semistructured questions elaborated by the researchers. All interviews were recorded on audiotape. Content analysis was used to determine the reasons for performing informal rehabilitation. Four major reasons, (i) biological, (ii) psychological, (iii) social, and (iv) spiritual, emerged from our content analysis to maintain for the stroke victims the highest possible quality of life. Improvement and prevention of further deterioration were the two main concepts in the biological and psychological reasons expressed by these Thai caregivers, whereas maintaining human relations and usual social activities were the two main considerations in the social reason. The main concepts in the spiritual reason were respecting the religious beliefs, superstitions, and culture of the caregivers or patients, improving patients' empowerment, and improving caregivers' satisfaction. These four reasons encompassed the biological, psychological, social, and spiritual aspects of a holistic approach to the definition of health. The health professional in Thailand should encourage stroke caregivers to continue providing informal rehabilitation services for their stroke relatives, as it might sustain the well being of stroke survivors during their stay at home.     

Aspirin withdrawal in patients treated with ticagrelor presenting with non‐ST elevation myocardial infarction

Essentials

• Strong P2Y₁₂ blockade may cause platelet inhibition that is only minimally enhanced by aspirin.
• We evaluated aspirin withdrawal on platelet reactivity in ticagrelor treated patients.
• Aspirin withdrawal resulted in increased platelet reactivity to arachidonic acid.
• Aspirin withdrawal caused little difference in adenosine diphosphate‐induced platelet aggregation.

Summary

Background

Recent studies have shown that the thromboxane A₂‐dependent pathway is dependent on the ADP–P2Y₁₂ pathway, and that strong P2Y₁₂ receptor blockade alone causes inhibition of platelet aggregation that is minimally enhanced by aspirin. Data from the PLATO trial suggested that, among ticagrelor‐treated patients, high‐dose versus low‐dose (< 100 mg day^?1) aspirin is associated with an increased risk fof ischemic events.

Objectives

To evaluate the impact of aspirin withdrawal on platelet reactivity in acute coronary syndrome (ACS) patients treated with a potent P2Y₁₂ blocker.

Patients/Methods

This was a current prospective, randomized, placebo‐controlled, double‐blind, cross‐over study. The study population comprised 22 consecutive ACS patients who underwent percutaneous coronary intervention and were treated with aspirin (100 mg day^?1) and ticagrelor. Thirty days post‐ACS, open‐label aspirin was stopped, and patients were randomized to either blinded aspirin or placebo for 2 weeks, with each patient crossing over to the other arm for an additional 2 weeks. Platelet reactivity to arachidonic acid and ADP determined with light‐transmission aggregometry (LTA) and VerifyNow was evaluated at baseline, and 2 weeks and 4 weeks later.

Results

Aspirin withdrawal resulted in an increase in arachidonic‐acid induced platelet reactivity as determined with both LTA (77.0% ± 11.3% versus 20.8% ± 4.4%) and VerifyNow (607.7 ± 10.6 aspirin reaction units [ARU] versus 408.5 ± 14.4 ARU). Platelet response to ADP, as determined with both LTA and VerifyNow, did not differ with either aspirin or placebo (32.9% ± 2.6% versus 35.8% ± 3.6%, and 33.5 ± 6.4 P2Y₁₂ reaction units (PRU) versus 29.6 ± 5.7 PRU, respectively).

Conclusions

Aspirin withdrawal early post‐ACS results in increased platelet reactivity in response to arachidonic acid, despite concomitant treatment with the potent P2Y₁₂ blocker ticagrelor.

     

Aptamer-targeted Antigen Delivery

Effective therapeutic vaccines often require activation of T cell-mediated immunity. Robust T cell activation, including CD8 T cell responses, can be achieved using antibodies or antibody fragments to direct antigens of interest to professional antigen presenting cells. This approach represents an important advance in enhancing vaccine efficacy. Nucleic acid aptamers present a promising alternative to protein-based targeting approaches. We have selected aptamers that specifically bind the murine receptor, DEC205, a C-type lectin expressed predominantly on the surface of CD8α⁺ dendritic cells (DCs) that has been shown to be efficient at facilitating antigen crosspresentation and subsequent CD8⁺ T cell activation. Using a minimized aptamer conjugated to the model antigen ovalbumin (OVA), DEC205-targeted antigen crosspresentation was verified in vitro and in vivo by proliferation and cytokine production by primary murine CD8⁺ T cells expressing a T cell receptor specific for the major histocompatibility complex (MHC) I-restricted OVA_257–264 peptide SIINFEKL. Compared with a nonspecific ribonucleic acid (RNA) of similar length, DEC205 aptamer-OVA-mediated antigen delivery stimulated strong proliferation and production of interferon (IFN)-γ and interleukin (IL)-2. The immune responses elicited by aptamer-OVA conjugates were sufficient to inhibit the growth of established OVA-expressing B16 tumor cells. Our results demonstrate a new application of aptamer technology for the development of effective T cell-mediated vaccines.     

Evolution of innate and adaptive effector cell functions during acute HIV-1 infection

Early events during acute human immunodeficiency virus type 1 (HIV-1) infection are critical in determining the course of disease progression. Cells of the innate and adaptive immune responses are involved in this acute response to infection; however, little is known about the coevolution of innate and adaptive effector cell populations during the initial phase of HIV-1 infection. Here, we have characterized the development of innate natural killer (NK) cell and adaptive HIV-1-specific CD8(+) T cell function during acute HIV-1 infection. Although NK cell populations were significantly expanded during acute infection before HIV-1 seroconversion, HIV-1-specific CD8(+) T cell responses were absent or weak and were inversely correlated with the level of NK cell activity. NK cell activity was directly correlated with the level of viral replication during acute HIV-1 infection and declined rapidly in subjects who initiated highly active antiretroviral therapy, whereas NK cell activity remained elevated in subjects who did not initiate therapy. Yet, reexposure to HIV-1 antigen during treatment discontinuation in chronic infection resulted in a synchronous increase in NK and CD8(+) T cell activity. Overall, these data demonstrate that expansion of the NK cell population precedes the development of adaptive HIV-1-specific CD8(+) T cells during acute infection but that both effector cell subsets respond with similar kinetics during chronic HIV-1 infection.     

CTLA-4 dysregulation of self/tumor-reactive CD8+ T-cell function is CD4+ T-cell dependent

Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) maintains peripheral tolerance by suppressing T-cell activation and proliferation but its precise role in vivo remains unclear. We sought to elucidate the impact of CTLA-4 expression on self/tumor-reactive CD8(+) T cells by using the glycoprotein (gp) 100-specific T-cell receptor (TCR) transgenic mouse, pmel-1. pmel-1 CLTA-4(-/-) mice developed profound, accelerated autoimmune vitiligo. This enhanced autoimmunity was associated with a small but highly activated CD8(+) T-cell population and large numbers of CD4(+) T cells not expressing the transgenic TCR. Adoptive transfer of pmel-1 CLTA-4(-/-) CD8(+) T cells did not mediate superior antitumor immunity in the settings of either large established tumors or tumor challenge, suggesting that the mere absence of CTLA-4-mediated inhibition on CD8(+) T cells did not directly promote enhancement of their effector functions. Removal of CD4(+) T cells by crossing the pmel-1 CLTA-4(-/-) mouse onto a Rag-1(-/-) background resulted in the complete abrogation of CD8(+) T-cell activation and autoimmune manifestations. The effects of CD4(+) CLTA-4(-/-) T cells were dependent on the absence of CTLA-4 on CD8(+) T cells. These results indicated that CD8(+) CLTA-4(-/-) T-cell-mediated autoimmunity and tumor immunity required CD4(+) T cells in which the function was dysregulated by the absence of CTLA-4-mediated negative costimulation.     

Nonoxynol-9 100 mg gel: multi-site safety study from sub-Saharan Africa

OBJECTIVES: To evaluate the safety of 100 mg nonoxynol-9 (N-9) gel, a vaginal microbicide, on the genital mucosa of women from Malawi and Zimbabwe in preparation for a phase III efficacy study. METHODS: HIV-uninfected women (180) were enrolled and randomized to either N-9 or placebo gel and instructed to insert gel into the vagina twice daily for 14 days. Follow up examinations were conducted at 7 and 14 days. RESULTS: The number of adverse events in the N-9 gel group was higher than in the placebo group (40% versus 13%; P < 0.01). Reported number of any genital symptoms was significantly higher in the N-9 group (38% N-9, 13% placebo; P = 0.01). The number of total epithelial disruptions was higher in the N-9 group (20% versus 3%; P < 0.01); however, the number of genital ulcers and abrasions in the N-9 group was low (2% and 3%, respectively) and not different from that in the placebo group (1% and 2%, respectively). CONCLUSIONS: N-9 gel 100 mg caused a significant increase in the rate of genital symptoms and epithelial disruptions compared with placebo. The clinical significance of these epithelial disruptions is unknown. Although these findings alone were not sufficient to cancel the planned phase III study, when considered together with the negative results from the COL-1492 effectiveness trial of 52.5 mg N-9 gel, the decision was made to cancel the planned phase III trial of 100 mg N-9 gel.