Dendritic cell-based approaches to cancer immunotherapy

Immunologic approaches to the treatment of malignancies are currently enjoying a resurgence of enthusiasm due to the discovery of tumour-associated antigens and the requirements for stimulating a tumour antigen-specific immune response. The goal of the newer strategies is to stimulate immunity against specific tumour-associated antigens, rather than to broadly, but non-specifically, stimulate the immune system. Since dendritic cells, professional antigen-presenting cells, play a central role in stimulating immune responses in vivo, there is considerable interest in immunising patients with autologous dendritic cells loaded with tumour antigens of interest. Methods for generating large numbers of dendritic cells under clinically-applicable conditions have been developed and it has been shown that they may be loaded with antigen in many different forms including proteins or peptides, RNA or DNA and cellular extracts. Ongoing research is seeking to optimise the purity, antigen loading and maturation of the dendritic cells. Phase I clinical trials have been initiated in order to study the safety and feasibility of immunisations with dendritic cells in humans with various malignancies. Phase II studies will be performed to establish which tumours and clinical scenarios will be most relevant for dendritic cell immunotherapy. Although the commercial applicability of dendritic cell-based immunotherapy has been recognised by the biotechnology industry, commercial availability of dendritic cell vaccines await phase III studies.     

Disease insight and treatment perception of men on active surveillance for early prostate cancer

Study Type – Survey (prospective cohort)
Level of Evidence 1b

OBJECTIVE

To investigate the levels of knowledge of prostate cancer and the perception of active surveillance (AS) in men on AS, as AS for early prostate cancer instead of radical treatment might partly solve the over‐treatment dilemma in this disease, but might be experienced as a complex and contradictory strategy by patients.

PATIENTS AND METHODS

In all, 150 Dutch men recently diagnosed with early prostate cancer participating in a prospective protocol‐based AS programme (PRIAS study) received questionnaires, including a 15‐item measure on their general knowledge of prostate cancer, and open‐ended questions on the most important disadvantages and advantages of AS, and on the specific perception of AS. We assessed knowledge scores and explored potentially associated factors, the stated (dis)advantages and specific perceptions.

RESULTS

The questionnaire response rate was 86% (129/150). Participants provided correct answers to a median (interquartile range) of 13 (12–14) of 15 (87%) knowledge items. Younger and higher educated men had higher knowledge scores. In line with a priori hypotheses, the most frequently reported advantage and disadvantage of AS were the delay of side‐effects and the risk of disease progression, respectively. Specific negative experiences included the feeling of losing control over treatment decisions, distress at follow‐up visits, and the desire for a more active participation in disease management. No conceptually wrong understandings or expectations of AS were identified.

CONCLUSIONS

We found adequate knowledge of prostate cancer levels and realistic perceptions of the AS strategy in patients with early prostate cancer and on AS. These findings suggest adequate counselling by the physician or patient self‐education.     

Outcome of active disease in ankylosing spondylitis: A prospective study

Background: People with ankylosing spondylitis (AS) typically experience episodic exacerbations, but the extent to which they subsequently experience a sustained reduction in disease markers below recognized thresholds for active disease is unclear. Objective: To investigate changes in, and associations between, disease markers over 18 months in people with active AS. Methods: Within a cohort of 89 participants with AS, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores of 4 or higher were used to identify those with active disease. Standard assessment tools were used to monitor participants prospectively at four consecutive six‐monthly intervals. Participants received standard treatments but none received anti‐tumor necrosis factor‐alpha (TNFα) medication during the study. Results: The median age of the cohort was 50 years (inter‐quartile range [IQR] 38.5–55.5), the median age of disease onset was 25 years (IQR 18–33) and the median disease duration was 18 years (IQR 13–27). Forty‐seven (53%) participants had a BASDAI score of 4 or higher on the first assessment, of whom 45 (51%) scored 4 or higher on all subsequent assessments. Furthermore, 38 (43%) and 16 (18%) participants scored BASDAI 5 or 6, respectively, or higher, throughout. BASDAI scores correlated strongly with Bath Ankylosing Spondylitis Functional Index (BASFI) scores. Compared with 19 (21%) participants whose BASDAI scores were consistently below 4 throughout, participants with persistently high BASDAI scores showed higher scores for anxiety and depression, and some evidence of functional deterioration during the study period. Conclusions: In this cohort, disease markers in most people with active AS were sustained above the standard threshold for active disease. This has important implications for planning care pathways and for optimal utilization of anti‐TNFα treatment. Copyright © 2009 John Wiley & Sons, Ltd.     

Effects of homeopathic doses of antibodies to S100 antigen on electric characteristics of neuronal membranes

Various dilutions of antibodies to brain-specific protein S100, including those prepared by multiple consecutive dilutions up to 10⁻¹² and 10⁻⁴⁰⁰ of total weight, produced similar effects on the membranes ofHelix pomatia giant neurons, which varied only quantitatively. They induced membrane depolarization, reduced the amplitude or completely blocked the action potential, accelerated the maximal rise of the action potential, reduced maximal conductance, and facilitated the steady-state inactivation of ionic channels. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 4, pp. 466–467, April, 1999     

急性等容血液稀释对血液成份及凝血功能的影响

目的：了解急性等容血液稀释对血液成份及凝血功能的影响，方法：选择20例估计出血量多的大手术患者，随机分为急性等容血液稀释组（简称稀释组）和对照组，每组10例，稀释组术前进行急性等容血液稀释，预计把Hct稀释至30％，监测并比较两组血液稀释毕，术毕，术后第1天，第7天Hb,Hct,Plt,Alb,Pt,Aptt,Fg变化，结果：稀释组稀释毕，术毕，术后第1天，第7天及对照组术毕，术后第1天，第7天，Hb,Hct,Plt值均极显著低于术前值（P＜0．01），稀释组术毕，术后第1天Hb,Hct极显著低于对照组同期值（P＜0．01），但第7天两组则无差别，两组术毕，术后第1天，第7天Alb显著低于术前值（P＜0．05），但两组上述各监测值均仍在安全范围内；两组稀释毕及术毕，术后Pt,Aptt,Fg与术前相比无差别（P＞0．05），结论：急性等容血液稀释可使患者Hb,Hct,Plt较显著下降，但经控制好稀释程度仍可维持在安全范围内，而结凝血功能影响轻微。     

补骨脂及其活性成分在肝损伤中的双重作用研究进展

中药补骨脂是一味传统的补肾壮阳药，但因其滋肾水而涵肝木，有促进肝脏疏泄、调畅气机及抗邪解毒之功效，临床应用广泛。现代药理学研究证实，补骨脂及其部分活性成分是一把“双刃剑”，对肝损伤具有保护作用的同时，也可导致肝损伤。本文就中药补骨脂及其活性成分对肝脏的这种双重作用进行综述，为其进一步开发和利用提供参考。     

Quantification of spinal cord atrophy from magnetic resonance images via a B-spline active surface model.

A method is presented that aims at segmenting and measuring the surface of the spinal cord from MR images in order to detect and quantify atrophy. A semiautomatic segmentation with very little intervention from an operator is proposed. It is based on the optimization of a B-spline active surface. The method allows for the computation of orthogonal cross-sections at any level along the cord, from which measurements are derived, such as cross-sectional area or curvature. An evaluation of the accuracy and reproducibility of the method is presented.     

狼毒的化学成分研究进展

对狼毒的化学成分和生物活性方面的研究进展进行综述.其所含多种化学成分,主要类型是黄酮类和萜类,还含有鞣质类、香豆素类、木脂素类及甾醇类化合物.具有显著的抗肿瘤、抗艾滋病病毒、抗白血病及驱虫作用,临床应用疗效显著,值得进一步研究.     

Principal components and Multidimensional scaling of auditory and visual event-related potential topography

Summary Principal components analysis and metric multidimensional scaling were used to assess auditory and visual event-related potential topography in healthy late-middle-aged and elderly adults (n=20). Binaurally elicited auditory evoked potentials and full-field checkerboard pattern reversal visual event-related potentials were recorded from 28 scalp sites. The zero-lag, cross-correlations of all waveforms for 300 msec post-stimulus epochs were obtained and separate analyses of the auditory and visual data were performed. Ultimately, three of the four dimensions identified in the principal components and multidimensional scaling solutions were similar and represented electrode site differences in (1) the anterior-posterior plane; (2) laterality; and, (3) the proximal-distal relation to midline. The remaining multidimensional scaling axis appeared to reflect effects specific to the modality of stimulation. Under auditory stimulation, the temporal and central-parietal sites were distinct from other scalp regions, whereas under visual stimulation, the occipital and frontal sites were distinctive. Although the results of the principal component analyses were conceptually similar to the multidimensional scaling outcomes, there were consistent differences between them. The findings provide empirical support for the validity of these multivariate methods in topographic analysis.     

活跃期进行连续硬膜外阻滞分娩镇痛的临床观察

目的：探讨连续硬膜外阻滞用于活跃期分娩镇痛，对产力，产程及母儿状况的影响。方法 将230例正常分娩的初产妇随机分为镇痛组和对照组。镇痛组于活跃期施行连续硬膜外阻滞分娩镇痛，其他产科处理措施同于对照组。观察两组的产痛程度，产程时间，胎儿宫内窘迫率，新生儿Apgar评分，新生儿窒息率，产后出血率，阴道助产率，催产素使用率等情况。结果：镇痛组与对照组相比，阵育强度有显著差异（P＜0．01），除第2产程时间稍长于对照组（P＜0．05），两组的胎儿宫内窘迫率，新生儿Apgar评分，新生儿窒息率，产后出血率，阴道助产率，催产素使用率均无显著性差异（P＞0．05）。结论 连续硬膜外阻滞用于活跃期分娩镇痛，镇痛效果确定，不影响产程进展，同时不增加产后出血，阴道助产及催产素的使用，对新生儿无不良影响。