Platelet-derived growth factor promotes human peripheral monocyte activation

Like in the polymorphonuclear leukocyte (PMN), the platelet-derived growth factor (PDGF) purified to homogeneity is capable of inducing monocyte activation responses as evaluated by generation of superoxide anion (O-.2) from membrane-associated oxidase system, release of granule enzymes, and enhanced cell adherence and cell aggregation. Superoxide anion release was maximized at 10 ng/mL PDGF and was comparable to that induced by 10(-7) mol/L formyl-methionyl-leucyl- phenylalanine. The potency of PDGF to induce this response in monocytes was of the same magnitude as that observed in PMNs. Similarly, lysozyme release and monocyte adherence were also increased in a dose-dependent manner and achieved maximal responses at 40 ng/mL concentration of PDGF. The PDGF concentration required to achieve maximal monocyte aggregation was two-fold (60 ng/mL) of that found for PMNs. In contrast to PMNs, a positive correlation (gamma = .93; P less than .01) was observed between the increases of PDGF concentration and beta- glucuronidase release. These findings indicate that PDGF can induce the full sequence of cell activation events in human monocytes similar to human PMNs.     

Assessment of the frequency and costs of posttransplantation hospitalizations in patients receiving tacrolimus versus cyclosporine

We assessed the frequency and costs of hospitalizations in patients receiving tacrolimus (FK506) compared with patients receiving cyclosporine A for immunosuppression during 1 year after kidney transplantation. Four hundred twelve cadaveric kidney transplant recipients were randomized onto a phase III, prospective, multicenter, clinical trial. Hospital billing data were collected for 1 year posttransplantation. Total inpatient costs were calculated from billed charges and standardized to 1995 US dollars. Medical resource utilization rates and inpatient costs were compared between treatment groups using unpaired Student's t-tests. Complete billing data (transplantation and all posttransplantation hospitalizations) were available for 65% (268 of 412) of the study patients. Among tacrolimus and cyclosporine patients with complete billing data, the rates of allograft rejection were 32% and 47%, respectively (P=0.009), and the rates of rehospitalization during the year after transplantation were 53% and 63%, respectively (P=0.080). The mean per-episode rehospitalization costs were significantly lower among tacrolimus-treated patients compared with cyclosporine-treated patients ($7,495 v $11,497; P=0.031), and the mean total rehospitalization costs were significantly lower in the tacrolimus group compared with the cyclosporine group ($8,550 v $14,869; P=0.029). In addition, the total 1-year hospitalization costs (including transplantation and posttransplantation hospitalizations) were significantly lower in the tacrolimus group compared with the cyclosporine group ($53,435 v $61,191; P=0.046). Compared with cyclosporine-based immunosuppression, tacrolimus-based immunosuppression for kidney transplant recipients was associated with a significantly lower rate of rejection, which was associated with significantly lower per-episode rehospitalization costs, lower total 1-year rehospitalization costs, and lower total 1-year hospitalization costs.     

临床试验中应用安慰剂的伦理学争议评价

在有效治疗存在的情况下，对于是否可以在临床试验中应用安慰剂对照组，存在很大争议。当第5版“赫尔辛基宣言”(2000)出台后，此争议更趋激烈。本就此争议进行了回顾，并且调查了香港医学研究人员在此争议中的态度。有关争议的内容主要包括四个方面。第一，从试验方法角度而论，应用安慰剂对照的设计是否在确定疗效方面具有优越性?第二，治疗的真实疗效是否应该包括安慰剂效应?第三，安慰剂对照组的参与是否面对发生更大不良反应事件的机会?第四，有效治疗的标准究竟应该是地区性的，还是国际性的?从初步研究的数据来看，香港研究人员对于在临床试验中有效治疗存在的情况下，是否可以应用安慰剂对照组似乎也存在意见分歧。因此，为减少此争议给香港医学研究人员带来的困惑，有必要进行一定的培训以达成共识。     

海藻酸盐的理化特性及其在组织工程研究和临床中的应用

目的:对藻酸钠和藻酸钙的理化特性及在骨、软骨组织工程研究和临床中的应用作一系统回顾。资料来源:检索2000/2006 Medline与藻酸钠或藻酸钙相关的文献,检索词"sodium alginate,Calcium alginate",并限定文章语言种类为"English";同时检索中国医院数字图书馆1994/2006中国医学核心期刊关于藻酸钠或藻酸钙的相关文献,检索词"藻酸钠,藻酸钙",限定文章语言种类为中文。同时手工检索相关书籍。资料选择:对检索到的与藻酸钠或藻酸钙相关文献212篇进行筛选,并排除综述类文献,符合纳入标准的有71篇。资料提炼:对71篇文献进行分类整理,排除重复性文献,纳入33篇文献,其中22篇关于海藻酸理化特性,11篇为临床应用。资料综合:①藻酸钠水溶液在钙离子的作用下发生侧向交联由液态变为凝胶态,该水凝胶具有很好的亲水性,营养物质易于渗透扩散,其酶解产物对人体无毒害作用。这类凝胶以其良好的生物相容性在骨或软骨组织工程中、在药物缓释系统、创伤修复、治疗返流性食管炎等临床过程和改善水质、净化环境等方面发挥重要作用。②藻酸钙凝胶是藻酸钠的置换物,是一种中性偏碱的基质材料,除机械强度较差外,它在生物相容性、可降解性、细胞-材料界面、三维立体多孔结构和可塑性等方面都有利于种子细胞的接种和生长,是理想的组织工程基质材料,尤其在骨和软骨组织工程中。结论:海藻酸盐主要从海藻中提取,其凝胶具有良好的生物相容性,在组织工程及临床应用方面有巨大的潜力。     

Frequency of platelet-specific antigens among Chinese in Taiwan

The frequencies of six platelet-specific antigens among Chinese in Taiwan are reported, which have not previously been well studied. HPA- 1a (PlA1) antigen was positive in all 1100 Chinese tested. HPA-4b (Yukb) antigen was positive in all 100 persons tested. HPA-2b (Ko(a), Sib(a)) antigen was positive in 9 percent of 100 persons tested, HPA-3a (Bak(a)) in 77 percent, and NAKa in 96 percent. HPA-4a (Yuk(a)) antigen occurred in 0 percent in this study but is estimated to be present in 0.5 percent of the Taiwanese population.     

Inflammation in Coronary Artery Disease and Acute Myocardial Infarction - is the Stage Set for Novel Therapies?

Acute myocardial infarction (AMI) constitutes the major cause of death in most nations and death rates and morbidity remain substantial in the years thereafter. Inflammation is a hallmark throughout the distinct stages of atherosclerotic lesion formation preceding AMI as well as at the time of plaque rupture and during the post-infarct repair phase. Epidemiological, genetic, clinical and experimental evidence converges on inflammation as a pivotal factor in disease progression and exacerbation. Harnessing its harmful consequences constitutes an attractive therapeutic approach to address this unmet medical need. Components of the innate and adaptive immune system with the characteristic cytokines interleukin-1 and tumor necrosis factor-α, respectively exert prominent functions in atherogenesis and post-infarct remodeling. Leukocyte subsets of the monocyte/macrophage and CD4+ T lymphocyte cell lineage interacting with a vast array of cells comprising platelets, neutrophils, dendritic cells, mast cells, vascular smooth muscle cells and fibroblasts orchestrate the inflammatory pathophysiology underlying plaque progression in the vasculature and fibrotic repair of the infarct. This pathophysiology is amenable to modification by drugs targeting cell proliferation, cell migration, osteogenic/fibrous turnover of the extracellular matrix ranging from antimetabolites, glucocorticoids, specific cytokine and leukotriene antagonists to classic immunosuppressive agents and vaccines directed specifically at certain disease-relevant antigens. Based on published data on clinical safety and clinical/experimental efficacy in inhibiting disease progression this review covers recent advances in this field and aims to propose candidate drugs for future clinical trials.     

Association between antidepressant drug use during pregnancy and child healthcare utilisation

Objective  To evaluate healthcare utilisation by children who were exposed to antidepressant drug use during pregnancy and those whose mothers stopped using antidepressants before pregnancy compared with a control group.
Design  Cohort study.
Setting  Health insurance records in the Netherlands.
Population  A total of 38 602 children born between 2000 and 2005.
Methods  Survey of child healthcare utilisation in relation to gestational antidepressant use.
Main outcome measure  Healthcare utilisation rates during the first year of life, with special emphasis to medical care related to cardiac disease.
Results  Children of mothers who used antidepressants during pregnancy showed increased healthcare use during the first year of life, independent of the mother's healthcare use. The relative risk of more than two visits to general practitioners was 1.5 (95% confidence interval, CI: 1.3–1.8) in the continuous antidepressant users group and 1.3 (95% CI: 1.2–1.5) in the group of children whose mothers stopped taking medication. In both study groups there was a trend towards more drug use for infections and inflammation compared with the control group. Children continuously exposed to antidepressants had an increased risk of cardiac interventions such as cardiovascular surgery or heart catheterisation, relative risk of 5.6 (95% CI: 1.8–17.4). The risk of physiotherapy was twice as high in the antidepressant group compared with the control group (relative risk 2.0; 95% CI: 1.5–2.6).
Conclusion  Antidepressant use during pregnancy is associated with increased child healthcare utilisation and increased risk of major cardiac interventions in early childhood.     

纳米羟基磷灰石／壳聚糖复合人工骨的成骨及再血管化

目的:通过纳米羟基磷灰石/壳聚糖(N-HA/CS)复合骨形态发生蛋白(BMP)制备N-HA/CS-BMP复合人工骨,初步了解其植入后成骨与血管长入之间的关系,以及复合人工骨的孔径对再血管化的影响。方法:①材料的制备:采用共沉淀法、粒子沥滤法制备N-HA/CS多孔复合材料,孔隙率为85%,孔径为100￣500μm;通过N-HA/CS与氧化锌粉末按质量比为8∶1的方式混合制备成致密复合材料;然后分别复合BMP制备N-HA/CS-BMP复合人工骨。②实验过程:20只新西兰兔,在兔双后肢胫骨近段内侧用直径为3.5mm手摇钻头钻2个孔制备骨缺损模型。随机取15只兔,右侧植入2块多孔N-HA/CS-BMP复合人工骨为多孔N-HA/CS BMP组,左侧植入2块致密N-HA/CS-BMP复合人工骨为致密N-HA/CS BMP组;另5只兔右侧植入2块多孔N-HA/CS为多孔N-HA/CS组,左侧植入2块致密N-HA/CS为致密N-HA/CS组。③观察指标:术后4,6,8周麻醉后墨汁灌注处死动物取出标本,行大体观察、X射线检查、组织学观察、Ⅰ型胶原免疫组化染色、显微计算机图像采集分析,了解各组成骨能力、血管化程度、复合人工骨的成骨与血管化之间的相互关系。结果:①一般情况:术后死亡2只动物,2只一侧肢体发生骨折,伤口均于2周左右愈合,未发生感染。②X射线检查:术后4,6周显示植入孔明显,材料与骨之间有密度减低的透光环,8周材料与骨结合紧密,透光环消失。③组织学观察:术后4,6周的材料内的炎性反应较重,主要是白细胞和巨噬细胞,8周的材料内炎性反应减轻;8周壳聚糖大部分降解,从而显现出羟基磷灰石的多孔结构。④显微计算机图像分析:多孔N-HA/CS BMP组血管密度和新生骨小梁面积大于其他3组(P<0.05),多孔N-HA/CS BMP组血管密度与骨小梁面积呈直线正相关关系(r=0.483,P=0.003)。⑤Ⅰ型胶原免疫组织化学染色显示结果支持显微计算机图像分析结果。结论:复合人工骨的成骨与血管化呈直线正相关关系,复合人工骨的成骨与血管化在早期是随着材料降解而完成的,多孔结构在晚期对血管化和成骨有利。