Should patients receive general anesthesia prior to extubation at the end of life?

Billings has proposed that any potentially conscious and imminently dying patient who is undergoing withdrawal of ventilator support should be offered general anesthesia to fully protect against suffering. Here we examine whether his proposal is compatible with the doctrine of double effect, a philosophical construct that is generally in accord with the legal requirements for palliative care in the United States. We review the essential elements of the doctrine of double effect, and emphasize the importance of pre-medicating patients before ventilator withdrawal (anticipatory dosing) and of titrating medications to the needs of the patient. The doctrine of double effect requires physicians to balance the risk of the patient suffering against the risk of hastening the patient's deathwhen titrating the medications used to provide comfort. We argue that the values and preferences of the patient should determine how these risks are balanced. We therefore agree with Billings that general anesthesia may be indicated for patients who prefer to minimize the risk of suffering while accepting a greater risk of having their death hastened. This approach would not be appropriate, however, for patients who place a higher value upon avoiding the risk of hastening death, even when this involves a greater risk of potential suffering.     

硼替佐米联合地塞米松与沙利度胺治疗多发性骨髓瘤的效果

目的比较硼替佐米＋地塞米松＋沙利度胺（BDT）方案与长春地辛＋表柔比星＋地塞米松＋沙利度胺（VADT）方案治疗多发性骨髓瘤（MM）的临床效果。方法MM病人67例,应用BDT方案治疗30例,VADT方案治疗37例,均治疗4个疗程,比较两组治疗前、治疗后β2-微球蛋白、免疫球蛋白、骨髓瘤细胞的变化,并比较两组疗效。结果BDT组及VADT组化疗后β2-微球蛋白、免疫球蛋白、骨髓瘤细胞均低于化疗前,差异有显著性（t=2．837～7．562,P％0．05）。BDT组完全缓解（CR）占13．0％,接近完全缓解（ncR）占20．0％,部分缓解（PR）占53．0％,微小反应（MR）占6．7％,总有效率93．3％;VADT组CR占3．0％,nCR占10．8％,PR占40．5％,MR占16．2％,总有效率70．3％,两组疗效比较,差异有显著性（Hc=51．67,P〈0．05）。结论BDT方案治疗MM效果优于VADT方案,且起效快,可改善病人的预后。     

Interferon-γ: Promising therapeutic target in atherosclerosis

Atherosclerosis is a chronic inflammatory disorder of the vasculature and is the primary cause of cardiovascular disease(CVD). CVD is currently the world's leading cause of death and the numbers are predicted to rise further because of a global increase in risk factors such as diabetes and obesity. Current therapies such as statins have had a major impact in reducing mortality from CVD. However, there is a marked residual CVD risk in patients on statin therapy. It is therefore important to understand the molecular basis of this disease in detail and to develop alternative novel therapeutics. Interferon-γ(IFN-γ) is a pro-inflammatory cytokine that is often regarded as a master regulator of atherosclerosis development. IFN-γ is able to influence several key steps during atherosclerosis development, including pro-inflammatory gene expression, the recruitment of monocytes from the blood to the activated arterial endothelium and plaque stability. This central role of IFN-γ makes it a promising therapeutic target. The purpose of this editorial is to describe the key role IFN-γ plays during atherosclerosis development, as well as discuss potential strategies to target it therapeutically.     

称重法和化学分析法评估人群膳食矿物质摄入量的比较

目的 探讨称重法和化学分析法评估人群矿物质摄入量的差异和相关性.方法 同时使用称重法和化学分析法对89名上海市居民进行膳食调查,并对两种调查方法测得的钙、镁、铁、锌、铜、锰摄入量进行比较分析.结果 称重法调查的6种矿物质元素的摄入量高于化学分析法(P<0.05),称重法调查的平均每天钙、镁、铁、锌、铜、锰摄入量比化学分析法分别高20.9%、67.4%、19.5%、84.4%、46.7%和33.3%;称重法与化学分析法测得的钙、镁、铁、锌、铜、锰摄入量均呈显著正相关(P<0.01),相关系数分别为0.571、0.672、0.521、0.524、0.538和0.691.结论 称重法测得的人群膳食矿物质摄入量高于化学分析法.     

Factors causing malnutrition in patients with chronic uremia

There is abundant evidence that patients with chronic renal failure (CRF), including those treated by hemodialysis or peritoneal dialysis, have evidence of malnutrition with decreased body weight and subnormal values of serum proteins (suggesting a loss of visceral protein stores). Potential causes of an abnormal nutritional status that have been identified include an inadequate intake of protein or calories, an inability to activate the metabolic responses that are needed to achieve nitrogen and protein balance, or the presence of a disease that prevents activation of these metabolic responses or acts to stimulate the breakdown of body protein stores. Three critical metabolic responses to a limited protein intake have been identified: a reduction in the irreversible degradation of amino acids and the degradation of protein breakdown and an increase in protein synthesis in response to a meal. Metabolic acidosis blocks the first two responses and hence contributes to malnutrition in patients with chronic uremia. Other factors that could contribute to malnutrition include an inadequate intake because of anorexia or hormonal imbalances that impair protein turnover. In evaluating CRF patients with malnutrition, the first task is to ensure an adequate intake and to eliminate factors that impair the ability to achieve nitrogen balance.     

Polymorphism of the thiopurine S-methyltransferase gene in African- Americans

The molecular basis for the genetic polymorphism of thiopurine S - methyltransferase (TPMT) has been estab-lished for Caucasians, but it remains to be elucidated in African populations. In the current study, we determined TPMT genotypes in a population of 248 African-Americans and compared it with allele frequencies in 282 Caucasian Americans. TPMT genotype was determined in all individuals with TPMT activity indicative of a heterozygous genotype (</=10.1 U/ml pRBC, n = 23African- Americans, n = 21 Caucasians) and a control group with TPMT activity indicative of a homozygous wild-type genotype (>10.2 U/ml pRBC, n = 23 African-Americans, n = 21 Caucasians). No mutant alleles were found in the high activity control groups. The overall mutant allele frequencies were similar in African-Americans and Caucasians (4.6 and 3.7% of alleles, respectively). However, while TPMT*3C was the most prevalent mutant allele in African-Americans (52.2% of mutant alleles), it represented only 4.8% of mutant alleles in Caucasians ( P < 0.001). In contrast, TPMT*3A and TPMT*2 were less common in African-Americans (17.4 and 8.7% of mutant alleles), whereas TPMT*3A was the most prevalent mutant allele in Caucasians (85.7% of mutant alleles). A novel allele ( TPMT*8 ), containing a single nucleotide transition (G644A), leading to an amino acid change at codon 215 (Arg-->His), was found in one African-American with intermediate activity. These data indicate that the same TPMT mutant alleles are found in American black and white populations, but that the predominant mutant alleles differ in these two ethnic groups.      

CC趋化因子受体4及其抑制剂研究进展

CC趋化因子受体4（CCR4）是G蛋白偶联受体家族成员之一,由包含7次跨膜结构域的多肽链组成,表达于多种细胞或组织中。CCR4通过与其内源性配体CCL17、CCL22及CKLF1作用介导多种炎症反应,尤其在哮喘发生和发展的病理过程中起重要作用,因此可能是某些炎性疾病、特别是哮喘的潜在治疗靶点。本文对CCR4及其抑制剂的研究进展做一综述。     

负载抗原的DC与CIK共培养对耐药乳腺癌细胞的杀伤作用

目的:观察负载抗原的树突状细胞(dendritic cell,DC)与细胞因子诱导的杀伤细胞(cytokine-induced killer cell,CIK)对高表达P-糖蛋白(P-glycoprotein,P-gp)的多药耐药(multidrug resistance,MDR)人乳腺癌MCF-7/ADR细胞的杀伤作用。方法:提取健康人外周血单个核细胞,常规诱导出CIK及DC;制备MCF-7/ADR细胞冻融抗原后冲击DC,并与CIK共培养作为实验组(冻融物DC-CIK组),未负载抗原的DC与CIK共培养作为对照组(DC-CIK组),同时设单独培养的CIK组或DC组作为空白对照组。流式细胞术分析细胞的表型及P-gp表达,ELISA法测定细胞上清中IL-12、IFN-γ水平,MTT法检测对MCF-7/ADR及MCF-7细胞株的杀伤活性。结果:冻融物DC-CIK组、DC-CIK组细胞增殖活性均大于CIK组(P<0.05)。冻融物DC-CIK组对MCF-7/ADR、MCF-7细胞的杀伤活性在效靶比10∶1、20∶1、40∶1时分别为(44.29±1.39)%、(58.24±3.52)%、(68.9±2.83)%和(33.51±2.18)、(40.43±2.3)%、(44.62±1.19)%,均高于DC-CIK组及CIK组(P<0.05);冻融物DC-CIK组对MCF-7/ADR耐药细胞株的杀伤活性高于非耐药细胞株MCF7(P<0.05);而对于非耐药株MCF-7细胞的杀伤活性,冻融物DC-CIK组和DC-CIK组之间差异无统计学意义(P>0.05)。结论:DC与CIK共培养细胞增殖活性和细胞毒活性均强于CIK,经冻融抗原冲击的DC与CIK共培养可以显著提高对MCF-7/ADR耐药细胞株的杀伤活性。