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。     

PaCO(2)/ETCO(2) gradient: early indicator of thrombolysis efficacy in a massive pulmonary embolism

End tidal CO(2) measurement may be helpful in detecting the efficacy of thrombolysis after a massive pulmonary embolism. We report the case of a 76-year-old man with a massive pulmonary embolism, who required early intubation and mechanical ventilation. Thrombolysis with rtpA (total dosage: 60 mg) was initiated. During this procedure, clinical data, arterial blood gases and end-tidal CO(2) with a capnograph were recorded. Before thrombolysis the P(a-ET)CO(2) gradient was raised to 25 mmHg. During thrombolysis, the clinical data improved and the P(a-ET) gradient fell to 14 mmHg. We postulate that the P(a-ET)CO(2) gradient seems to be a reasonable indicator of efficacy of thrombolysis in this setting. However, the gradient did not return to normal values (4-5 mmHg). The possible reasons for this may be that during mechanical ventilation there was a large ventilation-perfusion ratio and the cardiac output may have still reduced. With these limitations, we conclude that the P(a-ET)CO(2) gradient should be evaluated as an indicator of pulmonary reperfusion in massive pulmonary embolism.     

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。     

Continuous venovenous haemofiltration in cancer patients with renal failure: a single-centre experience

Objective To assess the effect of continuous venovenous hemodiafiltration (CVVHDF) in cancer patients with acute renal failure.Patients and methods Retrospective study of all patients with acute renal failure requiring dialysis and treated with CVVHDF in a medical intensive care unit (ICU) from a cancer hospital.Results From January 1997 until December 2002, 32 cancer patients were treated with CVVHDF for acute renal failure. Their characteristics were: male/female 23/9, median age 61 years, haematological/solid tumours 16/16, and median APACHE II and IGS II scores 31/67. The number of organ failures was 1/2/3/4 in respectively 10/6/13/2 patients. Complete, partial or absence of resolution of acute renal failure was noted in 13, 8 and 11 patients. Sixteen patients (50%) died in the ICU and 15 (47%) were discharged alive from the hospital. In univariate analysis, variables statistically significantly adversely associated with hospital mortality were renal failure of renal origin, bone marrow transplant, increasing number of organ failures, reduced lymphocyte count, elevated bilirubin and lower creatinine levels, increased thromboplastin time, younger age, increased APACHE II and IGS II, ARDS and mechanical ventilation. In multivariate analysis, two models were used including either APACHE II or IGS II. The number of organ failures was found as the only significant prognostic factor in both models (p=0.01). Elevated phosphate level was a poor prognostic factor for hospital mortality (p=0.04) in the model including APACHE II.Conclusions In the experience of a single centre, CVVHDF is effective in the treatment of acute renal failure in cancer patients. The increasing number of organ failures was the single independent poor predictive factor for hospital mortality. Cancer characteristics and general gravity scores were not predictive factors.     

Functional effects of systemically administered agonists and antagonists of mu,delta, and kappa opioid receptor subtypes on body temperature in mice

We have investigated the roles of peripheral and central mu, delta, and kappa opioid receptors and their subtypes in opioid-induced hypothermia in mice. Measuring rectal temperature after i.p. injection, opioid agonists [morphine, fentanyl, SNC80 ((+)-4-[(alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)3-methoybenzyl]-N,N-diethylbenzamide), U50,488H ((trans-(dl)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzeneacetamide), and loperamide)] were tested alone or with opioid antagonists [naloxone, beta-funaltrexamine, naloxonazine, naltrindole, 7-benzylidenenaltrexone (BNTX), naltriben, nor-binaltorphimine, 2-(3,4-dichlorophenyl)-N-methyl-N-[(1S)-1-(3-isothiocyanatophenyl)-2-(1-pyrrolidinyl)ethyl]acetamide (DIPPA), and methyl-naltrexone] given 15 min after the agonist. All agonists produced dose-related hypothermia, although at low doses, morphine and U50,488H produced hyperthermia. The effects of morphine and fentanyl were antagonized by naloxone and by the mu(1) antagonist naloxonazine. The delta(2) antagonist naltriben potentiated the hypothermic effect of mu agonists. SNC80-induced hypothermia was blocked by the delta antagonist naltrindole but not by the delta(1) antagonist BNTX. Depending on the dose, the delta(2) antagonist naltriben produced either a potentiation or an attenuation of the effect of SNC80. U50,488H-induced hypothermia was antagonized by the kappa antagonist nor-binaltorphimine but not by acute treatment with the irreversible kappa antagonist DIPPA. The peripherally acting opioid loperamide produced hypothermia that could be blocked by several mu-, delta-, or kappa-selective antagonists as well as the peripherally acting antagonist methyl-naltrexone. Methyl-naltrexone produced a weak potentiation of morphine-, fentanyl-, and U50,488H-induced hypothermia, whereas a significant attenuation of SNC80-induced hypothermia was observed. In conclusion, at high doses, morphine- and fentanyl-induced hypothermia may involve composite action on mu, kappa, and possibly delta opioid receptors after initial activation. In the mediation of delta opioid-induced hypothermia, no clear selectivity between the delta(1) and delta(2) subtypes was defined. The studies provide new evidence that maintenance of the initial effects of agonist/receptor activation vary with the agonist and the receptor. The existence of both central and peripheral components of opioid-induced hypothermia is also emphasized.     

Overestimation of advanced oxidation protein products in uremic plasma due to presence of triglycerides and other endogenous factors

BACKGROUND: Advanced oxidation protein products (AOPP), a suggested protein biomarker of oxidative stress, are elevated in patients with chronic kidney disease (CKD), who also often suffer from hypertriglyceridemia. METHODS: The analysis included plasma AOPP, TG, cholesterol, albumin and total protein, inflammation and oxidative stress markers from healthy subjects, non-dialyzed CKD, HD and CAPD patients. We studied, at two different European centres, effects of a meal, comparison between serum and plasma, L-index (indicating turbidity), spiking with fat and protein, and centrifugation on the AOPP concentrations. AOPP was measured at 340 nm and expressed as chloramine-T equivalents. RESULTS: AOPP correlated with TG levels not only in CKD patients, but also in healthy subjects. Weak to absent correlations were observed between AOPP and markers of inflammation and oxidative stress in CKD patients. A meal increased the TG levels several-fold paralleled by a rise in measured AOPP to patient levels. Spiking of the plasma with Intralipid or protein resulted in increased absorbances at 340 nm, due to turbidity or real absorbance, while centrifugation similarly decreased the apparent AOPP and TG levels. CONCLUSIONS: AOPP concentration, especially due to the influence of turbidity at all levels of TG concentration, but also due to other factors on top of TG, is overestimated in all plasma samples, including controls at fasting and non-fasting conditions. Thus, AOPP is a questionable biomarker of oxidative stress and inflammation in CKD patients.     

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.     

Life as Death Scholars: Passion,Personality, and Professional Perspectives

In death-averse American society, the field of thanatology is often socially and academically isolating. The purpose of this article is to describe the experiences of a group of death scholars and share insights gained as members of an interdisciplinary team. They discuss the ways in which they have created a special “safe” space for death study collaboration. The melding of their individual passions, personalities, and professional perspectives has allowed them to form a productive and satisfying work environment. Additional discourse in this field is needed on the nature and processes of such death-studies groups.