翁丹西隆的合成

以环己酮为起始原料,经与苯肼缩合、氧化、Mannich 反应制得1,2,3,9-四氢-3-二甲胺基甲基-4H-咔唑-4-酮盐酸盐(5),后者再与2-甲基咪唑缩合、甲基化合成翁丹西隆,总收率为10.4%。     

Adverse drug reactions: physicians' opinions versus a causality assessment method

Since spontaneous reporting of adverse drug reactions depends on the physician's opinion of the relationship between the drug and the adverse event, we compared physicians' opinions with the scores obtained by the causality assessment method used in France. During a 2 month period, all physicians who reported adverse drug reactions (ADRs) to our pharmacovigilance centre expressed their opinions on the causal link by means of visual analogue scales. ADR reports were then assessed with the French causality assessment method by a clinical pharmacologist who was blind to physicians' opinions.The assessment by both physicians and the standardized method was performed for 75 ADR cases involving 120 drugs. Physicians used a wide range of assessments, with a preponderance of extreme scores, resulting in a U-shaped distribution, while the standardized method gave generally low scores. Scores given by physicians were very high (causality considered very likely or likely) in 60% of cases and very low (causality considered unlikely or dubious/possible) in 32% of cases. Scores obtained using the causality assessment method were low (causality dubious/possible) in 89% of cases and causality considered likely in only 11 cases, essentially in cases with positive rechallenge. Complete agreement occurred in only 6% of cases. Adding complete agreement and minor discrepancies raised the percentage to 49%.     

Adverse reactions to non-ionic contrast media with special regard to high-risk patients

Non-ionic contrast media (CM) are proven to be significantly safer than the high osmolar ionic contrast media (HOCM). Nevertheless deaths are reported after administration of non-ionic agents. The aim of the study was to investigate the rate of adverse reactions to non-ionic CM with special regard to high-risk patients and the effects of premedication with H1-and H2-receptor antagonists.In a prospective study conducted over about 2 years 12 995 examinations with intravenous or intra-arterial non-ionic CM were evaluated. Premedication with H1-and H2-antagonists was used in 1276 high-risk patients with known adverse reaction to CM, history of allergy or severe cardiac or pulmonary disease. 229 patients received no premedication inspite of known risk factors. In total, there were 143 (1.10%) adverse reactions (mild in 0.58%, moderate in 0.41% and severe in 0.05%). In high-risk patients there were adverse reactions in 4.37% without and in 1.57% with premedication. There were no severe adverse reactions in the high-risk patients after premedication. The age of the patient, CM dosage and CM concentration were not shown to be risk factors in the present study. In conclusion, the additional premedication with H1- and H2-antagonists could be an effective agent to reduce the risk of mild and moderate adverse reactions and to avoid severe adverse reactions in high-risk patients. Correspondence to: U. Fink     

No evidence for an altered mRNA expression or protein level of haematopoietic cell phosphatase in CD34+ bone marrow progenitor cells or mature peripheral blood cells in polycythaemia vera

Abstract: Polycythaemia vera (PV) is a myeloproliferative disorder characterized by haematopoietic progenitor cells being hypersensitive to cytokines such as erythropoietin, interleukin-3, stem cell factor and insulin-like growth factor 1, which results in an increased production of mature blood cells. The pathogenetic cellular mechanism(s) behind this hypersensitivity to cytokines is unknown, but the number of cytokine receptors and the interaction between ligand and receptor are normal in PV. Interest has therefore focused on post-receptor mechanism(s). Haematopoietic cell phosphatase (HCP) is an intracellular tyrosine phosphatase that has been demonstrated to regulate proliferative signals negatively induced by the cytokines mentioned above. Moreover, motheaten mice that genetically lack HCP have an increased amount of erythroid progenitors that are hypersensitive to Epo, and patients with familial polycythaemia have been shown to exhibit a mutation of the Epo receptor gene that includes the docking site for HCP. We therefore studied mRNA expression of HCP in pure populations of CD34⁺ cells, granulocytes, platelets and lymphocytes from patients with PV, chronic myeloid leukaemia (CML) or essential thrombocythemia (ET), as well as healthy controls. Using a polymerase chain reaction analysis employing specific primers for HCP, we failed to detect any abnormalities of HCP expression in PV in any of the cell populations that were examined. Moreover, HCP mRNA expression was similar in ET and CML compared to controls. Finally, Western blot analysis revealed a normal HCP protein content in PV granulocytes and platelets. We therefore conclude that neither an impaired expression of the HCP gene nor a defect in HCP protein synthesis is present in PV, and does not seem to play a role in the aetiology of this disorder.     

临床输液反应的分析与预防

目的对临床发生的输液反应进行分析,找出发生的原因,探讨预防措施。方法:对30例输液反应资料进行分析。结果:以热原反应最为多见,占76.67%,而过敏反应,占16.67%,局部反应,占6.67%。结论:严格执行消毒制度,遵守无菌操作规程,把好药品和输液器具质量关,合理用药,注意配伍等是减少临床输液反应的关键。     

Recent Ⅳ-drug users with chronic hepatitis C can be efficiently treated with daily high dose induction therapy using consensus interferon:An open-label pilot study

INTRODUCTION Under physiological conditions, interferon-α (IFN-α) is a key cytokine produced by virtually all cells in the mammalian organism in response to a variety of bacterial and viral stimuli. In response to viral infection, IFN-α produced by the infected target cells induces a number of cellular genes involved in inhibition of viral replication. In addition, IFN-α is secreted by stimulated NK-cells and T-cells and exerts a multitude of immune stimulatory effects of innate a…     

去除白细胞输血的临床意义

目的:评估去除白细胞输血的临床应用价值。方法:251例患者接受了去除白细胞红细胞悬液761U,(每人1￣8U不等),对其中200U红细胞悬液滤除白细胞前、后分别进行白细胞计数和血红蛋白测定,并对其输血反应进行了观察。结果:发现应用白细胞滤器后,其白细胞数比过滤前显著减低,过滤前、后白细胞数分别为(6.16±1.44)×109/L与(0.12±0.10)×109/L(P<0.01),血红蛋白过滤前、后无显著性差异,分别为:(161.58±23.31)g/L与(157.84±22.35)g/L,P>0.05。251例接受去白细胞受血者均未出现输血反应。结论:白细胞滤器能有效去除白细胞,去除白细胞能减少非溶血性输血反应。     

磁共振增强扫描中欧乃影不良反应的临床观察及预防措施

目的探讨欧乃影在临床应用中不良反应的发生和预防措施。方法观察2003年10月至2006年7月所作1000例增强扫描者静脉注射欧乃影0.2mL/kg(其量浓度(c)为0.5mol/L)后,不良反应发生的情况。结果1000例患者中,出现不良反应6例,其中,非过敏反应3例,轻度过敏反应3例,无中度及重度过敏反应。结论欧乃影在磁共振增强扫描中不良反应发生率低,临床应用安全。