血吸虫病化学治疗的研究 Ⅱ.α-取代-β-(5-硝基-2-呋喃)丙烯酰胺及酯类衍生物的合成

本文报导α-取代-β-(5-硝基-2-呋喃)丙烯酰胺及酯类衍生物85个的合成。这类化合物系分别以糠醛或硝基糠醛与相应的羧酸钾盐经Perkin反应缩合后,按一般方法制成酰胺及酯;或以相应的硝基呋喃丙烯酰胺经溴化;或通过氮内酯中间体经水解、醇解和氨解而制备。经动物篩选后发现有13个化合物对感染日本血吸虫小白鼠有作用,其中α—甲基—β-(5-硝基-2-呋喃)丙烯酰正丁胺(I₆,F-30058),α-甲基-β-(5-硝基-2-呋喃)丙烯酰乙醇胺(I₁₀,F-30141)及α-甲基-β-(5-硝基-2-呋喃)丙烯酰-2′-羟基丙胺(I₁₁,F-30111)三个具有较好抑制作用。     

9－（2－膦酰甲氧乙基）腺嘌呤及其位置异构体3－（2－膦酰甲氧乙基）腺嘌呤的合成和抗病毒活性研究

９－（２－膦酰甲氧乙基）腺嘌呤及其位置异构体３－（２－膦酰甲氧乙基）腺嘌呤的合成和抗病毒活性研究刘晓辉，王琳，贯宝和，孔漫，张兴权，陶佩珍，陈鸿珊（中国医学科学院、中国协和医科大学药物研究所，北京１０００５０；中国医学科学院、中国协和医科大学医药生物...     

中药鸦胆子化学成分的研究 (一)鸦胆子油

据本草纲目拾遗,鸦胆子一名苦参子,可治痔、治痢、治泻,其油治脱癌;裴鉴及周太炎二氏报告,鸦胆子系苦木科植物 Brucea javanica(L)Merr.的果实;吴其浚植物名实图考内载:一种鸦蛋子生云南与鸦胆子不同能治痔云。考我国于1751年何梦瑶氏曾用鸦胆子作治痢,1765年赵学敏氏在本草纲目拾遗上亦谓可治痢,张锡纯、李克惠二氏云可治慢性痢及久痢。近二十年来我国学者关于鸦胆子研究不论在化学、生理、药理方面以及临床试验均有报告,认为有截疟及治痢之效,但有中毒现象。作者由其仁中分出一种苦味甙,据浙江医学院陈志康氏研究谓有治肺吸血虫病之效。其油据于光元及李宝实二氏报告可治疣及乳头瘤。全慈光氏报告可治阿米巴痢、疟疾及杀虫。Power 及 Lees 报告,全果实含有油脂20%;其成分为油酸、亚麻仁油酸、软脂酸及硬脂酸,并含一种烟化物名 Pentatriacotane-C,熔点     

Surgical hip dislocation in symptomatic cam femoroacetabular impingement: what matters in early good results?

In order to assess outcome and possible predictors of early good results, a prospective study on 22 patients who were treated with save surgical hip dislocation for symptomatic isolated cam-type femoroacetabular impingement (FAI) was performed. After a follow-up of 6 and 12 months, standard clinical and radiographic parameters were recorded. A statistically significant improvement of the clinical status according to the Harris hip score could be assessed at six months (p-value = 0.003) and 12 months (p-value = 0.001) post-surgery. By comparing standard clinical and radiographic preoperative parameters with various follow-up outcomes, we revealed no specific parameter with predictive value. These findings are important for centers that have just started to use this surgical technique and are still identifying their learning curve.     

Validation of the treatment identification strategy of the HEDIS addiction quality measures: concordance with medical record review

Background  

Strategies to accurately identify the occurrence of specific health care events in administrative data is central to many quality improvement and research efforts. Many health care quality measures have treatment identification strategies based on diagnosis and procedure codes - an approach that is inexpensive and feasible but usually of unknown validity. In this study, we examined if the diagnosis/procedure code combinations used in the 2006 HEDIS Initiation and Engagement quality measures to identify instances of addiction treatment have high concordance with documentation of addiction treatment in clinical progress notes.     

A sequence-specific polymerase chain reaction assay for mitochondrial DNA polymorphisms in human platelets and white cells

BACKGROUND: Because mitochondria are abundant in white cells and are also present in platelets, polymorphic sequences in mitochondrial DNA (mtDNA) represent a unique target for polymerase chain reaction (PCR)- based detection of donor material. STUDY DESIGN AND METHODS: A PCR assay was developed that uses sequence-specific primers (SSP) focused on two continent-specific mtDNA polymorphisms. Results were validated by the use of informative restriction endonucleases. Three commercially available methods to extract mtDNA from white cell-reduced human platelets was compared. In preparation for in vivo studies, in vitro mixing studies designed to mimic transfusion were conducted to investigate the performance of the SSP-PCR assay. RESULTS: The gene sequences of two representative examples of amplicons obtained with the new SSP-PCR matched the sequence expected from the published genetic code. Fifteen individuals were classified as either positive (n = 6) or negative (n = 9) for the Asian polymorphism by the use of published primers known to flank the polymorphic site followed by digestion with appropriate restriction enzymes. Results with SSP-PCR were nearly perfectly concordant with those of restriction enzyme analysis. Although the use of three DNA extraction methods allowed the preparation of mtDNA that was suitable for PCR, large and consistent differences (ranging from 10- to 1000-fold) in endpoint sensitivity were found. In vitro mixing studies reproducibly documented that the SSP-PCR assay could detect as little as 1 percent of donor platelets mixed with recipient blood. CONCLUSION: PCR-SSP can be reliably used to identify human mtDNA polymorphisms. By optimization of the method of mtDNA extraction, the sensitivity of PCR-SSP assay was greatly increased. This assay should prove useful in investigations of allogeneic platelet transfusions without cell labeling. It may also be applied to studies of the donor cell microchimerism that follows transfusion or transplantation.     

Treatment of progressive Hodgkin's disease with intensive chemoradiotherapy and autologous bone marrow transplantation

Twenty-six patients with progressive Hodgkin's disease after conventional chemotherapy received intensive chemoradiotherapy and autologous bone marrow transplantation (ABMT); 19 also received additional involved-field radiotherapy. Twenty-one patients [81%, 95% confidence intervals (CI) 61% to 94%] attained complete (n = 18) or partial responses. Ten patients (38%, 95% CI 20% to 59%) are disease- free a median of 4.5 years later (range 3.5 to 7.0 years), including seven patients with continuous complete responses. The likelihood of overall response was not significantly influenced by any clinical or treatment variable examined. However, there was a trend favoring patients with higher Karnofsky scores, and higher scores were associated with attainment of complete responses (P = .06 and P = .02, respectively, Mann-Whitney U test). Both higher Karnofsky scores and shorter durations of disease before transplantation were associated with improved survival in a stepwise Cox multivariate analysis. The chief cause of failure was progression at sites previously involved with Hodgkin's disease. No patient relapsed in the marrow, and two of three patients with a history of marrow involvement with Hodgkin's disease achieved durable complete responses after transplantation. These data suggest that inadequate pretransplant conditioning, and not the reinoculation of occult tumor cells in the autologous marrow, caused most relapses. Fatal treatment-related toxicity occurred in six patients. Three patients died of idiopathic interstitial pneumonitis; each had previously received local mediastinal irradiation before intensive chemoradiotherapy. Intensive chemoradiotherapy and ABMT produces durable responses in some patients with Hodgkin's disease incurable with conventional therapy. Use of such therapies at the first sign of failure with conventional chemotherapy and development of more effective conditioning regimens should further improve results.     

Increased circulating CSF-1 (M-CSF) in myeloproliferative disease: association with myeloid metaplasia and peripheral bone marrow extension

Myeloproliferative disease (MPD) is heterogeneous in phenotypic expression and may display features consistent with expansion and activation of the monocyte/macrophage population during its course. The role of colony-stimulating factor-1 (CSF-1) in the pathophysiology of MPD was investigated by measuring circulating CSF-1 levels and examining their relationship to disease phenotype. Serum CSF-1 concentrations, measured by radioimmunoassay, were elevated in all MPD phenotypes. CSF-1 levels differed significantly between groups of patients with essential thrombocythemia, polycythemia vera, and postpolycythemic or agnogenic myeloid metaplasia (in ascending order). CSF-1 serum levels were positively correlated with spleen size and the degree of peripheral bone marrow extension, determined by scintigraphy using a macrophage-seeking isotope. There was no correlation between CSF-1 concentration and circulating levels of erythrocytes, neutrophils or platelets, or the presence of bone marrow fibrosis. Elevated serum CSF-1 levels appear to be associated with an expanded monocyte/macrophage population in MPD. In view of the known cooperativity between CSF-1 and other growth factors in regulating hematopoiesis, the finding of increased serum CSF-1 concentrations and its association with myeloid metaplasia and bone marrow extension may indicate a pathophysiologic role for CSF-1 in determining the phenotypic expression of MPD.     

Effect of n-3 and n-6 fatty acids on proliferation and differentiation of promyelocytic leukemic HL-60 cells

Promyelocytic leukemic HL-60 cells were incubated with different fatty acids. Arachidonic acid (AA; 20:4, n-6) and eicosapentaenoic acid (EPA; 20:5, n-3) were the most potent inhibitors of proliferation in a dose- dependent way. Retinoic acid (RA) was used as a positive control. Inhibitors of cyclooxygenase and lipoxygenase or addition of antioxidants did not influence the effect of EPA or AA on cell proliferation. Increased capacity to generate superoxide anions after phorbol ester treatment and a reduced serglycin messenger RNA level in cells treated with AA or EPA indicated that these fatty acids induced differentiation in HL-60 cells similar to that induced by RA. However, down-regulation of the c-myc mRNA level, also typical for differentiation with RA in HL-60 cells, was not observed in cells incubated with AA or EPA. Flow cytometric analyses showed that in cultures incubated with AA or EPA, the proportion of cells in the G1 phase of the cell cycle increased. Similar effects were observed with RA. By flow cytometry and light scatter analyses it could be shown that AA made 8% of the cells apoptotic and 7% necrotic. The corresponding numbers were 21% and 10% for RA-treated cells, and 19% and 32% for EPA- treated cells. The present study shows that AA and EPA reduce the proliferation rate of HL-60 cells. This is mediated by mechanisms independent of eicosanoids or lipid peroxidation products and is due to effects both on apoptosis/necrosis and cell differentiation.