A comparison of polymerase chain reaction and an infectivity assay for human immunodeficiency virus type 1 titration during virus inactivation of blood components

Three examples of human plasma-derived concentrates, intermediate- purity factors VIII and IX, and fibrinogen were spiked with tissue culture-grown human immunodeficiency virus type 1 (HIV-1) strain RF. All examples were freeze-dried and heated at 80 degrees C for 72 hours by using validated production process models. HIV-1 infectivity was measured by a syncytial infectivity assay in C8166 cells and then compared with levels determined by nested HIV polymerase chain reaction (PCR). The infectivity assay demonstrated a reduction index of at least 4.5 log10, while PCR showed an average 1.7 log10. Large amounts of HIV- 1 RNA (10(5)) were still detectable by PCR in samples in which infectivity assays failed to detect any HIV-1. These data suggest that HIV-1 PCR levels do not parallel HIV-1 infectivity levels during virus- inactivation procedures involved in coagulation factor concentrate production. PCR was able to detect the RNA associated with inactivated HIV-1 particles in the factor concentrates, which allows the conclusion that PCR is not a useful test with which to monitor virus-inactivation procedures such as heating at 80 degrees C for 72 hours. This judgment contrasts with the more definite and sensitive role of PCR in diagnosing HIV-1 infection in patients in whom a positive HIV-1 PCR result correlates with active HIV-1 infection and with PCR's usefulness in monitoring virus removal.     

Dual actions of lysergic acid diethylamide tartrate (LSD), 2-bromo-D-lysergic acid diethylamide bitartrate (BOL) and methysergide on dorsal root potentials evoked by stimulation of raphe nuclei

A variety of drugs reported to antagonize serotonin were found to affect spinal cord potentials evoked by electrical stimulation of the caudal raphe nuclei of the cat. These brain stem-evoked dorsal root potentials (DRPs) consisted of a short latency depolarization (DRP-1), which was evoked by stimulation of a wide variety of sites in the medial brain stem and a long latency potential (DRP-2), which was elicited only when stimuli were applied near the raphe. The ability of serotonergic antagonists to increase or decrease these DRPs was dependent on the dose of the drug administered. High doses of lysergic acid diethylamide tartrate (LSD), 2-bromo-D-lysergic acid diethylamide bitartrate (BOL), methysergide and cinanserin each produced an immediate inhibition of DRP-2 and a simultaneous enhancement of DRP-1, both of which recovered by approximately 30 min. Each of the drugs produced a dose-related inhibition of DRP-2 at high doses, with LSD being the most potent and cinanserin the least potent. In contrast, low doses of LSD, BOL and methysergide elicited little or no immediate change in either DRP-2 or DRP-1, but produced an enhancement of DRP-2 which developed slowly over a period of 60 to 90 min. This increase in DRP-2 was most dramatic after administration of LSD and was not accompanied by changes in DRP-1. The inhibition of DRP-2 by high doses of LSD, BOL, methysergide and cinanserin may result primarily from inhibition of postsynaptic serotonergic receptors located on the primary afferent terminals. The increase in DRP-2 produced by low doses of LSD, BOL and methysergide is postulated to result from an interaction with receptors distinct from those which produced the inhibition of DRP-2 at higher doses.     

The diagnosis of the carrier state for the Lesch--Nyhan syndrome.

Skin biopsies from the mother of a classical case of the Lesch-Nyhan syndrome grew only wild type fibroblasts. This suggested that she is not a heterozygous carrier of the mutant X-linked structural gene which causes the syndrome, and that a fresh mutation caused the disorder in her son. Evidence of mosaicism was sought in skin fibroblasts, hair follicles, jejunal mucosa, cultured bone marrow cells and phytohaemagglutinin (PHA) stimulated lymphocytes from known hemizygotes and heterozygotes for the so-called complete, and partial deficiencies of hypoxanthine guanine phosphoribosyltransferase (HGPRT). These studies were designed to determine the genetic status of the mother of the propositus and to determine if the genetic diagnosis could be improved by the simultaneous study of this wider range of tissues. The results are compatible with the mother of the propositus being a non carrier of a mutant gene causing the Lesch-Nyhan syndrome in her son. Only the study of cultured skin fibroblasts, and of the enzyme levels in hair follicles, contributed diagnostically useful information in this case.     

Cost-effectiveness of drotrecogin alfa (activated) for the treatment of severe sepsis in Germany

Drotrecogin alfa (activated) (Xigris; Eli Lilly and Company, Indianapolis, IN) significantly reduced mortality in severe sepsis in the PROWESS trial. We evaluate the cost-effectiveness of drotrecogin alfa (activated) as an adjunct to standard therapy from the German healthcare payer’s perspective with respect to patients with 1) severe sepsis and 2) severe sepsis and multiple organ failure the approved European indication. Hospital resource use based on PROWESS was valued using German unit costs. German life-tables and long-term survival assumptions determined life-years gained. European and German healthcare resource use data are examined in the sensitivity analysis. We assumed a unit price of €237.50 for drotrecogin alfa (activated). Per patient treated, drotrecogin alfa (activated) increased costs by €7,500, and hospital costs by €900 for all patients (€7,400 and €1,500 respectively for the approved indication) and survival by 0.59 life years (0.87 life years respectively for the approved indication). Thus drotrecogin alfa (activated) cost €14,100 (€17,700 discounting life years at 3%) per life year gained for all patients (€10,200 and €12,900, respectively, for the approved indication). Testing the unit cost of drotrecogin alfa (activated), pattern of resource use, and survival benefit, demonstrated that cost-effectiveness lies well within the range of other life saving interventions in Germany representing good economic value.     

Hematopoietic cell transplantation for Crohn’s disease;is it time?

INTRODUCTION Crohn’s disease (CD) is a chronic inflammatory disease of the gastrointestinal tract which commonly affects young adults. It follows a relapsing and remitting course and there is no known cure. However, approximately 10% to 15% have chronic …     

高迁移率族蛋白B1诱导巨噬细胞Janus激酶/信号转导及转录激活子通路活化的研究

目的 初步探讨高迁移率族蛋白B1(HMGB1)致炎效应的信号转导机制。方法 清洁级雄性Wistar大鼠，取其腹腔巨噬细胞，培养3d后以10mg／L HMGB1刺激。刺激完毕后直接在培养瓶中裂解细胞，分别采用免疫沉淀、免疫印迹法和凝胶阻滞分析等技术观察不同时间点Janus激酶2(JAK2)、信号转导及转录激活子—1(STAT1)以及STAT3的活化情况。结果 HMGB1可诱导大鼠腹腔巨噬细胞STAT1、STAT3在短时间内(2h)活化，其中STAT3活化最为迅速，10min即可达到活化高峰。但HMGB1不能在短时间内(2h)诱导JAK2活化。结论 JAK／STAT途径可能参与了HMGB1致炎效应的信号转导机制。     

国人全膝关节假体置换胫骨近端截骨面至腘血管距离的测量及意义

目的:测量国人全膝关节假体置换术胫骨近端截骨面后缘至腘窝血管之间的距离,以期为临床全膝关节置换术中避免损伤腘窝血管提供参考数据。方法:选择2006-06/12于解放军第二军医大学长征医院体检的50名正常成人(53膝),男29名(31膝),女21名(22膝)。所有观察对象均知情同意,且得到医院伦理道德委员会批准。对所有膝关节进行MRI扫描,在胫骨外侧平台以下10mm水平横断面上辨认腘动静脉,并测量胫骨近端截骨面后缘至腘窝动静脉的距离。结果:53膝全部进入结果分析,无脱落。①男性胫骨近端截骨面后缘至腘动脉、腘静脉平均距离为(6.7±2.5,7.3±2.3)mm,95%可信区间分别为5.8～7.6mm,6.5～8.1mm。②女性胫骨近端截骨面后缘至腘动脉、腘静脉平均距离为(6.6±1.9,7.1±2.7)mm,95%可信区间分别为:5.8～7.4mm,5.9～8.3mm。③不同性别观察对象胫骨近端截骨面后缘至腘血管的距离差异无显著性意义(P>0.05)。结论:腘窝血管紧邻全膝关节假体置换术胫骨近端截骨面后缘,不同性别间无明显差异。全膝关节假体置换术中进行胫骨近端截骨,特别是后方操作时需特别谨慎,以避免损伤腘窝血管。     

The effectiveness of feminist pedagogy in empowering a community of learners

The purpose of this study was to determine whether a pedagogy grounded in feminist ideals has the potential to empower students to make changes consistent with those ideals in their personal and professional lives. In Phase I, qualitative data were collected through e-mail questionnaires from students in two nursing schools, one in Canada and one in the United States. Findings were used to identify an appropriate tool to measure the empowering influence of feminist pedagogy. In Phase 2, a pretest-posttest design used Barrett's Power as Knowing Participation in Change Tool (PKPCT) to measure student empowerment. A clinical setting was added in a third baccalaureate nursing program. A total of 218 students participated in seven course offerings-four classroom and three clinical. One hundred one matched pairs were obtained, for an overall response rate of 46%. Repeated measures ANOVA revealed that overall empowerment scores, as measured by the PKPCT, and classroom empowerment (CE), as measured by the addition of a variable (i.e., the ability to contribute in class), increased significantly from pretest to posttest. Interaction between Sites 1 and 2 was also significant. Regression analysis indicated posttest CE scores added to pretest PKPCT and CE scores provided a strong model to predict overall empowerment scores, measured by the PKPCT at Time 2 (R2 = .703). Despite limitations related to loss of follow up and low response rates at one site, the results of this study supported both hypotheses: that empowerment would increase over the course of the class in which feminist pedagogical principles were used, and that classroom empowerment is likely to extend beyond the classroom to personal and work environments.     

Induction of tolerance to parental parathyroid grafts using allogeneic thymus tissue in patients with DiGeorge anomaly

DiGeorge anomaly can affect both thymic and parathyroid function. Although athymia is corrected by allogeneic thymus transplantation, treatment options for hypoparathyroidism have been unsatisfactory. Parathyroid transplantation offers the potential for definitive cure but remains challenging because of graft rejection. Some allogeneic parathyroid grafts have functioned in adult recipients in the context of immunosuppression for renal transplantation. Other efforts have attempted to reduce the allogenicity of the parathyroid grafts through manipulation of the parathyroid tissues before transplantation (by using encapsulation or special culture techniques). Recently, we demonstrated the efficacy of parental parathyroid transplantation when combined with allogeneic thymus transplantation in an infant with complete DiGeorge anomaly. The recipient developed tolerance toward the parathyroid donor. The parathyroid graft has functioned for 5 years after transplantation without the need for continued immunosuppression or calcium supplementation. We observed that matching of the allogeneic thymus graft to the parathyroid donor HLA class II alleles that are unshared with the recipient appears to be associated with the induction of tolerance toward the parathyroid graft. Further work is needed to determine the optimal means for using combined allogeneic thymus and parental parathyroid transplantation to correct hypoparathyroidism in patients with both complete and partial DiGeorge anomaly.