腰椎定点牵压与硬膜外隙注药疗法单独或联合应用治疗腰椎间盘突出症

目的:对比观察硬膜外隙注药与腰椎定点牵压疗法及其联合应用治疗腰椎间盘突出症的疗效。方法:①选择2004-01/2006-01解放军总医院康复医学科门诊诊治的腰椎间盘突出症患者180例,男125例,女55例,年龄20～65岁。患者对治疗方案知情同意。按随机数字表法将患者分为3组:硬膜外隙注药组、腰椎定点牵压疗法组、联合治疗组,每组60例。硬膜外隙注药组:骶管注射利多卡因注射液、胞二磷胆碱、维生素B12、地塞米松混合液,每5d注射1次,共4次。腰椎定点牵压疗法组:采用胸带与下肢固定带牵引,待牵引床启动逐渐使患者腰脊柱拉伸时,术者双手拇指关节突关节连线,由上腰段向腰骶段滑行推压,当拇指推压到病变间隙时,牵引力须达到患者体质量1.5倍左右,迅速向脊柱前方施压。共2次。联合治疗组为两种疗法联合应用。每2次硬膜外隙注药后施行腰椎定点牵压疗法疗法1次,共2次。②于治疗前和治疗后3,6个月采用疼痛强度评分评估疼痛程度(0～10分,0分为无痛,10分为最痛),治疗前和治疗后3个月观察临床体征和评估疗效,疗效评估依据胡有谷的腰椎间盘突出症和国家中医药管理局(1994年)制定的中医病症诊断疗效标准。③计量和计数资料差异比较分别采用t检验和χ2检验。结果:腰椎间盘突出症患者180例均进入结果分析。①疼痛强度变化:治疗后3个月3组疼痛强度评分均较治疗前降低,其中联合治疗组与治疗前比较,差异明显(χ2=2.13,P<0.01)。治疗后6个月,各组病例的疼痛症状大多数获得控制,其中联合治疗组疼痛强度评分与治疗前比较,差异明显(χ2=4.03,P<0.01),联合治疗组和硬膜外隙注药组疼痛强度评分明显低于腰椎定点牵压疗法组(χ2=5.62,6.16,P<0.05)。②临床体征变化:各组治疗后3个月4项体征均较治疗前改善,其中联合治疗组直腿抬高试验阳性患者数明显少于硬膜外隙注药组和腰椎定点牵压疗法组(7,19,14例,χ2=9.24,9.14,P<0.01)。③疗效:联合治疗组治疗有效率明显高于其他硬膜外隙注药组和腰椎定点牵压疗法组[100%(60/60),88%(53/60),92%(55/60),χ2=6.26,6.04,P<0.01],而其他2组间比较,差异不明显(χ2=8.63,P>0.05)。结论:硬脊膜外注药及腰椎定点牵压疗法均是治疗腰椎间盘突出症的有效疗法,联合应用疗效更好。     

FcR gamma-chain is essential for both surface expression and function of human Fc gamma RI (CD64) in vivo

Most Ig receptors exist as hetero-oligomeric complexes with separate ligand binding (alpha) and signal transducing (beta, gamma, or zeta) subunits. For Fc gamma RIIIa and Fc epsilon RI, association with the FcR gamma-chain is essential for surface expression. However, the human high affinity IgG receptor, hFc gamma RI, was found to be surface- expressed by itself in transient transfection models. We have now analyzed the integrity of hFc gamma RI expression in more detail in stable transfectants. In vitro we noted that, in the absence of FcR gamma-chain, surface expression of hFc gamma RI rapidly declined to background levels, in both IIA1.6 B cells and NIH3T3 fibroblasts. The effect of FcR gamma-chain on hFc gamma RI surface expression in vivo was evaluated by using two newly generated transgenic mouse lines, selectively expressing hFc gamma RI on myeloid cells. These transgenic mice were crossed with FcR gamma-chain-deficient mice. Analysis of blood monocytes and peritoneal macrophages showed that surface expression of hFc gamma RI was reduced by approximately 80%. The remaining approximately 20% of receptors were still capable of binding IgG-opsonized RBC, suggesting FcR gamma-chain not to be critical for hFc gamma RI ligand-binding capacity. Importantly, however, hFc gamma RI signaling capacity was lost in FcR gamma-chain-deficient cells. No phagocytosis could be observed using either ligand sensitized (EA- IgG2a) or CD64-targeted erythrocytes (using a bispecific antibody) in both hFc gamma RI transgenic lines. This documents the FcR gamma-chain to be indispensable for both surface membrane expression and function of human Fc gamma RI in vivo.     

Establishment of a system to standardize acceptability criteria for alanine aminotransferase activity in donated blood

A multilaboratory study was conducted to develop a system for standardizing alanine aminotransferase (ALT) acceptability criteria ("cutoffs") for donated blood. Without standardized cutoffs, each laboratory must develop its own cutoff, and this may not make optimal use of ALT testing to reduce transmission of non-A, non-B hepatitis (NANB). Defining an ALT acceptability criterion in absolute terms is necessary because relative cutoffs based on local donor populations may be affected by the prevalence of NANB in each community. This study involved 16 laboratories using 23 different analytic systems. The ALT results of the analysis of a plasma reference sample could be used to translate mathematically a single, absolute cutoff to units applicable to each analytic system. The distribution of ALT results in 1.4 million donations from across the country was established; basing the cutoff on this sample avoids the problems inherent in using a local donor base to establish a cutoff. We propose the implementation of a system to standardize ALT acceptability criteria to an activity level defined by analysis of a nationwide donor sample.     

Predictors of growth and body composition in HIV‐infected children beginning or changing antiretroviral therapy

Objectives

The aim of the study was to describe growth and body composition changes in HIV‐positive children after they had initiated or changed antiretroviral therapy (ART) and to correlate these with viral, immune and treatment parameters.

Methods

Ninety‐seven prepubertal HIV‐positive children were observed over 48 weeks upon beginning or changing ART. Anthropometry and bioelectrical impedance analysis results were compared with results from the National Health and Nutrition Examination Survey 1999–2002 (NHANES) to generate z‐scores and with results for HIV‐exposed, uninfected children from the Women and Infants Transmission Study (WITS). Multivariate analysis was used to evaluate associations between growth and body composition and disease parameters.

Results

All baseline lean and fat mass measures were below those of controls from NHANES. Weight, height and fat free mass (FFM) index (FFM/height²) z‐scores increased over time (P=0.004, 0.037 and 0.027, respectively) and the waist:height ratio z‐score decreased (P=0.045), but body mass index and per cent body fat z‐scores did not change. Measures did not increase more than in uninfected WITS controls. In multivariate analysis, baseline height, mid‐thigh circumference and FFM z‐scores related to CD4 percentage (P=0.029, P=0.008 and 0.020, respectively) and change in FFM and FFM index z‐scores to CD4 percentage increase (P=0.010 and 0.011, respectively). Compared with WITS controls, baseline differences in height and mid‐thigh muscle circumference were also associated with CD4 percentage. Case–control differences in change in both subscapular skinfold (SSF) thickness and the SSF:triceps skinfold ratio were inversely associated with viral suppression. No measures related to ART class(es) at baseline or over time.

Conclusions

In these HIV‐positive children, beginning or changing ART was associated with improved growth and lean body mass (LBM), as indicated by FFM index. Height and LBM related to CD4 percentage at baseline and over time. Altered fat distribution and greater central adiposity were associated with detectable virus but not ART class(es) received.     

Analysis of serious non‐AIDS events among HIV‐infected adults at Latin American sites

Objective

Acquired immune deficiency appears to be associated with serious non‐AIDS (SNA)‐defining conditions such as cardiovascular disease, liver and renal insufficiency and non‐AIDS‐related malignancies. We analysed the incidence of, and factors associated with, several SNA events in the LATINA retrospective cohort.

Materials and methods

Cases of SNA events were recorded among cohort patients. Three controls were selected for each case from cohort members at risk. Conditional logistic models were fitted to estimate the effect of traditional risk factors as well as HIV‐associated factors on non‐AIDS‐defining conditions.

Results

Among 6007 patients in follow‐up, 130 had an SNA event (0.86 events/100 person‐years of follow‐up) and were defined as cases (40 with cardiovascular events, 54 with serious liver failure, 35 with non‐AIDS‐defining malignancies and two with renal insufficiency). Risk factors such as diabetes, hepatitis B and C virus coinfections and alcohol abuse showed an association with events, as expected. The last recorded CD4 T‐cell count prior to index date (P=0.0056, with an average difference of more than 100 cells/μL) and area under the CD4 cell curve in the year previous to index date (P=0.0081) were significantly lower in cases than in controls. CD4 cell count at index date was significantly associated with the outcome after adjusting for risk factors.

Conclusions

The incidence and type of SNA events found in this Latin American cohort are similar to those reported in other regions. We found a significant association between immune deficiency and the risk of SNA events, even in patients under antiretroviral treatment.     

A crucial role for TNF-α in mediating neutrophil influx induced by endogenously generated or exogenous chemokines,KC/CXCL1 and LIX/CXCL5

Background and purpose:

Chemokines orchestrate neutrophil recruitment to inflammatory foci. In the present study, we evaluated the participation of three chemokines, KC/CXCL1, MIP-2/CXCL2 and LIX/CXCL5, which are ligands for chemokine receptor 2 (CXCR2), in mediating neutrophil recruitment in immune inflammation induced by antigen in immunized mice.

Experimental approach:

Neutrophil recruitment was assessed in immunized mice challenged with methylated bovine serum albumin, KC/CXCL1, LIX/CXCL5 or tumour necrosis factor (TNF)-α. Cytokine and chemokine levels were determined in peritoneal exudates and in supernatants of macrophages and mast cells by elisa. CXCR2 and intercellular adhesion molecule 1 (ICAM-1) expression was determined using immunohistochemistry and confocal microscopy.

Key results:

Antigen challenge induced dose- and time-dependent neutrophil recruitment and production of KC/CXCL1, LIX/CXCL5 and TNF-α, but not MIP-2/CXCL2, in peritoneal exudates. Neutrophil recruitment was inhibited by treatment with reparixin (CXCR1/2 antagonist), anti-KC/CXCL1, anti-LIX/CXCL5 or anti-TNF-α antibodies and in tumour necrosis factor receptor 1-deficient mice. Intraperitoneal injection of KC/CXCL1 and LIX/CXCL5 induced dose- and time-dependent neutrophil recruitment and TNF-α production, which were inhibited by reparixin or anti-TNF-α treatment. Macrophages and mast cells expressed CXCR2 receptors. Increased macrophage numbers enhanced, while cromolyn sodium (mast cell stabilizer) diminished, LIX/CXCL5-induced neutrophil recruitment. Macrophages and mast cells from immunized mice produced TNF-α upon LIX/CXCL5 stimulation. Methylated bovine serum albumin induced expression of ICAM-1 on mesenteric vascular endothelium, which was inhibited by anti-TNF-α or anti-LIX/CXCL5.

Conclusion and implications:

Following antigen challenge, CXCR2 ligands are produced and act on macrophages and mast cells triggering the production of TNF-α, which synergistically contribute to neutrophil recruitment through induction of the expression of ICAM-1.     

d-生物素的立体专一性全合成研究

对confaione的d-生物素(1)全合成进行了改进,从半胱氨酸计算,总收率3.7%。5与4-溴代三苯膦丁酸甲酯进行Wittig-Schlosser缩合反应可立体专一性地转化成反式-烯(6)。以叠氮三甲基硅烷代替叠氮化锂亲核进攻9分子中C3-溴原子,可显著地提高顺式-叠氮内酰胺10的收率。