Is there benefit in referring patients with fibromyalgia to a specialist clinic?

OBJECTIVE: To examine the benefit of specialist rheumatology consultation and followup for the first 238 patients referred to a tertiary care fibromyalgia (FM) clinic with emphasis on final diagnosis and outcome. METHODS: A retrospective chart review was performed for the first 238 patients attending a rheumatology subspecialty FM clinic. The main variables of interest were management received at the clinic, final diagnosis, and outcome. RESULTS: The final diagnosis was FM in 68%, and some other condition in the remaining 32%. Specialist contact was identified as useful in 73% of the total patient group, 96 with FM and 74 with non-FM. In the patients with FM who received followup in the clinic, outcome was judged favorable in 54%, whereas 46% showed no change or decline in health status. CONCLUSION: An important value of specialist rheumatology contact for patients with a symptom suggestive of diffuse musculoskeletal pain is to ensure that some other potentially treatable condition is not overlooked, rather than the provision of ongoing care for those with FM. Continued followup in a specialist clinic for patients with a primary diagnosis of FM is of questionable benefit.     

Down-regulation of CXCR4 expression in MT4 cells by a recombinant vector expressing antisense RNA to CXCR4 and its potential anti-HIV-1 effect

CXC-chemokine receptor (CXCR4) is one principle co-receptor for the entry of T cell line (T)-tropic HIV-1 virus into a cell. In order to find more efficacious therapeutic possibilities for people with an HIV-1 infection, we explored the inhibitory effects of antisense RNA on CXCR4 expression in MT4 cells. First, we used to RT-PCR to obtain DNA fragments from healthy adult peripheral blood mononuclear cells; these fragments targeted the initiation region of CXCR4 mRNA translation. We then constructed a recombinant retroviral vector, pLXSN-X4a (containing antisense RNA to CXCR4). After packaging by PA317 cells, the pseudovirion of the recombinant vector had formed and succeeded in transfecting MT4 cells (a kind of T-tropic HIV-1 susceptibility cell line). The PCR and RT-PCR results showed that the recombinant vector had integrated into the genome of MT4 cells and had been transcribed. The expression of CXCR4 on the surface of MT4 cells transfected with antisense RNA was reduced by 30%, compared with those cells transfected with blank vector or untransfected cells. No change in the DNA synthesis rates or in cell proliferation was found in any of the transfected cells. After a challenge with HIV-1 SF33, the cells transfected with antisense RNA vector (pLXSN-X4a) produced reduced p24 levels compared with the cells transfected with blank vector (pLXSN) or untransfected cells. These results indicated that these CXCR4-antisense expressing cells could resist T-tropic HIV-1 infection and could retain normal biological functions. These studies provide useful data for further experiments in this area.     

Analysts on heart rate variability and deceleration capacity of heart rate in preschoolers with viral myocarditis

目的 探讨病毒性心肌炎患儿心率变异性(HRV)与心率减速力(DC)各项指标变化的临床意义.方法 对56例病毒性心肌炎患儿与58例正常对照儿童进行24h动态心电图检查,应用美国DMS公司的动态心电分析系统软件,对HRV及DC各项参数进行分析对比;并分析DC与其他各项指标之间的相关性.结果 与正常对照儿童比较,病毒性心肌炎患儿时域分析的各项参数包括正常窦性RR间期的标准差(SDNN)、每5 min时段内平均正常窦性RR间期的标准差(SDANN)、全程RR间期差的均方根(RMSSD)及频域分析的低频功率(LF)的差异均无统计学意义(P＞0.05),而高频功率(HF)显著减低,差异有统计学意义(P＜0.05),且DC显著减低,差异有统计学意义(P＜0.01).相关性分析中,DC与SDNN、LF、HF均成正相关,其中与HF的相关性最强(r=0.51,P＜0.01).结论病毒性心肌炎患儿存在迷走神经功能受损,心率变异性中的HF与DC反映迷走神经功能的指标均显著降低,且两者具有很大相关性.     

The roles of extracellular signal-regulated kinase 1/2 pathway in regulating osteogenic differentiation of murine preosteoblasts MC3T3-E1 cells on roughened titanium surfaces

Surface roughness of titanium-based implants may enhance osteogenic differentiation of cells in vitro and bone-to-implant contact in vivo. Nevertheless, how surface roughness regulates the signaling pathway of osteoblasts is little understood. The study intended to investigate specifically the roles of extracellular signal-regulated kinase 1/2 (ERK1/2) pathway in regulating osteogenic differentiation of MC3T3-E1 murine preosteoblast cells on Ti surfaces. Substrates applied were two groups of titanium disks: (1) sand-blasted and acid-etched rough surfaces (SLA) and (2) smooth pretreated Ti surfaces (PT). Surface morphology of the two groups was examined by scanning electron microscope, and cell morphology cultured on Ti disks was observed by confocal microscope. The levels of alkaline phosphatase (ALP) activity and calcium deposition were measured and compared between the two groups. Real-time polymerase chain reaction was applied to detect the expression levels of osteogenic genes including runt related protein 2 (Runx2), osterix (OSX), osteocalcin (OCN) and osteoprotegerin (OPN) of the cells cultured on the two groups of substrates and on SLA surfaces treated with ERK1/2 inhibitor, PD98095. ERK1/2 activities in MC3T3-T1 cells were measured by Western-blotting on the two surfaces with or without PD98095. Cells cultured on rougher SLA surfaces displayed a more differentiated morphology. ALP activities at 7 days and 14 days and the calcium deposition at 28 days were significantly higher on SLA surfaces. The expression levels of Runx2, OSX, OPN and OCN were upregulated by the effect of surface roughness and PD98095 further upregulated the expression levels of these osteogenic genes on SLA surfaces. ERK1/2 phosphorylation was continuously inhibited by surface roughness at 2 days, 4 days and 6 days. In contrast, no marked alterations in ERK1/2 phosphorylation on PT surfaces were observed. PT surfaces treated with PD98095 (50 μM) and SLA surfaces without PD98095 both demonstrated reduced ERK1/2 phosphorylation of the cells, and the inhibitive effect of SLA surfaces was milder than that of PD98095. In conclusion, ERK1/2 pathway may be a negative regulator of cell differentiation in a dosage-dependent manner, and the enhancing effect of surface roughness on osteoblastic differentiation may be mediated through inhibiting ERK1/2 pathway.     

Evaluation of a Recombinant Multiepitope Peptide for Serodiagnosis of Toxoplasma gondii Infection

Detection of Toxoplasma gondii infection with sensitive and specific methods is a key step in the prevention and treatment of toxoplasmosis. Among the available diagnostic tests, serology is commonly used. Although serological tests give satisfactory results, the production of reliable reagents remains laborious and expensive. There is therefore a real need to acquire specific and effective recombinant antigens for the serodiagnosis of T. gondii infection. In this study, a multiepitope peptide was designed and successfully expressed in Escherichia coli, and then IgG and IgM enzyme-linked immunosorbent assays (ELISAs) were developed and evaluated. Our results showed that the new multiepitope antigen is one of the most promising recombinant antigens which could be used in routine screening of human toxoplasmosis.     

CD44 antibody-targeted liposomal nanoparticles for molecular imaging and therapy of hepatocellular carcinoma

Most hepatocellular carcinoma (HCC) therapies fail to target cancer stem cells (CSCs) and monitor cancer progression or regression. The purpose of this study was to evaluate the possibility of cancer imaging and simultaneously monitoring targeted therapy in a single animal by anti-CD44 antibody-mediated liposomal nanoparticle. In this study, an in situ liver tumor model was applied for therapy by injecting 1.0 × 10(6) HepG2 cells carrying a reporter system encoding a double fusion (DF) reporter gene consisting of firefly luciferase (Fluc) and green fluorescent protein (GFP) into the liver of NOD/SCID mice. A strategy was developed which specifically targeted HCC via anti-CD44 antibody-mediated liposomal nanoparticle delivery, loaded of either doxorubicin (Dox) or a triple fusion (TF) gene containing the herpes simplex virus truncated thymidine kinase (HSV-ttk) and renilla luciferase (Rluc) and red fluorescent protein (RFP). The NOD/SCID mice were subsequently treated with ganciclovir (GCV) and the growth status of tumor was monitored by optical bioluminescence imaging (BLI) of Fluc and specific targeting of the liposomal nanoparticle was tracked by Rluc imaging. CD44 antibody-mediated liposomal nanoparticle, loaded of TF plasmids, were shown to be useful for monitoring and evaluating targeting efficacy and gene therapy by non-invasive molecular imaging. Here, we demonstrate the time intensive preclinical steps involved in molecular target identification, validation, and characterization by dual molecular imaging. This targeted and traceable therapeutic strategy has potential advantages to overcome the problems of conventional tumor therapy and may open a new application for the treatment of HCC by targeting CSCs.     

右美托咪定的实验研究和临床应用(英文)

右美托咪定(DEX)是高选择性α2肾上腺素受体激动药,起效快,作用时间短、兼具有镇静、镇痛作用、且无呼吸抑制,近来在临床上越来越受到重视。研究证明,右美托咪定在达到并维持足够的镇静水平的同时,具有独特的易于唤醒的特点,同时可减少其他镇静药物的用量。右美托咪定诱导的镇静类似于非快速动眼睡眠,故可提高睡眠质量,有利于免疫系统恢复。右美托咪定的镇痛作用呈剂量依赖性,且有封顶效应。右美托咪定和阿片类药物联合应用,不仅增强阿片类药物的镇痛作用,还可以减少阿片类药物的用量,有效预防阿片类药物过量所致的不良反应。右美托咪定有血流动力学稳定作用,但也可以引起心动过缓和低血压;右美托咪定还可降低术后躁动、恶心、呕吐的发生率。右美托咪定用于长期使用阿片类药物的患者,未出现明显的撤药反应,同时可以治疗阿片类药物引起的痛觉过敏。右美托咪定和布比卡因混合液用于骶管阻滞,提供足够的镇痛作用同时,显著延长骶管阻滞时间。对于神经外科手术患者,右美托咪定不抑制体感诱发电位,不影响术中神经系统功能评估。由于右美托咪定独特的无呼吸抑制的显著特点,在众多需要保持患者自主呼吸的临床麻醉应用中是一种较理想的药物。总之,右美托咪定这些特性将使得其在未来的...     

海藻酸多糖衍生物治疗大鼠骨质疏松

背景：作者既往研究发现海藻酸多糖衍生物有促进骨细胞生长的作用。目的：探索海藻酸多糖衍生物治疗骨质疏松的效果。方法：60只Wistar雌性大鼠随机分成对照组,治疗组和模型组,每组20只。治疗组和模型组大鼠用维甲酸诱导产生骨质疏松模型。治疗组大鼠每只每公斤每天10mg多糖衍生物灌胃,模型组每只每公斤每天10mg葡萄糖灌胃,持续2周。观察大鼠股骨病理形态学和骨组织形态计量学变化。结果与结论：与对照组相比,模型组大鼠股骨骨小梁面积、平均骨小梁厚度、骨小梁密度显著降低,而髓腔质间隔宽度则明显增加;经过海藻多糖衍生物治疗后,治疗组大鼠股骨平均骨小梁密度,平均骨小梁厚度和骨小梁面积较模型组均显著上升,同时髓腔质间隔宽度明显下降;说明海藻酸性多糖能有效促进骨细胞生长,可治疗和预防骨质疏松。     

海藻酸多糖衍生物治疗大鼠骨质疏松

背景:作者既往研究发现海藻酸多糖衍生物有促进骨细胞生长的作用.目的:探索海藻酸多糖衍生物治疗骨质疏松的效果.方法:60 只Wistar 雌性大鼠随机分成对照组,治疗组和模型组,每组20 只.治疗组和模型组大鼠用维甲酸诱导产生骨质疏松模型.治疗组大鼠每只每公斤每天10 mg 多糖衍生物灌胃,模型组每只每公斤每天10 mg 葡萄糖灌胃,持续2 周.观察大鼠股骨病理形态学和骨组织形态计量学变化.结果与结论:与对照组相比,模型组大鼠股骨骨小梁面积、平均骨小梁厚度、骨小梁密度显著降低,而髓腔质间隔宽度则明显增加;经过海藻多糖衍生物治疗后,治疗组大鼠股骨平均骨小梁密度,平均骨小梁厚度和骨小梁面积较模型组均显著上升,同时髓腔质间隔宽度明显下降;说明海藻酸性多糖能有效促进骨细胞生长,可治疗和预防骨质疏松.