胶体磷酸铬^32P关节腔内注射改善佐剂型关节炎大鼠的相关指标

目的:观察胶体磷酸铬32P关节腔内注射治疗大鼠佐剂型关节炎的效果。方法:实验于2006-07/09在南京市第一医院动物实验室完成。选择6～8周龄清洁级SD雌性大鼠30只,按随机数字表法分为3组,正常对照组、模型组、胶体磷酸铬32P治疗组,每组10只。大鼠左足跖皮内注射完全弗氏佐剂0.1mL免疫法制备佐剂型关节炎模型。胶体磷酸铬32P治疗组于造模后10d左踝关节腔内注射37GBq/L胶体磷酸铬32P0.02mL,即0.74MBq,正常对照组和模型组分别给予等量生理盐水左踝关节腔内注射。①每2周观察1次大鼠左踝关节左右径宽度。②关节炎指数评定采用关节炎评分法(0～4分),分数越高,症状越重。③于用药后2,4,6周采用99Tcm-MDP显像感兴趣区分析法计算大鼠左踝关节区和右胫腓骨的放射性计数比。④于用药后4,6周测定血清肿瘤坏死因子和白细胞介素1β水平。⑤于用药后4,6周观察大鼠滑膜组织和软骨组织病理学改变。结果:纳入大鼠30只,均进入结果分析。①用药后2周模型组大鼠左踝关节左右径宽度大于正常对照组[分别为(7.82±0.36),(5.89±0.35)mm],差异有显著性意义(t=12.16,P<0.001),胶体磷酸铬32P治疗组大鼠左踝关节左右径宽度大于模型组,差异无显著性意义(P>0.05)。用药后6周胶体磷酸铬32P治疗组大鼠左踝关节左右径宽度小于模型组[分别为(6.87±0.27),(7.25±0.26)mm],差异有显著性意义(t=2.87,P<0.05)。②用药后2周和4周胶体磷酸铬32P治疗组大鼠关节炎指数高于模型组,用药后6周胶体磷酸铬32P治疗组大鼠关节炎指数低于模型组,两组间差异均无显著性意义(P>0.05)。③用药后2周模型组大鼠感兴趣区放射性计数比高于正常对照组(分别为2.05±0.20,1.46±0.15),差异有显著性意义(t=7.46,P<0.001)。用药后6周胶体磷酸铬32P治疗组大鼠感兴趣区放射性计数比低于模型组(分别为1.52±0.18,1.78±0.24),差异有显著性意义(t=2.45,P<0.05)。④用药后4,6周模型组大鼠血清肿瘤坏死因子和白细胞介素1β水平高于正常对照组,差异有显著性意义[用药后4周分别为(2.039±0.344),(1.115±0.192)μg/L;(0.305±0.034),(0.192±0.041)μg/L,t=7.42,6.71,P<0.001。用药后6周分别为(1.694±0.305),(1.126±0.256)μg/L;(0.259±0.027),(0.191±0.019)μg/L,t=4.03,5.83,P<0.01,0.001]。用药后4,6周胶体磷酸铬32P治疗组在血清肿瘤坏死因子和白细胞介素1β水平与模型组比较,差异无显著性意义(P>0.05)。⑤用药后4周胶体磷酸铬32P治疗组和模型组滑膜组织增生和炎症细胞浸润均较明显;用药后6周胶体磷酸铬32P治疗组与正常对照组比较仍有滑膜组织增生和炎症细胞浸润,与模型组比较滑膜组织增生程度明显减轻,而炎症细胞浸润程度稍轻。用药后6周胶体磷酸铬32P治疗组大鼠左踝关节的软骨组织未见有异常改变。结论:胶体磷酸铬32P关节腔注射可减轻完全弗氏佐剂免疫大鼠受注射关节的滑膜增生程度,改善关节肿胀症状,疗效肯定。     

Thrombosis in inflammatory bowel disease: clinical setting, procoagulant profile and factor V Leiden

Patients with inflammatory bowel disease have an increased frequency of thromboembolism, and microvascular thrombosis has been proposed as a contributory pathogenic factor. The mechanism of enhanced procoagulant activity is not understood. We examined the clinical setting of thromboembolic events in 52 patients with Crohn's disease or ulcerative colitis, and assessed the procoagulant laboratory profile, including Factor V Leiden, in a subset of 20 patients to identify procoagulant risk factors. Patients who developed thrombosis tended to be young; 60% of thrombotic events occurred in patients under 50 years. Multiple thromboembolic episodes occurred in 13% and unusual sites of thrombosis (e.g. intracardiac, cerebral, inominate veins) in 11%. No risk factor was identifiable in 52% of cases and two-thirds of thromboses occurred in an out-patient setting. The mortality rate was 8%. Evidence for inflammatory disease activity was found in only 45% of patients with ulcerative colitis at the time of the thromboembolic event, in contrast to 89% of those with Crohn's disease. Assays for specific coagulation defects were negative in all cases tested (protein S, C were normal in 17/17; anti-thrombin III, anti-phospholipid antibodies and activated protein C resistance were negative in 20/20, and only 1/20 patients was found to be heterozygous for Factor V leiden. Thrombosis in inflammatory bowel disease is important because it occurs in a young population, often in unusual sites, and has a high mortality. The development of thrombosis is related to active inflammatory disease in most patients with Crohn's disease but apparently not in those with ulcerative colitis. Since approximately half of the patients had no other identifiable risk factor, there remains a substantial group of patients with IBD who develop thrombosis for unknown reasons.      

Incorporating and evaluating an integrated gender-specific medicine curriculum: a survey study in Dutch GP training

Background  

We recently set standards for gender-specific medicine training as an integrated part of the GP training curriculum. This paper describes the programme and evaluation of this training.     

Hantavirus reservoir Oligoryzomys longicaudatus spatial distribution sensitivity to climate change scenarios in Argentine Patagonia

Background  

Oligoryzomys longicaudatus (colilargo) is the rodent responsible for hantavirus pulmonary syndrome (HPS) in Argentine Patagonia. In past decades (1967–1998), trends of precipitation reduction and surface air temperature increase have been observed in western Patagonia. We explore how the potential distribution of the hantavirus reservoir would change under different climate change scenarios based on the observed trends.     

Foot and leg problems are important determinants of functional status in community dwelling older people

Purpose.?To determine whether foot and leg problems are independently associated with functional status in a community sample of older people after adjusting for the influence of socio-demographic, physical and medical factors.

Method.?Data were analysed from the Health Status of Older People project, a population-based study involving a random sample of 1000 community-dwelling people aged 65?–?94 years (533 females, 467 males, mean age 73.4 years?±?5.87). A structured interview and brief physical examination were used to investigate the associations between self-reported foot and leg problems and functional status. Functional status was assessed using: (i) timed ‘Up & Go’ test, (ii) self-reported difficulty climbing stairs, (iii) self-reported difficulty walking one kilometer, (iv) self-reported difficulty performing instrumental activities of daily living (IADLs), and (v) self-reported history of one or more falls in the previous 12 months. These associations were then explored after adjusting for socio-demographic, physical and medical factors.

Results.?Thirty-six percent of the sample reported having foot or leg problems. Univariate analyses revealed that people with foot and leg problems were significantly more likely to exhibit poorer functional status in all parameters measured. After adjusting for socio-demographic, physical and medical factors, foot and leg problems remained significantly associated with impaired timed ‘Up & Go’ performance (OR?=?2.15, 95%CI 1.55?–?2.97), difficulty climbing stairs (OR?=?3.33, 95%CI 1.98?–?5.61), difficulty walking one kilometer (OR?=?3.13, 95%CI 2.09?–?4.69), and history of falling (OR?=?1.73, 95%CI 1.26?–?2.37).

Conclusions.?Foot and leg problems are reported by one in three community-dwelling people aged 65 years and older. Independent of the influence of age, gender, common medical conditions and other socio-demographic factors, foot and leg problems have a significant impact on the ability to perform functional tasks integral to independent living.     

Mobilization of early hematopoietic progenitor cells with BB-10010: a genetically engineered variant of human macrophage inflammatory protein- 1 alpha

BB-10010 is a genetically engineered variant of human macrophage inflammatory protein-1 alpha with improved solution properties. We show here that it mobilizes stem cells into the peripheral blood. We investigated the mobilizing effects of BB-10010 on the numbers of circulating 8-day spleen colony-forming units (CFU-S8), CFU-S12, and progenitors with marrow repopulating ability (MRA). A single subcutaneous dose of BB-10010 caused a twofold increase in circulating numbers of CFU-S8, CFU-S12, and MRA 30 minutes after dosing. We also investigated the effects of granulocyte colony-stimulating factor (G- CSF) and the combination of G-CSF with BB-10010 on progenitor mobilization. Two days of G-CSF treatment increased circulating CFU-S8, CFU-S12, and MRA progenitors by 25.7-, 19.8-, and 27.7-fold. A single administration of BB-10010 after 2 days of G-CSF treatment increased circulating CFU-S8, CFU-S12, and MRA even further to 38-, 33-, and 100- fold. Splenectomy resulted in increased circulating progenitor numbers but did not change the pattern of mobilization. Two days of treatment with G-CSF then increased circulating CFU-S8, CFU-S12, and MRA by 64-, 69-, and 32-fold. A single BB-10010 administration after G-CSF treatment further increased them to 85-, 117-, and 140-fold, respectively, compared with control. We conclude that BB-10010 causes a rapid increase in the number of circulating hematopoietic progenitors and further enhances the numbers induced by pretreatment with G-CSF. BB- 10010 preferentially mobilized the more primitive progenitors with marrow repopulating activity, releasing four times the number achieved with G-CSF alone. Translated into a clinical setting, this improvement in progenitor cell mobilization may enhance the efficiency of harvest and the quality of grafts for peripheral blood stem cell transplantation.     

A randomised controlled trial to determine the effect on response of including a lottery incentive in health surveys [ISRCTN32203485]

Background

Postal questionnaires are an economical and simple method of data collection for research purposes but are subject to non-response bias. Several studies have explored the effect of monetary and non-monetary incentives on response. Recent meta-analyses conclude that financial incentives are an effective way of increasing response rates. However, large surveys rarely have the resources to reward individual participants. Three previous papers report on the effectiveness of lottery incentives with contradictory results. This study aimed to determine the effect of including a lottery-style incentive on response rates to a postal health survey.

Methods

Randomised controlled trial. Setting: North and West Birmingham. 8,645 patients aged 18 or over randomly selected from registers of eight general practices (family physician practices). Intervention: Inclusion of a flyer and letter with a health questionnaire informing patients that returned questionnaires would be entered into a lottery-style draw for £100 of gift vouchers. Control: Health questionnaire accompanied only by standard letter of explanation. Main outcome measures: Response rate and completion rate to questionnaire.

Results

5,209 individuals responded with identical rates in both groups (62.1%). Practice, patient age, sex and Townsend score (a postcode based deprivation measure) were identified as predictive of response, with higher response related to older age, being female and living in an area with a lower Townsend score (less deprived).

Conclusion

This RCT, using a large community based sample, found that the offer of entry into a lottery style draw for £100 of High Street vouchers has no effect on response rates to a postal health questionnaire.