Missense mutation in a von Willebrand factor type A domain of the alpha 3(VI) collagen gene (COL6A3) in a family with Bethlem myopathy

The Bethlem myopathy is a rare autosomal dominant proximal myopathy characterized by early childhood onset and joint contractures. Evidence for linkage and genetic heterogeneity has been established, with the majority of families linked to 21q22.3 and one large family linked to 2q37, implicating the three type VI collagen subunit genes, COL6A1 (chromosome 21), COL6A2 (chromosome 21) and COL6A3 (chromosome 2) as candidate genes. Mutations of the invariant glycine residues in the triple-helical domain-coding region of COL6A1 and COL6A2 have been reported previously in the chromosome 21-linked families. We report here the identification of a G-->A mutation in the N-terminal globular domain-coding region of COL6A3 in a large American pedigree (19 affected, 12 unaffected), leading to the substitution of glycine by glutamic acid in the N2 motif, which is homologous to the type A domains of the von Willebrand factor. This mutation segregated to all affected family members, to no unaffected family members, and was not identified in 338 unrelated Caucasian control chromosomes. Thus mutations in either the triple-helical domain or the globular domain of type VI collagen appear to cause Bethlem myopathy.      

Adding pharmacists to primary care teams reduces predicted long‐term risk of cardiovascular events in Type 2 diabetic patients without established cardiovascular disease: results from a randomized trial

Aim To determine the impact of adding pharmacists to primary care teams on predicted 10‐year risk of cardiovascular events in patients with Type 2 diabetes without established cardiovascular disease. Methods This was a pre‐specified secondary analysis of randomized trial data. The main study found that, compared with usual care, addition of a pharmacist resulted in improvements in blood pressure, dyslipidaemia, and hyperglycaemia for primary care patients with Type 2 diabetes. In this sub‐study, predicted 10‐year risk of cardiovascular events at baseline and 1 year were calculated for patients free of cardiovascular disease at enrolment. The primary outcome was change in UK Prospective Diabetes Study (UKPDS) risk score; change in Framingham risk score was a secondary outcome. Results Baseline characteristics were similar between the 102 intervention patients and 93 control subjects: 59% women, median (interquartile range) age 57 (50–64) years, diabetes duration 3 (1–6.5) years, systolic blood pressure 128 (120–140) mmHg, total cholesterol 4.34 (3.75–5.04) mmol/l and HbA_1c 54 mmol/mol (48–64 mmol/mol) [7.1% (6.5–8.0%)]. Median baseline UKPDS risk score was 10.2% (6.0–16.7%) for intervention patients and 9.5% (5.8–15.1%) for control subjects (P = 0.80). One‐year post‐randomization, the median absolute reduction in UKPDS risk score was 1.0% greater for intervention patients compared with control subjects (P = 0.032). Similar changes were seen with the Framingham risk score (median reduction 1.2% greater for intervention patients compared with control subjects, P = 0.048). The two risk scores were highly correlated (rho = 0.83; P < 0.001). Conclusion Adding pharmacists to primary care teams for 1 year significantly reduced the predicted 10‐year risk of cardiovascular events for patients with Type 2 diabetes without established cardiovascular disease.     

A framework for discussion on how to improve prevention, management, and control of hypertension in Canada

Increased blood pressure is a leading risk for premature death and disability. The causes of increased blood pressure are intuitive and well known. However, the fundamental basis and means for improving blood pressure control are highly integrated into our complex societal structure both inside and outside our health system and hence require a comprehensive discussion of the pathway forward. A group of Canadian experts was appointed by Hypertension Canada with funding from Public Health Agency of Canada and the Heart and Stroke Foundation of Canada, Canadian Institute for Health Research (HSFC-CIHR) Chair in Hypertension Prevention and Control to draft a discussion Framework for prevention and control of hypertension. The report includes an environmental scan of past and current activities, proposals for key indicators, and targets to be achieved by 2020, and what changes are likely to be required in Canada to achieve the proposed targets. The key targets are to reduce the prevalence of hypertension to 13% of adults and improve control to 78% of those with hypertension. Broad changes in government policy, research, and health services delivery are required for these changes to occur. The Hypertension Framework process is designed to have 3 phases. The first includes the experts' report which is summarized in this report. The second phase is to gather input and priorities for action from individuals and organizations for revision of the Framework. It is hoped the Framework will stimulate discussion and input for its full intended lifespan 2011-2020. The third phase is to work with individuals and organizations on the priorities set in phase 2.     

乐脉颗粒促进鸡胚绒毛尿囊膜血管的生成

目的:乐脉颗粒在缺血性心脑血管病的治疗中具有较好的效果,其是否通过促进血管生成而发挥作用还不清楚。观察乐脉颗粒对鸡胚绒毛尿囊膜血管生成的影响。方法:实验于2005-03/08在江西省重点实验室南昌大学第二附属医院分子中心完成。①实验材料:新西兰大白兔8只,体质量2～2.5kg;新鲜白皮种蛋70只,质量50～60g。②实验方法:种蛋在(37.5±0.5)℃条件下孵育,种蛋受精率90%以上。第7天开窗暴露鸡胚绒毛尿囊膜建立鸡胚绒毛尿囊膜模型。将60枚存活鸡胚随机分为生理盐水组、正常血清组、乐脉血清组、内膜损伤血清组、内膜损伤乐脉治疗组以及血管内皮生长因子(20mg/L)组,每组10枚鸡胚。新西兰大白兔腹主动脉用球囊导管损伤建立血管内膜损伤模型,乐脉血清组及内膜损伤乐脉治疗组给予乐脉颗粒25mg/(kg·d)喂饲,各组7d后取血清。第8天,在鸡胚绒毛尿囊膜上放一直径为5mm的滤膜作为载体,分别加样5μL,1次/d,连续3d,③实验评估:第11天取鸡胚绒毛尿囊膜,数码相机拍照后平铺于载玻片上,计数载体周围血管数目及滤膜周围0.5cm范围内的血管分支点数并进行比较。结果:纳入大白兔8只,存活鸡胚60枚,均进入结果分析,无脱落。与正常血清组相比较,乐脉血清组鸡胚绒毛尿囊膜周围血管总数明显增多,血管以载体为中心呈辐辏状生长,差异具有显著性意义(P<0.05);与正常血清组相比较,内膜损伤血清组血清载体周围血管数量明显增多,差异具有极显著性意义(P<0.01);与内膜损伤乐脉治疗组相比较,血管总数差异无显著性。结论:①兔乐脉颗粒血清能够明显促进鸡胚绒毛尿囊膜上血管生成。②血管内膜损伤7d后的血清能够促进鸡胚绒毛尿囊膜上血管生成。     

Resistant hypertension

Resistant hypertension is most often due to insufficient medical therapy. With a patient history, physical examination and focused laboratory tests, sufficient information can be gathered to lead to further directed medical therapy, which most often includes a diuretic as part of the drug regimen. Patients may require four or more classes of antihypertensives, some at high doses to achieve control. The clinician must be prepared to use sufficient medications at sufficient doses to achieve blood pressure targets. Referral to a hypertension specialist is appropriate if blood pressure remains uncontrolled despite therapy with three antihypertensive medications.     

The 2001 Canadian recommendations for the management of hypertension: Part two--Therapy

OBJECTIVE: To provide updated, evidence-based recommendations for the therapy of hypertension in adults. OPTIONS: For patients with hypertension, a number of antihypertensive agents may control blood pressure. Randomized trials evaluating first-line therapy with thiazides, beta-adrenergic antagonists, angiotensin-converting enzyme inhibitors, calcium channel blockers, alpha-blockers, centrally acting agents or angiotensin II receptor antagonists were reviewed. OUTCOMES: The health outcomes that were considered were changes in blood pressure, cardiovascular morbidity, and cardiovascular and/or all-cause mortality rates. Economic outcomes were not considered due to insufficient evidence. EVIDENCE: MEDLINE was searched for the period March 1999 to October 2001 to identify studies not included in the 2000 revision of the Canadian Recommendations for the Management of Hypertension. Reference lists were scanned, experts were polled, and the personal files of the subgroup members and authors were used to identify other published studies. All relevant articles were reviewed and appraised, using prespecified levels of evidence, by content experts and methodological experts. VALUES: A high value was placed on the avoidance of cardiovascular morbidity and mortality. BENEFITS, HARMS AND COSTS: Various antihypertensive agents reduce the blood pressure of patients with sustained hypertension. In certain settings, and for specific classes of drugs, blood-pressure lowering has been associated with reduced cardiovascular morbidity and/or mortality. RECOMMENDATIONS: The present document contains detailed recommendations pertaining to treatment thresholds, target blood pressures, and choice of agents in various settings in patients with hypertension. The main changes from the 2000 Recommendations are the addition of a section on the treatment of hypertension in patients with diabetes mellitus, the amalgamation of the previous sections on treatment of hypertension in the young and old into one section, increased emphasis on the role of combination therapies over repeated trials of single agents and expansion of the section on the treatment of hypertension after stroke. Implicit in the recommendations for therapy is the principle that treatment for an individual patient should take into consideration global cardiovascular risk, the presence and/or absence of target organ damage, and comorbidities. VALIDATION: All recommendations were graded according to strength of the evidence and voted on by the Canadian Hypertension Recommendations Working Group. Individuals with potential conflicts of interest relative to any specific recommendation were excluded from voting on that recommendation. Only those recommendations achieving high levels of consensus are reported here. These guidelines will continue to be updated annually.     

激光小角光散射仪测定右旋糖酐分子量

激光小角光散射仪(LALLS)由于采用了激光光源,具有光强度高、单色性强、准直性好等特点,可以在微量样品池及很低浓度的溶液中进行小角度(3°～7°)散射光强的测量,溶质的瑞利系数与其分子量有如下关系:     

雪灵芝对二乙基亚硝胺诱导大鼠肝癌组织细胞的抑制作用

目的：验证雪灵芝是否具有抑制大鼠肝癌的功效。方法：实验于2003—09/2004—08在广西疾病预防控制中心SPF级动物实验室完成。选用健康成年SD大鼠160只。按体质量分层随机分为5组：空白对照组、模型组、雪灵芝高剂量组、雪灵芝中剂量组和雪灵芝低剂量组，每组32只。雪灵芝高、中、低剂量组大鼠分别灌胃2．500，1．250，0．625mL/kg雪灵芝溶液，阴性对照组和模型组灌胃等量蒸馏水，1次／d，连续60d。第61天开始雪灵芝高、中、低剂量组和模型组灌胃二乙基亚硝胺溶液，对照组灌胃等量的生理盐水。于停止灌胃90d后各组处死一半受试大鼠（雌雄各半），检测血常规及血清主要生化指标，观察各脏器大体形态改变、脏器的癌变程度。1周后给剩余大鼠灌胃雪灵芝溶液（不含二乙基亚硝胺）。7周后处死余下的一半雄性大鼠，进行相同操作。8周后处死余下的全部大鼠，操作及检测方法同前。结果：纳入的160只SD大鼠，145只进入结果分析，15只脱落。①病理切片检查结果：除阴性对照组，其他各组大鼠肝组织均发生癌变或癌前病变。雪灵芝高、中、低剂量组的癌前病变发生率与模型组相近（P〉0．05）；癌变的发生率均低于模型组，差异有显著性意义（P〈0．05，0．01）。②大体标本检查结果：阴性对照组大鼠肝脏的大体标本均无异常改变，其他各组大鼠的肝脏有些可见表面粗糙等病理改变。模型组大体标本病理改变的阳性率高于雪灵芝高、中、低剂量组，差异有显著性意义（P〈0．05）。肉眼观模型组癌变发生率高于其他各组。③其他脏器检查结果：模型组2只大鼠有肝癌肺转移。结论：以较大剂量的二乙基亚硝胺连续灌胃30d可以复制大鼠肝癌模型；雪灵芝对二乙基亚硝胺诱导的大鼠肝癌具有预防和抑制的作用。     

Improvements in patient-reported outcomes associated with an intervention to enhance quality of care for rural patients with type 2 diabetes: results of a controlled trial

OBJECTIVE: The aim of this study was to examine patient-reported outcomes in a controlled trial of a multifaceted provider-level intervention to improve quality of care for rural patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted a before/after intervention study with concurrent controls in two rural regions in Alberta, Canada. The intervention consisted of six monthly visits by a multidisciplinary health care team and was primarily directed at primary care providers. Clinical and patient-reported outcomes were assessed after 6 months. Patient-reported outcomes included changes in health-related quality of life (Health Utilities Index Mark 3 [HUI3]), satisfaction with care, lifestyle (Diabetes Lifestyle Form), and adherence to self-care activities. Analysis of covariance was used to assess differences over time between the control and intervention regions. RESULTS: A total of 200 intervention and 172 control subjects were included in this analysis. After adjusting for important clinical and demographic differences, a statistically significant and clinically important improvement in the overall HUI3 score was seen at the 6-month follow-up in the intervention region (0.06 [95% CI 0.02-0.10]) compared with the control region (0.01 [-0.04 to 0.04]) (P = 0.03 for the difference between groups). Satisfaction with general medical care (P < 0.001 between groups) and diabetes care (P < 0.001 between groups) increased among patients in the intervention region compared with the control region. Self-efficacy, attitudes, and beliefs about diabetes control all increased in the intervention region when compared with the control region, but adherence to self-care activities did not. CONCLUSIONS: A provider-level intervention directed at improving quality of clinical care for patients with type 2 diabetes also had a favorable impact on overall health-related quality of life, satisfaction with care, and other humanistic outcomes.