Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism

Parathyroid hormone secretion is negatively regulated by a 7- transmembrane domain, G-protein coupled Ca(2+)-sensing receptor. We hypothesized that activating mutations in this receptor might cause autosomal dominant hypoparathyroidism (ADHP). Consistent with this hypothesis, we identified, in two families with ADHP, heterozygous missense mutations in the Ca(2+)-sensing receptor gene that cosegregated with the disorder. None of 50 normal controls had either mutation. We also identified a de novo, missense Ca(2+)-sensing receptor mutation in a child with severe sporadic hypoparathyroidism. The amino acid substitution in one ADHP family affected the N-terminal, extracellular domain of the receptor. The other mutations involved the transmembrane region. Unlike patients with acquired hypoparathyroidism, patients with these mutations had hypercalciuria even at low serum calcium concentrations. Their greater hypercalciuria presumably reflected activation of Ca(2+)-sensing receptors in kidney cells, where the receptor negatively regulates calcium reabsorption. This augmented hypercalciuria increases the risk of renal complications and thus has implications for the choice of therapy.      

Potential short-term economic benefits of improved glycemic control: a managed care perspective

OBJECTIVE: There are limited data relating glycemic control to medical costs among patients with diabetes. The goal of this study was to examine the potential impact of improved glycemic control on selected short-term complications of diabetes and associated costs in a managed care setting. RESEARCH DESIGN AND METHODS: Using a retrospective cohort design and automated databases from January 1994 to 30 June 1998, adult members of the Fallon Clinic who were diagnosed with diabetes were identified and assigned to one of three study groups based on each patient's mean HbA1c level: good control (<8%), fair control (8-10%), and poor control (> 10%) groups. Inpatient (hospital or skilled nursing facility) admissions for selected acute (short-term) complications, represented by selected infections, hyperglycemia, hypoglycemia, and electrolyte disturbances, and the associated medical charges were evaluated across the three HbA1c groups. Multivariate analyses were used to control for differences in several potential confounding factors among the study groups. All findings were expressed on a 3-year basis. RESULTS: Of 2,394 patients with diabetes, approximately 10% (251) had at least one inpatient stay for a short-term complication, accounting for 447 admissions. Over 3 years, the adjusted rate of inpatient treatment ranged from 13 per 100 patients with good glycemic control to 16 per 100 patients with fair glycemic control and 31 per 100 patients with poor glycemic control (P < 0.05). The corresponding mean adjusted charges were approximately $970, $1,380, and $3,040, respectively Among the 30% of the study population with long-term diabetic complications, the results were more marked; the adjusted admissions per 100 patients (mean charges) were estimated to be 30 ($2,610), 38 ($3,810), and 74 ($8,320) over 3 years for patients with an HbA1c of <8, 8-10, and > 10%, respectively. CONCLUSIONS: In typical practice, better glycemic control is associated with a reduced rate of admission for selected short-term complications and, therefore, reduced medical charges for these complications over a 3-year period. The potential short-term economic benefits are important to consider when making decisions regarding the adoption and use of new interventions for the management of diabetes.     

富血小板血浆对人骨髓间充质干细胞成骨分化的抑制效应

目的:一些理论质疑富血小板血浆对骨前体细胞成骨分化的作用,本实验拟验证富血小板血浆对体外培养的人骨髓间充质干细胞成骨分化的抑制效应。方法:实验于2005-05/11在南方医科大学组织工程试验室(省级)完成。①实验方法:抽取6名健康志愿者髂前上棘骨髓5mL进行体外细胞培养扩增,静脉血10mL以二次离心法制得富血小板血浆。诱导骨髓间充质干细胞时富血小板血浆与骨髓间充质干细胞均来自同一个体。②碱性磷酸酶染色:取第4代骨髓间充质干细胞,分为两组:富血小板血浆组加入富血小板血浆使终浓度为100g/L,单纯血清培养组仅加入等量胎牛血清。培养后第7天进行碱性磷酸酶染色,阳性细胞为胞质中呈现黑色颗粒或块状沉淀。③矿化结节染色:取第4代骨髓间充质干细胞,分组同上。培养后第19天以0.1%茜素红-TrisHcl(pH8.3)37℃下放置30min,矿盐沉积染色阳性为红色。④Cbfa1基因表达:取第4代骨髓间充质干细胞,分组同上。培养后第3,7,12,16天RT-PCR法检测骨髓间充质干细胞Cbfa1基因的表达。⑤形态学观察:实验过程中使用相差显微镜观察各组细胞生长情况及形态学变化。结果:①骨髓间充质干细胞碱性磷酸酶染色结果:培养后第7天,富血小板血浆组碱性磷酸酶阳性细胞数量较单纯血清培养组明显减少,且阳性细胞内灰黑色颗粒也明显减少,为弱阳性。②骨髓间充质干细胞矿化结节染色结果:培养后第19天,单纯血清培养组可见细胞表面有较多的矿盐沉积,但未形成明显的矿化结节。富血小板血浆组细胞表面只有稀少的矿盐沉积。③骨髓间充质干细胞cbfa1mRNA的表达:培养后第3,7,12,16天,随着培养时间的延长单纯血清培养组与富血小板血浆组cbfa1基因表达量均逐渐增高,同一时间点两组间cbfa1基因的表达基本相似。④骨髓间充质干细胞形态学变化:富血小板血浆组骨髓间充质干细胞增殖旺盛,细胞达到单层汇合的时间较单纯血清培养组明显缩短。单纯血清培养组细胞在完全汇合后开始出现聚合现象(14～16d),但趋向性不明显,未完全形成团簇;富血小板血浆组细胞在完全汇合后未出现聚合现象,细胞密集生长。培养初期两组细胞以梭形为主,多角形细胞较少,培养至14～16d单纯血清培养组多角形细胞较富血小板血浆组增多。结论:富血小板血浆可抑制人骨髓间充质干细胞碱性磷酸酶的分泌与矿盐沉积,对人骨髓间充质干细胞成骨分化的直接效应是抑制其分化。     

Education and Experience with Breast Health Maintenance and Breast Cancer Care: A Study of Obstetricians and Gynecologists

Breast cancer is one of the most common malignancies in the United States. A survey regarding the practice, training, and knowledge of breast health maintenance and cancer screening was conducted with a response rate of 59%. Most respondents reported adequate knowledge and that continuing educational efforts were at least adequate. Most recognize the importance of family history and incorporate patient inquiry and referral to genetics practitioners into their practice. A considerable portion does not inquire about hereditary risk factors and feel “not qualified” to manage genetic counseling and screening. Continued training is needed about hereditary predisposition to breast disease.     

Cost analysis of amlodipine versus enalapril in patients with coronary artery disease and normal blood pressure

Objectives

To analyse 2-year hospitalization and cost data collected during a prospective, double-blind, randomized, controlled trial comparing amlodi-pine, enalapril and placebo in normotensive patients with coronary artery disease (CAD).

Methods

All patients who were enrolled in the CAMELOT study were included in this economic substudy. Patients with CAD and normal blood pressure were randomized to amlodipine, enalapril or placebo, and followed up for 24 months (between 1999 and 2004). Data on hospitalizations and medication use were obtained from the clinical trial. Costs were assigned from secondary sources. Total costs ($US, year 2004 values) were estimated as the sum of costs associated with cardiovascular hospitalizations, study medications and concomitant cardiovascular medications. Costs and resource use were analysed by treatment arm overall and for selected patient subgroups. Cost differences were evaluated using nonparametric bootstrap techniques.

Results

Of 1991 patients enrolled, 663 were treated with amlodipine, 673 were treated with enalapril and 655 were treated with placebo. Significantly fewer patients were hospitalized for cardiovascular reasons in the amlodipine group (16.4%) than in the placebo group (22.7%;p < 0.01), but not compared with the enalapril group (20.1%;p = 0.09). The amlodipine group also had numerically fewer days in hospital per patient (1.1) than the enalapril (1.3) and placebo (1.5) groups. Mean 2-year per-patient costs in the amlodipine group were estimated to be $US609 and $US717 lower than for the placebo and enalapril groups, respectively.

Conclusions

These results suggest that use of amlodipine may reduce costs of care among CAD patients with normal blood pressure.     

既往疾病史和胆道癌关系的全人群病例对照研究

目的　研究分析既往疾病史和胆道癌 (包括胆囊癌、肝外胆管癌和壶腹部癌 )的关系。方法　自 1997年 6月～ 2 0 0 1年 5月 ,在上海市区开展了一项大规模的基于全人群的胆道癌的病例对照研究 ,共收集、调查了 6 6 4例胆道癌新病例和 894例人群对照。结果　研究发现既往有胆囊炎疾病史者患胆囊癌、肝外胆管癌的危险性升高 ,调整的比数比分别为 2 .2 (95 %CI =1.3～ 3.6 )和 1.9(95 %CI=1.0～ 3.3)。糖尿病患者患胆囊癌的危险性增加 ,调整的比数比为 1.5 (95 %CI=0 .9～ 2 .5 ) ,在非胆结石者中调整的比数比为 2 .0 (95 %CI=0 .9～ 4 .5 ) ;此外 ,研究还发现肝硬化者患肝外胆管癌的危险性明显增加 ,调整的比数比为 3.0 (95 %CI=1.0～ 9.1) ,在非胆结石者中调整的比数比为 4 .9(95 %CI=1.2～ 19.8)。结论　该项研究为论证胆囊炎症增加患胆道癌的危险性提供了依据 ,研究还提示糖尿病和肝硬化分别提高患胆囊癌和肝外胆管癌的危险性。     

Age- and gender-specific risk of death after first hospitalization for heart failure

Background  

Hospitalization for heart failure (HF) is associated with high-in-hospital and short- and long-term post discharge mortality. Age and gender are important predictors of mortality in hospitalized HF patients. However, studies assessing short- and long-term risk of death stratified by age and gender are scarce.