Telomere length in breast cancer patients before and after chemotherapy with or without stem cell transplantation

High-dose chemotherapy and peripheral blood stem cell transplantation (PBSCT) may accelerate telomere length loss in haematopoietic stem cells. As data including pre-and post-treatment samples are lacking, we studied leukocyte telomere length and telomerase activity before and after treatment in breast cancer patients randomized to receive 5 adjuvant courses FEC (5-FU, epirubicin and cyclophosphamide) (n = 17), or 4 x FEC followed by high-dose cyclophosphamide, thiotepa, carboplatin and autologous PBSCT (n = 16). Haemoglobin, MCV, leukocyte-and platelet numbers were assessed prior to (t(0)), 5 months after (t(1)) and 9 months after chemotherapy (t(2)); these parameters were decreased at t(1)and t(2)compared to t(0)(high-dose: all parameters; standard-dose: leukocytes and platelets), and all parameters were lower after high-dose than standard-dose treatment at t(1). Paired individual leukocyte samples of t(0)and t(1)showed telomere length change (determined by telomere restricted fragment (TRF) assay) ranging from +0.8 to -2.2 kb, with a decreased TRF length in 9 patients of both groups. Telomerase activity (determined by TRAP assay) was below detection limit in leukocyte samples of t(0)and t(1). Thus, standard-and high-dose chemotherapy negatively affect haematological reconstitution in this setting. In individual patients, telomere length can be remarkably changed following haematological proliferative stress after treatment.     

Lives through time: an ideographic approach to the study of resilience

The authors describe and illustrate an ideographic method for the study of resilience. The method assumes that resilience is an unfolding and dynamic process in which the individual and the social environment interact to produce a life course over time. Using retrospective and prospective data, the authors present a case study of a profoundly troubled boy, first seen as a preschooler and then followed up in early adulthood with a battery of clinical interviews. The methodology presented provides a way to study resilience as a dynamic process and to reveal and make sense of counterintuitive findings. In contrast to historical or epidemiological methods, the approach also permits exploration of the role of intrapsychic processes in facilitating change.     

Unilateral hypertrophic osteoarthropathy in a patient with an infected axillary-axillary bypass graft

Hypertrophic osteoarthropathy (HO) is a specific clinicoradiologic entity, the most common cause of which is the presence of pulmonary lesions. Eight cases of aortic graft infection and aortoenteric fistulae in association with HO have been recognized. A case of an infected axillary-axillary graft presenting as unilateral HO of the upper limb is reported, and its unusual features are used to postulate a mechanism underlying HO.     

Emergency department utilization by adolescents in the United States

BACKGROUND: Adolescents in the United States have been shown to underutilize primary care services and therefore may rely heavily on emergency service. Although several small studies have explored local emergency services for youth, there are no published reports of adolescent utilization of emergency services on a national scale. Furthermore, emergency services data have not been aggregated according to the age subgroups used by the current guidelines for adolescent care. OBJECTIVE: To explore the utilization of emergency departments in the United States by early (11 to 14 years), middle (15 to 17 years), and late (18 to 21 years) adolescent subgroups. DESIGN: Secondary analysis of the emergency department component of the 1994 National Hospital Ambulatory Medical Care Survey. SETTING: Nationally representative sample of 418 emergency departments in the United States. PATIENTS: Approximately 26,547 visits by patients of all ages, representing 93.4 million total visits in 1994 and 14.8 million adolescent visits. OUTCOME MEASURES: Number of visits, health insurance, reasons for visits, urgency of visits, resulting diagnoses, and hospitalization rates. RESULTS: Adolescents accounted for 15.4% of the population and 15.8% of emergency department visits in 1994. Late adolescents were overrepresented in emergency department visits relative to their population proportion (6.8% of visits, 5.3% of population), whereas early adolescents were underrepresented (4.6% of visits, 5.9% of population). Lack of health insurance was more common among 11- to 21-year-olds (26.2%) than either children (13.6%) or adults (22.7%). By ages 18 to 21 years, 40.5% of male visits and 27.6% of female visits were uninsured. Injury-related visits were more common among adolescents (28.6%) than either children (23.1%) or adults (18.2%). Injury was the leading reason for visits among all adolescent age-sex subgroups (36.6% to 42.0% of male visits and 14.1% to 27.2% of female visits) except females aged 18 to 21 years for whom digestive reasons ranked first (18.8%). Injury was the leading diagnosis for all adolescent age-sex subgroups, with peaks at early adolescence of 61.6% for males and 45.8% for females. Across all adolescent age-sex subgroups, 3.1% to 5.3% of visits resulted in hospitalization, and 41.0% to 52.5% of visits were urgent. These rates did not differ from those of children but were lower than those of adults. CONCLUSIONS: Utilization of emergency departments increases and health insurance decreases during adolescence, suggesting that adolescents with inadequate health insurance may rely heavily on emergency departments for their health care needs. Most adolescent visits to emergency departments are not urgent and might be better treated through nonemergency, primary care sites.     

Fine-scale human genetic structure in Western France

The difficulties arising from association analysis with rare variants underline the importance of suitable reference population cohorts, which integrate detailed spatial information. We analyzed a sample of 1684 individuals from Western France, who were genotyped at genome-wide level, from two cohorts D.E.S.I.R and CavsGen. We found that fine-scale population structure occurs at the scale of Western France, with distinct admixture proportions for individuals originating from the Brittany Region and the Vendée Department. Genetic differentiation increases with distance at a high rate in these two parts of Northwestern France and linkage disequilibrium is higher in Brittany suggesting a lower effective population size. When looking for genomic regions informative about Breton origin, we found two prominent associated regions that include the lactase region and the HLA complex. For both the lactase and the HLA regions, there is a low differentiation between Bretons and Irish, and this is also found at the genome-wide level. At a more refined scale, and within the Pays de la Loire Region, we also found evidence of fine-scale population structure, although principal component analysis showed that individuals from different departments cannot be confidently discriminated. Because of the evidence for fine-scale genetic structure in Western France, we anticipate that rare and geographically localized variants will be identified in future full-sequence analyses.     

胸腺内注射异基因抗原对同种异体鼠坐骨神经移植免疫反应的影响

目的:降低移植神经的抗原性、抑制异体神经移植中的排斥反应是目前的研究焦点。观察小鼠胸腺内注射异基因抗原对异体鼠坐骨神经移植存活的干预作用。方法:实验于2006-06/2007-05在哈尔滨医科大学附属第四医院实验室完成,实验方法符合动物伦理学要求。①选用雄性C57BL/6(H-2b)供体鼠32只,雌性Balb/c(H-2d)受体鼠44只,将坐骨神经移植受体鼠按随机数字表法分为4组(n=11):主要组织相容性复合物(H-2b)抗原注射组自供体小鼠的脾细胞中提取抗原注入受体鼠胸腺内,于2周后移植供体鼠坐骨神经;免疫抑制剂组移植前3d开始腹腔注射环孢霉素A;异体神经移植组、自体神经移植组单纯进行异体及自体神经移植。②于神经移植3周后进行电生理学、组织学及免疫学检测。结果:44只受体鼠全部进入结果分析。①坐骨神经移植段的神经传导速度:异体神经移植组显著小于主要组织相容性复合物(H-2b)抗原注射组(P<0.05),自体神经移植组显著大于主要组织相容性复合物(H-2b)抗原注射组(P<0.05),主要组织相容性复合物(H-2b)抗原注射组与免疫抑制剂组差异无显著性意义(P>0.05)。②组织学检查证明自体神经移植组及主要组织相容性复合物(H-2b)抗原注射组均有大量神经纤维再生,并已通过移植体。③混合淋巴细胞反应及迟发型超敏反应结果:主要组织相容性复合物(H-2b)抗原注射组对供体小鼠淋巴细胞反应呈特异性减弱,与异体神经移植组及免疫抑制剂组比较其差异具有显著性意义(P<0.05)。结论:胸腺内注射异基因主要组织相容性复合物抗原可诱导对异体坐骨神经移植的特异性免疫耐受,神经恢复效果优于单纯异体神经移植,等同于免疫抑制剂使用组。     

补中益气汤对环磷酰胺致骨质疏松小鼠骨生物力学的影响

目的:观察环磷酰胺对小鼠骨生物力学的影响,观察补中益气汤和葡萄糖酸钙对环磷酰胺造成的小鼠骨质疏松的防治作用。方法:实验于2005-10/2006-01在广东医学院药理教研室完成。选取昆明种小鼠40只,体质量(20±2)g,雌雄各半,按体质量对等原则随机分为4组,正常对照组、环磷酰胺模型组、环磷酰胺合用补中益气汤组、环磷酰胺合用葡萄糖酸钙组,每组10只。补中益气汤的制备:称取炙黄芪200g,党参60g,炙甘草100g,白术60g,当归60g,升麻60g,柴胡60g,陈皮60g,切碎,加水煎煮2次,滤过,滤液浓缩至1700mL,冰箱保存备用。正常对照组灌胃给予生理盐水10mL/(kg·d),环磷酰胺模型组灌胃给予环磷酰胺20mg/(kg·d);环磷酰胺合用补中益气汤组灌胃给予环磷酰胺20mg/(kg·d)的同时灌胃给予补中益气汤20mL/(kg·d);环磷酰胺合用葡萄糖酸钙组灌胃给予环磷酰胺20mg/(kg·d)的同时灌胃给予葡萄糖酸钙0.5mg/(kg·d)。均自由饮水和进食标准饲料。于实验第30天称质量后,处死动物,取肝脏、脾脏、胸腺称质量,根据动物体质量计算器官指数,同时取右侧股骨供骨生物力学测定用。结果:40只小鼠均进入结果分析。与正常对照组比较,环磷酰胺模型组骨生物力学指标最大载荷、弹性载荷、刚度系数均减少[(12.11±2.06)N,(8.15±2.57)N,(45.89±6.33)N/mm;(14.98±1.54)N,(10.17±1.17)N,(56.34±9.49)N/mm,P<0.05,P<0.01]。与环磷酰胺模型组比较,环磷酰胺合用补中益气汤组、环磷酰胺合用葡萄糖酸钙组生物力学指标最大载荷、刚度系数增高[环磷酰胺模型组:(12.11±2.06)N,(45.89±6.33)N/mm;环磷酰胺合用补中益气汤组:(15.52±2.67)N,(57.68±11.19)N/mm;环磷酰胺合用葡萄糖酸钙组:(17.10±2.96)N,(63.69±11.11)N/mm,P<0.05,P<0.01]。与环磷酰胺合用葡萄糖酸钙组比较,环磷酰胺合用补中益气组表现为各生物力学指标与环磷酰胺合用葡萄糖酸钙组相似,差异无显著性意义。结论:环磷酰胺能使小鼠骨结构性质和材料性质下降,补中益气汤和葡萄糖酸钙均能对抗环磷酰胺导致的骨质量下降,预防骨质疏松。