Chromosome Arm-Specific Long Telomeres: A New Clonal Event in Primary Chronic Myelogenous Leukemia Cells

Previous studies demonstrated that critically shortened telomere lengths correlate with the chromosome instability in carcinogenesis. However, little has been noticed regarding the correlation of long telomeres at specific chromosomes with malignant disorders. We studied relative telomere lengths (RTLs) for individual chromosomes using the quantitative fluorescence in situ hybridization technique in a cohort of 32 patients with chronic myeloid leukemia (CML) and 32 normal samples. We found that telomeres at some specific chromosome arms remain well maintained or even lengthened in a high frequency (27/32) of leukemia cases. In particular, 10 chromosome arms, 4q, 5p, 7q, 11p, 13p, 13q, 14p, 15p, 18p, and Xp, with long telomeres were consistently identified in different samples, and six of them (4q, 5p, 13p, 13q, 14p, and Xp) with relatively long telomeres were also observed in normal samples, but they appeared in lower occurrence rate and shorter RTL than in CML samples. Our results strongly indicate the presence of a special leukemia cell population, or a clone, originated from a common progenitor that is characterized with chromosome arm-specific long telomeres. We suggest that relatively long telomeres located at key chromosomes could be preferentially maintained or further elongated during the early stage of malignant transformation.     

The RAFT network: 5 years of distance continuing medical education and tele-consultations over the Internet in French-speaking Africa

Continuing education of healthcare professionals is a key element for the quality and efficiency of a health system. In developing countries, this activity is usually limited to capitals, and delocalized professionals do not have access to such opportunities, or to didactic material adapted to their needs. This limits the interest of such professionals to remain active in the periphery, where they are most needed to implement effective strategies for prevention and first-line healthcare. Telemedicine tools enable the communication and sharing of medical information in electronic form, and thus facilitate access to remote expertise. A physician located far from a reference center can consult its colleagues remotely in order to resolve a difficult case, follow a continuous education course over the Internet, or access medical information from digital libraries or knowledge bases. These same tools can also be used to facilitate exchanges between centers of medical expertise: health institutions of a same country as well as across borders. Since 2000, the Geneva University Hospitals have been involved in coordinating the development of a network for eHealth in Africa (the RAFT, Réseau en Afrique Francophone pour la Télémédecine), first in Mali, and now extending to 10 French-speaking African countries. The core activity of the RAFT is the webcasting of interactive courses. These sessions put the emphasis on knowledge sharing across care professionals, usually in the form of presentations and dialogs between experts in different countries. The technology used for the webcasting works with a slow (25 kbits/s) internet connection. Other activities of the RAFT network include visioconferences, teleconsultations based on the iPath system, collaborative knowledge bases development, support for medical laboratories quality control, and the evaluation of the use of telemedicine in rural areas (via satellite connections) in the context of multisectorial development. Finally, a strong emphasis is put on the development of capacities for the creation, maintenance, and publication of quality medical didactic contents. Specific courses are organized for the national coordinators of the network to develop these competencies, with the help of the Health-On-the-Net Foundation. The richness of the plurality of knowledge and know-how must be steered towards emulation and sharing, respectful of each partner's identity and culture. Collaborations with UNESCO and WHO have been initiated to address these challenges.     

一个男运动员的性腺机能低下与富含胡萝卜素饮食的关系(英文)

目的:报道了一个年轻男运动员大量摄入胡萝卜素后引发性腺机能低下的独特病例。病例报告:一名20岁的患者,在先前一年里坚持自己设计的高胡萝卜素、低动物脂肪的饮食,就诊时症状为肌肉逐渐萎缩、身体活动能力以及性欲减低、勃起功能下降。临床上,他表现出明显的胡萝卜素过量的体征:掌心和脚底都呈黄色。当他的饮食正常化二周后,胡萝卜素 B 值达到了正常范围的上限。方法:在恢复均衡饮食前和恢复均衡饮食3、6和12个月后,分别进行下丘脑、垂体和睾丸功能的重复刺激测试。结果:在均衡饮食数月后,促性腺激素和性腺类固醇由最初测得的非常低的基础值和刺激值逐渐恢复正常,并且胡萝卜素 B 值也有所恢复。诊断9—12个月后,荷尔蒙分泌物和性反应完全恢复。结论:这是第一个与摄入过量胡萝卜素有关的下丘脑式性腺机能低下的病例。     

Intermittent preventive treatment using artemisinin-based combination therapy reduces malaria morbidity among school-aged children in Mali

Objective  To assess the efficacy of intermittent preventive treatment (IPT) against malaria in school-aged children.
Methods  This was an open randomized controlled trial of seasonal IPT among school children (IPTsc) aged 6–13 years in Kollé, Mali. The study began in September 2007 and completed follow-up in May 2008. Students were randomized to one of three study arms: Sulfadoxine–pyrimethamine plus artesunate (SP/AS), amodiaquine plus artesunate (AQ/AS) or vitamin C. All students received two full treatment doses, given 2 months apart during the season of high transmission from September to December. Groups were compared with respect to incidence of clinical malaria, asymptomatic parasitemia and haemoglobin concentration.
Results  A total of 296 students were randomized, and retention in the study was 99.3%. Clinical malaria incidence in the SP/AS and AQ/AS arms was reduced by 66.6% and 46.5%, respectively, vs . vitamin C ( P  < 0.001). There were fewer clinic visits for any cause among the children receiving SP/AS or AQ/AS ( P  = 0.024). The prevalence of asymptomatic parasitemia was fivefold higher in the vitamin C arm than either SP/AS or AQ/AS at each post-treatment evaluation ( P  < 0.001). At the end of the transmission period, children treated with IPT had lower rates of anaemia (SP/AS, 17.7%; AQ/AS, 16.0%; vitamin C, 29.6%; P  = 0.039).
Conclusion  IPT among school children reduced the rates of clinical malaria, all-cause acute clinic visits, asymptomatic parasitemia and anaemia among school-aged children.     

Monitoring circulating epithelial tumour cells (CETC) to gauge therapy: in patients with disease progression after trastuzumab persisting CETC can be eliminated by combined lapatinib treatment

Background

In breast cancers, the gene for the growth factor receptor HER2 can be amplified leading to increased aggressiveness and metastasis formation. The monoclonal antibody trastuzumab prolongs relapse-free survival highly significantly but eventually many patients relapse.

Method

In this study, CETC were monitored using the Maintrac^® method during adjuvant trastuzumab treatment and during subsequent treatment with capecitabine/lapatinib.

Results

In one patient, trastuzumab led to marginal reduction in CETC with disease progress. The combination of capecitabine/lapatinib was preliminarily capable to eliminate all CETC, however, CETC reappeared. The second patient received adjuvant taxane together with trastuzumab and 1 year of further trastuzumab during which CETC increased. After stopping trastuzumab skin metastases occurred. Capecitabine/lapatinib led to complete CETC elimination with stable disease.

Conclusions

In patients with lack of CETC reduction in spite of trastuzumab treatment correlated with disease progression the combination of capecitabine/lapatinib highly efficiently led to rapid elimination of CETC warranting further monitoring during such studies.

     

The adaptation of Rice yellow mottle virus to the eIF(iso)4G-mediated rice resistance

The rymv1-3 allele of the eIF(iso)4G-mediated resistance to Rice yellow mottle virus (RYMV) is found in a few Oryza glaberrima cultivars. The same resistance-breaking (RB) mutations emerged in the central domain of the VPg after inoculation of isolates of different strains. The RB mutations were fixed, often sequentially, at codons 41 and 52 which paralleled an increase in virus accumulation. RB mutations also emerged after inoculation of an avirulent infectious clone, indicating that they were generated de novo in resistant plants. Only virus isolates with a threonine at codon 49 of the VPg broke rymv1-3 resistance, those with a glutamic acid did not. A small subset of these isolates overcame rymv1-2 resistance, but following a specific pathway. Comparison with the RB process of rymv1-2, a resistance allele found in a few Oryza sativa cultivars, showed similarities in the mode of adaptation but revealed converse virulence specificity of the isolates.