Lineage promiscuity in hemopoietic differentiation and leukemia

An increasing number of reports document instances in which individual leukemic cells coexpress markers normally believed to be restricted to a single lineage. This has been interpreted by McCulloch and colleagues as aberrant programming or lineage infidelity and contrasts with earlier suggestions that lineage fidelity of gene expression was usually maintained in leukemia. We argue that several examples of infidelity are suspect on technical grounds, whereas others are bona fide and require explanation, eg, partial rearrangements and expression of Ig heavy-chain and/or T cell receptor genes in inappropriate cells and terminal deoxynucleotidyl transferase in leukemic myeloblasts. Individual examples of truly aberrant gene expression may well occur in leukemia but with insufficient regularity to be of general significance. We suggest that verifiable and consistent examples of apparent lineage infidelity do not reflect genetic misprogramming but rather the existence of a transient phase of limited promiscuity of gene expression occurring in normal biopotential or multipotential progenitors and able to be preserved as a relic in leukemic blast cell populations that are in maturation arrest. This alternative explanation has interesting implications for mechanisms of hematopoietic differentiation and leads to some testable predictions.     

Colchicine for recurrent pericarditis in children

The incidence of recurrence of acute pericarditis in children varies from 15% to 30% and is accompanied by a high morbidity. Various treatment modalities have been used with variable success rates and side effects. La Serna et al. (Lancet 1987; 26: 1517) were the first to treat adults with recurrent pericarditis with colchicine, and were followed by other authors. To our knowledge no studies in children have been reported. In this paper, we present three children who suffered from viral or idiopathic recurrent pericarditis, despite multiple courses of non-steroidal anti-inflammatory drugs (NSAIDs) and/or corticosteroids. They responded remarkably well to colchicine, which was administered for 6 months with no adverse reactions. They continue to do well 18, 11 and 12 months after cessation of treatment, respectively.     

Fecal contamination in child day care centers: cloth vs paper diapers.

OBJECTIVES. Cloth diapers with front closure and all-in-one design were compared with paper diapers containing absorbent gel material for their influence on fecal contamination of the environment in licensed child day care centers. METHODS. One infant room and two toddler rooms in each of four day care centers were monitored for the presence of fecal bacteria. Microbial samples were taken from the play/sleep area, the diaper-changing area, and the hands of the caregivers and the children. Sampling was done twice weekly for two 4-week periods. Each center used either cloth or paper diapers during the first period, changing to the other diaper type during the second period. RESULTS. A total of 1722 samples were cultured, 881 during the first 4 weeks and 841 during the second 4 weeks. The frequency of isolation of fecal organisms ranged from a low of 12% of the total bacteria isolates at a center using cloth diapers, to highs of 46% and 45%, respectively, at a center using first paper and then cloth diapers. Sink faucets and the hands of the caregivers and the children were often contaminated. CONCLUSIONS. Analysis of the results of comparisons between cloth and paper diapers showed no significant difference in the frequency (F = .380, P < .535) or the intensity of fecal contamination in child day care centers.     

Induced drug resistance inhibits selection of initiated cells and cancer development

Compounds exerting a mitoinhibitory effect on normal hepatocytes are potent promoters in the resistant hepatocyte model of chemical carcinogenesis in combination with stimulation of regenerative growth by partial hepatectomy or treatment with carbon tetrachloride. 2- Acetylaminofluorene (2-AAF) almost completely inhibits liver cell regeneration after partial hepatectomy, allowing only resistant cells to participate in regenerative growth. After initiation by diethylnitrosamine and promotion with 2-AAF and partial hepatectomy (PH), focal growth of initiated cells generates liver lesions which occupy 40% of the hepatic volume three weeks after PH. In this work the mechanism for the anti promoting effects of phenobarbital and 3- methylcholantrene were investigated as well as their effects on the development of malignant hepatocellular carcinoma in the resistant hepatocyte model. Treatment with phenobarbital or, especially, 3- methylcholanthrene rendered normal rat hepatocytes resistant to the mitoinhibitory effect of 2-AAF. In combination with 2-AAF/PH, 3- methylcholanthrene shortened the regenerative growth period to less than one week. In the Solt-Farber protocol for experimental hepatocarcinogenesis, treatment with phenobarbital or 3- methylcholanthrene during promotion with 2-AAF/PH permitted hepatocytes surrounding the focal lesions to respond with regenerative growth. The foci and surrounding liver grew until the liver/body mass index reached the control value. With phenobarbital treatment the total focal volume was 20% of the liver volume three weeks after PH, whereas the corresponding value in the case of 3-methylcholanthrene was only 1%. Labelling index data supported the conclusion that growth of the liver lesions in the resistant hepatocyte model was dependent on differential inhibition of normal hepatocyte growth by the promoter and that the size of the foci obtained was related to the length of time after PH required to complete liver regeneration. 3-methylcholanthrene induced 2- AAF resistance prevented the development of large persistent nodules and hepatocellular carcinoma while phenobarbital delayed cancer development with several month. The data thus supports the idea that the degree of clonal expansion during promotion determines the size of the population at risk for malignant transformation, as well as the final frequency of carcinomas.      

Venous Thromboembolism Risk in Patients With Locoregional Urothelial Tract Tumors

Background

Venous thromboembolism (VTE) is common in cancer patients, but there is limited data on patients with urothelial tract tumors (UTT). We previously identified several associative factors for increased VTE rates in patients with metastatic UTT. In this study, we assessed the frequency, associative factors, and impact on survival of VTE in patients with locoregional UTT.

铒激光擦皮术后色素沉着的防治对策

０　引言　东方人接受皮肤磨削术治疗后色素沉着的发生率明显高于西方人．尽管采用了目前被认为是最适宜亚洲人的铒激光治疗,色素沉着仍可发生．因此,在实施该手术治疗前应严格掌握适应证,制定严密的预防治疗措施,使得色素沉着的发生率降至最低,从而最大限度的防止医疗纠纷的发生．１　对象和方法１．１　对象　２１例患者,男２例,女１９例,平均年龄２９．２（０８～４８）岁．皱纹祛除８例,浅表疤痕７例,浅咖啡斑、黑子５例,不良纹眉１例．铒激光其它适应证：①老年斑;②细小皱纹;③“白皮肤”雀斑;④痤疮后疤痕⑤色素减退…     

Inhaled dry powder mannitol in children with cystic fibrosis: A randomised efficacy and safety trial

Introduction

Inhaled mannitol has beneficial effects on lung function, mucociliary clearance, quality of life and sputum properties. This trial examined the efficacy of inhaled mannitol in children with cystic fibrosis (CF).

TRIPS,the Doha Declaration and increasing access to medicines: policy options for Ghana

There are acute disparities in pharmaceutical access between developing and industrialized countries. Developing countries make up approximately 80% of the world's population but only represent approximately 20% of global pharmaceutical consumption. Among the many barriers to drug access are the potential consequences of the Trade Related Aspects of Intellectual Property Rights (TRIPS) Agreement. Many developing countries have recently modified their patent laws to conform to the TRIPS standards, given the 2005 deadline for developing countries. Safeguards to protect public health have been incorporated into the TRIPS Agreement; however, in practice governments may be reluctant to exercise such rights given concern about the international trade and political ramifications. The Doha Declaration and the recent Decision on the Implementation of Paragraph 6 of the Doha Declaration on the TRIPS Agreement and Public Health may provide more freedom for developing countries in using these safeguards. This paper focuses on Ghana, a developing country that recently changed its patent laws to conform to TRIPS standards. We examine Ghana's patent law changes in the context of the Doha Declaration and assess their meaning for access to drugs of its population. We discuss new and existing barriers, as well as possible solutions, to provide policy-makers with lessons learned from the Ghanaian experience.