Results of 58872 and 58921 trials in acute myeloblastic leukemia and relative value of chemotherapy vs allogeneic bone marrow transplantation in first complete remission: the EORTC Children Leukemia Group report.

The first EORTC (European Organization of Research and Treatment of Cancer) acute myeloblastic leukemia (AML) pilot study (58872) was conducted between January 1988 and December 1991. Out of 108 patients, 78% achieved complete remission (CR), and event-free survival (EFS) and survival rates (s.e., %) at 7 years were 40 (5) and 51% (6%), respectively. It indicated that mitoxantrone could be substituted for conventional anthracyclines in the treatment of childhood AML without inducing cardiotoxicity. The aim of the next EORTC 58921 trial was to compare the efficacy and toxicity of idarubicin vs mitoxantrone in initial chemotherapy courses, further therapy consisting of allogeneic bone marrow transplantation (alloBMT) in patients with an HLA-compatible sibling donor or chemotherapy in patients without a donor. Out of 177 patients, recruited between October 1992 and December 2002, 81% reached CR. Overall 7-year EFS and survival rates were 49 (4) and 62% (4%), respectively. Out of 145 patients who received the first intensification, 39 had a sibling donor. In patients with or without a donor, the 7-year disease-free survival (DFS) rate was 63 (8) and 57% (5%) and the 7-year survival rate was 78 (7) and 65% (5%), respectively. Patients with favorable, intermediate and unfavorable cytogenetic features had a 5-year EFS rate of 57, 45 and 45% and a 5-year survival rate of 89, 67 and 53%, respectively.     

Windows 99: a source of suburban pediatric trauma

BACKGROUND: Falls from windows in urban areas cause a significant number of pediatric injuries. Window falls have not been well described in the nonurban setting. We describe the epidemiology of window falls from residential homes among pediatric patients at a suburban Level I trauma center. METHODS: A review of patients admitted from January 1991 through November 1999 to a center serving a rapidly growing suburban area was performed. RESULTS: A total of 2,322 children, ages 0-14 years, were admitted during the study period. Falls comprised 41% of these admissions, and 11% of falls were from windows, greater than twice the national average. More than 39% of children who fell from windows were admitted directly to the intensive care unit. Overall mortality rate was 4%. Ages 0 to 4 years comprised the largest percentage (83%), and all children who died were in this age group. Children < or = 4 years were more likely to have an Abbreviated Injury Score > or = 2 (head injury) than those ages 10 to 14 years (p = 0.032). More than 31% of all children injured in window falls seen at the study institution between 1991 and 1999 were admitted in the last 2 years. CONCLUSION: Pediatric falls from windows in this suburban area appear to be increasing, with an incidence greater than the national average. Children at greatest risk are less than 4 years old. Further research in injury prevention at the national level aimed at suburban areas may be warranted.     

Influence of Amodiaquine on the Antimalarial Activity of Ellagic Acid: Crystallographic and Biological Studies

In the search for new antimalarial drugs, design of hybrid molecules is recommended to improve biological activity and to decrease the risk of parasite resistance development. Ellagic acid, as an inhibitor of Plasmodium glutathione, presents an original mode of action and thus appears as a promising antiplasmodial compound. A new complex (AQ–EA) consisting of the well‐known antimalarial drug, amodiaquine, and ellagic acid was obtained. The studied crystal structure of AQ–EA showed that the triclinic centrosymmetrical unit cell of the crystal contains two molecules of amodiaquine (AQ) and two symmetrically independent molecules of ellagic acid (EA). The packing of the molecules in the crystal is dominated by hydrogen bonds between AQ and EA. The antiplasmodial activity of the hybrid complex AQ–EA was also determined and compared with the values of IC₅₀ for AQ and EA separately. Potentiation assays between both molecules were conducted to understand the pharmacological interactions between AQ and EA against Plasmodium falciparum in vitro. The hybrid complex AQ–EA (IC₅₀ of 47 nm ) showed improved antiplasmodial activity in comparison with EA alone.     

Forced swimming test in mice: a review of antidepressant activity

Rationale Among all animal models, the forced swimming test (FST) remains one of the most used tools for screening antidepressants.Objective This paper reviews some of the main aspects of the FST in mice. Most of the sensitivity and variability factors that were assessed on the FST are summarized.Mechanisms We have summarized data found in the literature of antidepressant effects on the FST in mice. From this data set, we have extrapolated information on baseline levels of strain, and sensitivity against antidepressants.Results We have shown that many parameters have to be considered in this test to gain good reliability. Moreover, there was a fundamental inter-strain difference of response in the FST.Conclusions The FST is a good screening tool with good reliability and predictive validity. Strain is one of the most important parameters to consider. Swiss and NMRI mice can be used to discriminate the mechanisms of action of drugs. CD-1 seems to be the most useful strain for screening purposes, but this needs to be confirmed with some spontaneous locomotor activity studies.Electronic Supplementary Material Supplementary material is available for this article at .     

Determination of malondialdehyde-induced DNA damage in human tissues using an immunoslot blot assay

Malondialdehyde (MDA) is a product of lipid peroxidation and prostaglandin biosynthesis. It is mutagenic and carcinogenic and the major adduct formed by reaction with DNA, a highly fluorescent pyrimidopurinone (M1-dG), has been detected in healthy human liver and leukocyte DNA. Analytical methods used so far for the detection of M1- dG have not been applied to a large number of individuals or variety of samples. Often, only a few microg of DNA from human tissues are available for analysis and a very sensitive assay is needed in order to detect background levels of M1-dG in very small amounts of DNA. In this paper, the development of an immunoslot blot (ISB) assay for the measurement of MI-dG in 1 microg of DNA is described. The limit of detection of the assay is 2.5 adducts per 10(8) bases. A series of human samples were analysed and levels of 5.6-9.5 (n = 8) and 3.1-64.3 (n = 42) of M1-dG per 10(8) normal bases were detected in white blood cell and gastric biopsy DNA, respectively. Results on four human samples were compared with those obtained using an HPLC/32P-post- labelling (HPLC/PPL) method previously developed and indicated a high correlation between M1-dG levels measured by the two assays. The advantages of ISB over other assays including HPLC/PPL, such as the possibility of analysing 1 microg DNA/sample and the fact that it is less time-consuming and laborious, means that it can be more easily used for routine analysis of a large number of samples in biomonitoring studies.      

Midwifery in New York

For many women living in New York, finding a licensed midwife to attend their birth at home is impossible. This article seeks to discuss the process by which Certified Professional Midwives (CPMs) can become licensed in New York and to explain a barriers to practicing outside the hospital. It will also explore what is being done to work toward making home-birth a more easily accessible option in New York.     

肿瘤治疗存在的问题及中西医结合的研究重点

目前的肿瘤治疗主要存在以下几个问题：(1)肿瘤的过度治疗普遍存在；(2)急功近利而缺乏长远规划；(3)综合治疗缺乏合理的内涵；(4)缺少有效的个体化治疗方案；(5)对中医药的优势认识不足、发挥不够。中西医结合在肿瘤防治中大有可为，应重点围绕以下几个方面开展研究工作：(1)加强中医对恶性肿瘤基础知识的认识和研究；(2)加强中西医结合治疗肿瘤合理化、规范化方案的研究；(3)加强中西医结合治疗恶性肿瘤疗效标准的研究；(4)加强中西医结合防治肿瘤术后复发、转移的研究。     

Effects of ciguatoxin on current and voltage clamped frog myelinated nerve fibre

The effects of 0.25 X 10(-9) and 1.25 X 10(-9) g/ml of purified ciguatoxin (CgTX) upon the node of Ranvier of frog isolated nerve fibres were investigated under current and voltage clamp conditions. When added to the external solution, CgTX induced spontaneous action potentials at a frequency of about 100 Hz, which were reversible upon removal of the toxin. Under voltage clamp conditions, CgTX modified neither linear leakage and capacity currents nor K current, but reversibly induced a maintained (late) inward current (IL) during long lasting depolarizations. IL, as well as the peak Na current, was suppressed by tetrodotoxin (300 nM). The steady-state inactivation curve of the Na current showed that a fraction of the current (corresponding to IL) did not inactivate. IL activated and reversed at voltages about 30 mV more negative than the peak Na current (recorded under control conditions or in the presence of CgTX). During a given depolarizing pulse, the amplitude of IL depended on the holding potential. IL was about three times greater when the holding potential was -70 mV rather than -120 mV. We conclude that CgTX specifically interacts with and modifies Na channels. We also conclude that the effects of CgTX depend on membrane potential.     

Reimagining care for young adults living with type 1 diabetes

Young adults living with type 1 diabetes often struggle to achieve what clinicians consider to be optimal levels of metabolic control. Despite the impact that this can have on a young person''s future risk of complications, there are relatively few studies reporting new ways of organizing or delivering care to this cohort. In this article, we explore some of the reasons why young adult diabetes care is challenging, and describe approaches to “re‐imagining” how care might be improved. The work is informed by the ‘Making Care Fit’ collaborative and by a program of research, entitled D1 Now, involving co‐design of a complex person‐centered intervention with young adults.