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Leukaemia in childhood
M Kruger
Continuing Medical Education , 2010,
Abstract: Leukaemia means white blood. It is a disease of the white blood cells and was first described by Virchow in 1845.1 Leukaemia can present as an acute disease, occurring more often in the younger age groups, or as a chronic disease, usually in the older age group. Acute leukaemia is rare, but about 1 in 2 000 people will develop the disease.2 The two acute forms in children are acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML). The chronic form is chronic myeloid leukaemia (CML).2,3
What Role for Angiogenesis in Childhood Acute Lymphoblastic Leukaemia?  [PDF]
P. Schneider,I. Dubus,F. Gouel,E. Legrand,J. P. Vannier,M. Vasse
Advances in Hematology , 2011, DOI: 10.1155/2011/274628
Abstract: The role of angiogenesis in acute leukaemia has been discussed since the cloning of the gene of vascular endothelial growth factor (VEGF) from the acute myelogenous leukemia cell line (HL60) and, thereafter, when the first studies reported increased bone marrow vascularity and elevation of angiogenic cytokines in acute lymphoblastic leukaemia (ALL). VEGF and basic fibroblast growth factor (bFGF) are the major proangiogenic cytokines that have been studied, and evaluation of their prognostic impact in childhood ALL has been reported in several studies, though with controversial results. The antiangiogenic response, contributing to the angiogenic balance, has scarcely been reported. The origin of the factors, their prognostic value, and their relevance as good markers of what really happens in the bone marrow are discussed in this paper. The place of antiangiogenic drugs in ALL has to be defined in the global treatment strategy. 1. Angiogenesis in Hematological Malignancies Angiogenesis is a highly regulated process balanced by inhibitors and stimulators of endothelial cell proliferation, endothelial cell migration, and capillary formation molecules. Cancer cells begin to promote angiogenesis early in tumorigenesis. This angiogenic switch is promoted by oncogene-driven tumor expression of proangiogenic proteins. The key mediator of angiogenesis is a proangiogenic factor, the vascular endothelial growth factor (VEGF). VEGF is a homodimeric glycoprotein which stimulates angiogenesis and vascular permeability by interacting with the tyrosine kinase receptor 2 (VEGFR-2 or KDR/Flk-1) and 1 (VEGFR-1 or Flt-1) [1]. These receptors belong to the superfamily of receptor tyrosine kinases (RTKs) and share a common structure with a single transmembrane domain. The central role of the VEGF-R2 in angiogenesis in general and in the development of solid tumors in particular has been widely demonstrated, and it is now considered as the main mediator of VEGFA effect on endothelial cells. Its interaction with VEGF is enhanced by neuropilin-1, which, thereby, has been proposed as a potential target to inhibit VEGF-driven angiogenesis [2]. One other major factor involved is the basic fibroblast growth factor (bFGF), a member of the FGF family of proteins, which interacts with tyrosine kinase receptors (FGFR-1 or FGFR-2) to exert mitogenic effects on endothelial, ectoderm-, and mesoderm-derived cells. Beyond its mitogenic activity, bFGF acts synergistically with VEGF in the angiogenic switch [3]. VEGF-A and bFGF are both major stimulators of angiogenesis that are commonly
Childhood leukaemia in the vicinity of German nuclear power plants - some missing links
Friedo Z lzer
Journal of Applied Biomedicine , 2010, DOI: 10.2478/v10136-009-0010-z
Abstract: A recent epidemiological study in Germany, the so-called KiKK study, came to the conclusion that there was a relationship between a child's risk of contracting leukaemia in the first 5 years of life and the distance of its residence from the nearest nuclear power plant. The risk of children inside a 5 km radius was found to be 2.19 times that of children outside, with a lower 95% confidence limit of 1.51. The study seems to be epidemiologically sound and solid, and its results agree with earlier evidence about childhood leukaemia in the vicinity of nuclear installations. It does not show, however, nor does it at all claim to show, that the phenomenon was due to radiation exposure. The measured doses in the area around German nuclear power plants are at least a factor 1000 smaller than what would be needed to explain the number of leukaemia cases observed. Additional evidence suggests that the main effect was a shift of the age distribution towards younger ages, with the overall incidence for all age groups not affected, which would be rather unexpected as a radiation effect. Still other studies have shown that elevated risks can even be observed around so-called "planning sites", where no nuclear facility has ever been built. It thus seems justified to speak of "missing links" between the elevated risk of childhood leukaemia around nuclear power plants on the one hand, and the radiation exposure caused by their normal operation on the other.
Childhood leukaemia in the vicinity of German nuclear power plants - some missing links
Friedo Zolzer
Journal of Applied Biomedicine , 2010,
Abstract: A recent epidemiological study in Germany, the so-called KiKK study, came to the conclusion that there wasa relationship between a child’s risk of contracting leukaemia in the first 5 years of life and the distance ofits residence from the nearest nuclear power plant. The risk of children inside a 5 km radius was found to be2.19 times that of children outside, with a lower 95% confidence limit of 1.51. The study seems to beepidemiologically sound and solid, and its results agree with earlier evidence about childhood leukaemia inthe vicinity of nuclear installations. It does not show, however, nor does it at all claim to show, that thephenomenon was due to radiation exposure. The measured doses in the area around German nuclear powerplants are at least a factor 1000 smaller than what would be needed to explain the number of leukaemia casesobserved. Additional evidence suggests that the main effect was a shift of the age distribution towardsyounger ages, with the overall incidence for all age groups not affected, which would be rather unexpectedas a radiation effect. Still other studies have shown that elevated risks can even be observed around so-called“planning sites”, where no nuclear facility has ever been built. It thus seems justified to speak of “missinglinks” between the elevated risk of childhood leukaemia around nuclear power plants on the one hand, andthe radiation exposure caused by their normal operation on the other.
Statistical adjustment of genotyping error in a case–control study of childhood leukaemia  [cached]
Cooper Matthew N,de Klerk Nicholas H,Greenop Kathryn R,Jamieson Sarra E
BMC Medical Research Methodology , 2012, DOI: 10.1186/1471-2288-12-141
Abstract: Background Genotyping has become more cost-effective and less invasive with the use of buccal cell sampling. However, low or fragmented DNA yields from buccal cells collected using FTA cards often requires additional whole genome amplification to produce sufficient DNA for genotyping. In our case–control study of childhood leukaemia, discordance was found between genotypes derived from blood and whole genome amplified FTA buccal DNA samples. We aimed to develop a user-friendly method to correct for this genotype misclassification, as existing methods were not suitable for use in our study. Methods Discordance between the results of blood and buccal-derived DNA was assessed in childhood leukaemia cases who had both blood and FTA buccal samples. A method based on applying misclassification probabilities to measured data and combining results using multiple imputations, was devised to correct for error in the genotypes of control subjects, for whom only buccal samples were available, to minimize bias in the odds ratios in the case–control analysis. Results Application of the correction method to synthetic datasets showed it was effective in producing correct odds ratios from data with known misclassification. Moreover, when applied to each of six bi-allelic loci, correction altered the odds ratios in the logically anticipated manner given the degree and direction of the misclassification revealed by the investigations in cases. The precision of the effect estimates decreased with decreasing size of the misclassification data set. Conclusions Bias arising from differential genotype misclassification can be reduced by correcting results using this method whenever data on concordance of genotyping results with those from a different and probably better DNA source are available.
A precautionary public health protection strategy for the possible risk of childhood leukaemia from exposure to power frequency magnetic fields
Myron Maslanyj, Tracy Lightfoot, Joachim Schüz, Zenon Sienkiewicz, Alastair McKinlay
BMC Public Health , 2010, DOI: 10.1186/1471-2458-10-673
Abstract: The Bradford-Hill Criteria are guidelines for evaluating the scientific evidence that low frequency magnetic fields cause childhood leukaemia. The criteria are used for assessing the strength of scientific evidence and here have been applied to considering the strength of evidence that exposures to extremely low frequency magnetic fields may increase the risk of childhood leukaemia. The applicability of precaution is considered using the risk management framework outlined in a European Commission (EC) communication on the Precautionary Principle. That communication advises that measures should be proportionate, non-discriminatory, consistent with similar measures already taken, based on an examination of the benefits and costs of action and inaction, and subject to review in the light of new scientific findings.The main evidence for a risk is an epidemiological association observed in several studies and meta-analyses; however, the number of highly exposed children is small and the association could be due to a combination of selection bias, confounding and chance. Corroborating experimental evidence is limited insofar as there is no clear indication of harm at the field levels implicated; however, the aetiology of childhood leukaemia is poorly understood. Taking a precautionary approach suggests that low-cost intervention to reduce exposure is appropriate. This assumes that if the risk is real, its impact is likely to be small. It also recognises the consequential cost of any major intervention. The recommendation is controversial in that other interpretations of the data are possible, and low-cost intervention may not fully alleviate the risk.The debate shows how the EC risk management framework can be used to apply the Precautionary Principle to small and uncertain public health risks. However, despite the need for evidence-based policy making, many of the decisions remain value driven and therefore subjective.Leukaemia is the most common type of childhood cancer
Vitamin and mineral supplements in pregnancy and the risk of childhood acute lymphoblastic leukaemia: a case-control study
John D Dockerty, Peter Herbison, David CG Skegg, Mark Elwood
BMC Public Health , 2007, DOI: 10.1186/1471-2458-7-136
Abstract: A national case-control study was conducted in New Zealand. The mothers of 97 children with ALL and of 303 controls were asked about vitamin and mineral supplements taken during pregnancy.There was no association between reported folate intake during pregnancy and childhood ALL (adjusted odds ratio (OR) 1.1, 95% confidence interval (CI) 0.5–2.7). Combining our results with the study from Western Australia and another study from Québec in a meta-analysis gave a summary OR of 0.9 (95% CI 0.8–1.1).Our own study, of similar size to the Australian study, does not support the hypothesis of a protective effect of folate on childhood ALL. Neither do the findings of the meta-analysis.Despite decades of research, the aetiology of childhood leukaemia remains enigmatic. There have been clear increases in the incidence rates of childhood leukaemia in New Zealand and other countries, highlighting the aetiological importance of unknown environmental factors [1]. There is a natural appeal to any evidence suggesting that a modifiable factor could be protective. In 2001, a case-control study from Western Australia showed a protective effect of maternal folate supplements (taken in pregnancy) on the risk of childhood common acute lymphoblastic leukaemia (ALL) [2]. The odds ratio (OR) for iron or folate supplementation was 0.4 (95% confidence interval (CI) 0.2–0.7). Most mothers used folate in conjunction with iron, so the authors could not report separate findings for folate alone. They suggested that the effect was likely to be from the folate or from iron and folate together.A case-control study from northern California looked at maternal diet and vitamin supplements in the twelve months before pregnancy, and found no statistically significant association between childhood ALL and any vitamin or iron supplements [3]. Total dietary folic acid, presumably including supplements, gave an odds ratio of 0.8 (95% CI 0.3–1.8). However use of folic acid supplements specifically was not repor
Classic and New Diagnostic Approaches to Childhood Tuberculosis  [PDF]
Gladys Guadalupe López ávalos,Ernesto Prado Montes de Oca
Journal of Tropical Medicine , 2012, DOI: 10.1155/2012/818219
Abstract: Tuberculosis in childhood differs from the adult clinical form and even has been suggested that it is a different disease due to its differential signs. However, prevention, diagnostics, and therapeutic efforts have been biased toward adult clinical care. Sensibility and specificity of new diagnostic approaches as GeneXpert, electronic nose (E-nose), infrared spectroscopy, accelerated mycobacterial growth induced by magnetism, and flow lateral devices in children populations are needed. Adequate and timely assessment of tuberculosis infection in childhood could diminish epidemiological burden because underdiagnosed pediatric patients can evolve to an active state and have the potential to disseminate the etiological agent Mycobacterium tuberculosis, notably increasing this worldwide public health problem. 1. Introduction Tuberculosis is the leading cause of death worldwide, with over 1.5 million deaths per year. This disease is caused by Mycobacterium tuberculosis, which is an acid-fast bacilli, and it is transmitted mainly by the airway [1]. While adult TB cases are often easily recognizable, due to typical symptoms (radiological features and a positive sputum smear), TB in childhood is frequently more difficult to diagnose due to the atypical radiological features and the difficulty to expectorate [2]. Furthermore, there is a significant morbidity and mortality in children worldwide [3], with a majority of cases of latent TB infection (LTBI) and active disease occurring in developing countries [4]. Childhood tuberculosis is commonly extrapulmonary, disseminated, and severe, especially in children under 3 years of age, and it is associated with high morbidity and mortality [5]. Approximately, 15–20% of all TB cases in sub-Saharan Africa are in children [6]. The natural history of TB in children and pediatric patients follows a series of steps. Phase 1 occurred 3–8 weeks after primary infection. This is the end of incubation period and the initiation of well-defined signs: fever, erythema nodosum, a positive tuberculin skin test response, and formation of the primary complex visible on chest radiography. Phase 2 occurred 1–3 months after the phase 1. In this period, the bacillus can migrate to other parts of the body via the blood and represented the period of the highest risk for the development of tuberculous meningitis and miliary tuberculosis in young children. This is the phase where dissemination of the bacillus most frequently occurs. Phase 3 occurred 3–7 months after primary infection. This is the period of pleural effusions in >5 years old
The usefulness of growth hormone treatment for psychological status in young adult survivors of childhood leukaemia: an open-label study
Jaap Huisman, Eline J Aukema, Jan Deijen, Silvia CCM van Coeverden, Gertjan JL Kaspers, Heleen JH van der Pal, Henriette A Delemarre-van de Waal
BMC Pediatrics , 2008, DOI: 10.1186/1471-2431-8-25
Abstract: Twenty young adult survivors of childhood ALL with reduced bone mineral density (<-1 SD) and/or low IGF-I SD-scores (<-1 SD) were included in the study. A final group of 13 patients (9 males and 4 females), mean age 23.7 ± 2.9 years (range 20 – 29.7) completed a 2-year treatment with GH.IQ and neuropsychological performance were assessed at pre-treatment (T1) and after one (T2) and two (T3) years. ANOVA was performed with assessment at T1, T2 and T3 as repeated measurements factor. Relations between test score changes and changes of IGF-I levels were determined by calculating the Pearson correlation coefficient.Scores on the cognitive tests were in the normal range. Verbal short- and long-term memory performance decreased between T1 and T2, and increased between T2 and T3. Performance at T3 was not significantly different from that at T1. Performance for sustained attention improved from T1 to T2 and from T1 to T3. Visual-spatial memory was improved after one year of GH treatment. A significant positive correlation was found for Δ IGF-I (T2-T1) with difference scores of visual-spatial memory (T2-T1 and T3-T1), indicating that IGF-I increase after one year of GH treatment is associated with increase in cognitive-perceptual performance at month 12 and 24.Since the level of intellectual functioning of our patient cohort was in the normal range the present finding that GH treatment has negative effects on verbal memory and positive on attention and visual-spatial memory warrants similar studies in other groups of ALL survivors. Also, a lower dose of GH should be determined inducing as much IGF as needed to improve verbal as well as visual cognitive functions. The present findings indicate that more knowledge is needed before GH treatment may be recommended to enhance cognitive functions in ALL survivors.In the last decades the prognosis of children with acute lymphoblastic leukaemia (ALL) has improved dramatically and long-term survival rates up to 80% have been reporte
Tissue Microarray : A rapidly evolving diagnostic and research tool.  [cached]
Jawhar Nazar
Annals of Saudi Medicine , 2009,
Abstract: Tissue microarray is a recent innovation in the field of pathology. A microarray contains many small rep-resentative tissue samples from hundreds of different cases assembled on a single histologic slide, and therefore allows high throughput analysis of multiple specimens at the same time. Tissue microarrays are paraffin blocks produced by extracting cylindrical tissue cores from different paraffin donor blocks and re-embedding these into a single recipient (microarray) block at defined array coordinates. Using this technique, up to 1000 or more tissue samples can be arrayed into a single paraffin block. It can permit simultaneous analysis of molecular targets at the DNA, mRNA, and protein levels under identical, stan--dardized conditions on a single glass slide, and also provide maximal preservation and use of limited and irreplaceable archival tissue samples. This versatile technique, in which data analysis is automated facilitates retrospective and prospective human tissue studies. It is a practical and effective tool for high- throughput molecular analysis of tissues that is helping to identify new diagnostic and prognostic markers and targets in human cancers, and has a range of potential applications in basic research, prognostic on--cology and drug discovery. This article summarizes the technical aspects of tissue microarray construction and sectioning, advantages, application, and limitations.
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