Is p190 bcr-abl rearrangement necessary for acute transformation in some p210 CML of childhood?

Chronic myeloid leukemia (CML) is a rare disease in childhood which is almost exclusively associated with bcr-abl p210 (M-bcr) rearrangements. It has been suggested that co-expression of p 190 and p210 may be a pathway of CML progression in adult patients. We report two cases of pediatric patients with a diagnosis of CML who presented co-expression of the p210 and p190 transcripts during progression to the blastic phase. The present data suggest that p190 may be a secondary event in at least some cases of childhood CML, suggesting an association with progression to a blastic crisis in these patients. (c) 2008 Elsevier Ltd. All rights reserved.

Differential expression of HDAC3, HDAC7 and HDAC9 is associated with prognosis and survival in childhood acute lymphoblastic leukaemia

Altered expression of histone deacetylases (HDACs) is a common feature in several human malignancies and may represent an interesting target for cancer treatment, including haematological malignancies. We evaluated the mRNA gene expression profile of 12 HDAC genes by quantitative real-time polymerase chain reaction in 94 consecutive childhood acute lymphoblastic leukaemia (ALL) samples and its association with clinical/biological features and survival. ALL samples showed higher expression levels of HDAC2, HDAC3, HDAC8, HDAC6 and HDAC7 when compared to normal bone marrow samples. HDAC1 and HDAC4 showed high expression in T-ALL and HDAC5 was highly expressed in B-lineage ALL. Higher than median expression levels of HDAC3 were associated with a significantly lower 5-year event-free survival (EFS) in the overall group of patients (P = 0.03) and in T-ALL patients (P = 0.01). HDAC7 and HADC9 expression levels higher than median were associated with a lower 5-year EFS in the overall group (P = 0.04 and P = 0.003, respectively) and in B-lineage CD10-positive patients (P = 0.009 and P = 0.005, respectively). Our data suggest that higher expression of HDAC7 and HDAC9 is associated with poor prognosis in childhood ALL and could be promising therapeutic targets for the treatment of refractory childhood ALL.

Low mRNA Expression of the Apoptosis-Related Genes CASP3, CASP8, and FAS Is Associated With Low Induction Treatment Response in Childhood Acute Lymphoblastic Leukemia (ALL)

Background. Defects in apoptosis signaling have been considered to be responsible for treatment failure in many types of cancer, although with controversial results. The objective of the present study was to assess the expression profile of key apoptosis-related genes in terms of clinical and biological variables and of the survival of children with acute lymphoblastic leukemia (ALL). Procedure. The levels of mRNA expression of the apoptosis-related genes CASP3, CASP8, CASP9, FAS, and BCL2 were analyzed by quantitative real-time PCR in consecutive samples from 139 consecutive children with ALL at diagnosis treated by the Brazilian protocol (GBTLI-ALL 99). Gene expression levels and clinical and biological features were compared by the Mann-Whitney test. Event-free survival (EFS) was calculated by Kaplan-Meier plots and log-rank test. Results. A significant correlation was detected between CASP3, CASP8, CASP9, and FAS expression levels (P<0.01) in ALL samples. Higher levels of BCL2 were significantly associated with white blood cell (WBC) count <50,000/mm(3) at diagnosis (P=0.01) and low risk group classification (P=0.008). Lower expression levels of CASP3, CASP8 and FAS gene were associated with a poor response at day 7 according the GBTLI-ALL 99 protocol (P=0.03, P=0.02 and P=0.008, respectively). There was a relationship between FAS gene expression lower than the 75th percentile and lower 5-year EFS (P=0.02). Conclusion. These findings suggest an association between lower expression levels of the pro-apoptotic genes and a poor response to induction therapy at day 7 and prognosis in childhood ALL. Pediatr Blood Cancer 2010;55:100-107. (C) 2010 Wiley-Liss, Inc.

Cost-effectiveness analysis of universal childhood vaccination against varicella in Brazil

This study conducts a cost-effectiveness analysis of a childhood universal varicella vaccination program in Brazil. An age and time-dependent dynamic model was developed to estimate the incidence of varicella for 30 years. Assuming a single-dose schedule; vaccine efficacy of 85% and coverage of 80%, the program could prevent 74,422,058 cases and 2905 deaths. It would cost R$ 3,178,396,110 and save R$ 660,076,410 to the society and R$ 365,602,305 to the healthcare system. The program is cost-effective (R$ 14,749 and R$ 16,582 per life-year saved under the societal and the healthcare system`s perspective, respectively). The program`s cost-effectiveness is highly sensitive to the vaccine price and number of doses. (C) 2008 Elsevier Ltd. All rights reserved.

Pooled analysis of recent studies on magnetic fields and childhood leukaemia

BACKGROUND: Previous pooled analyses have reported an association between magnetic fields and childhood leukaemia. We present a pooled analysis based on primary data from studies on residential magnetic fields and childhood leukaemia published after 2000. METHODS: Seven studies with a total of 10 865 cases and 12 853 controls were included. The main analysis focused on 24-h magnetic field measurements or calculated fields in residences. RESULTS: In the combined results, risk increased with increase in exposure, but the estimates were imprecise. The odds ratios for exposure categories of 0.1-0.2 mu T, 0.2-0.3 mu T and >= 0.3 mu T, compared with <0.1 mu T, were 1.07 (95% Cl 0.81-1.41), 1.16 (0.69-1.93) and 1.44 (0.88-2.36), respectively. Without the most influential study from Brazil, the odds ratios increased somewhat. An increasing trend was also suggested by a nonparametric analysis conducted using a generalised additive model. CONCLUSIONS: Our results are in line with previous pooled analyses showing an association between magnetic fields and childhood leukaemia. Overall, the association is weaker in the most recently conducted studies, but these studies are small and lack methodological improvements needed to resolve the apparent association. We conclude that recent studies on magnetic fields and childhood leukaemia do not alter the previous assessment that magnetic fields are possibly carcinogenic. British Journal of Cancer (2010) 103, 1128-1135. doi: 10.1038/sj.bjc.6605838 www.bjcancer.com (c) 2010 Cancer Research UK

Physical disability, recent illnesses and health self-assessment in a population-based study in Sao Paulo, Brazil

Objectives. To investigate health self-assessment and to estimate the prevalence of chronic diseases and recent illnesses in people with and without physical disabilities (PD) in the state of Sao Paulo, southeastern Brazil. Study design. A Cross-sectional study comprising two population-based health surveys conducted in 2002 and 2003. Methods. A total of 8317 persons (165 with PD) were interviewed in the two studies. Variables concerning to health self-assessment; chronic disease and recent illness were compared in the people with and without PD. Negative binomial regression was used in the analysis. Results. Subjects with PD more often assessed their health as poor/very poor compared to non-disabled ones. They reported more illnesses in the 15 days prior to interview as well as more chronic diseases (skin conditions, anaemia, chronic kidney disease, stroke, depression/anxiety, migraine/headache, pulmonary diseases, hypertension, diabetes, arthritis/arthrosis/rheumatic conditions and heart disease). This higher disease prevalence can be either attributed to disability itself or be associated to gender, age and schooling. Conclusions. Subjects with PD had more recent illnesses and chronic diseases and poorer health self-assessment than non-disabled ones. Age, gender, schooling and disability have individual roles in disease development among disabled people.

UBE2A Deficiency Syndrome: Mild to Severe Intellectual Disability Accompanied by Seizures, Absent Speech, Urogenital, and Skin Anomalies in Male Patients

We describe three patients with a comparable deletion encompassing SLC25A43, SLC25A5, CXorf56, UBE2A, NKRF, and two non-coding RNA genes, U1 and LOC100303728. Moderate to severe intellectual disability (ID), psychomotor retardation, severely impaired/absent speech, seizures, and urogenital anomalies were present in all three patients. Facial dysmorphisms include ocular hypertelorism, synophrys, and a depressed nasal bridge. These clinical features overlap with those described in two patients from a family with a similar deletion at Xq24 that also includes UBE2A, and in several patients of Brazilian and Polish families with point mutations in UBE2A. Notably, all five patients with an Xq24 deletion have ventricular septal defects that are not present inpatients with a point mutation, which might be attributed to the deletion of SLC25A5. Taken together, the UBE2A deficiency syndrome in male patients with a mutation in or a deletion of UBE2A is characterized by ID, absent speech, seizures, urogenital anomalies, frequently including a small penis, and skin abnormalities, which include generalized hirsutism, low posterior hairline, myxedematous appearance, widely spaced nipples, and hair whorls. Facial dysmorphisms include a wide face, a depressed nasal bridge, a large mouth with downturned corners, thin vermilion, and a short, broad neck. (C) 2010 Wiley-Liss, Inc.

Circulating renin-angiotensin system and catecholamines in childhood: is there a role for birthweight?

There have been only a few reports on the sympathoadrenal and renin-angiotensin systems in children of small gestational age. The purpose of the present study was to investigate plasma levels of ACE (angiotensin-converting enzyme) activity, angiotensin and catecholamines in 8- to 13-year-old children and to determine whether there are correlations between the components of these systems with both birthweight and BP (blood pressure) levels. This clinical study included 66 children (35 boys and 31 girls) in two groups: those born at term with an appropriate birthweight [AGA (appropriate-for-gestational age) group, n = 31] and those born at term but with a small birthweight for gestational age [SGA (small-for-gestational age) group, n = 35]. Concentrations of angiotensin, catecholamines and ACE activity were determined in plasma. Circulating noradrenaline levels were significantly elevated in SGA girls compared with AGA girls (P = 0.036). In addition, angiotensin 11 and ACE activity were higher in SGA boys (P = 0.024 and P = 0.050 respectively). There was a significant association of the circulating levels of both angiotensin 11 and ACE activity with BP levels in our study population. Although the underlying mechanisms that link restricted fetal growth with later cardiovascular events are not fully understood, the findings in the present study support the link between low birthweight and overactivity of both sympathoadrenal and renin-angiotensin systems into later childhood.