Swee L Thein

..Our results are compatible with the hypothesis that ACS episodes predispose children to increased airway obstruction...

..Importantly, if AHR is to be correctly diagnosed, some SCA children will require to undergo both cold air and exercise challenge testing...

..Our results suggest this abnormality is independent of other lung function abnormalities...

..02). cfDNA levels may be useful in monitoring response to hydroxyurea therapy in SCD...

..We provide data from 30 SCD patients (10 with alpha-thalassaemia) demonstrating that co-existing alpha-thalassaemia significantly affects several standard measures of HC efficacy in SCD...

..Recent findings have provided new insights regarding HbF regulatory pathways, providing new opportunities for derepression of fetal globin gene expression and HbF induction...

..This review highlights the milestones and key developments in Hb research most relevant to hematologists, and that have impacted our understanding and management of the thalassemias and sickle cell disease...

..Illumination of such modifying factors may guide future therapeutic interventions and improve prediction of disease severity, with implications for genetic counseling, prenatal diagnosis and implementation of high risk therapy...

..Altogether, the incidence of hyperfiltration was 71% and microalbuminuria 37%, making nephropathy a common complication of sickle cell anemia...

..On this basis, stability of the candidate housekeeping genes was ranked according to repeatability of the gene expression differences among 31 samples...

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..Integrating multiplex genetic testing with clinical and laboratory data to generate predictive models shows potential, but such genetic approaches also require large datasets...

..The results support a key role for the HBS1L-related genetic variants in HbF control and illustrate the biological complexity of the mechanism of 6q QTL as a modifier of fetal hemoglobin levels in the beta hemoglobinopathies...

..This article reviews the clinical and hematologic diversity encountered in beta thalassemia with an overview of the modifier genes that moderate their disease expression...

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..These genetic results have already provided remarkable insights into molecular mechanisms that underlie the hemoglobin 'switch'...

..In some families, the subtle altered levels in AHSP related to the AHSP genotype appears to be a relevant contributory factor in the haematological phenotype...

..CCU mortality for SCD patients was 19.6%, comparable to a CCU-wide mortality of 17.6% during the study period in the same institution. Re-admission to CCU was high (16% over the 8-year period) but did not increase mortality risk...

..The 2p15 BCL11A quantitative trait locus accounts for 15.1% of the trait variance...

..We have started to distinguish effects originating from European and African ancestral populations in our admixed study populations...

..005) and total white cell counts (P < 0.05) in steady state. The study shows that plasma DNA concentration may have potential as a biomarker in sickle cell patients...

..With the goal to generate haplotype signatures from patients experimentally, we have investigated the suitability of an existing nanofluidic assay platform to perform phase alignment with single-nucleotide polymorphism alleles...

..6 +/- 2.7 nmol/L, in patients with sickle cell disease, 7.0 +/- 8.9 nmol/L; in patients with end-stage renal disease, 30.5 +/- 15.7 nmol/L; and patients with penetrant hereditary hemochromatosis, 1.4 +/- 0.8 nmol/L...

..We aimed to quantify the levels of fetal and total cfDNA on prospectively collected samples, to understand their correlation with other variables and to clarify their diagnostic value...

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..A significant variation in cf-DNA was found between ethnic groups, which should be taken into consideration in future studies measuring cf-DNA...

..46) despite substantial differences in average ancestry. The data confirm ethnic differences in FC levels and indicate the potential usefulness of these populations for admixture mapping of genes for FC levels...

..000005) and elevated levels in inflammation (P < 0.0007). In summary a validated method has been developed for the determination of hepcidin concentrations in clinical samples...

..These results support the notion that changes of F-cell abundance can be an indicator of more general shifts in hematopoietic patterns in humans...

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..We postulate that the increased R-R2 is associated with haemolysis rather than transfusional iron load in sickle cell disease...

..Each additional [TA] repeat is associated with an increase in mean serum bilirubin levels of 21% and cholelithiasis risk of 87% in SCD...

..The data suggest that GATA-1 regulates numerous genes of various functions on chromosome 6q...

..Improved understanding of the molecular basis of the disease complications, such as iron overloading, has also provided clues for potential molecular targets at the tertiary level...

..02). The ACS children had been diagnosed as asthmatic at a median of 3.5 (range 0.5-7) years prior to their first ACS episode. In conclusion, these results suggest asthma exacerbations may predispose to ACS episodes...

..This article reviews the clinical and haematological diversity encountered in beta thalassaemia and their relationship with the underlying genotypes...

..We summarize current knowledge of genetic modulation of sickle-related renal dysfunction. We outline the evidence for various treatment options and discuss others for which little evidence currently exists...

..The most common reason for admission was acute chest syndrome (43%). 88% of admissions required blood transfusion, of which 74% had exchange blood transfusions. The mortality among children with SCD admitted to PICU is low...

..These observations suggest that differences in the intrinsic levels of cMYB may account for some of the variation in adult HbF levels. The possible mechanism of cMYB influencing gamma- to beta-globin switching is discussed...

..60; 95% C.I. 2.93-4.28; P <0.0001). Conclusion:These results suggest that measurement of end-tidal carbon monoxide levels is a reliable and useful method to monitor haemolysis in children with sickle cell disease...

..These assays are potentially useful to study hydroxyurea metabolism further, develop optimal dosing regimes and monitor compliance with treatment...

..This is consistent with a view that although NS is potentially a rare complication of symptomatic acute HPV B19 infection, exposure to HPV B19 is not associated with an increased risk of renal disease...

..Our results confirm recently published findings that LBR mutations cause Pelger-Huët...

..We also observed BCL11A and GATA-1 binding in a known auto-regulatory promoter element of the GATA1 locus...

..The lower levels of bilirubin and other markers of haemolysis with increased exposure to air pollutants could be mediated by increased exposure to NO...

..Because previous attempts to describe patterns of liver disease have not reflected clinical experience, we aimed to characterize the presentation, clinicopathologic findings, and natural history of such patients...

..The results of analysis in a large Indian kindred indicate that there is an interaction between the XmnI-Ggamma site and a QTL on chromosome 8q that is influencing the production of fetal Hb...

..The results suggest that two QTLs on chromosome 3q influence platelet count variation in the Asian Indian kindred, with the GPIX transmembrane mutation and the 3' UTR SNP in THPO being strong candidates...

..This result provides strong evidence that a quantitative trait locus exists on chromosome 8q that influences the developmental switch from fetal to adult hemoglobin...

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..The effect of high wind and low humidity is likely to be related to skin cooling...

..The discovery of these factors may also suggest new approaches for therapeutic augmentation of fetal hemoglobin production in patients with SCD and beta thalassemia. ..