A5049244658- Hemoglobinopathies and Related Disorders
- Iron Metabolism and Disorders
- Blood groups and transfusion
- Erythrocyte Function and Pathophysiology
- Pharmacological Effects and Toxicity Studies
- Erythropoietin and Anemia Treatment
- Trace Elements in Health
- Adrenal Hormones and Disorders
- Folate and B Vitamins Research
- Sexual Differentiation and Disorders
- Acute Myeloid Leukemia Research
- Drug Transport and Resistance Mechanisms
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Chemical Synthesis and Analysis
- Prenatal Screening and Diagnostics
- Venous Thromboembolism Diagnosis and Management
- Diagnosis and Treatment of Venous Diseases
- Neonatal Health and Biochemistry
- Acute Lymphoblastic Leukemia research
- Bone and Joint Diseases
- Hormonal Regulation and Hypertension
- Blood disorders and treatments
- Hormonal and reproductive studies
- Advanced MRI Techniques and Applications
- Metal complexes synthesis and properties
University College London
2016-2025
University College London Hospitals NHS Foundation Trust
2011-2025
Guy's and St Thomas' NHS Foundation Trust
2024
King's College Hospital NHS Foundation Trust
2024
University College Hospital
2010-2024
Diurnal (United Kingdom)
2016-2024
Royal London Hospital
2015-2024
University of London
1990-2023
Creighton University
2023
University of Arizona
2023
Background— The goal of this study was to determine the predictive value cardiac T2* magnetic resonance for heart failure and arrhythmia in thalassemia major. Methods Results— We analyzed liver serum ferritin 652 major patients from 21 UK centers with 1442 scans. relative risk values <10 ms (compared >10 ms) 160 (95% confidence interval, 39 653). Heart occurred 47% within 1 year a <6 270 64 1129). area under receiver-operating characteristic curve predicting significantly greater...
Measurement of myocardial iron is key to the clinical management patients at risk siderotic cardiomyopathy. The cardiovascular magnetic resonance relaxation parameter R2* (assessed clinically via its reciprocal, T2*) measured in ventricular septum used assess cardiac iron, but calibration and distribution data humans are limited.Twelve human hearts were studied from transfusion-dependent after either death (heart failure, n=7; stroke, n=1) or transplantation for end-stage heart failure...
Summary Heart failure from iron overload causes 71% of deaths in thalassaemia major, yet reversal siderotic cardiomyopathy has been reported. In order to determine the changes myocardial during treatment, we prospectively followed patients commencing intravenous desferrioxamine for iron‐induced a 12‐month period. Cardiovascular magnetic resonance assessments were performed at baseline, 3, 6 and 12 months included left ventricular (LV) function liver T2*, which is inversely related...
This aim of this statement is to report an expert consensus on the diagnosis and treatment cardiac dysfunction in β-thalassemia major (TM). does not cover other hemoglobinopathies, including thalassemia intermedia sickle cell anemia, which a different spectrum cardiovascular complications typical. There are considerable uncertainties field, with few randomized controlled trials relating chronic myocardial siderosis but none acute heart failure. The principles iron loading TM directly...
Background Following a clinical evaluation of deferasirox (Exjade) it was concluded that, in addition to baseline body iron burden, ongoing transfusional intake should be considered when selecting doses. The 1-year EPIC study, the largest ever investigation conducted for an chelator, is first evaluate whether fixed starting doses deferasirox, based on intake, with dose titration guided by serum ferritin trends and safety markers, provides clinically acceptable chelation patients (aged >or=2...
Patients with transfusion-dependent β-thalassemia need regular red-cell transfusions. Luspatercept, a recombinant fusion protein that binds to select transforming growth factor β superfamily ligands, may enhance erythroid maturation and reduce the transfusion burden (the total number of units transfused) in such patients.
Betibeglogene autotemcel (beti-cel) gene therapy for transfusion-dependent β-thalassemia contains autologous CD34+ hematopoietic stem cells and progenitor transduced with the BB305 lentiviral vector encoding β-globin (βA-T87Q) gene.In this open-label, phase 3 study, we evaluated efficacy safety of beti-cel in adult pediatric patients a non-β0/β0 genotype. Patients underwent myeloablation busulfan (with doses adjusted on basis pharmacokinetic analysis) received intravenously. The primary end...
Beta-thalassemia and particularly its transfusion-dependent form (TDT) is a demanding clinical condition, requiring life-long care follow-up, ideally in specialized centers by multidisciplinary teams of experts. Despite the significant progress TDT diagnosis treatment over past decades that has dramatically improved patients’ prognosis, management remains challenging. On one hand, diagnostic therapeutic advances are not equally applied to all patients across world, several high-prevalence...
Blood transfusion therapy is life-saving for patients with beta-thalassaemia and sickle cell disease (SCD), but often results in severe iron overload. This pilot study examined whether the biomarkers of tissue injury or inflammation differ these two diseases. Plasma malondialdehyde (MDA) was significantly increased 1.8-fold thalassaemia relative to control patients. In contrast, MDA SCD not different from controls. multivariate analysis, strongest predictors elevated were liver concentration...
Summary Deferasirox is a once‐daily, oral iron chelator developed for treating transfusional overload. Preclinical studies indicated that the kidney was potential target organ of toxicity. As patients with sickle cell disease often have abnormal baseline renal function, primary objective this randomised, open‐label, phase II trial to evaluate safety and tolerability deferasirox in comparison deferoxamine population. Assessment efficacy, as measured by change liver concentration (LIC) using...
Abstract Objectives/methods: This 1‐yr prospective phase II trial evaluated the efficacy of deferasirox in regularly transfused patients aged 3–81 yrs with myelodysplastic syndromes (MDS; n = 47), Diamond–Blackfan anaemia (DBA; 30), other rare anaemias ( 22) or β‐thalassaemia 85). Dosage was determined by baseline liver iron concentration (LIC). Results: In LIC ≥7 mg Fe/g dry weight, initiated at 20 30 mg/kg/d produced statistically significant decreases P < 0.001); these were greatest...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis, physicochemical properties, and biological evaluation of N-substituted 2-alkyl-3-hydroxy-4(1H)-pyridinones: orally active iron chelators with clinical potentialPaul S. Dobbin, Robert C. Hider, Adrian D. Hall, Paul Taylor, Patience Sarpong, John B. Porter, Gaoyi Xiao, Dick van der HelmCite this: J. Med. Chem. 1993, 36, 17, 2448–2458Publication Date (Print):August 1, 1993Publication History Published online1 May 2002Published inissue 1...
There is a need to standardise non-invasive measurements of liver iron concentrations (LIC) so clear inferences can be drawn about body levels that are associated with hepatic and extra-hepatic complications overload. Since the first demonstration an inverse relationship between biopsy LIC magnetic resonance (MR) using proof-of-concept T2* sequence, MR technology has advanced dramatically shorter minimum echo-time, closer inter-echo spacing constant repetition time. These important advances...
Levels of circulating red blood cell (RBC)-derived vesicles are increased in sickle anaemia (SCA) and thalassaemia intermedia (TI) but the mechanisms, effects controlling factors may differ. This study found that levels intravascular haemolysis were linked as shown by correlation between plasma Hb. Vesicle 6-fold greater SCA 4-fold TI than controls. The proportion Hb within was with a significantly higher TI. We examined whether subpopulations RBC expressing phosphatidylserine (PS) source...