Iron-chelating therapy and the treatment of thalassemia
TL;DR: The toxicity of this agent mandates a careful evaluation of the balance between risk and benefit of deferiprone in patients with thalassemia, in most of whom long-term deferoxamine is safe and efficacious therapy.
About: This article is published in Blood.The article was published on 1997-02-01 and is currently open access. It has received 1050 citations till now. The article focuses on the topics: Thalassemia & Anemia.
Citations
More filters
TL;DR: Survival and complication-free survival of patients with thalassemia major continue to improve, especially for female patients born shortly before or after the availability of iron chelation.
Abstract: BACKGROUND AND OBJECTIVES: Seven Italian centers reported data on survival, causes of death and appearance of complications in patients with thalassemia major. The interactions between gender, birth cohort, complications, and ferritin on survival and complications were analyzed. DESIGN AND METHODS: Survival after the first decade was studied for 977 patients born since 1960 whereas survival since birth and complication appearance was studied for the 720 patients born after 1970. Better survival was demonstrated for patients born in more recent years (p<0.00005) and for females (p=0.0003); 68% of the patients are alive at the age of 35 years. In the entire population 67% of the deaths were due to heart disease. RESULTS: There was a significant association between birth cohort and complication-free survival (p<0.0005). The prevalence of complications was: heart failure 6.8%, arrhythmia 5.7%, hypogonadism 54.7%, hypothyroidism 10.8%, diabetes 6.4%, HIV infection 1.7%, and thrombosis 1.1%. Lower ferritin levels were associated with a lower probability of heart failure (hazard ratio =3.35, p<0.005) and with prolonged survival (hazard ratio = 2.45, p<0.005), using a cut-off as low as 1,000 ng/mL. INTERPRETATION AND CONCLUSIONS: Survival and complication-free survival of patients with thalassemia major continue to improve, especially for female patients born shortly before or after the availability of iron chelation.
1,064 citations
Cites background from "Iron-chelating therapy and the trea..."
...In fact, ferritin, being an acute phase reactant, is increased in chronic disease, malignancy, or inflammatory disorders, and in the presence of increased erythropoietin.(24) Ascorbic acid deficiency can lead to decreased synthesis and release of ferritin, even in the presence of massive iron stores....
[...]
TL;DR: Both R2 and R2* can accurately measure hepatic iron concentration throughout the clinically relevant range of HIC with appropriate MRI acquisition techniques, despite significant differences in technique and instrumentation.
883 citations
TL;DR: A full appreciation of folate's history as a public health issue, its biology, and an overview of available biomarkers and their interpretation across a range of clinical and population-based uses are provided.
Abstract: The Biomarkers of Nutrition for Development (BOND) project is designed to provide evidence-based advice to anyone with an interest in the role of nutrition in health. Specifically, the BOND program provides state-of-the-art information and service with regard to selection, use, and interpretation of biomarkers of nutrient exposure, status, function, and effect. To accomplish this objective, expert panels are recruited to evaluate the literature and to draft comprehensive reports on the current state of the art with regard to specific nutrient biology and available biomarkers for assessing nutrients in body tissues at the individual and population level. Phase I of the BOND project includes the evaluation of biomarkers for 6 nutrients: iodine, iron, zinc, folate, vitamin A, and vitamin B-12. This review represents the second in the series of reviews and covers all relevant aspects of folate biology and biomarkers. The article is organized to provide the reader with a full appreciation of folate's history as a public health issue, its biology, and an overview of available biomarkers (serum folate, RBC folate, and plasma homocysteine concentrations) and their interpretation across a range of clinical and population-based uses. The article also includes a list of priority research needs for advancing the area of folate biomarkers related to nutritional health status and development.
813 citations
TL;DR: This study presents a readily available noninvasive method of measuring and imaging LICs in vivo using clinical 1.5-T magnetic resonance imaging units and revealed high degrees of sensitivity and specificity of R2 to biopsy LICs at the clinically significant LIC thresholds.
810 citations
TL;DR: This review focuses on the evolution of iron chelators from initial lead compounds through to the development of novel chelating agents, many of which show great potential to be clinically applied in the treatment of iron overload disease and cancer.
Abstract: The evolution of iron chelators from a range of primordial siderophores and aromatic heterocyclic ligands has lead to the formation of a new generation of potent and efficient iron chelators. For example, various siderophore analogs and synthetic ligands, including ICL670A [4-[3,5-bis-(hydroxyphenyl)-1,2,4-triazol-1-yl]-benzoic acid], 4'-hydroxydesazadesferrithiocin, and Triapine, have been developed from predecessors and illustrate potent iron-mobilizing or antineoplastic activities. This review focuses on the evolution of iron chelators from initial lead compounds through to the development of novel chelating agents, many of which show great potential to be clinically applied in the treatment of iron overload disease and cancer.
690 citations
Cites background from "Iron-chelating therapy and the trea..."
...One study monitoring the safety of long-term deferiprone administration found a worsening of liver fibrosis in thalassemia patients (Olivieri et al., 1998)....
[...]
References
More filters
5,223 citations
TL;DR: Using linkage-disequilibrium and full haplotype analysis, this paper identified a 250-kilobase region more than 3 megabases telomeric of the major histocompatibility complex (MHC) that is identical-by-descent in 85% of patient chromosomes.
Abstract: Hereditary haemochromatosis (HH), which affects some 1 in 400 and has an estimated carrier frequency of 1 in 10 individuals of Northern European descent, results in multi-organ dysfunction caused by increased iron deposition, and is treatable if detected early. Using linkage-disequilibrium and full haplotype analysis, we have identified a 250-kilobase region more than 3 megabases telomeric of the major histocompatibility complex (MHC) that is identical-by-descent in 85% of patient chromosomes. Within this region, we have identified a gene related to the MHC class I family, termed HLA-H, containing two missense alterations. One of these is predicted to inactivate this class of proteins and was found homozygous in 83% of 178 patients. A role of this gene in haemochromatosis is supported by the frequency and nature of the major mutation and prior studies implicating MHC class I-like proteins in iron metabolism.
3,477 citations
Journal Article•
TL;DR: Using linkage–disequilibrium and full haplotype analysis, a region more than 3 megabases telomeric of the major histocompatibility complex (MHC) that is identical–by–descent in 85% of patient chromosomes is identified, containing a gene related to the MHC class I family, termed HLA–H, containing two missense alterations.
3,420 citations
Book•
01 Jan 1972TL;DR: This short review of free radicals discusses certain types of free radical, such as nitroxyl-radicals and free radicals stabilized by steric or derealization features, which are stable enough to be crystallised and stored at temperatures above 0°.
Abstract: Free radicals are molecules or molecular fragments containing a single unpaired electron. In general, free radicals are reactive chemically, some (e.g. HO•) being extremely reactive. However, certain types of free radical, such as nitroxyl-radicals and free radicals stabilized by steric or derealization features, are much less reactive and a few (e.g. diphenyl picryl hydrazyl) are stable enough to be crystallised and stored at temperatures above 0°. Table 1 gives the general structures of free radicals that will be discussed in this short review.
1,643 citations
TL;DR: In a group of patients seen at a referral center, chronic post-transfusion hepatitis C was a progressive disease and, in some patients, led to death from either liver failure or hepatocellular carcinoma.
Abstract: Background The extent of serious complications in people who have acquired chronic hepatitis C after a blood transfusion is unclear. Methods We studied 131 patients with chronic post-transfusion hepatitis C who were referred to our center between February 1980 and June 1994. Eighty-two other patients were excluded because they had multiple transfusions, hemophilia, intravenous drug use, human immunodeficiency virus infection, hepatitis B infection, hemochromatosis, or alcoholic liver disease. Liver biopsies were performed in 101 patients; biopsies were not performed in the other 30 patients, all with signs of cirrhosis, because the results of coagulation tests were abnormal. Results The mean age of the patients was 57 years (range, 21 to 81) at the time of our initial evaluation. The mean age at the time of the blood transfusion was 35 years (range, 1 to 76). The mean duration of follow-up after presentation to us was 3.9 years (range, 1 to 15). Eighty-eight of the patients (67.2 percent) initially had fa...
1,188 citations