Accurate evaluation of iron overload is necessary to establish the diagnosis of hemochromatosis and guide chelation treatment in transfusion-dependent anemia. The liver is the primary site for iron storage in patients...Accurate evaluation of iron overload is necessary to establish the diagnosis of hemochromatosis and guide chelation treatment in transfusion-dependent anemia. The liver is the primary site for iron storage in patients with hemochromatosis or transfusion-dependent anemia, therefore, liver iron concentration (LIC) accurately re? ects total body iron stores. In the past 20 years, magnetic resonance imaging (MRI) has emerged as a promising method for measuring LIC in a variety of diseases. We review the potential role of MRI in LIC determination in the most important disorders that are characterized by iron overload, that is, thalassemia major, other hemoglobinopathies, acquired anemia, and hemochromatosis. Most studies have been performed in thalassemia major and MRI is currently a widely accepted method for guiding chelation treatment in these patients. However, the lack of correlation between liver and cardiac iron stores suggests that both organs should be evaluated with MRI, since cardiac disease is the leading cause of death in this population. It is also unclear which MRI method is the most accurate since there are no large studies that have directly compared the different available techniques. The role of MRI in the era of genetic diagnosis of hemochromatosis is also debated, whereas data on the accuracy of the method in other hematological and liver diseases are rather limited. However, MRI is a fast, non-invasive and relatively accurate diagnostic tool for assessing LIC, and its use is expected to increase as the role of iron in the pathogenesis of liver disease becomes clearer.展开更多
Iron is essential for all organisms including microbial,cancer and human cells. More than a quarter of the human population is affected by abnormalities of iron metabolism, mainly from iron deficiency and iron overloa...Iron is essential for all organisms including microbial,cancer and human cells. More than a quarter of the human population is affected by abnormalities of iron metabolism, mainly from iron deficiency and iron overload. Iron also plays an important role in free radical pathology and oxidative damage which is observed in almost all major diseases, cancer and ageing. New developments include the complete treatment of iron overload and reduction of morbidity and mortality in thalassaemia using deferiprone and selected deferiprone/deferoxamine combinations and also the use of the maltol iron complex in the treatment of iron deficiency anaemia. There is also a prospect of using deferiprone as a universal antioxidant in non iron overloaded diseases such as neurodegenerative, cardiovascular, renal, infectious diseases and cancer. New regulatory molecules of iron metabolism such as endogenous and dietary chelating molecules, hepcidin, mitochondrial ferritin and their role in health and disease is under evaluation. Similarly, new mechanisms of iron deposition, removal, distribution and toxicity have been identified using new techniques such as magnetic resonance imaging increasing our understanding of iron metabolic processes and the targeted treatment of related diseases. The uniform distribution of iron in iron overload between organs and within each organ is no longer valid. Several other controversies such as the toxicity impact of non transferrin bound iron vs injected iron, the excess levels of iron in tissues causing toxicity and the role of chelation on iron absorption need further investigation. Commercial interests of pharmaceutical companies and connections to leading journals are playing a crucial role in shaping worldwide medical opinion on drug sales and use but also patients' therapeutic outcome and safety. Major controversies include the selection criteria and risk/benefit assessment in the use of deferasirox in thalassaemia and more so in idiopathic haemochromatosis, thalassaemia intermedia and ex-thalass展开更多
Thalassaemia major(TM) and Friedreich's ataxia(FA) are autosomal recessive inherited diseases related to the proteins haemoglobin and frataxin respectively. In both diseases abnormalities in iron metabolism is the...Thalassaemia major(TM) and Friedreich's ataxia(FA) are autosomal recessive inherited diseases related to the proteins haemoglobin and frataxin respectively. In both diseases abnormalities in iron metabolism is the main cause of iron toxicity leading to increased morbidity and mortality. Major efforts are directed towards the prevention of these diseases and also in their treatment using iron chelation therapy. Both TM and FA are endemic in Cyprus, where the frequency per total population of asymptomatic heterozygote carriers and patients is the highest worldwide. Cyprus has been a pioneering nation in preventing and nearly eliminating the birth of TM and FA patients by introducing an organized health structure, including prenatal and antenatal diagnosis. Effective iron chelation therapy, improved diagnostic methods and transfusion techniques as well as supportive therapy from other clinical specializations have improved the survival and quality of life of TM patients.Despite the tiresome clinical management regimes many TM patients are successful in their professional lives, have families with children and some are now living well into their fifties. The introduction of deferiprone led to the elimination of cardiac failure induced by iron overload toxicity, which was the major cause of mortality in TM. Effective combinations of deferiprone with deferoxamine in TM patients caused the fall of body iron to normal physiological ranges. In FA different mechanisms of iron metabolism and toxicity apply to that of TM, which can be targeted with specific iron chelation protocols. Preliminary findings from the introduction of deferiprone in FA patients have increased the hopes for improved and effective therapy in this untreatable condition. New and personalised treatments are proposed in TM and FA. Overall, advances in treatments and in particular of chelation therapy using deferiprone are transforming TM and FA from fatal to chronic conditions. The paradigm of Cyprus in the prevention and treatment of TM can be used for 展开更多
According to global annual estimates hunger/malnutrition is the major cause of death(36 of 62 million). Cardiovascular diseases and cancer(5.44 of 13.43 million) are the major causes of death in developed countries, w...According to global annual estimates hunger/malnutrition is the major cause of death(36 of 62 million). Cardiovascular diseases and cancer(5.44 of 13.43 million) are the major causes of death in developed countries, while lower respiratory tract infections, human immunodeficiency virus infection/acquired immunodeficiency syndrome, diarrhoeal disease, malaria and tuberculosis(10.88 of 27.12 million) are the major causes of death in developing countries with more than 70% of deaths occurring in children. The majority of approximately 800 million people with other rare diseases, including 100000 children born with thalassaemia annually receive no treatment. There are major ethical dilemmas in dealing with global health issues such as poverty and the treatment of orphan and rare diseases. Of approximately 50000 drugs about 10% are orphan drugs, with annual sales of the latter approaching 100 billion USD. In comparison, the annual revenue in 2009 from the top 12 pharmaceutical companies in Western countrieswas 445 billion USD and the top drug, atorvastatin, reached 100 billion USD. In the same year, the total government expenditure for health in the developing countries was 410 billion USD with only 6%-7% having been received as aid from developed countries. Drugs cost the National Health Service in the United Kingdom more than 20 billion USD or 10% of the annual health budget. Uncontrollable drug prices and marketing policies affect global health budgets, clinical practice, patient safety and survival. Fines of 5.3 billion USD were imposed on two pharmaceutical companies in the United States, the regulatory authority in France was replaced and clinicians were charged with bribery in order to overcome recent illegal practises affecting patient care. High expenditure for drug development is mainly related to marketing costs. However, only 2 million USD was spent developing the drug deferiprone(L1) for thalassaemia up to the stage of multicentre clinical trials. The criteria for drug development, price levels and use ne展开更多
目的总结去铁酮(DFP)引起重型β地中海贫血(β-TM)患儿粒细胞缺乏的临床表现,提高对该类副作用的临床认识。方法回顾1例重型β地中海贫血患儿因口服去铁酮引起粒细胞缺乏的相关资料,并进行文献复习。结果女性患儿,7岁1月,因重型β地中...目的总结去铁酮(DFP)引起重型β地中海贫血(β-TM)患儿粒细胞缺乏的临床表现,提高对该类副作用的临床认识。方法回顾1例重型β地中海贫血患儿因口服去铁酮引起粒细胞缺乏的相关资料,并进行文献复习。结果女性患儿,7岁1月,因重型β地中海贫血予输血治疗,5周前开始口服去铁酮片除铁治疗,6d前出现反复发热、咳嗽,血常规检查提示粒细胞缺乏,给予抗感染、抗真菌、重组人粒细胞刺激因子等治疗,好转出院。系统检索中国生物医学文献数据库、中国知网、万方数据库、Pubmed、Embase、Web of Science数据库,共8例儿童β-TM因口服DFP致粒细胞缺乏的报道,均为英文文献。9例患儿(含本例)均表现发热,粒细胞缺乏持续1周以上,其中5例发生在服用去铁酮半年内。经积极治疗后均好转出院。结论粒细胞缺乏是去铁酮的严重不良反应,用药前半年内应密切监测粒细胞情况;发现粒细胞缺乏时立即停用去铁酮,并应避免再次使用去铁酮进行除铁治疗。展开更多
文摘Accurate evaluation of iron overload is necessary to establish the diagnosis of hemochromatosis and guide chelation treatment in transfusion-dependent anemia. The liver is the primary site for iron storage in patients with hemochromatosis or transfusion-dependent anemia, therefore, liver iron concentration (LIC) accurately re? ects total body iron stores. In the past 20 years, magnetic resonance imaging (MRI) has emerged as a promising method for measuring LIC in a variety of diseases. We review the potential role of MRI in LIC determination in the most important disorders that are characterized by iron overload, that is, thalassemia major, other hemoglobinopathies, acquired anemia, and hemochromatosis. Most studies have been performed in thalassemia major and MRI is currently a widely accepted method for guiding chelation treatment in these patients. However, the lack of correlation between liver and cardiac iron stores suggests that both organs should be evaluated with MRI, since cardiac disease is the leading cause of death in this population. It is also unclear which MRI method is the most accurate since there are no large studies that have directly compared the different available techniques. The role of MRI in the era of genetic diagnosis of hemochromatosis is also debated, whereas data on the accuracy of the method in other hematological and liver diseases are rather limited. However, MRI is a fast, non-invasive and relatively accurate diagnostic tool for assessing LIC, and its use is expected to increase as the role of iron in the pathogenesis of liver disease becomes clearer.
文摘Iron is essential for all organisms including microbial,cancer and human cells. More than a quarter of the human population is affected by abnormalities of iron metabolism, mainly from iron deficiency and iron overload. Iron also plays an important role in free radical pathology and oxidative damage which is observed in almost all major diseases, cancer and ageing. New developments include the complete treatment of iron overload and reduction of morbidity and mortality in thalassaemia using deferiprone and selected deferiprone/deferoxamine combinations and also the use of the maltol iron complex in the treatment of iron deficiency anaemia. There is also a prospect of using deferiprone as a universal antioxidant in non iron overloaded diseases such as neurodegenerative, cardiovascular, renal, infectious diseases and cancer. New regulatory molecules of iron metabolism such as endogenous and dietary chelating molecules, hepcidin, mitochondrial ferritin and their role in health and disease is under evaluation. Similarly, new mechanisms of iron deposition, removal, distribution and toxicity have been identified using new techniques such as magnetic resonance imaging increasing our understanding of iron metabolic processes and the targeted treatment of related diseases. The uniform distribution of iron in iron overload between organs and within each organ is no longer valid. Several other controversies such as the toxicity impact of non transferrin bound iron vs injected iron, the excess levels of iron in tissues causing toxicity and the role of chelation on iron absorption need further investigation. Commercial interests of pharmaceutical companies and connections to leading journals are playing a crucial role in shaping worldwide medical opinion on drug sales and use but also patients' therapeutic outcome and safety. Major controversies include the selection criteria and risk/benefit assessment in the use of deferasirox in thalassaemia and more so in idiopathic haemochromatosis, thalassaemia intermedia and ex-thalass
文摘Thalassaemia major(TM) and Friedreich's ataxia(FA) are autosomal recessive inherited diseases related to the proteins haemoglobin and frataxin respectively. In both diseases abnormalities in iron metabolism is the main cause of iron toxicity leading to increased morbidity and mortality. Major efforts are directed towards the prevention of these diseases and also in their treatment using iron chelation therapy. Both TM and FA are endemic in Cyprus, where the frequency per total population of asymptomatic heterozygote carriers and patients is the highest worldwide. Cyprus has been a pioneering nation in preventing and nearly eliminating the birth of TM and FA patients by introducing an organized health structure, including prenatal and antenatal diagnosis. Effective iron chelation therapy, improved diagnostic methods and transfusion techniques as well as supportive therapy from other clinical specializations have improved the survival and quality of life of TM patients.Despite the tiresome clinical management regimes many TM patients are successful in their professional lives, have families with children and some are now living well into their fifties. The introduction of deferiprone led to the elimination of cardiac failure induced by iron overload toxicity, which was the major cause of mortality in TM. Effective combinations of deferiprone with deferoxamine in TM patients caused the fall of body iron to normal physiological ranges. In FA different mechanisms of iron metabolism and toxicity apply to that of TM, which can be targeted with specific iron chelation protocols. Preliminary findings from the introduction of deferiprone in FA patients have increased the hopes for improved and effective therapy in this untreatable condition. New and personalised treatments are proposed in TM and FA. Overall, advances in treatments and in particular of chelation therapy using deferiprone are transforming TM and FA from fatal to chronic conditions. The paradigm of Cyprus in the prevention and treatment of TM can be used for
文摘According to global annual estimates hunger/malnutrition is the major cause of death(36 of 62 million). Cardiovascular diseases and cancer(5.44 of 13.43 million) are the major causes of death in developed countries, while lower respiratory tract infections, human immunodeficiency virus infection/acquired immunodeficiency syndrome, diarrhoeal disease, malaria and tuberculosis(10.88 of 27.12 million) are the major causes of death in developing countries with more than 70% of deaths occurring in children. The majority of approximately 800 million people with other rare diseases, including 100000 children born with thalassaemia annually receive no treatment. There are major ethical dilemmas in dealing with global health issues such as poverty and the treatment of orphan and rare diseases. Of approximately 50000 drugs about 10% are orphan drugs, with annual sales of the latter approaching 100 billion USD. In comparison, the annual revenue in 2009 from the top 12 pharmaceutical companies in Western countrieswas 445 billion USD and the top drug, atorvastatin, reached 100 billion USD. In the same year, the total government expenditure for health in the developing countries was 410 billion USD with only 6%-7% having been received as aid from developed countries. Drugs cost the National Health Service in the United Kingdom more than 20 billion USD or 10% of the annual health budget. Uncontrollable drug prices and marketing policies affect global health budgets, clinical practice, patient safety and survival. Fines of 5.3 billion USD were imposed on two pharmaceutical companies in the United States, the regulatory authority in France was replaced and clinicians were charged with bribery in order to overcome recent illegal practises affecting patient care. High expenditure for drug development is mainly related to marketing costs. However, only 2 million USD was spent developing the drug deferiprone(L1) for thalassaemia up to the stage of multicentre clinical trials. The criteria for drug development, price levels and use ne
文摘目的总结去铁酮(DFP)引起重型β地中海贫血(β-TM)患儿粒细胞缺乏的临床表现,提高对该类副作用的临床认识。方法回顾1例重型β地中海贫血患儿因口服去铁酮引起粒细胞缺乏的相关资料,并进行文献复习。结果女性患儿,7岁1月,因重型β地中海贫血予输血治疗,5周前开始口服去铁酮片除铁治疗,6d前出现反复发热、咳嗽,血常规检查提示粒细胞缺乏,给予抗感染、抗真菌、重组人粒细胞刺激因子等治疗,好转出院。系统检索中国生物医学文献数据库、中国知网、万方数据库、Pubmed、Embase、Web of Science数据库,共8例儿童β-TM因口服DFP致粒细胞缺乏的报道,均为英文文献。9例患儿(含本例)均表现发热,粒细胞缺乏持续1周以上,其中5例发生在服用去铁酮半年内。经积极治疗后均好转出院。结论粒细胞缺乏是去铁酮的严重不良反应,用药前半年内应密切监测粒细胞情况;发现粒细胞缺乏时立即停用去铁酮,并应避免再次使用去铁酮进行除铁治疗。
