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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Laser microprobe mass analysis (LAMMA) is an investigational method which is a powerful tool for the identification and quantitation of various elements present in small volumes of tissue. LAMMA is highly sensitive and capable of rapidly detecting concentrations of 1-3 p.p.m. of most metallic elements, in precisely localized cellular compartments. In order to further assess its value, cultured skin fibroblasts and biopsy tissues from human subjects and experimental animals were probed by LAMMA, and the results were correlated with ultrastructural findings. Biopsy samples were obtained from patients suffering from Gaucher disease, and from patients and animals with pathologic iron or copper metabolism. No significant abnormalities were detected in the cultured fibroblasts from patients with Gaucher disease, in contrast to the iron content of tissue biopsy Gaucher cells, which was markedly increased, apparently as a consequence of erythrophagocytosis. Particularly intense iron-related peaks were found in liver cytosiderosis due to neonatal or genetic haemochromatosis, thalassaemia major and in animal models of iron overload. An additional finding was the presence of aluminium accumulation in siderosomes of different cells. In liver biopsy samples from human Wilson's disease and from rats with an inherited disorder causing copper toxicosis, copper-containing compounds were identified and localized, and their relative concentration was estimated by LAMMA. The present study showed that LAMMA is a valuable technique for the localization and estimation of relative abundance of trace elements in various tissues containing excessive amounts of metals.
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PMID:The application of laser microprobe mass analysis to the study of biological material. 857 93

Iron deposition occurs in parenchymal cells of the liver in two major defects in human subjects (i) in primary iron overload (genetic haemochromatosis) and (ii) secondary to anaemias in which erythropolesis is increased (thalassaemia). Transfusional iron overload results in excessive storage primarily in cells of the reticule endothelial system. The storage patterns in these situations are quite characteristic. Excessive iron storage, particularly in parenchymal cells eventually results in fibrosis and cirrhosis. There is no animal model or iron overload which completely mimics genetics haemochromatosis but dietary iron loading with carbonyl iron or ferrocene does produce excessive parenchymal iron stores in the rat. Such models have been used to study iron toxicity and the action of iron chelators in the effective removal of excessive iron stores.
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PMID:Hepatic iron deposition in human disease and animal models. 874 2

A number of studies have shown that regular chelation therapy with deferoxamine is effective in patients with secondary hemochromatosis. However, compliance with these regimen is difficult to obtain in most cases because long-term administration is burdensome. In 3 patients, one each with myelodysplastic syndrome, aplastic anemia and thalassemia intermedia, self-administered subcutaneous one-shot administration of deferoxamine at a dose of 500 mg once or twice daily was carried out over a long period. In all three patients serum ferritin level decreased significantly and the progression of hemochromatosis was prevented. Liver density on computed tomography scan also decreased in one patient. This regimen, in which the patient self-administered deferoxamine subcutaneously one or twice a day is seems to be the most practical method to protect against the progression of hemochromatosis.
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PMID:[Long-term efficacy of subcutaneous administration of deferoxamine in patients with secondary hemochromatosis]. 884

Regular blood transfusions in patients with beta-thalassaemia major lead to secondary hemochromatosis in the majority of cases. As a consequence of chronic iron overload, many endocrinopathies may occur. The most frequent endocrine dysfunction is hypogonadotropic hypogonadism, which is mainly responsible for osteopenia in as much as 80% of thalassemic patients. The frequencies of other endocrine disorders (hypothyroidism, diabetes mellitus and hypoparathyroidism) are lower. We investigated 5 female patients aged 22-25 years for endocrine dysfunction and bone density. All presented with hypogonadotropic hypogonadism and amenorrhea (four primary and one secondary). 4 patients showed absent or delayed pubertal development and short stature (below 10th percentile). In all five, hypogonadism is the most relevant cause of osteopenia as demonstrated by osteodensitometry. Endocrine disorders, especially absent pubertal development, should be detected in good time and treated with hormonal replacement. Established osteopenia is treated hormonally and with vitamin D3 and calcium.
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PMID:[Osteopenia in beta-thalassemia major]. 898 99

Transfusional iron overload leading to cardiopathy and other severe complications continues to be a major problem in chronically transfused homozygous beta-thalassaemia patients. It is well known that young red cells (neocytes) survive longer after transfusion and therefore may contribute to the extension of the intervals between transfusions. We evaluated the impact of neocytes in the total annual blood requirements and consequently the transfusional iron load in 18 thalassaemia patients. A two-period study comparing transfusions of standard red cells versus neocytes in the same group of patients was performed. Neocytes were harvested by density separation using the Neocel System. The method of preparation was simple with relatively low costs and required no special equipment. There was a significant difference (p < 0.005) in PK and MCV values of the neocyte and older red cell (gerocyte) fractions indicating that a good separation of the two populations was achieved. All patients had a reduction in blood requirements during the neocyte period. The total annually transfused red blood cells and concomitant iron blood load were significantly reduced (p < 0.001) by 20.2 +/- 9.1%. However, the response was variable. Seven of the 18 patients had a large reduction in blood consumption (24.8-34.8%), 9 others ranged between 10.7 and 21.6%, and in 2 the reduction was less than 10%. This reduction in blood requirements and in the transfused iron may change the chelation index resulting in more efficient iron chelation therapy and perhaps reduce the cost of the haemochromatosis therapy on a long-term basis. We conclude that the use of neocyte therapy using this system can benefit the majority of chronically transfused patients by reducing transfusional iron overload and related complications and may lead to a much better quality of life.
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PMID:The impact of neocyte transfusion in the management of thalassaemia. 912 27

Few reports exist concerning heart transplantation in recipients with end-stage myocardiopathy-associated heart failure caused by iron overload occurring with beta-thalassaemia, Diamond-Blackfan syndrome or haemochromatosis. Seven potential transplant candidates (six male, one female, mean age 26 years) with such heart failure, following desferrioxamine application subcutaneously over a number of years, and intravenously during their hospitalization before transplantation, were retrospectively analysed. Five were New York Heart Association (NYHA) class IV, three experienced one or more resuscitations immediately before transplantation could be performed. Continuous, high-volume, veno-venous haemofiltration was necessary in two patients. One of these two candidates additionally had to be bridged, first with a right ventricular, then with a biventricular assist device. Five of the seven patients survived, two with haemochromatosis, one with beta-thalassaemia major and one with Diamond-Blackfan syndrome following transplantation. One non-transplanted candidate with beta-thalassaemia major has been recompensated for 5 years. Survival was 14-74 months. Our results demonstrate the feasibility and indication of transplantation in patients with such heart failure and the satisfying outcome of immunosuppression is described.
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PMID:Heart transplantation for end-stage heart failure caused by iron overload. 916 90

Iron overload caused by lifelong transfusion-dependent anaemias, such as beta-thalassaemia major, usually results in lethal cardiac toxicity in the second decade of life if not treated by iron chelation. There is no physiological mechanism for excreting the excess iron accumulated from blood transfusions and, unlike hereditary haemochromatosis, venesection is not an option. Therefore, chelation therapy is the only way to remove excess iron. This must be removed while not depriving cells of the essential iron needed for normal metabolism. Additionally, the iron chelator must prevent iron from participating in the generation of harmful free radicals. Parenteral chelation therapy with deferoxamine (desferrioxamine) is well established as promoting negative iron balance, reversing cardiac toxicity, and prolonging life expectancy well into the fourth decade of life and, most likely, beyond. Unfortunately, poor compliance with the rigours of parenteral treatment in a minority of patients limits its regular use, resulting in reduced life expectancy in these patients. Use of deferoxamine in excessive dosages may result in growth retardation, sensorineural ototoxicity and ocular toxicity, as well as bone deformities. These effects can be largely avoided if the dosage is adjusted to take account of the degree of iron overload (using the therapeutic index) and if the mean daily dose does not exceed 40 mg/kg. Nevertheless, it is recommended that patients be regularly monitored for such adverse effects. Deferiprone (L1; CP20) is an orally absorbed bidentate hydroxypyridinone iron chelator that can induce urinary iron excretion, promote negative iron balance and reduce hepatic iron levels in some transfusion-dependent patients, particularly in those who are markedly iron overloaded and have not received regular deferoxamine therapy. The long term efficacy and toxicity of deferiprone are the subjects of some controversy, and the published results of randomised controlled trials are awaited. Preliminary results suggest that when currently recommended dosages of deferiprone (75 mg/kg/day) are used, hepatic iron settles at levels that still put most patients at an increased risk from iron overload. A number of adverse effects may occur, and require cessation of therapy in up to 30% of patients. These effects include arthritis, nausea and (most seriously) agranulocytosis in 0.6 to 4% of patients. The risk of the latter complication means that frequent white blood cell counts are mandatory for patients taking this drug. There remains an urgent need to identify an orally active chelator regimen that is as effective as deferoxamine and has an acceptable degree of tolerability.
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PMID:A risk-benefit assessment of iron-chelation therapy. 942 39

Iron deficiency affects approx. 20% of the world population. Due to predominantly vegetarian diets that reduce the bioavailability of food iron drastically, deficiency states are most widely distributed in developing countries. In addition, iron demand is increased by blood losses and by fast growth which increases the risk of iron deficiency in infants, young adolescents, and in menstruating and pregnant women. The symptoms of iron deficiency include impaired physical and intellectual performance. Iron supplementation may help to break the vicious cycle between inadequate nutrition and poverty. Fortification programs have to consider social and health aspects, including provision against iron overload. Excess iron stores may promote cancer and increase the cardiovascular risk, though the latter is a subject of current debate. The best approach to control such risks is individual iron supplementation geared to the demand by adequate laboratory controls. However, this approach is too costly for general application in developing countries. Food-iron fortification has successfully reduced iron deficiency in many trials and, in comparison, is much cheaper. As iron deficiency is widely distributed in most developing countries, the risk of inducing iron overload in the general population is low. Genetically determined diseases that may lead to siderosis, such as hereditary haemochromatosis or thalassaemia major, show a limited geographic and ethnic distribution. Such subgroups can be largely avoided by targeting food-iron fortification to infants, young adolescents, or pregnant women. Food vehicle and iron compound have to be matched in order to optimise iron bioavailability and to avoid rancidity in food, spoiling its taste and odour. The fortification of salt, sugar and spice mixtures or of bakery products with a short shelf-life are valid approaches to this end. Alternatively, haem iron can be used to fortify cereal-based food staples in developing countries such as tortillas or chappaties. Thus, a variety of options is available to solve the technical problems of food iron fortification. However, optimal solutions have to be tailored to the individual situation in each country.
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PMID:Iron supplementation. 985 25

Iron overload is the main cause of morbidity and mortality in patients with thalassaemia major. In order to establish if the presence of the mutations recently described in the haemochromatosis gene affects the severity of iron overload in thalassaemia patients, we compared the prevalence of mutations C282Y and H63D in 216 young adults regularly transfused and chelated in North-Eastern Italy with the frequency found in a group of blood donors from the same area. For each patient, mean serum ferritin over the last 3 years, liver iron concentration, and the presence of diabetes, hypogonadism and heart disease, were considered. The frequency of the C282Y allele was 1.9% in patients with thalassaemia major and 2.3% in blood donors (P=ns). The frequency of the H63D allele was 16.2% in patients with thalassaemia major and 15.3% in blood donors (P=ns). When age, liver iron concentration and mean yearly serum ferritin levels were compared in patients with and without mutations C282Y and H63D, no significant differences were found. Also, the prevalence of iron-induced complications was not significantly different between patients carrying or not carrying the mutations. The presence of the HH mutations does not seem to influence the degree of iron overload and its consequences in regularly transfused and chelated patients with thalassaemia major.
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PMID:The haemochromatosis mutations do not modify the clinical picture of thalassaemia major in patients regularly transfused and chelated. 985 37

The correction of anemia in patients with chronic renal failure (CRF) has become the most important application of recombinant human erythropoietin (rHuEpo). The merits of rHuEpo therapy in patients with CRF are overt. Firstly, patients with CRF have an absolute deficiency in endogenous erythropoietin production and a relatively low maintenance dose of rHuEpo (often less than 100 IU/kg body weight per week) is effective in avoiding regular transfusions in the majority of the patients with CRF. Secondly, rHuEpo is able to avoid long-term complications of frequent transfusions (hemochromatosis, transfusion-transmissible diseases). Thirdly, patients with uremia notice a considerable improvement in quality of life (QOL) after initiation of rHuEpo. These advantages justify administration of this costly drug in CRF patients. The use of rHuEpo outside the setting of uremia do, however, not cover the complete spectrum of beneficial effects as compared to its use in (pre)dialysis patients. The aim of this overview is to provide some annotations on recently approved (cisplatin-induced anemia, preoperative anemia, zidovudine-related anemia) and possibly future (several types of malignancy and inflammation) indications for rHuEpo in non-uremic patients, leaving out the correction of anemia due to relatively uncommon disorders in the Dutch population (such as sickle cell anemia and thalassemia).
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PMID:Erythropoietin treatment for non-uremic patients: a personal view. 1004 90


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