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

Adequate iron chelation in thalassaemia has resulted in a striking improvement in survival, with a reduction of cardiac mortality at age 15 years from 14-3%, and a predicted survival at age 36 years of 85%. Long term desferrioxamine (DF) therapy in thalassaemic children should be started between 2-4 years of age. In addition to daily 8-12 h subcutaneous infusions, intermittent high dose (9-16 g) i.v. supplementation over 24-48 h may be given on the occasion of blood transfusions. In established myocardiopathy continuous i.v. DF infusion at 100-125 mg/kg/d may result in improved myocardial function. In addition, there is considerable current interest in the use of DF in conditions unrelated to iron overload by preventing the formation of free-radicals in inflammatory reactions, or by S-phase inhibition of cell proliferation. Although at present highly experimental, this novel approach may have important implications for the management of patients with inflammatory conditions and perhaps in the control of protozoal infections. Over the last decade several hundred candidate compounds have been studied in cell cultures and in animal models and a number of orally effective iron chelators have been identified, all of which are superior to DF in their in vivo iron chelating effect. Although we do not yet have a new drug which is immediately available for replacing DF in clinical practice, significant progress has already been made, and some of the most promising candidate drugs are currently undergoing extensive toxicity tests in anticipation of their development for large-scale clinical use.
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PMID:Iron chelation. 218 44

The mechanism(s) underlying the apparent resistance to malaria in certain inherited red cell disorders and iron deficiency anaemia remain poorly understood. The possibility that microcytic erythrocytes might inhibit parasite development, by physical restriction or reduced supply of nutrients, has been considered for many years, and never formally investigated. We sought to determine whether in vitro growth studies of P. falciparum could provide evidence to suggest that small red cell size contributes to malaria resistance in those red cell disorders in which microcytosis is a characteristic feature. Invasion and development of P. falciparum in iron deficient red cells (mean values for mean cell volume [MCV] 66 fl, mean cell haemoglobin [MCH] 19 pg) and in the red cells of two gene deletion forms of alpha-thalassaemia (mean MCV 71 fl, MCH 22 pg) were normal, assessed both morphologically, and by 3H-hypoxanthine incorporation. Although parasite appearances were normal in all cell types, morphological abnormalities were noted in iron deficient and thalassaemic cells parasitized by mature stages of P. falciparum, notably cellular ballooning and extreme hypochromia of the red cell cytoplasm. Using electron microscopy, the red cell cytoplasm in parasitized thalassaemic cells showed reduced electron density and abnormal reticulation. Normal invasion rates were observed following schizogony in microcytic cells of both types. Our findings indicate that whilst minor morphological abnormalities may be detected in parasitized iron deficiency and thalassaemic erythrocytes, development of P. falciparum in these conditions is not limited by small erythrocyte size.
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PMID:Unrestricted growth of Plasmodium falciparum in microcytic erythrocytes in iron deficiency and thalassaemia. 218 91

The majority of anemias in the United States are characterized by low mean corpuscular volume and thus are classified as microcytic. Iron deficiency, chronic disease and thalassemia traits are the three leading causes of microcytic anemia. The true cause of anemia must always be sought so that the prevalence estimates of iron deficiency are accurate and so that appropriate treatment can be initiated for the anemic individual. In both the clinical setting and in surveys, the most frequent differential diagnosis of microcytic anemia will involve distinguishing between iron deficiency and chronic disease. Erythrocyte sedimentation rate (ESR), zeta-sedimentation rate (ZSR), and C-reactive protein (CRP) are elevated in a variety of diseases. These indicators may help differentiate the anemia of chronic disease from iron deficiency, so that iron deficiency is not overestimated in hospitalized and aged populations. The red cell distribution width (RDW) appears to be elevated to a greater extent in iron deficiency than in chronic disease or thalassemia traits. RDW and CRP are two of several indicators of iron status in the third National Health and Examination Survey (NHANES III).
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PMID:Iron: nutrition monitoring and nutrition status assessment. 224 93

L1 was given to eight patients with beta-thalassaemia major who had previously been treated with deferoxamine (DF) for 4-10 years. The patients' ages ranged from 11 to 27 years. Serum ferritin values ranged from 1.3 to 11.5 x 10(3) micrograms/l. L1 was given twice daily at a daily dose of 55-80 mg/kg body weight and was continued for 10 months in two patients, 9 months in three, 7 months in two patients and 4 months in one patient. As previously observed with DF, each patient's urinary iron excretion (UIE) varied greatly from day to day. The mean UIE of the eight patients ranged from 11 to 49 mg/d (0.2-0.87 mmol/d) on subcutaneous DF and from 16 to 53 mg/d (0.28-0.95 mmol/d) on L1. Two patients excreted significantly more and one patient significantly less iron while on L1. If the UIE was calculated as mmol Fe/mmol creatinine there was no statistically significant difference. Serum ferritin values fluctuated widely in all, with a consistent downward trend in three, no change in four and an increase in one of two non-splenectomized patients. This patient's splenomegaly and need for transfusions continued to increase while on L1. No toxicities attributable to the drug were detected during the period of study and tolerance of the drug was excellent.
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PMID:L1 (1,2-dimethyl-3-hydroxypyrid-4-one) for oral iron chelation in patients with beta-thalassaemia major. 226 18

This paper describes the status of iron stores, the incidence and the hematological characteristics of iron deficiency anemia in children heterozygous for beta-thalassemia. In beta-thalassemia heterozygotes, iron stores were similar to the controls in infancy and tended to increase with age, reaching levels of moderate iron overload solely in adult males. Iron deficiency anemia occurred less frequently in children heterozygous for beta-thalassemia as compared to normal controls, while no difference between the two groups was observed in the incidence of iron deficiency. Ineffective erythropoiesis, typical of heterozygous beta-thalassemia, by causing an increase of iron absorption may limit the effect of iron shortage. At similar levels of iron depletion, however, children heterozygous for beta-thalassemia develop a more severe anemia as compared to non beta-thalassemic children. With the exception of two children, HbA2 levels in the presence of iron deficiency anemia remain in the range of heterozygous beta-thalassemia. In conclusion, our results indicate that children heterozygous for beta-thalassemia have normal iron stores but are relatively protected against the development of iron deficiency. When iron deficiency anemia develops, its clinical expression is usually more severe than in non beta-thalassemic children.
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PMID:Iron stores and iron deficiency anemia in children heterozygous for beta-thalassemia. 227 77

The authors describe 22 cases of beta-thalassaemia minor in 11 boys and 11 girls from Czech families. The children suffer as a rule mild hypochromic anaemia with marked microcytosis and rather elevated red cell values. The serum ferritin values are normal, serum iron is normal or slightly elevated. In all children the ratio of haemoglobin A2 is raised (to 4-7%) and in 40% the ratio of haemoglobin F is raised (to 1.5 to 5.9%). There are no differences between boys and girls in the investigated parameters. The boy have, as compared with adult men with beta-thalassaemia minor, significantly lower values of red blood cells and serum ferritin. There are no significant differences between girls and adult women suffering from this disease.
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PMID:[Beta thalassemia in pediatric practice. A group of 22 pediatric patients]. 228 50

Disorders of hemoglobin synthesis affect the musculoskeletal system by either causing replacement of bone by hematopoietic tissue, precipitating bone and soft tissue ischemia and necrosis, or a combination of both processes. Less frequently, joints are involved by synovial ischemia, synovial deposition of iron, or microfracture of subchondral bone. Osteopenia is a significant problem in both thalassemia and sickle cell anemia and may result in vertebral and long bone fractures. Growth disturbances are frequently seen but are not often appreciated until adolescence because of improved hematologic management. The cause of the growth problems is multifactorial and may be related to hormonal deficiencies, iron overload, hypoxia, or local trauma to the growth plate secondary to significant osteopenia.
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PMID:Musculoskeletal problems in hemoglobinopathy. 229 57

The histological features of thalassemic bone are imperfectly known, and the roles of bone marrow hyperactivity, iron overload or vitamin D deficiency in the pathogenesis of the disease are not clearly identified. In this study we examined iliac crest biopsies from 17 transfusion-dependent children with homozygous beta-thalassemia and severe radiological skeletal thalassemic changes, including widening of medullary spaces and osteoporosis. Rachitic lesions were not observed. Serum ferritin concentrations were increased in all but one subject. Iron deposits were histochemically detected in bone marrow, at the marrow-bone interface, along cement lines and mineralizing perimeters. Minor changes were present in trabecular bone, and osteomalacia was absent. By contrast, cortical bone exhibited severe changes including fissures and focal mineralization defects. Plasma 25-hydroxyvitamin D (25(OH)D) concentrations measured during the winter (December-May, 6.5 +/- 4.9 ng/ml, mean +/- SD, n = 6) and during the summer (June-November, 13.8 +/- 8.4 ng/ml, n = 9) did not differ from those of age-matched children living in the same country. Seven patients had moderate hypocalcemia but no biological signs suggestive of vitamin D deficiency: all had normal alkaline phosphatase activity, normal or slightly elevated plasma phosphate, only two had low plasma 25(OH)D concentrations and two others supranormal values of plasma immunoreactive parathyroid hormone. These results show that iron overload and vitamin D deficiency do not seem to play an important role in the pathogenesis of thalassemic bone disease, which is characterized by cortical lesions probably related to marrow hyperactivity.
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PMID:Bone disease in children with homozygous beta-thalassemia. 230 56

The ferritin concentration in peripheral blood lymphocyte extracts was measured in 10 normal subjects, 7 patients with homozygous beta-thalassaemia, and 5 patients with iron-deficiency anaemia. The mean intracellular ferritin content was found increased in beta-thalassaemia and reduced in iron-deficient patients. Incubation of mononuclear cells in phytohaemagglutinin medium led to an increase of DNA synthesis concomitant with an increased number of lymphocytes bearing transferrin receptor and interleukin-2 receptor as measured by immunofluorescent technique. Although there was an immunological impairment of lymphocytes in patients with either iron depletion or iron loading compared to normal subjects, their ability to express transferrin receptor and interleukin-2 receptor on their cell surface was normal.
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PMID:Expression of cell-surface transferrin receptor following in vitro stimulation of peripheral blood lymphocytes in patients with beta-thalassaemia and iron-deficiency anaemia. 232 91

A standard magnetic resonance imaging (MRI) system allowing spin echo times of 10 ms was used to quantitate liver iron concentration in nine healthy normal subjects and 13 patients with various grades of iron overload. Body iron status was estimated by measuring the serum ferritin concentration. In 11 subjects (two normal healthy controls, eight patients with HLA-related hereditary haemochromatosis and one patient with thalassaemia major) non-haem hepatic iron concentration was determined chemically in biopsy specimens (dry weight), in parallel to serum ferritin and MRI-T2 relaxation times. A moderate correlation (r = 0.79) was obtained for the correlation of the T2-relaxation rate (1/T2) and serum ferritin of the 22 subjects investigated. A much closer correlation (r = 0.98) was observed for the 1/T2 liver iron relationship in the 10 subjects analysed by liver biopsy. It is concluded from these preliminary observations, that MR-imaging may provide a useful non-invasive tool for the quantitative determination of liver iron in iron overload-syndromes.
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PMID:Non-invasive quantitation of liver iron-overload by magnetic resonance imaging. 233 43


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