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

The effects of intramuscular injection and subcutaneous infusion of desferrioxamine (D.F.) on urinary iron excretion were compared in eleven patients with thalassaemia major and one with congenital sideroblastic anaemia who were being maintained on regular blood-transfusions. Total (48-hour) urinary iron excretion ranged from 3-3 to 40-3 mg (mean 16-3 mg) in nine patients who received 750 mg D.F. intramuscularly before transfusion and from 3-9 to 32-3 mg (mean 11-9 mg) in ten patients who received D.F. by the same route after transfusion. In all 9 patients studied before transfusion, continuous subcutaneous infusion of 750 mg D.F. over 24 hours increased iron excretion by 61-5 to 135-8% (mean 101+/-25-4 S.D.%) compared with intramuscular injection of a similar dose. In the 10 patients studied after transfusion, the iron excretion produced by continuous subcutaneous infusion was from 18-9 to 213% (mean 128+/-74-3%) more than that produced by a single intramuscular injection of D.F. When the subcutaneous dose over 24 hours was increased to 1500 mg in six patients, 48-hour iron excretion ranged from 29-2 to 81-2 mg (mean 52-4 mg) and was increased by 80-2--794% (mean 429%) compared with the excretion when 750 mg was given by intramuscular injection. It is concluded that continuous subcutaneous infusion of D.F. produces more iron excretion in patients with iron overload than intramuscular injection. Providing a suitable portable pump can be carried by the patients, continuous subcutaneous infusion of desferrioxamine may prove a valuable means of preventing or treating iron overload in anaemic patients maintained on regular transfusions.
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PMID:Subcutaneous infusion and intramuscular injection of desferrioxamine in patients with transfusional iron overload. 6 49

The effect of 12 and 24 h continuous subcutaneous infusion of desferrioxamine (D.F.) on urinary iron excretion was compared in 13 patients with beta-thalassaemia major and 1 with congenital sideroblastic anaemia, all of whom were receiving regular blood-transfusions. 750 mg D.F. given over a 12 h period, gave a mean total (30 h) iron excretion of 17-5 mg, which was not statistically different from the mean iron excretion of 21-5 mg when the same dose was delivered over 24 h. 1500 mg D.F. gave a mean urinary iron excretion of 28-1 mg with a 12 h infusion, which was significantly less than the mean iron excretion of 39-6 mg with 24 h infusion. The 1500 mg dose gave a significant increase in iron excretion compared with the 750 mg dose when given by either 12 h or 24 h infusion. 7 of 8 patients, given D.F. over a 12 h period, had increased iron excretion when the dose was increased from 750 to 2000 mg. When the dose was increased to 4000 mg, however, the effect on iron excretion was variable. On the other hand, ascorbic-acid therapy was invariably associated with increased iron excretion after subcutaneous D.F. In twelve studies at different dose levels of D.F., ascorbate therapy was associated with increased iron excretion ranging from 24 to 245%. It is concluded that in most patients with transfusional iron overload subcutaneous D.F over a 12 h period, at a dose ranging from 2 to 4 g daily with ascorbic-acid saturation, is at present the most satisfactory method of removing excess iron.
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PMID:Effect of dose, time, and ascorbate on iron excretion after subcutaneous desferrioxamine. 6 69

Iron absorption and rates of iron accumulation were analysed in a group of patients with beta-thalassaemia intermedia. Iron absorption was strikingly increased and there was a progressive iron loading with increasing age. Balance studies indicated that by the time many of these patients reach the third or fourth decades their total iron loads may be of a similar magnitude to those of transfusion-dependent beta-thalassaemia homozygotes. If these patients are to be protected from cardiac, hepatic, and endocrine complications of iron overload in middle life it will be necessary to reduce gastrontestinal iron absorption, starting from early childhood.
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PMID:Iron absorption and loading in beta-thalassaemia intermedia. 9 Sep 18

Two conditions are liable to lower the alpha:beta globin biosynthesis ratio in reticulocytes: iron deficiency and alpha-thalassaemia. The present paper studies the effect of haemin on reticulocytes from 12 patients who have alpha-thalassaemia and/or are iron deficient. The alpha:beta globin biosynthesis ratio was improved in all these cases. 4 showed initially an alpha:beta synthesis ratio usually associated with alpha-thalassaemia type-1; on the addition of haemin the ratio rose to that associated with alpha-thalassaemia type-2. In the other 8 patients the ratio was initially typical for alpha-thalassaemia type-2, and on addition of haemin the ratio became normal. It is suggested that in iron deficient patients a diagnosis of alpha-thalassaemia type-1 or type-2 cannot be made unless haemin has been added to the test system. If this is not done iron deficiency alone can cause the alpha:beta globin synthesis ratio to resemble that associated with alpha-thalassaemia type-2, and iron deficiency in combination with alpha-thalassaemia type-2 can cause the ratio to resemble that typical for alpha-thalassaemia type-1. Reticulocytes from 8 alpha-thalassaemic patients without iron deficiency did not show a marked haemin effect (less than 5%), and in 1 patient with iron overload, the ratio actually fell by about 10%.
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PMID:Interaction between iron deficiency and alpha-thalassaemia: the in vitro effect of haemin on alpha-chain synthesis. 9 95

The auditory function of 75 children affected by homozygous beta0-thalassemia, managed with a low transfusion scheme and treated irregularly with low doses of desferrioxamine, and of 75 controls were examined. In 12 patients a mild bilateral conductive hearing impairment due to bony hypertrophy and/or adenoid hypertrophy was found. In 43 cases a moderate monolateral or bilateral sensory-neural hearing loss at high frequencies with recruitment phenomenon was observed. Ferritin levels were determined in a randomly chosen group of these patients with (14) and without heaing loss (11). In the subjects with sensory-neural hearing loss the mean ferritin levels were significantly higher than in those with no hearing defect. There was no obvious relation between sensory-neural damage on the one hand and Hb levels and unit of blood transfused on the other. The results of this study suggest that iron overload could be a cause of damage in the high frequency elements of the auditory mechanism. Intermittent hypoxia and slow 8th nerve compression due to bony hypertrophy as causes of auditory involvement are also discussed.
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PMID:Auditory involvement in thalassemia major. 10 1

Abnormal platelet aggregation was found in eight (44%) of 18 patients with beta-thalassaemia major and transfusional iron overload. The aggregation defect bore no correlation with the degree of hepatic fibrosis, liver function tests, whether or not splenectomy had been performed, the degree of iron overload, haematocrit, platelet count, serum vitamin E level, or leucocyte ascorbate concentration. Only three of the 18 patients showed prolonged bleeding times as well as abnormal platelet aggregation, and only one of these suffered clinically significant haemorrhage. The results show that a proportion of patients with beta-thalassaemia major have abnormal platelet function. It is possible, however, that the in vitro abnormality might be due partly to artefacts induced by manipulations required to remove the abnormal thalassaemic red cells, and this may explain the much lower incidence of significant haemorrhage.
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PMID:Platelet function in beta-thalassaemia major. 46 99

This report details the results of studies performed in nine patients with homozygous beta-thalassemia evaluating platelet function and prostaglandin formation. Platelet malonyldialdehyde (MDA) formation in the presence of N-ethyl maleimide (NEM 1 mM) or thrombin (0.5 u/ml) was used as an indicator of platelet prostaglandin synthesis. The data on the nine patients revealed two distinct subgroups of patients. Six of nine thalassemics, demonstrated platelet abnormalities. Their mean bleeding time was 7.5 +/- 2.5 min (1 SD), significantly prolonged (P less than 0.005) when compared to a value of 3.5 +/- 1.0 min in normal controls. MDA formation in the presence of NEM was significantly decreased (P less than 0.005) to 2.41 +/- 0.49 (1 SD) when compared to a control value of 3.24 +/- 0.33 nmoles MDA/10(9) platelets. Similarly, the mean value for thrombin induced MDA was 0.98 +/- 0.18 nmoles which was decreased (P less than 0.02) when compared to a value of 1.26 +/- 0.2 in the controls. Platelet aggregations with adenosine diphosphate (ADP), epinephrine, and collagen were abnormal in all six patients. However, when platelets from these patients were mixed with platelets from donors who had ingested aspirin 2-8 hr before donation mutual correction and secondary irreversible aggregation of the mixture resulted. No mutual correction was observed when the thalassemic platelets were preincubated with aspirin in vitro before mixing with platelets from donors who had recently ingested aspirin. Although the total amount of platelet malonyldialdehyde formed by the thalassemic platelets in response to NEM and thrombin was decreased when compared to normal controls, this reduction was not the cause of the platelet aggregation abnormalities. This appears to be so because the amount of MDA, and, thus, prostaglandin endoperoxides synthesized by these platelets in response to external stimuli was sufficient to cause irreversible aggregation of platelets from donors who had recently ingested aspirin, and were, therefore, unable to synthesize their own endogenous platelet endoperoxides. In the remaining three patients, bleeding times, platelet aggregation, and MDA formation was normal. No correlation was observed between the platelet abnormalities noted and the magnitude of iron overload, presence of fibrin degradation products, liver function abnormalities, or the use of iron chelators in the individual patient. Family studies were normal. Although the platelet dysfunction does not appear to be of major significance in the usual patient with thalassemia major under normal circumstances, antiplatelet aggregating agents should be used with caution. Aspirin inhibits platelet endoperoxide and prostaglandin formation and this effect may potentiate the platelet dysfunction present in some patients with thalassemia major.
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PMID:Platelet dysfunction in homozygous beta-thalassemia. 52 94

Iron overload was found in 3 patients who had undergone partial gastrectomy: a 61-year-old woman developed iron overload because she may have had idiopathic haemochromatosis and had also been given parenteral iron; in a 62-year-old man with thalassaemia minor, iron overload may have developed because of increased oral iron ingestion, low serum folate, increased, albeit ineffective, erythropoiesis and sideroblastic anaemia; a 74-year-old man with thalassaemia minor developed iron overload without exogenous therapy and died from a hepatoma. These cases illustrate that partial gastrectomy fails to protect patients from developing iron overload, particularly if given uncontrolled iron therapy.
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PMID:Iron overload despite partial gastrectomy. 53 65

Homozygous beta-thalassaemia is a disease in which there is a progressive iron overload from infancy to death in early adulthood. Liver biopsies from 10 patients in various stages of this disease were examined by electron microscopy. A number of round or oval lysosomal structures, containing lamellae different from myelin figures, were seen in all patients, including those with minimal iron overload. Ferritin molecules were seen either in relationship with the lamellae forming arrays, or in paracrystalline arrangement, or with no organized form. There were practically no ferritin molecules in sub-cellular compartments other than cell sap and lysosomes. The density of cell sap ferritin was constant beyond infancy, but the number of iron-laden lysosomes increased with age. The stages in the process of iron seclusion, seen even in advanced phases of iron overload, are described. Ferritin is thought to accumulate in lysosomes by a transmembraneous movement, but other explanations are considered.
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PMID:Ferritin in human liver cells of homozygous beta-thalassaemia: ultrastructural observations. 60 78

The ultrastructure of sinusoidal cells was studied in 18 liver biopsies from patients with homozygous beta-thalassemia. No conspicuous iron was seen in sinusoidal cells from biopsies obtained before transfusion therapy was initiated, although electron-dense iron was present in some parenchymal cells. Biopsies following the high transfusion regime showed progressive increase in the size and number of iron-containing lysosomes in both parenchymal and sinusoidal cells. This study confirms the view that transfusional iron is largely segregated in reticuloendothelial cells. Examination of stained and unstained sections showed the Kupffer cells and endothelial cells had different types of iron-containing lysosome that were also dissimilar from most iron-containing lysosomes seen in hepatocytes. The described cell-specific morphological features of the lysosomes facilitate the identification of various cells during iron overload. The importance of phagocytic sinusoidal cells during chronic iron overload is stressed.
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PMID:Hepatic sinusoidal cells in iron overload. Ultrastructural observations. 75 May 49


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