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

In order to evaluate the interrelations of splenectomy, iron overload and cirrhosis, histologic specimens of liver and spleen were examined and correlated in 12 children with beta-thalassemia major. All patients had received blood transfusions since infancy. Correlations seemed to exist between splenic hemosiderosis and splenic weight, and between the latter and the age at time of splenectomy. All liver samples showed varying hemosiderosis, not correlated with the number of transfusions or the children's age. Irregular liver cirrhosis existed in three children, 7, 8, and 14 years after splenectomy. No cirrhosis existed in any of the children where the spleen was in situ. Splenectomy in children with thalassemia may carry the long-term risk of liver cirrhosis.
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PMID:Splenectomy, iron overload and liver cirrhosis in beta-thalassemia major. 82 69

Serum half-lives for antipyrine were normal or shorter than normal in 19 subjects between 7 and 23 yr of age with beta-thalassemia major. The mean antipyrine serum half life (+/-SE) for the group as a whole was 8.5 +/- 0.6 hr. The mean antipyrine half-lives (t1/2) for the younger subjects were within the range reported for normal children, while the mean t1/2 for the older males approached the values reported for normal adult males. The mean t1/2 for the older females was shorter than has been reported for normal adult females. The mean apparent volume of distribution for antipyrine (+/-SE) in the subjects with thalassemia was 0.69 +/- 0.01 L/kg. Thus, total body water appears to be increased in thalassemia. The mean metabolic clearance rate for antipyrine (+/-SE) in the group as a whole (1.07 +/- 0.08 ml/min/kg) is substantially higher than the metabolic clearance rates for antipyrine reported in normal adults. Thus, the relatively short t1/2s of antipyrine in subjects with thalassemia are attributable to rapid rates of clearance of the drug. The data indicate that antipyrine clearance is unimpaired in patients with thalassemia despite evidence of liver damage and iron overload. Our study supports the proposition that hepatic microsomal hemoprotein synthesis is not adversely affected in homozygous beta-thalassemia.
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PMID:Antipyrin clearance in homozygous beta-thalassemia. 97 19

Patients with severe thalassaemia major suffer endocrine and other abnormalities before their eventual death from iron overload due to repeated blood transfusions. The endocrine status of 31 thalassaemic patients aged 2-5 to 23 years was investigated. Exact data were available on the rate and duration of blood transfusion in all of them and in many the liver iron concentration was also known. Although the patients were euthyroid, the mean serum thyroxine level was significantly lower, and the mean thyrotrophic hormone level significantly higher, compared with the values found in normal children. Forty oral glucose tolerance tests with simultaneous insulin levels were performed in 19 children, of whom 5 developed symptomatic diabetes and one had impaired tolerance. Previous tests on all 6 patients were available and some showed raised insulin levels possibly due to insulin resistance. 2 patients had clinical hypoparathyroidism and are described. The parathyroid hormone levels determined by radioimmunoassay in 25 patients were below the mean for the age group in all and outside the reference range in 16. Nonfasting plasma calcium levels were not reduced. Puberty was delayed in some patients. Concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) measured in urine from 7 girls and 5 boys showed considerable variation. In the boys there was an overall tendency for FSH and LH excretion to be low with regard to age, but with respect to puberty rating FSH exretions were normal or low and LH normal or raised. The girls showed a tendency for LH but not FSH excretion to be raised in relation to puberty rating. The severity of the endocrine changes was related to the degree of iron loading and is discussed in relation to previous work in which the iron loading has rarely been accurately indicated nor parathyroid status assessed.
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PMID:Hormonal changes in thalassaemia major. 100 88

2-3-Dihydroxybenzoic acid was evaluated as a potentially useful, orally effective iron-chelating drug by performing iron balance studies in patients with beta-thalassaemia major. The administration of this substance at 25 mg/kg/d to five patients for 8 d caused an average increase in iron excretion of 4.5 mg/d. When the drug was administered at 25 mg/kg q.i.d. to eight patients for 21 d, iron excretion increased to 6.5 mg/d. Chelation was highly specific for iron with changes in magnesium and calcium excretion being insignificant. The drug was well tolerated with side effects limited to gastrointestinal complaints which ameliorated when the drug was taken with food. These studies provide a rationale for further evaluation of 2,3-dihydroxybenzoic acid in patients with iron overload.
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PMID:Chelation studies with 2,3-dihydroxybenzoic acid in patients with beta-thalassaemia major. 100 20

Because of its high prevalence in Italy, thalassemia is officially considered a disease of major social importance. Several centers have been established for the specific purpose of population screening and treatment of patients with Cooley disease. Survival, in some cases up to 20 years, has been reached by the therapeutic methods adopted, consisting mainly of an intensive transfusion program combined with splenectomy. We now face serious logistic, social, and financial problems, raised by the increasing number of patients living, estimated at around 12,000. The iron overload is not adequately controlled by the routine use of desferrioxamine. Studies of iron kinetics in heterozygotes demonstrate specific alteration of iron metabolism (not related to the exogenous transfusion-induced overload). Therefore, treatment with iron-chelating agents might be indicated in at least some of these subjects.
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PMID:Thalassemia in Italy: treatment of Cooley disease and iron kinetics in heterozygotes. 100 35

During a study of pathogenetic mechanisms in the hepatic cirrhosis of thalassaemia major, 16 liver biopsies were examined by electron microscopy. Previous ultrastructural studies of liver cells during iron overload have shown electron-dense iron as lysosomal haemosiderin, and as lysosomal and cell-sap ferritin. In this study, all biopsies, regardless of the patient's age, showed ferritin molecules within lysosomes in a specific pattern in relationship with regularly arranged lamellae. This membrane-associated lysosomal ferritin is considered to be a stage in the segregation of iron seen in iron overload. The dimensions and electron density of individual ferritin molecules indicate differences between cell sap and lysosomal ferritin. Intracellular ferritin transport and iron-seclusion mechanisms are reconsidered in view of these findings. The liver biopsies of thalassaemic infants also provide information about the causal relationship between iron overload and collagen deposition. Since the collagen deposition precedes any morphological evidence of cellular injury (other than the increased iron content), the primary cirrhotogenic factor in thalassaemia is apparently not cell necrosis but possibly excessive collagen deposition induced by iron.
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PMID:The liver in thalassaemia major: ultrastructural observations. 105 35

Urinary iron excretion was measured in patients with sickle cell anemia and relateddiseases. Iron concentration in urine was determined by atomic absorption spectrophotometry and daily total iron excretion was calculated from this and total daily urine volume. Normal subjects excreted a mean of 88 pg Fe per day (95 per cent confidence limitsof 0 to 120 pg). Nine persons with sickle cell trait had normal Fe excretion rates.However, abnormally high iron excretion was present in the first urine sample obtainedfrom 27/31 patients with SS, 3/7 with SC, 1/2 with CC, and 1 with S-thalassemia. Iron excretion varied very significantly from day-to-day in individual patients. The results of studies attemting to relate this to increase excretion during activityas compared to rest were negative. No clear relationship of iron excretion to painfulcrisis could be shown, but remarkable rises in urine iron occurred in two patients who developed a hyperhemolytic crisis. These studies suggest that urinary iron reflects intravascular hemolysis primarily. No correlation was evident between urine iron and the patients' age, transfusion history, or serum iron values suggesting increased urinary iron excretion cannot be attributed to iron overload in sickle cell anemia.
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PMID:Urinary iron in patients with sickle cell anamia. 115 Nov 37

Non-transferrin-bound iron (NTBI) in plasma is toxic due to its ability to participate in free radical formation with resultant peroxidation and damage to cell membranes and other biomolecules. NTBI concentration was determined in serum in 12 normal volunteers and in 52 patients with beta-thalassaemia major by a modification of the method described by Singh et al (1990). There was no detectable NTBI in normal individuals. In the patients NTBI values ranged from -1.5 to 9.0 mumol/l (mean +/- SD: 3.6 +/- 2.3). The patients' serum ferritin concentrations ranged from 207 to 11,400 micrograms/l (2674 +/- 2538), total serum iron from 20 to 61 mumol/l (39.5 +/- 9.6) and transferrin saturation from 44 to 110% (84.5 +/- 13.8). The NTBI correlated significantly with serum ferritin (r = 0.467, P < 0.001), total serum iron (r = 0.608, P < 0.001) and transferrin saturation (r = 0.481, P < 0.005). When patients were grouped according to their compliance with desferrioxamine (DFX) therapy, the good compliers had significantly lower NTBI concentrations compared to the poor compliers (poor: 5.4 +/- 1.8 mumol/l v good: 2.7 +/- 1.7 mumol/l, P < 0.001). There was also a significant difference between the level of NTBI and whether or not the patients had complications of iron overload (5.2 +/- 1.7 mumol/l v 2.9 +/- 1.6 mumol/l, P < 0.001). During this study 10 patients were entered into a trial of the oral iron chelator 1,2- dimethyl-3-hydroxypyrid-4-one (L1). Their NTBI values were observed during the first 6 months of the trial and showed a significant fall (paired t-test: P = 0.007). These results suggest that the level of NTBI may prove helpful in assessing the efficiency of chelation in patients with transfusion dependent anaemia and help to predict organ damage.
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PMID:Serum non-transferrin-bound iron in beta-thalassaemia major patients treated with desferrioxamine and L1. 141 25

Seventy-two transfusion-dependent iron loaded thalassemia patients were investigated for thyroid dysfunction by estimating circulating thyroid hormones (T4 and T3) and basal thyroid stimulating hormone (TSH). They were also evaluated for their liver function (biochemically) and iron overload by estimating serum ferritin. Thyroid failure (hypothyroidism) was documented in 14 patients (19.4%). In all, 3 groups were seen, i.e. Group 1: Normal T4, T3, TSH (58 patients: 80.6%); Group 2: Compensated hypothyroidism characterized by normal T4, T3 and raised TSH (9 patients: 12.5%); Group 3: Decompensated hypothyroidism characterized by decreased T4 and increased TSH (5 patients: 6.9%). Interestingly, impaired thyroid function could not be correlated with age, amount of blood transfused, liver dysfunction or degree of iron overload. It is postulated that an inter-play between chronic hypoxia, liver dysfunction and iron overload may be responsible for the thyroid damage.
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PMID:Thyroid dysfunction in multi-transfused iron loaded thalassemia patients. 145 22

Patients with homozygous beta-thalassemia are at increased risk of serious infections. Yersinia enterocolitica is an organism with a predilection for these and other iron-overloaded patients. Three young adult patients with beta-thalassemia who were chronically transfused and developed yersiniosis are reported. Iron overload and desferrioxamine use are predisposing factors, as supported by clinical, animal, and in vitro data. Iron excess both immunologically compromises the host and greatly enhances yersinial growth. Desferrioxamine may make host iron even more bioavailable to Yersinia. Recognition of this association and unusual manifestations in these patients such as an appendicitis-like syndrome may direct clinicians to earlier antiyersinial therapy and temporary cessation of chelation.
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PMID:Yersinia infections in patients with homozygous beta-thalassemia associated with iron overload and its treatment. 152 3


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