Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In patients with thalassemia intermedia in whom hyperabsorption of iron may result in serious organ dysfunction, an orally effective iron-chelating drug would have major therapeutic advantages, especially for the many patients with thalassemia intermedia in the Third World. We report reduction in tissue iron stores and normalization of serum ferritin concentration after 9-month therapy with the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) in a 29-year-old man with thalassemia intermedia and clinically significant iron overload (SF 2,174 micrograms/L, transferrin saturation 100%; elevated AST and ALT, abnormal cardiac radionuclide angiogram) who was enrolled in the study with L1 75 mg/kg/day after he refused deferoxamine therapy. L1-Induced 24-hour urinary iron excretion during the first 6 months of therapy was (mean +/- SD, range) 53 +/- 30 (11 to 109) mg (0.77 mg/kg), declining during the last 3 months of L1 to 24 +/- 14 (13-40) mg (0.36 mg/kg), as serum ferritin decreased steadily to normal range (present value, 251 micrograms/L). Dramatic improvement in signal intensity of the liver and mild improvement in that of the heart was shown by comparison of T1-weighted spin echo magnetic resonance imaging with images obtained immediately before L1 administration was observed after 9 months of L1 therapy. Hepatic iron concentration decreased from 14.6 mg/g dry weight of liver before L1 therapy to 1.9 mg/g liver after 9 months of therapy. This constitutes the first report of normalization of serum ferritin concentration in parallel with demonstrated reduction in tissue iron stores as a result of treatment with L1. Use of L1 as a therapeutic option in patients with thalassemia intermedia and iron overload appears warranted.
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PMID:Reduction of tissue iron stores and normalization of serum ferritin during treatment with the oral iron chelator L1 in thalassemia intermedia. 158 21

To study the potential of multivariate classification methods in order to obtain more insight into abnormal laboratory data from patients with sickle cell disease, we investigated standard haematological and clinical chemical variables of 18 controls and 37 apparently healthy persons with heterozygous sickle cell disease (Hb AS), all women, using both univariate and multivariate classification methods. In the univariate method, those with Hb AS showed decreased serum log aspartate aminotransferase (log AST) activity, mean corpuscular volume and mean corpuscular haemoglobin (MCH) and increased sodium concentration. The multivariate method identified sodium, potassium, urea, uric acid, log AST, alanine aminotransferase and MCH as the variables that produced maximal separation between persons with Hb As and controls. It increased the 'non-error rate' for classification of persons with Hb AS by 16.4% compared with classification based on the variable, MCH, that produced maximal separation by the univariate method. The frequency distribution of percentage Hb S in the Hb AS group proved bimodal with maximal separation at 37.0% Hb S. The subgroup with 37.0% or less (n = 16) was considered to have concomitant heterozygous alpha-thalassaemia-2. In the univariate method the subgroup characterized by greater than 37.0% Hb S (n = 21) had increased serum sodium and uric acid concentrations, perhaps related to sickle cell nephropathy, whereas the subgroup with less than or equal to 37% Hb S did not. The multivariate method added information to the univariate method by additionally identifying abnormalities in serum potassium and urea concentrations in the former subgroup.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Potential of descriptive linear discriminant analysis for studying clinical chemical and haematological data from persons with heterozygous sickle cell disease. 189 49

Seventeen of 73 (23.3%) multiply transfused patients with thalassaemia major (age range, 1-39 years) tested positive for antibody to hepatitis C virus (anti-HCV). Eleven of the 24 patients regularly transfused in countries outside Britain were anti-HCV seropositive; only six of the 49 regularly transfused in Britain were seropositive. The incidence of anti-HBs and anti-HBc was similar to that of anti-HCV in both the British and foreign patients. The anti-HCV seropositive patients showed significantly higher plasma aspartate aminotransferase activities (AST), mean (SD) 10.2 (70.3) U/l, and serum ferritin concentrations, 4067 (2708) micrograms/l, than the anti-HCV seronegative patients (AST, 33.9 (15.6) U/l; serum ferritin 2051 (2092) U/l), respectively. Among the 36 patients who had earlier undergone liver biopsy 10 of 21 with histological features of chronic active hepatitis or cirrhosis, or both, were seropositive for anti-HCV whereas only one of 15 without histological evidence of chronic viral hepatitis was seropositive for anti-HCV. It is concluded that HCV is a major cause of chronic hepatitis in patients with thalassaemia major and is associated with raised AST activity and serum ferritin concentration compared with patients seronegative for anti-HCV.
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PMID:Antibody to hepatitis C virus in multiply transfused patients with thalassaemia major. 211 95

Forty-three patients with hematopoietic disease were treated with intensive chemotherapy and radiotherapy, followed by allogeneic bone marrow transplantation (BMT) from 28 HLA-identical and 10 one to two antigen haploidentical sibling donors and autologous BMT (5 cases). Of these cases, there were 21 with acute nonlymphocytic leukemia (ANLL), 5 with acute lymphocytic leukemia (ALL), 6 with chronic myelocytic leukemia (CML), 2 with Hodgkin's disease (HD), 8 with severe-form aplastic anemia (SAA) and 1 with thalassemia. Complications of BMT were evaluated including acute graft-versus-host disease (GVHD), interstitial pneumonia (IP), veno-occlusive liver disease (VOD), abnormalities of liver function (LF), and alteration of hepatitis B virus (HBV) markers. In thirty-three patients who were followed up for more than 3 months, we found that the incidence of moderate to severe acute GVHD (9.1%) and IP (two cases, 4.7%) were low. No VOD occurred in our series. During the follow-up period, 27 out of 35 patients (77%) had high alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels, even up to 1000 U/liter; however, only one patient succumbed to a hepatitis-related complication. Previous hepatic damage from HBV infection before BMT does not appear to increase the risk of posttransplant morbidity and mortality.
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PMID:Complications of bone marrow transplantation in Chinese. 232 72

Liver biopsies were performed on 51 regularly transfused patients with beta thalassaemia, age range 5-36 (mean 18.6) years, who had received regular subcutaneous desferrioxamine (DFX) treatment for periods between one and eight years (40 for eight years). The biopsy specimens were examined by light microscopy and immunofluorescence for hepatitis B virus surface and core antigens (HBsAg and HBcAg), and the iron content was determined chemically. The results were compared with serum ferritin concentration and aspartate transaminase (AST) activity and with hepatitis B virus serology. Biopsy specimens, in which chemical liver iron had been determined in 12, were also available from 17 patients. Mean serum ferritin (+/- SD) had fallen from 5885 (3245) micrograms/l to 1638 (976) micrograms/l in 36 patients after eight years' chelation, while mean (+/- SD) liver iron concentration had fallen from 2945 (900) micrograms/100 mg dry weight to 857 (435) micrograms/100 mg dry weight in 12 of them. All biopsy specimens examined were negative for HBs and HBc antigens. The presence of histological features of hepatitis was associated with increased liver iron content, increased fibrosis, and with progression of fibrosis between the two biopsies. Procollagen III peptide was assayed in 28 patients but did not correlate with the degree of hepatitis, fibrosis, or with chemical liver iron content. We conclude that with regular subcutaneous DFX, mean concentrations of serum ferritin and liver iron are maintained in these patients at about five and 10 times the normal value, respectively, and that progression of liver damage is more likely to be due to viral hepatitis, presumably related to the parenterally transmitted non-A, non-B agents than to iron overload.
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PMID:Iron state and hepatic disease in patients with thalassaemia major, treated with long term subcutaneous desferrioxamine. 312 79

A low molecular weight iron-binding substance that promotes bacterial growth in vitro by increasing iron availability was identified in human blood and urine. Partial purification and physical characterization indicate that this factor is similar to the host-associated iron transfer factor (HAITF) previously isolated from mammalian tissue. HAITF was found to be significantly elevated in the blood of patients with thalassemia who have transfusional siderosis. The level of HAITF in the blood of these patients was also found to correlate with that of serum iron and serum glutamic-oxaloacetic transaminase (SGOT) but not with that of serum ferritin. Thus, elevated blood levels of HAITF may explain the increased susceptibility to infection seen in patients with iron overload. Its physiologic role, however, may involve the transport of iron within cells.
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PMID:Host-associated iron transfer factor in normal humans and patients with transfusion siderosis. 370 Nov 90

Thirty-four of 99 multiply transfused Chinese (49 females, 50 males) with thalassaemia major were positive for antibody to hepatitis C virus. There was no sex predominance in seropositivity with 18 females and 16 males positive. The mean (+/- SD) age and units of blood transfused were significantly higher in the seropositive patients (167 +/- 48 months, 206 +/- 82 units respectively) than the seronegative patients (113 +/- 56 months, 124 +/- 80 units respectively). The seropositive patients had higher mean (+/- SD) serum alanine aminotransferase, aspartate aminotransferase and ferritin concentrations (91 +/- 82 IU/L, 67 +/- 38 IU/L, 4797 +/- 2522 ng/ml respectively) than the seronegative patients (38 +/- 29 IU/L, 48 +/- 28 IU/L, 3620 +/- 2140 ng/ml respectively). Serum ferritin had an independent and significant effect on serum alanine aminotransferase in addition to that of seropositivity to hepatitis C virus.
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PMID:Hepatitis C virus antibody in multiply transfused Chinese with thalassaemia major. 769 Jun 34

Between 1990-1992, 18 patients with beta-thalassemia/Hb E age between 2-13 years (mean 7.4 +/- 3 years) were examined. Three patients were splenectomized and the rest were nonsplenectomized. They were divided into 3 groups. Group A:5 nonsplenectomized and 3 splenectomized patients had high transfusion rates with subcutaneous desferrioxamine injections. Five patients in group B received only high transfusion whereas in 5 patients in group C the levels pretransfusion Hb were maintained between 6-7 g/dl. The mean blood consumption in the nonsplenectomized groups were 220 +/- 25.3, 221 +/- 59 and 175.4 +/- 45.4 ml/kg/year in groups A, B and C, respectively. In group A, the mean blood requirement was 40% higher in the nonsplenectomized group. In the high transfusion regimen the spleen size did not increase and serum aspartate aminotransferase showed a striking fall in the majority of cases. The absolute increases in serum ferritin were 843.2 +/- 395, 861 +/- 252 and 1,262 +/- 440 ng/ml in groups A, B and C, respectively. These data demonstrated that high transfusion with desferrioxamine injection could improve the clinical well being of the patients.
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PMID:High transfusion in children with beta-thalassemia/Hb E: clinical and laboratory assessment of 18 cases. 788 17

In Brazil, clinicians followed 32 transfusion-dependent beta-thalassemia patients, 1-49 years old, at the Regional Blood Center and the Department of Hematology of University Hospital of the School of Medicine of Ribeirao Preto to determine the prevalence of hepatitis B virus (HBV), hepatitis C virus (HCV), HIV-1, and HTLV-1. They also measured serum levels of ferritin and alanine aspartate transaminase (ALAT) to examine liver iron content and liver damage, respectively. 46.8% tested positive for antibodies to HCV, which was much higher than that of voluntary blood donors of the Regional Blood Center (1.4%) or of other countries. Yet it was about the same as that of multitransfused patients in the UK (23.2%), Italy (92.9%), and Saudi Arabia (33.3%). 3 of these 15 patients also tested positive for HBV markers. 15.5% tested positive only for HBV markers. 37.5% had no hepatitis markers. Hepatitis-positive people were older than those who tested negative for hepatitis (15.2 years vs. 8.5 years; p .05). The number of units of blood transfused and the levels of ferritin and ALAT were not statistically different between the 2 groups (192.1-336 vs. 135.2 and 36.6-52.3 U/l vs. 36.7 U/l, respectively). 75% of the HCV positive patients received more than 100 units of packed red blood cells while only 42% did in the HCV negative group. 2 people tested positive for HIV-1 1 of whom also tested positive for anti-HBs-Ag and the other for HCV antibodies. The HIV-1 cases had become infected before the blood bank began screening for HIV-1 in 1987. None of the patients receiving blood from the center became infected with HIV-1, yet 60% of hemophiliacs treated at the hospital were HIV-1 infected. No one tested positive for HTLV-1, even though all 32 patients had received more than 6250 units of blood not screened for HTLV-1. This reflected the low incidence of HTLV-1 in the general population (0.05%). No one was positive for HBs-Ag or HBe-Ag.
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PMID:The frequency of blood-born viral infections in a population of multitransfused Brazilian patients. 827 57

The physiological role of GH secretion on growth retardation remains to be elucidated especially in patients with beta-thalassemia. In the present study, we investigated IGF-1 circulating levels as well as GH release following GHRH alone or combined with some inhibitors of somatostatin: pyridostigmine and arginine. In thalassemic patients lower IGF-1 circulating levels appear to be negatively correlated with both aspartate aminotransferase and alanine aminotransferase as well as with ferritin circulating levels indicating a probable role of hepatic hemosiderosis in IGF-1 production. The authors however suggest that reduced IGF-1 secretion is not the main cause of growth retardation since this would have elicited an enhanced response of GHRH in the presence of a normal hypothalamic pituitary axis. In contrast, they noticed that GH response to GHRH when expressed as area under the curve was lower in thalassemic patients compared to controls. The combination of GHRH with either pyridostigmine or arginine induced a GH secretion in thalassemics which was comparable to that of controls. The results of this study lead to conclude that the alteration of GH secretion is due, in such patients, to an increased somatostatin activity.
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PMID:GH secretion in thalassemia patients with short stature. 852 76


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