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

Thalassemia major is a severe and transfusion-dependent anemia that occurs in persons homozygous for a mutation that affects the capacity for synthesis of the beta-globin subunit of hemoglobin. Characterization of the molecular defects that cause beta-thalassemia is providing insight into the mechanism of globin gene regulation. Newer approaches to the management of thalassemia major include more effective chelation by use of subcutaneous desferrioxamine and attempts to obtain young erythrocytes with a longer potential for survival in recipient patients. Development of more effective chelators that may be given orally is an ongoing effort. Noninvasive evaluation of cardiac structure and function in patients with thalassemia major suggests that myocardial iron deposits begin at an early age, causing functional impairment long before the onset of clinical symptoms. Prevention or reversal of these cardiac abnormalities remains the goal of chelation therapy.
 ...
PMID:Thalassemia major: molecular and clinical aspects. NIH Conference. 39 Nov 18

Heterozygous classical beta-thalassemia was found in 13 subjects of pure German descent, 11 of them from the Bergische Land (NW Germany) during the past three years. Clinically it became manifest in a moderate degree of anemia with marked hypochromia and reduced mean corpuscular volume. The number of red blood corpuscles and the value for serum iron were ascertained to be in the upper limits of normal or raised. The diagnosis of Mediterranean anemia was confirmed by hemoglobin electrophoresis with a rise in HbA2 of more than 3%. A slight increase in HbF may also occur. The importance of genetic counseling of thalassemia patients is emphasized. The occurrence of thalassemia even in pure German populations must be increasingly reckoned with.
 ...
PMID:[Thalassemia minor in families of German descent in the Bergische Land (author's transl)]. 40 46

Iron deficiency anaemia secondary to menorrhagia was observed in a woman of Greek Cypriot origin. Moderate thrombocytopenia was also present. Treatment with parenteral and oral iron produced a transient thrombocytosis, the platelet count then returning to normal. Subsequent analysis revealed that she also carried the alpha1-thalassaemia trait. Previous reports of thrombocytopenia responsive to iron treatment are reviewed.
 ...
PMID:Thrombocytopenia and iron deficiency anaemia in a patient with alpha1-thalassaemia trait. Response to iron therapy. Case report. 41 76

A patient of 14 years suffering from secondary haemosiderosis and thalassaemia major was treated with i.v. desferrioxamine in doses up to 3 g/d. Urine iron loss ranged from 46-158 mg/d. Despite improvement in cardiac and hepatic status the patient developed acute renal insufficiency of the pre renal type. The possible role of desferrioxamine in this complication is discussed. Desferrioxamine given s.c. or i.v. effects a marked urinary iron loss but its use may not be without significant complications.
 ...
PMID:Acute renal insufficiency occurring during intravenous desferrioxamine therapy. 45 59

A thalassemia screening program was implemented at our institution using the finding of a mean corpuscular volume less than 80 fl as the index of abnormality. Further evaluation using hemoglobin (Hb) electrophoresis and serum iron studies was carried out according to the scheme detailed below. A diagnosis of thalassemia was made in 33 women (42 pregnancies). Eight patients had alpha-thalassemia trait, 23 beta-thalassemia trait, and two Hb H disease. Thalassemia trait did not have any adverse effect on pregnancy outcome. In two couples the fetuses were at risk for homozygous disease and in one couple the fetus was at risk for sickle cell beta-thalassemia. The screening program described is an effective and inexpensive means of detecting thalassemia in an antenatal population and is applicable to most every clinic or office setting.
 ...
PMID:Thalassemia and pregnancy: results of an antenatal screening program. 46 58

The rarity of hemoglobin (Hb) H disease in combination with sickle trait may be due in part to the absence of actual Hb H in individuals who, nonetheless, have inherited the deletion of three alpha-globin genes. We describe here a boy with persistent microcytic, hypochromic anemia despite adequate iron stores, who exhibited splenomegaly with a normal reticulocyte count and only rare inclusions in circulating erythrocytes. Starch gel electrophoresis and isoelectric focusing at age 5 yr showed 21% Hb S, persistent Hb Bart's, but no Hb H. Recticulocyte alpha/non-alpha globin chain synthesis ratio was 0.58 at age 5. The mother (Asian) had laboratory evidence of alpha-thalassemia trait and the father (Black) had sickle trait. The nature of alpha-thalassemia in this patient was investigated both by liquid hybridization and by the Southern method of gene mapping, in which DNA is digested with restriction endonucleases and the DNA fragments that contained the alpha-globin structural gene identified by hybridization with complementary DNA. The patient had only one alpha-globin structural gene, located in a DNA fragment shorter than that found in normal or alpha-thalassemia trait individuals, but similar to that present in other patients with Hb H disease. Morphologic studies of bone marrow by light and electron microscopy revealed erythroid hyperplasia with inclusions in polychromatic and orthochromatic erythroblasts, suggesting early precipitation of an unstable hemoglobin. The lack of demonstrable Hb H may be the result of both diminished amounts of beta(A) available for Hb H formation (since one beta-globin gene is beta(S)) and the greater affinity of alpha-chains for beta(A) than beta(S)-globin chains leading to the formation of relatively more Hb A than Hb S. The presence of a beta(S) gene may thus modify the usual clinical expression of Hb H disease.
 ...
PMID:Modification of hemoglobin H disease by sickle trait. 47 66

Ferrokinetic studies were carried out in 8 patients with heterozygous beta-thalassaemia with anaemia of varying severity. Effective and ineffective erythropoiesis, mean red cell lifespan and non-erythroid iron turnover were estimated from the experimental data through a mathematical model of iron kinetics. Erythropoietic activity was markedly increased in all patients, but was variably ineffective (from 10 to 74%). A negative correlation (r = 0.855, P less than 0.01) was found between the amount of ineffective erythropoiesis and Hb level. Red cell lifespan was variably shortened and there was a negative correlation between the degree of daily peripheral haemolysis and Hb level (r = 0.733, P less than 0.05). Non-erythroid iron turnover was increased in most patients. The results provide quantitative measurements of the mechanisms responsible for the wide variation of the Hb level in heterozygous beta-thalaeeaemia. Ineffective erythropoiesis seems to be the major reason for the anaemia. Peripheral haemolysis contributes to it, especially in the most severely affected patients. The increased non-erythroid iron turnover may be responsible for the pathology which characterizes heterozygotes in the adult life.
 ...
PMID:Quantitative evaluation of the mechanisms of the anaemia in heterozygous beta-thalassaemia. 49 74

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.
 ...
PMID:Platelet dysfunction in homozygous beta-thalassemia. 52 94

The sickle-cell gene contributes substantially to the presentation of anaemia in certain areas of the Arabian Peninsula. However, the clinical presentation of the homozygous state of Hb S is less severe than that observed in other ethnic groups, such as American negroes. In the present paper, biosynthesis studies performed on reticulocytes from heterozygotes and homozygotes for the Hb S give further indications of the mild nature of sickle-cell disease in Arabia. Comparison of two affected families, from Saudi Arabia and Jordan, showed that clinical manifestation of the disease is mirrored by the biochemical and haematological findings in affected individuals. The results are discussed in terms of the effect of co-existing thalassaemia and/or iron deficiency with Hb S. It is suggested that both genetic and acquired conditions play a role in the clinical features of the disease. The mechanisms responsible for regulation of alpha-chain synthesis by iron (haem) deficiency are discussed.
 ...
PMID:On the nature of sickle-cell disease in the Arabian Peninsula. 53 90

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.
 ...
PMID:Iron overload despite partial gastrectomy. 53 65


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>