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)

We studied pituitary-gonadal function in 11 male and 5 female patients, aged 12-30 yr, with severe beta-thalassemia and chronic iron overload. All had normal basal serum cortisol, T4, and PRL concentrations and normal serum cortisol and GH responses to insulin-induced hypoglycemia and TSH responses to TRH. Of the 11 male patients (all over 17 yr of age), only 3 attained full pubertal development and 4 had subnormal serum LH and FSH responses to GnRH. As a group, their mean basal serum testosterone (T) level was low [11.7 +/- 4.9 (+/- SE) nmol/L; normal, 10-40 nmol/L], and 9 of the 11 male patients responded to hCG with a rise in serum T. Two of the 3 female patients over 17 yr of age were prepubertal with undetectable serum estradiol (E2) levels and absent serum LH and FSH responses to GnRH; the other female patient had regular menstrual cycles and normal serum E2 levels and LH and FSH responses to GnRH. Six of the prepubertal patients (4 males and 2 females, aged 17-30 yr) were studied serially for 3 yr after the start of chelation therapy. Despite a fall of median serum ferritin from 11,910 to 1,303 pmol/L, there was no progression of puberty, and their basal and GnRH-stimulated serum LH and FSH and serum T or E2 levels did not change. Three of these patients (1 male and 2 female) then received pulsatile sc GnRH therapy in addition to chelation therapy for 6 months with no improvement. We conclude that chronic iron overload in patients with severe thalassemia leads to variable degrees of hypogonadotropic hypogonadism, which do not respond to chelation therapy given late in the course of the disease. The hypogonadism in most patients was due to pituitary hyporesponsiveness to GnRH.
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PMID:Hypogonadotropic hypogonadism in severe beta-thalassemia: effect of chelation and pulsatile gonadotropin-releasing hormone therapy. 249 34

The effect of iron chelation using subcutaneous desferrioxamine on the iron-overloaded heart was studied prospectively over 4 years in 23 asymptomatic patients (mean age 13.2 +/- 5.3 years) with thalassaemia major and transfusion-dependent anaemia. The haemoglobin was maintained greater than 10 g/dl by transfusion and chelation therapy to achieve a negative iron balance. Chelation was closely supervised to ensure compliance. Despite an increase in calculated iron load due to transfusion from 34 +/- 27 g to 63 +/- 28 g, there was a sequential fall in serum ferritin levels from 3148 +/- 1956 ng/ml to 2228 +/- 1825 ng/ml (P less than 0.05). Abnormalities of left ventricular (LV) function, assessed by radionuclide angiography, were present at rest or during exercise in 18 of 23 patients (78%) prior to therapy. Normal LV function was restored in 11 of these 18 patients, five continuing to have abnormal function and two dying. There was a significant increase in resting LVEF from 50 +/- 8% to 57 +/- 6% (P less than 0.01). Peak exercise LVEF rose from 51 +/- 11% to 65 +/- 7% (P less than 0.001). We conclude that the common subclinical abnormalities of LV function induced by iron overload in unchelated patients with thalassaemia major can be reversed with long-term subcutaneous infusions of desferrioxamine.
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PMID:Sustained normalization of cardiac function by chelation therapy in thalassaemia major. 260 72

The prevalence of probable homozygous alpha+ thalassaemia in Zimbabwe was found to be 3.25 percent in a survey of hospital patients (n = 2,000), 7.6 percent in a Batonga village (n = 66), and 5.3 percent in 16 kindreds (n = 94) investigated for iron overload. The diagnosis was based on finding a reduced mean cell volume (MCV), reduced mean cell haemoglobin (MCH), increased red cell count (RBC), and a normal Haemoglobin. These cases usually had a normal red cell distribution width (RDW), and of three discriminant functions tested the MCV2 x MCH was the most useful. Iron deficiency was excluded in the community based surveys. The importance of recognizing these changes is emphasized so that inappropriate iron therapy is not given.
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PMID:Homozygous alpha+ thalassaemia in Zimbabwe: an unrecognized cause of hypochromia and microcytosis. 261 73

Twenty-nine patients with beta-thalassaemia major were treated in two Johannesburg hospitals between 1979 and 1984. They belonged to two ethnic groups--Mediterranean and Asian--and 53% were under the age of 6 years, the oldest being 20 years. Eight patients underwent splenectomy. All were regularly transfused and their quality of life greatly improved. The complication of regular transfusions is iron overload, which contributes to morbidity and mortality. Despite adequate iron excretion as a result of subcutaneous desferrioxamine (DFO) infusions, the patients showed significant iron overload, which suggested poor compliance in the home use of DFO and was the main long-term problem in the treatment of beta-thalassaemia major. Education needs to be directed at communities at risk and their doctors so that new cases can be prevented and the financial and emotional cost eased. If patients are given full support in complying with therapy, their life expectancy should be greatly increased.
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PMID:Beta-thalassaemia--the Johannesburg experience. 265 40

Regular subcutaneous desferrioxamine therapy has prolonged the life and reduced the incidence of cardiac, endocrine and liver complications of iron overload in patients with thalassaemia major and other refractory transfusion-dependent anaemias. Its full impact will be apparent only when patients who began this treatment as children 10 years ago reach adult life. The major problems with s.c. DF therapy are its cost and the difficulty of patient compliance with a painful and cumbersome method of administration. Attempts to maintain normal iron stores in these patients has resulted in significant toxicity caused by the excessive use of DF. Although recent studies have shown that long-term subcutaneous calcium diethylene triamine penta-acetic acid (Ca-DTPA) can be used as an effective alternative to s.c. DF (Wonke et al, 1988), this treatment presents additional potential problems of zinc depletion which can be prevented only by careful management. The prospects of an inexpensive, orally active iron chelator are now real (Kontoghiorghes and Hoffbrand, 1988) and it is to be hoped that long-term results at least as good as those with s.c. DF will be achievable. Such oral chelators may be available to a far wider group of patients, than s.c. DF, and the problems of cost and compliance may be diminished.
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PMID:Results of long-term subcutaneous desferrioxamine therapy. 266 Sep 32

We report two cases of severe Yersinia enterocolitica infection in children with homozygous thalassemia. One patient had septicemia and the other had mesenteric adenitis. Two factors can enhance the infectivity of Yersinia enterocolitica in children with thalassemia: iron overload and deferoxamine therapy. Laparotomy and cefotaxime-netilmicin therapy were successful in the patient with mesenteric adenitis. In the patient with septicemia, cefotaxime-netilmicin, then doxycycline-netilmicin failed, and recovery was finally achieved under rifampicin-netilmicin. Because of the possibility of septicemic dissemination secondary to digestive Yersinia enterocolitica infection in children with thalassemia, we advocate immediate discontinuation of deferoxamine and prescription of oral antimicrobial therapy (trimethoprim-sulfamethoxazole for instance) in every thalassemic patient with febrile diarrhea.
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PMID:[Yersinia enterocolitica infections and thalassemia major in children]. 266 80

Iron-chelating treatment is indicated in all children on prolonged transfusion therapy (i.e., chiefly patients with thalassemia and Blackfan-Diamond anemia). The purpose of iron-chelating treatment is to prevent the development of manifestations of iron overload including cardiac hemosiderosis and insulin-dependent diabetes mellitus (which are two potentially fatal complications), hepatic cirrhosis, hypoparathyroidism, hypothyroidism, and delayed puberty. Deferoxamine is the only effective iron-chelating agent and should be given in a daily dose of 40 mg/kg at initiation of the transfusion program. Administration is by subcutaneous infusions from 8 to 10 hours per day. The goal of iron-chelating treatment is to maintain serum ferritin levels between 500 and 1,000 ng/ml. This long-term treatment is a significant burden for patients and it can be hoped that non-toxic iron-chelating agents, active by mouth, will become available.
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PMID:[Iron chelation in children]. 268 51

Homozygous beta-thalassemic mice show many of the features seen in human beta-thalassemia, such as decreased hemoglobin, hematocrit, and red blood cell count as well as increased reticulocyte count. They also exhibit splenomegaly and a decrease in osmotic fragility of red cells. beta-thalassemic mice were examined for spontaneous iron overload at ages ranging from 20 to 595 days. Accumulation of iron was shown to occur in the spleen, liver, and kidneys but not in the heart. Sections of spleen, liver, kidney, and heart were stained for iron and subjectively scored. Image analysis microscopy was used to examine sections of spleen and liver. Nonheme iron in the four tissues was quantitated using the bathophenanthroline sulfonate colorimetric assay. An increase in tissue iron occurred primarily in the spleen, even before weaning, despite the low iron content of milk. Iron accumulation in the absence of blood transfusion is of interest because iron overload is the major cause of death in human beta-thalassemia.
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PMID:Tissue iron deposition in untransfused beta-thalassemic mice. 271 22

Iron chelation therapy must be associated with the regular blood transfusions required for thalassaemia and other chronic anemias. We report here a study concerning 4 groups of patients, aged 6 to 28, regularly transfused at Necker Enfants-Malades hospital: a) 20 with thalassaemia major; b) 6 with thalassaemia intermedia; c) 2 with sickle cell disease and d) 2 with Blackfan-Diamond syndrome. The transfusion regimen consisting of monthly or quarterly transfusions varied as a function of the groups. Desferal was used in all patients. The dosage and the route of administration (IV, IM, SC) were adapted to the amount of iron transfused and to the nature of the disease. The serum ferritin level was considered as the indicator of the iron overload. Comparisons were established between the quantities of iron transfused, ferritin levels, and parameters such as dosage, route of administration and compliance to Desferal. During the period of study 3 patients died from cardiac failure due to transfusional hemosiderosis. Endocrine complications (diabetes 2 cases, hypocalcemia 3 cases, hypothyroidism 1 case and delayed puberty 7 cases) were observed. This high incidence of complications induced by post-transfusional iron overload has recently prompted us to improve the quality of chelation therapy through the use of the services of a specialized center where patients as well as their families can be trained more adequately in home care and self-treatment.
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PMID:[Treatment of post-transfusion iron overload by deferoxamine]. 273 4

Clinical evidence suggests that individuals with chronic iron overload may be at increased risk of bacterial infection. We studied this question by using a unique model in which mice homozygous for a deletion in the gene encoding for the beta-major globin develop moderate anemia, splenomegaly, and tissue iron overload, a syndrome similar to beta-thalassemia in humans. Mice heterozygous for the gene deletion were phenotypically normal. Homozygous mice were significantly more susceptible to infection with Listeria monocytogenes than were heterozygous mice (P less than 0.01). This increased susceptibility was associated with a greater number of organisms in the liver and spleen than was found in heterozygous mice (P less than 0.05). However, histologic studies demonstrated similar inflammatory responses within these organs in homozygous and heterozygous mice. The increased susceptibility of homozygous mice to infection with L. monocytogenes was not seen when homozygotes were immunized with a low dose of L. monocytogenes. Although the results were not as striking as with L. monocytogenes, homozygous mice were also found to be more susceptible to infection with Salmonella typhimurium than were heterozygous mice (P less than 0.05). Splenic mononuclear cells from homozygous mice demonstrated less responsiveness in vitro to the mitogens concanavalin A and phytohemagglutinin than did those from heterozygotes (P less than 0.05). These data suggest that there is a generalized defect in innate immunity in homozygous mice which makes them more susceptible to infection by L. monocytogenes and S. typhimurium. The site of this immunological defect is not known but is most likely in the mononuclear phagocyte and may be due to tissue iron overload.
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PMID:Resistance to infection in murine beta-thalassemia. 292 37


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