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

Puberty is normally associated with a decline in tissue sensitivity to insulin. However, normal glucose homoeostasis is maintained by compensatory increases in glucose-stimulated insulin secretion. Here we describe studies performed in healthy children which have determined the site of insulin resistance (hepatic vs. peripheral) and whether this resistance extends to other substrates such as amino acid and free fatty acid metabolism. The changes in insulin action and secretion that are normally seen during puberty lead us to question the role of insulin resistance in other childhood conditions that are complicated by the later development of type I or type II diabetes, namely thalassaemia major and Turner's syndrome. These studies showed that in patients with thalassaemia and Turner's syndrome, insulin resistance and increased insulin secretion are very early metabolic defects that appear before the development of diabetes.
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PMID:Insulin-resistant syndromes in children. 826 87

To better understand the pathophysiology of glucose intolerance secondary to iron overload in patients with thalassemia major, we performed tolbutamide-modified frequently sampled iv glucose tolerance tests (FSIGTs) in 10 thalassemic patients (6 males and 4 females; 21.7 +/- 1.2 yr old; body mass index, 19.7 +/- 0.6 kg/m2) and 10 healthy controls (5 males and 5 females; 22.4 +/- 1.3 yr; body mass index, 20.6 +/- 0.5 kg/m2). Insulin secretion and action were quantified by application of the minimal model of glucose kinetics and the combined model of insulin and C-peptide kinetics to the FSIGT data. The insulin sensitivity index was significantly lower in thalassemia patients [72 +/- 12 min-1(nmol/mL)] compared to controls [158 +/- 21 min-1(nmol/mL); P = 0.0026]. The integrated insulin response during the FSIGT was significantly greater in thalassemia patients than in controls after tolbutamide injection (P = 0.042). The difference in insulin levels was apparently due to reduced hepatic insulin extraction in thalassemia (78 +/- 2% vs. 68 +/- 3%; P = 0.0251). Seven of the 10 thalassemia patients were studied prospectively at 6-month intervals for 6-12 months. Repeated measures analysis of variance indicated that across a 6-month interval, there was a decrease in the total integrated insulin response (P = 0.002), with no change in insulin sensitivity (P = 0.86). In conclusion, patients with thalassemia major have significant insulin resistance, which may be compensated for by an elevated circulating insulin level. The elevated insulin level in response to tolbutamide appears to be due to reduced hepatic extraction of insulin and not to an enhanced insulin secretory response. Over time, patients with thalassemia experience a reduction in their circulating insulin levels. Persistent insulin resistance along with a progressive reduction in circulating insulin levels may lead to glucose intolerance and diabetes mellitus, which have a high prevalence in patients with thalassemia major.
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PMID:Factors determining glucose tolerance in patients with thalassemia major. 834 55

Hyperinsulinemia and insulin resistance precede the development of diabetes in patients with thalassemia major on hypertransfusion/desferoxamine therapy. To examine whether these early metabolic defects could be reversed, seven nondiabetic patients with thalassemia (17 +/- 4 y) were studied for 12 mo before and during 12 mo of low-dose treatment with glyburide (1.25 to 3.75 mg/d), a second-generation oral hypoglycemic agent. Plasma glucose responses to oral glucose (1.75 g/kg body weight) were normal before and after glyburide. Plasma insulin responses were markedly increased before glyburide therapy (area under insulin response curve 86 +/- 15 and 96 +/- 15 versus 40 +/- 5 nmol/min/L in normal controls, p < 0.001). However, insulin responses to glucose fell significantly after 3 mo of glyburide (to 52 +/- 7 nmol/min/L, p < 0.05 versus pretreatment) and were normalized after 12 mo (42 +/- 7 nmol/min/L, p = NS versus controls). The rate of insulin-stimulated glucose metabolism during euglycemic insulin clamps (40 mU/m2/min) was low in the patients before treatment (163 +/- 10 versus 215 +/- 17 mg/m2/min in controls, p < 0.05) and increased to 205 +/- 30 mg/m2/min after 3 mo of glyburide. The treatment was well tolerated. In conclusion, in nondiabetic, hyperinsulinemic, thalassemic patients, chronic glyburide therapy normalizes insulin responses to oral glucose. To the extent that insulin hypersecretion contributes to the development of diabetes in thalassemia, glyburide therapy may provide a means of postponing this complication of the disease.
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PMID:Correction of hyperinsulinemia by glyburide treatment in nondiabetic patients with thalassemia major. 851 Oct 23

We studied the prevalence of HCV antibody seropositivity and serum alanine concentrations in a random sample of healthy Egyptian children (n = 110) as well as in four high risk groups of children. Group 1 included 18 children with thalassemia major, group 2 included 17 children with insulin-dependent diabetes mellitus (IDDM), group 3 included 21 children with schistosomal hepatic fibrosis (SHF), and group 4 included 20 children with chronic rheumatic heart disease (RHD). The prevalence rate of HCV seropositivity was 12 per cent in normal children, 44 per cent in thalassemic children, 29 per cent in children with IDDM, 38 per cent in children with SHF and 0 per cent in patients with RHD. The liver size was significantly larger in HCV seropositive normal children as well as in HCV seropositive children with thalassemia and SHF compared to the seronegative children in each group respectively (P < 0.05). In all groups serum alanine transferase concentrations were significantly higher in HCV seropositive v. seronegative children. This pointed out to the high risk of continuous parenchymal hepatic damage in these children following acute HCV infection. In summary, our data revealed a relatively high prevalence of HCV antibody seropositivity in healthy Egyptian children compared to reports from other countries, and a significantly high prevalence of HCV seropositivity in children with thalassemia, IDDM, and SHF which carries a considerably high risk for development of chronic liver disease in these patients.
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PMID:Prevalence of hepatitis-C antibody seropositivity in healthy Egyptian children and four high risk groups. 860 41

Homozygous transfusion-dependent beta-thalassemia patients manifest cardiac, hepatic, endocrine, and metabolic disorders attributable to chronic anoxia and iron overload. Short stature, delayed sexual maturation, diabetes mellitus, hypothyroidism, hypoparathyroidism, and metabolic bone disease can and should be diagnosed as early as possible so that the intervention can be fruitful. Primary or secondary amenorrhea is due primarily to pituitary gonadotrope hemosiderosis, as attested by pathology data and the demonstration in vivo of nonstimulable follicle-stimulating hormone and luteinizing hormone release and secretion after the exogenous administration of gonadotropin-releasing hormone or its agonistic analogs. Ovulation can be achieved with the use of exogenous gonadotropins provided that the ovary has no siderosis (as seen in neglected patients) or damage induced by drugs used for bone marrow transplantation. Once pregnancy is achieved, it should be considered high risk and be dealt with or cared for by an expert team to ensure a successful outcome.
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PMID:Reproductive health in patients with beta-thalassemia. 895 76

Regular blood transfusions in patients with beta-thalassaemia major lead to secondary hemochromatosis in the majority of cases. As a consequence of chronic iron overload, many endocrinopathies may occur. The most frequent endocrine dysfunction is hypogonadotropic hypogonadism, which is mainly responsible for osteopenia in as much as 80% of thalassemic patients. The frequencies of other endocrine disorders (hypothyroidism, diabetes mellitus and hypoparathyroidism) are lower. We investigated 5 female patients aged 22-25 years for endocrine dysfunction and bone density. All presented with hypogonadotropic hypogonadism and amenorrhea (four primary and one secondary). 4 patients showed absent or delayed pubertal development and short stature (below 10th percentile). In all five, hypogonadism is the most relevant cause of osteopenia as demonstrated by osteodensitometry. Endocrine disorders, especially absent pubertal development, should be detected in good time and treated with hormonal replacement. Established osteopenia is treated hormonally and with vitamin D3 and calcium.
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PMID:[Osteopenia in beta-thalassemia major]. 898 99

Oxidant-induced damage has been proposed to be the underlying mechanism for loss of membrane phospholipid asymmetry in the erythrocyte membrane. In sickle cell disease, thalassemia, and diabetes as well as in senescent erythrocytes, an apparent correlation between oxidative damage and loss of phosphatidylserine asymmetry has been reported. In the present study, erythrocytes were subjected to various levels of oxidative stress and/or sulfhydryl modifying agents. The transmembrane location of phosphatidylserine (PS) was assessed by FITC-conjugated annexin V labeling and the PS-dependent prothrombinase assay. Transbilayer movement of spin-labeled PS was used to determine aminophospholipid translocase activity. Our data show that cells did not expose PS as the result of oxidative stress induced by phenylhydrazine, hydrogen peroxide, tert-butyl hydroperoxide, cumene hydroperoxide, or sulfhydryl modification by N-ethylmaleimide (NEM) and diamide, even under conditions that led to severe cellular damage and impairment of aminophospholipid translocase activity. In contrast, the increase of intracellular calcium induced by treatment with calcium and ionophore A23187 leads to a rapid scrambling of the lipid bilayer and the exposure of PS, which can be exacerbated by the inhibition of aminophospholipid translocase activity. Oxidation of the cells with hydrogen peroxide or phenylhydrazine did not affect A23187-induced uptake of calcium, but partly inhibited calcium-induced membrane scrambling. In conclusion, oxidative damage of erythrocytes does not induce exposure of phosphatidylserine on the membrane surface, but can interfere with both aminophospholipid translocase activity and calcium-induced randomization of membrane phospholipids.
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PMID:Oxidative damage does not alter membrane phospholipid asymmetry in human erythrocytes. 918 59

The incidence of endocrine dysfunction in relation to the detailed genotype of beta-thalassaemia is investigated in this study. In addition, the association of genotype to specific clinical features of beta-thalassaemia is examined, together with the relationship between serum ferritin levels and endocrine complications. Ninety-seven patients were included, all with transfusion dependent beta-thalassaemia. Patients were divided into 2 categories; group 1 consisted of patients with a beta0/beta0 genotype with or without a concomitant alpha-globin gene deletion as well as patients with beta0/beta+ or beta+/beta+ genotype and normal alpha-globin chain synthesis. Group 2 included patients with beta+/beta+ or beta+/beta0 genotype and one alpha-globin chain deletion and those with a moderate amount of beta-globin chain synthesis (beta++) and normal alpha-globin chain synthesis. The results showed that group 1 patients were more likely to have severe clinical disease (p=0.005). Sixty-four patients (66%) had at least 1 endocrine disorder and 39 (40%) had multiple endocrinopathies; the most common abnormality was hypogonadotrophic hypogonadism (HH). There was a significant association between patients with group 1 genotypes and the presence of HH and impaired glucose tolerance or diabetes. A positive correlation was demonstrated between serum ferritin concentrations and the presence of thyroid or parathyroid dysfunction.
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PMID:Incidence of endocrine complications and clinical disease severity related to genotype analysis and iron overload in patients with beta-thalassaemia. 929 54

Patients with beta-thalassemia often present with abnormalities in growth and other endocrine functions. Growth hormone (GH) secretion is controlled via somatostatin and growth hormone releasing hormone (GHRH). Recently, Hexarelin, a new potent GH secretagogue (His-D-2-Methyl-Trp-Ala-Trp-D-Phe-Lys-NH2), was synthesized. Our study was designed to assess and compare its efficacy as a GH secretagogue to GHRH 1-29 in beta-thalassemia. Eighteen patients, regularly transfused and chelated, were studied; 11 were short statured. None had diabetes mellitus, hypothyroidism, hypopara-thyroidism or major organ failure. We measured GH at 0, 30, 60, 90, 120 min after GHRH 1-29 or Hexarelin administration. Hexarelin p.o. or i.v. evoked a brisk rise of serum GH which was significantly higher (p < 0.01) than that induced by GHRH 1-29 i.v. In conclusion, Hexarelin has greater GH releasing capacity than GHRH 1-29 at 1 microgram/kg i.v. and can thus be viewed as a potential therapeutic agent in GH deficient states.
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PMID:Growth hormone release by the novel GH releasing peptide hexarelin in patients with homozygous beta-thalassemia. 936 40

The non-healing leg ulcer is examined by discussing three disease processes: peripheral vascular occlusive disease (PVOD), chronic venous insufficiency (CVI), and vasculitis. For PVOD, management decisions are based on risk factors and disease history. Comprehensive management includes the discontinuation of smoking, exercise conditioning and regulation of diabetes, hyperlipidemia, hypertension, and the appropriate application of anticoagulant/antiplatelet drugs. Methods of surgical management include bypass with autogenous or synthetic material in addition to reconstructive surgery with patch angioplasty or extra-anatomic bypass, amputation, percutaneous transluminal angioplasty/stents, thrombolytic infusion, atherectomy, intraluminal ultrasound, and angioscopy. The optimal healing environment for all ulcers prevents contamination, pain, and fluid loss. In CVI, higher venous pressure in the veins of the lower limb during exercise results in ambulatory venous hypertension and ulceration. Various theories are associated with the disease and ulceration process; the classic treatment of elevation, ambulation, and compression for venous disease remains unchallenged. Diagnosis is based on history, physical examination, invasive venography, and/or non-invasive studies. Two groups of vasculitic disorders that share varying degrees of vascular inflammation and necrosis are arteritis (lupus, erythematosus, periarteritis nodosa, dermatomyositis) and blood dyscrasias (sickle cell disease, thalassemia). Leg ulcers associated with vasculitis are due to inadequate tissue oxygenation at the local level, are typically chronic, slow to heal, and commonly recur.
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PMID:The non-healing leg ulcer: peripheral vascular disease, chronic venous insufficiency, and ischemic vasculitis. 939 80


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