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)

To assess the influence of diminished oestrogen production on bone density, we studied 23 amenorrhoeic women and 20 controls (age range 16-29 years) divided into four groups: group 1: 6 patients with idopathic hypogonadotrophic hypogonadism with primary amenorrhoea (IHH); group 2: 5 patients with delayed puberty owing to thalassaemia major (TM); group 3: 12 patients with secondary hypothalamic amenorrhoea (HA); group 4: 20 women with normal menses (controls). Secondary sexual characteristics had developed in all except the women with TM. Groups 1 and 2 had never menstruated and group 3 had been amenorrhoeic for 6 months to 3 years. The control group was studied during the follicular phase of the cycle. None of the patients were taking oestrogens at the time of observation. Plasma concentrations were determined for 17 beta-oestradiol (E2), deidroepiandrosterone sulphate (DHEA-S), cortisol (F), prolactin (PRL), thyroid hormones (T3 and T4), and gonadotrophins (LH and FSH). Spinal bone mineral density (BMD g/cm2) was assessed by dual photon absorbiometry. BMD (mean +/- 1SD) was reduced in the patients (group 2: 0.920 +/- 0.95; group 1: 0.980 +/- 0.94; and group 3: 1.037 +/- 0.75) as compared with the controls (1.290 +/- 0.95) (P less than 0.01). In the three groups of patients, plasma E2 levels were lower than 50 pg/ml and were positively correlated with the BMD. As expected, plasma gonadotrophin levels were highly and significantly reduced (P less than 0.01) in the patients, compared with that of the controls. These results suggest that reduced spinal BMD in hypogonadic women may be related to the lack of oestrogenic influence on bone metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduced spinal bone density in young women with amenorrhoea. 183 88

In this study, 50 thalassemia patients were tested using dual-energy X-ray absorptiometry (DEXA) and in vivo neutron activation analysis (IVNAA) to determine their bone mineral status. Both techniques were suitable for this purpose. Lower age was found to correspond to lower liver iron content and higher bone mineral content in the normal range. Patients undergoing treatment with transfusion had higher bone mineral content. Osteopenic patients had higher hepatic iron content than those with normal bone status. In the case of DEXA, bone mineral content (BMC) divided by height cubed was found to be a better indicator of bone mineral status than the BMD usually given. Liver density as determined by DEXA correlates well with hepatic iron.
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PMID:A study on children's condition thalassemia using neutron activation analysis and other techniques. 771 Aug 41

Patients with beta-thalassemia major (beta-thalassemia) frequently have bone disorders of multifactorial etiology. We attempted to analyze the relationship between the bone mineral density ([BMD] measured by dual-photon absorptiometry) and auxanologic parameters, degree of siderosis, function of the growth hormone (GH)/insulin-like growth factor-I (IGF-I)/IGF-binding protein-3 (IGFBP3) axis, calcium-phosphate balance, parathyroid hormone (PTH), and cytokines (interleukin-1beta [IL-1] and tumor necrosis factor-alpha [TNF-alpha]) in 30 prepubertal children with beta-thalassemia major and 15 age-matched children with constitutional short stature (CSS), who have normal glucose tolerance and thyroid function. Children with beta-thalassemia had a significantly decreased BMD and mean BMD% for age and sex (0.75+/-0.24 g/cm2 and 71%+/-10%, respectively) versus children with CSS (1.06+/-0.3 g/cm2 and 92%+/-7%, respectively). Thalassemic patients had significantly lower circulating concentrations of IGF-I and IGFBP3 (49+/-21 ng/mL and 1.2+/-0.25 mg/L, respectively) compared with control children (153+/-42 ng/mL and 2.1+/-0.37 mg/L, respectively). The GH response to provocation by clonidine and glucagon was defective (peak GH < 7 microg/L) in 12 of the 30 thalassemic children. Serum concentrations of IL-1beta and TNF-alpha did not differ among the two study groups. Hypocalcemia was detected in five of the 30 thalassemic patients: hypoparathyroidism was diagnosed in two of the five and rickets in the other three. BMD was highly correlated with the circulating concentrations of IGF-I and IGFBP3, as well as with the auxanologic parameters (age, weight, height, height standard deviation score [HSDS], and body mass index [BMI]). It is suggested that increasing the circulating IGF-I concentration through aggressive nutritional therapy and/or GH/IGF-I therapy with supplementation with vitamin D and/or calcium might improve bone growth and mineralization and prevent the development of osteoporosis and consequent fractures in these patients. Such therapy requires blinded controlled trials.
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PMID:Bone mineral density in prepubertal children with beta-thalassemia: correlation with growth and hormonal data. 959 44

An increasing number of adult thalassaemics have been complaining of aches and pains of varying degrees of severity. In a minority the pains are debilitating and there is stiffness in movement. This study is an attempt to understand the osteoporosis of thalassaemia using DEXA and MRI as the main investigative tools. 122 patients with homozygous beta-thalassaemia were examined by DEXA. It was found that almost half had BMD below two standard deviations from the mean for the normal population, especially in the lumbar spine. There was no marked worsening with age. However the proportion of patients who had their first transfusion after the 3rd year (especially after the 6th) was significantly greater in those with the low BMD. There is also an excess of hypogonadic thalassaemics amongst those with low BMD. 72 thalassaemics were examined by MRI of marrow. Hypercellular, dark marrow on T1 weighted images found in young patients (20-30 yr) was replaced by fatty marrow in later life (30-40 yr). In a group of 21 older thalassaemics (33-62 yr) extreme bone marrow expansion was expressed by the reappearance of hypercellular areas, giving the impression of patchiness which affects not only the diaphyses but also the metaphyses. These patients mostly (66%) had thalassaemia intermedia and had started irregular transfusion after the 6th year of life. About 75% had a BMD below 2 SD. The conclusion is that patients who were late in receiving blood and especially those with thalassaemia intermedia had a more expanded bone marrow with pressure on cortical bone which caused pain in several cases. An attempt was made in 10 patients to reduce marrow hyperplasia by using hydroxyurea. Results showed a relief of pain and modification of magnetic signal intensity.
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PMID:Bone pain in thalassaemia: assessment of DEXA and MRI findings. 1009 Nov 46

Hepatitis C virus (HCV) infection may occur in infants and children, although it is much less common than it is in adults. The main transmission routes include mother-to-infant transmission, use of HCV infected blood products, unsterile needles or syringes and other invasive procedures. The natural course of HCV infection in children is variable: some (20-40%) develop an acute resolving infection and spontaneous regression occurs in approximately one-third of infants of HCV infected mothers before 2 years of age. Approximately 60-80% of HCV infected children develop a chronic infection with varying degrees of activity and fibrosis, mostly mild during childhood. However, the potential risks of liver cirrhosis and hepatoma during later life are obvious. Interferon is the main agent used to treat HCV infection in children. The response to interferon at the end of 4-12 months of therapy ranges from 25-90%. A sustained response was found in 36-56% of children 6-36 months after the end of therapy. The duration of therapy is recommended to be 12 months. At the end of 3 months, an evaluation of the response is indicated in the majority of children, except those with thalassemia, in whom evaluation of response should be conducted at the end of 6 months of therapy. The benefit of other therapies, such as combination therapy with interferon and ribavirin in children with hepatitis C is currently under investigation.
Baillieres Best Pract Res Clin Gastroenterol 2000 Apr
PMID:Treatment of chronic hepatitis C virus infection in children. 1089 Mar 26

Beta-thalassaemia major and sickle-cell disease (SCD) reduce lifespan and quality of life for >300000 children and young adults worldwide. The only cure for both disorders is allogeneic stem cell transplantation (SCT). The decision-making processes in recommending SCT for patients with thalassaemia and SCD are different. For thalassaemia, where transfusion-related iron overload is universal, SCT should be offered to all patients <17 years because long-term survival and thalassaemia-free survival are about 80 and 70% respectively. For thalassaemics unable to comply with medical treatment, SCT offers a significant survival advantage; however, for patients with optimal medical care, short-term survival after SCT is inferior to medical treatment, and SCT instead offers a life free from transfusions and iron chelation. The clinical heterogeneity of SCD means that SCT is recommended only for selected patients with severe disease, particularly sickle-related neurological problems, for whom long-term survival and SCD-free survival after SCT approach 92 and 86% respectively. We here review the evidence available to help physicians evaluate the role of SCT for individual patients with thalassaemia major or SCD.
Best Pract Res Clin Haematol 2001 Dec
PMID:Allogeneic transplantation for haemoglobinopathies. 1192 23

Patients with beta-thalassaemia major are susceptible to osteopenia due to several factors which interfere with bone remodeling. It is known that bone metabolism and skeletal consolidation result from a complex sequence of hormonal changes, where the concerted actions of GH, IGF-I and sex hormones and their receptors, are responsible for the timing and attainment of skeletal consolidation. IGF-I and the corresponding binding protein (IGFBP-III), markers of bone metabolism and lumbar and femoral neck BMD were measured in 28 adult patients, undergoing hormonal replacement and chelation therapy and a hypertransfusion program, with beta-thalassaemia major (12 males with mean age 22.5+/-3.1 and 16 females with mean age 27.5+/-8.2), and in 28 healthy volunteers matched for age, anthropometric features and sex to the patients. BMD values, both at lumbar and femoral neck level were significantly lower (p<0.001 and p<0.05) by 18.7 and 4.2% respectively, in patients than in the controls. Markers of bone resorption [pyridinoline (Pyr) 78.1+/-15.7 vs 47.5+/-11.2 pmol/pmol urinary creatinine, p<0.001 and deoxypyridinoline (D-Pyr) 21.9+/-3.5 vs 14.5+/-5.4 pmol/ micromol urinary creatinine, p<0.001] were higher in patients than in controls, whereas the marker of bone formation was slightly lower [osteocalcin (BGP) 3.8+/-0.6 vs 4.6+/-1.7 pmol/ml, p<0.05]. Plasma levels of IGF-I (21.07+/-5.12 vs 35.25+/-8.33 nmol/ml, p<0.001) and IGF binding protein III (IGFBP-III) (1.9+/-0.4 vs 2.5+/-0.1 mg/ml, p<0.001) were lower in patients than in controls and positively correlated with BMD L2-L4 (r=0.57, p<0.05 and r=0.47, p<0.05 respectively), BMD neck (r=0.40, p<0.05 and r=0.34, p<0.05 respectively) and BGP (r=0.52, p<0.05 and r=0.34, p<0.05 respectively). Our beta-thalassaemic patients, in spite of normalizing hemoglobin levels, adequate hormone replacement and chelation therapies, showed osteopenia and an unbalanced bone turnover with an increased resorptive phase and a decreased formation phase probably correlated to low levels of IGF-I and IGFBP-III observed in our study.
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PMID:Osteoporosis and beta-thalassemia major: role of the IGF-I/IGFBP-III axis. 1203 Jun 5

Effective management of iron overload in thalassaemia requires monitoring both for iron toxicity and the effects of excessive chelation. Careful monitoring together with adherence to established regimens using desferrioxamine (DFO) results in a 78% survival rate at 40 years of age at UCLH, with steadily improving survival as progressive cohorts receive chelation earlier in life. By contrast, survival is considerably below this in non-specialist centres. The prognostic significance of the measures being used in monitoring should be known so that decisions about chelation management are evidence-based. Serum ferritin measurement, although easy to perform frequently, is subject to variability and falsely high or falsely low values in relation to body iron are frequently obtained. However, there is evidence that persistently high ferritin values above 2500 microg/l have poor prognostic significance in patients treated with DFO. Liver iron predicts total body iron in a more predictable way than serum ferritin in thalassaemia. Liver iron concentrations of 15 mg/g dry weight appear to predict those patients who develop heart failure in subjects treated with DFO. The prognostic significance of this measurement or indeed other measurements of iron overload in patients treated with other chelation regimens is not known. Recent advances with MRI imaging have aroused interest in its use for monitoring patients with thalassaemia. A recent publication suggests a relationship between left ventricular ejection fraction and cardiac T2*, the value of which shortens with increasing iron concentrations in the liver and hence by inference in the heart. The prognostic value of this technique has not yet been demonstrated in prospective studies and hence changes in therapy based on this measurement alone should be considered with caution at this time. The value of monitoring to decrease morbidity from iron overload is also discussed, particularly with reference to the estimation of iron deposition in the pituitary.
Best Pract Res Clin Haematol 2002 Jun
PMID:Monitoring chelation therapy to achieve optimal outcome in the treatment of thalassaemia. 1240 11

Iron chelation therapy is the only therapeutic approach that leads to enhanced iron excretion in beta-thalassaemia major and other transfusion-dependent patients. Although desferrioxamine has been used in such treatment over the last three decades, it is not an ideal drug due to its poor oral availability. Consequently extensive research effort has been directed towards the identification of non-toxic, orally active iron chelators. An ideal candidate must possess a range of critical physicochemical and biological properties, such as high selectivity and affinity for iron(III), tightly controlled distribution and metabolic profiles and low toxicity. Unfortunately, hexadentate ligands are generally associated with poor oral bioavailability, whereas many tridentate and bidentate molecules are orally active. The tridentate triazoles have been investigated for clinical potential; they are readily absorbed from the gastrointestinal tract and promote iron excretion with high efficacy. In similar fashion, several bidentate hydroxypyridinones have been demonstrated to possess potential as oral chelating agents.
Best Pract Res Clin Haematol 2002 Jun
PMID:Oral iron chelators--development and application. 1240 12

Labile plasma iron (LPI) represents a component of non-transferrin-bound iron (NTBI) that is both redox-active and chelatable, capable of permeating into organs and inducing tissue iron overload. It appears in various types of hemosiderosis (transfusional and non-transfusional) and in other iron-overload conditions. Sustained levels of LPI could over time compromise organ (e.g. heart) function and patient survival. With the advent of methods for measuring LPI in the clinical setting, it has become possible to assess the implications of LPI in the management of iron overload based on regimens of iron chelation. As LPI is detected primarily in patients with transfusional iron overload and other forms of hemosiderosis, we review here regimens of iron chelation with deferrioxamine and deferiprone (separately or combined) in terms of their efficacy in minimizing daily exposure to LPI in thalassemia major and thalassemia intermedia patients.
Best Pract Res Clin Haematol 2005 Jun
PMID:LPI-labile plasma iron in iron overload. 1573 90


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