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[PMID]: 29318368
[Au] Autor:Mirlohi MS; Yaghooti H; Shirali S; Aminasnafi A; Olapour S
[Ad] Address:Hyperlipidemia Research Center, School of Allied Medical Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
[Ti] Title:Increased levels of advanced glycation end products positively correlate with iron overload and oxidative stress markers in patients with ß-thalassemia major.
[So] Source:Ann Hematol;97(4):679-684, 2018 Apr.
[Is] ISSN:1432-0584
[Cp] Country of publication:Germany
[La] Language:eng
[Ab] Abstract:The impaired biosynthesis of the ß-globin chain in ß-thalassemia leads to the accumulation of unpaired alpha globin chains, failure in hemoglobin formation, and iron overload due to frequent blood transfusion. Iron excess causes oxidative stress and massive tissue injuries. Advanced glycation end products (AGEs) are harmful agents, and their production accelerates in oxidative conditions. This study was conducted on 45 patients with major ß-thalassemia who received frequent blood transfusions and chelation therapy and were compared to 40 healthy subjects. Metabolic parameters including glycemic and iron indices, hepatic and renal functions tests, oxidative stress markers, and AGEs (carboxymethyl-lysine and pentosidine) levels were measured. All parameters were significantly increased in ß-thalassemia compared to the control except for glutathione levels. Blood glucose, iron, serum ferritin, non-transferrin-bound iron (NTBI), MDA, soluble form of low-density lipoprotein receptor, glutathione peroxidase, total reactive oxygen species (ROS), and AGE levels were significantly higher in the ß-thalassemia patients. Iron and ferritin showed a significant positive correlation with pentosidine (P < 0.01) but not with carboxymethyl-lysine. The NTBI was markedly increased in the ß-thalassemia patients, and its levels correlated significantly with both carboxymethyl-lysine and pentosidine (P < 0.05). Our findings confirm the oxidative status generated by the iron overload in ß-thalassemia major patients and highlight the enhanced formation of AGEs, which may play an important role in the pathogenesis of ß-thalassemia major.
[Mh] MeSH terms primary: Blood Transfusion
Glycation End Products, Advanced/blood
Iron Overload/etiology
Oxidative Stress
Transfusion Reaction/physiopathology
beta-Thalassemia/blood
[Mh] MeSH terms secundary: Adolescent
Adult
Biomarkers/blood
Chelation Therapy/adverse effects
Combined Modality Therapy/adverse effects
Cross-Sectional Studies
Deferoxamine/therapeutic use
Female
Humans
Iran
Iron Overload/prevention & control
Male
Pyridones/therapeutic use
Scavenger Receptors, Class E/blood
Young Adult
beta-Thalassemia/therapy
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (Biomarkers); 0 (Glycation End Products, Advanced); 0 (OLR1 protein, human); 0 (Pyridones); 0 (Scavenger Receptors, Class E); 2BTY8KH53L (deferiprone); J06Y7MXW4D (Deferoxamine)
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[Js] Journal subset:IM
[Da] Date of entry for processing:180111
[St] Status:MEDLINE
[do] DOI:10.1007/s00277-017-3223-3

  2 / 8953 MEDLINE  
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[PMID]: 29240028
[Au] Autor:Vucak J; Turudic D; Milosevic D; Bilic M; Salek Z; Rincic M; Bilic E
[Ad] Address:Primary Health Care Pediatrician, Sibenik.
[Ti] Title:Genotype-phenotype Correlation of ß-Thalassemia in Croatian Patients: A Specific HBB Gene Mutations.
[So] Source:J Pediatr Hematol Oncol;40(2):e77-e82, 2018 Mar.
[Is] ISSN:1536-3678
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:An analysis of genotype-phenotype correlation was performed for 14 patients with beta-thalassemia who had been registered in Referral Centre for hematology and oncology of the University Hospital Centre, Zagreb, Croatia. HBB gene mutations were determined using a gene-specific Q5 High-Fidelity PCR analysis with direct DNA sequencing of amplified transcripts. Mahidol score index used for classification of thalassemia severity was found to be low for all the patients enrolled in the study, indicating a mild ß-thalassemia phenotype with no signs of disease progression. Most of the patients have already described gene mutations: IVS-II-666 C>T (HBB:c.316-185C>T) and IVS-II-16 G>C (HBB:c.315+16G>C). Each of the aforementioned mutations was found in (11/14; 78,57%) and (10/14; 71,43%) of our patients, respectively. Recently published HBB:c.9T>C mutation was found in 8 of 14 (57,14%) in our study group. IVSII-74 T>G (HBB:c.315+74T>G) is a worldwide mutation found in 6 of 14 (42.86%) of our patients. All these mutations occur among Croatian children with no obvious Indian/Near Eastern/Iranian ancestry. We also identified 7 de novo mutations (c.316-135het_dupT, c.316-133A>G, c.93-54G>A, c.316-68_316-67het_insCGG, c.316-342delA, c.316-312delT, c.316-209delT) of mild severity phenotype according to Mahidol classification score index. We did not find children or adults with thalassemia major severity phenotype.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1712
[Cu] Class update date: 180220
[Lr] Last revision date:180220
[St] Status:In-Data-Review
[do] DOI:10.1097/MPH.0000000000001039

  3 / 8953 MEDLINE  
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[PMID]: 29451225
[Au] Autor:Nashwan AJ; Yassin MA; Babu GDJ; Nair SLK; Libo-On IL; Hijazi HA; De Sanctis V; Soliman A
[Ad] Address:Nurse Research Scientist, Medical Oncology/Hematology Department, National Center for Cancer Care & Research - Hamad Medical Corporation, Doha, Qatar;. yassinmoha@gmail.com.
[Ti] Title:Quality of life among adolescents aged 14 to 18 years with Beta-Thalassemia Major (TM) in Qatar.
[So] Source:Acta Biomed;89(2-S):16-26, 2018 Feb 16.
[Is] ISSN:0392-4203
[Cp] Country of publication:Italy
[La] Language:eng
[Ab] Abstract:BACKGROUND: Thalassemia  is a heterogeneous group of inherited disorders of hemoglobin synthesis. It is a common disease in Mediterranean, Southeast Asia, Indian subcontinent, and Middle East countries, including Qatar. PURPOSE: The aim of this study was to assess the quality of life (QOL) among patients aged 14 to 18 years with thalassemia major (TM) in Qatar and correlates their QOL with bio-demographic data of the patients compared to healthy controls. MATERIALS AND METHODS: This cross-sectional study measured the QOL in adolescents with thalassemia major who were attending ambulatory units in a tertiary hospital in Qatar. Forty children and adolescents with TM and 40 healthy participants were enrolled in the study. Forty-two (52.5%) participants were males and 38 (47.5%) females. Data were collected utilizing PedsQLTM 4.0 generic core scale and were analyzed using the appropriate statistical method. RESULTS: Children with TM had significantly lower and more variable overall quality of life score (69.1 ± 16.8) compared to healthy matched children (77 ± 12.8), (p <0.001). Both groups were not different from the physical, emotional, and social domains. Thalassemic  adolescents had also a significantly lower school performance. CONCLUSIONS: TM adversely affects the QOL of children and adolescents and this necessitates applying more efforts to help them improve and achieve a desirable quality of life. Patients with TM need more attention in schools that can be accomplished by implementing a special program for their management that needs a mutual collaboration between Ministry of Public Health (MoPH) and Ministry of Education (MoE) in Qatar.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180216
[Lr] Last revision date:180216
[St] Status:In-Data-Review
[do] DOI:10.23750/abm.v89i2-S.7083

  4 / 8953 MEDLINE  
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[PMID]: 28471307
[Au] Autor:Bonifazi F; Conte R; Baiardi P; Bonifazi D; Felisi M; Giordano P; Giannuzzi V; Iacono A; Padula R; Pepe A; Caterina Putti M; Ruggieri L; Carlo Del Vecchio G; Filosa A; Maggio A; Ceci A; HTA-THAL Multiregional Registry
[Ad] Address:a Fondazione per la Ricerca Farmacologica Gianni Benzi Onlus , Valenzano ( BA ), Italy.
[Ti] Title:Pattern of complications and burden of disease in patients affected by beta thalassemia major.
[So] Source:Curr Med Res Opin;33(8):1525-1533, 2017 Aug.
[Is] ISSN:1473-4877
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:OBJECTIVES: Despite the correct application of blood transfusions and chelation treatments, beta thalassemia patients have many complications. Systematic population analyses on types and frequency of these complications are very few. The aim of this study is to characterize the complications, their risk factors and their clinical and economic impact. METHODS: Complications at baseline and events occurring during one observational year were analyzed in 272 patients aged >12 years. Risk factors were analyzed through chi-squared and unpaired t tests. Logistic regression was applied to perform the risk factors multivariate analysis. RESULTS: A total of 554 complications (1-6 per patient) affected 82.3% of patients. Cardiac complications were less represented than expected. Musculoskeletal diseases were the most represented complications followed by hepatic, sexual and endocrine diseases. Splenectomized patients, born before 1970 and aged >40 years, starting iron chelation therapy when aged >4 years or after receiving more than 20 blood transfusions, presented a significantly higher number of complications. A total of 885 adverse events requiring 34125 additional medical services occurred in 1 year. Of these, 34.9% were related to treatments and 65.1% to other causes. Event numbers, additional medical interventions and cost increased progressively in patients affected by one or more complication compared to patients with no complications. CONCLUSIONS: The pattern of complications changes according to birth cohort and differentiates older from younger patients. The burden of the disease and its costs increase after the onset of the first complication, therefore prevention of complications is fundamental in these patients.
[Mh] MeSH terms primary: Blood Transfusion/methods
Chelation Therapy/methods
beta-Thalassemia/complications
[Mh] MeSH terms secundary: Adolescent
Adult
Child
Female
Humans
Logistic Models
Male
Young Adult
beta-Thalassemia/therapy
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180213
[Lr] Last revision date:180213
[Js] Journal subset:IM
[Da] Date of entry for processing:170505
[St] Status:MEDLINE
[do] DOI:10.1080/03007995.2017.1326890

  5 / 8953 MEDLINE  
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[PMID]: 29427184
[Au] Autor:Nemtsas P; Arnaoutoglou M; Perifanis V; Koutsouraki E; Spanos G; Arnaoutoglou N; Chalkia P; Pantelidou D; Orologas A
[Ad] Address:First Department of Neurology, University General Hospital of Thessaloniki AHEPA, St.Kiriakidis 1, P.O, 546 36, Thessaloniki, Greece. pnemtsas@med.auth.gr.
[Ti] Title:Polyneuropathy and myopathy in beta-thalassemia major patients.
[So] Source:Ann Hematol;, 2018 Feb 09.
[Is] ISSN:1432-0584
[Cp] Country of publication:Germany
[La] Language:eng
[Ab] Abstract:The thalassemias are the most common single gene disorder in the world. Nowadays, the average life expectancy of patients in developed countries has increased significantly, while, there was an increase of complications. We aimed to investigate peripheral neuropathy and myopathy in this patient group using a neurophysiological study. We performed nerve conduction studies and electromyography of upper and lower extremities on 36 beta-thalassemia major (ß-thal) patients. The electrophysiological findings were correlated with demographic data and laboratory parameters of the disease. Patients with ß-thal present polyneuropathy or myopathy at (50%). Polyneuropathy was detected in (38.9%) and myopathy in (27.8%), while polyneuropathy and myopathy were present at (16.7%) with an overlap of the diseases in 1/3 of the patients. There was not a statistically significant correlation of polyneuropathy and myopathy with age, sex, splenectomy, nor with respect to laboratory parameters, hemoglobin, and ferritin. However, there was a statistically significant correlation of polyneuropathy and myopathy with iron overload, as recorded by the magnetic resonance imaging (MRI) of the heart and the liver. Our findings suggest that iron overload plays a key role in the pathogenesis of polyneuropathy and myopathy in ß-thal patients, and performing heart and liver MRI for the prediction of such lesions in an annual basis is warranted.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180210
[Lr] Last revision date:180210
[St] Status:Publisher
[do] DOI:10.1007/s00277-018-3251-7

  6 / 8953 MEDLINE  
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[PMID]: 29384898
[Au] Autor:Zhang X; Hao W; Xu T; Liu S; Jiang H
[Ti] Title:Diagnosis and treatment of neoplastic post-transplant lymphoproliferative disorder following hematopoietic stem cell transplant in ß-thalassemia: A pediatric case report.
[So] Source:Medicine (Baltimore);96(52):e9055, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:INTRODUCTION: Post-transplant lymphoproliferative disorder (PTLD) is the most common form of lymphoproliferation in childhood and is associated with significant morbidity and mortality. In this report we reviewed the case of a pediatric patient who experienced PTLD after allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen (HLA)-identical sibling. METHODS: The clinical characteristics, diagnosis, and treatment of PTLD after sibling HSCT in a 4-year-old boy with severe ß-thalassemia was retrospectively reviewed. RESULTS: Medical records revealed the patient developed a fever and superficial lymphadenopathy and soft palate enlargement 8 months post-HSCT. Pathologic diagnosis indicated non-Hodgkin lymphoma (B-cell type), which resulted in a reduced dose of immunosuppressant and the initiation of chemotherapy (administered according to the BFM95 protocol for 2 courses; 4 courses of rituximab therapy was also administered). Currently, the patient has been disease-free for over 3 years. There are no specific guidelines for the treatment of PTLD. The status of stem cell implantation after transplantation, and graft versus host disease should be evaluated jointly, and rituximab therapy and chemotherapy with BFM-95 may be used for treatment of pediatric PTLD after HSCT. CONCLUSION: The current case represents a unique opportunity to review a pediatric patient with ß-thalassemia. The successful treatment of post-transplant non-Hodgkin B lymphoma may help other physicians in the management of similar pediatric cases.
[Mh] MeSH terms primary: Hematopoietic Stem Cell Transplantation/adverse effects
Lymphoma, Non-Hodgkin/diagnosis
Lymphoma, Non-Hodgkin/therapy
beta-Thalassemia/therapy
[Mh] MeSH terms secundary: Child, Preschool
HLA Antigens
Humans
Lymphoma, Non-Hodgkin/etiology
Male
beta-Thalassemia/complications
[Pt] Publication type:CASE REPORTS; JOURNAL ARTICLE
[Nm] Name of substance:0 (HLA Antigens)
[Em] Entry month:1802
[Cu] Class update date: 180209
[Lr] Last revision date:180209
[Js] Journal subset:AIM; IM
[Da] Date of entry for processing:180201
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009055

  7 / 8953 MEDLINE  
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[PMID]: 29365300
[Au] Autor:Gupta A; Jain P
[Ad] Address:Max Super Specialty Hospital, Dehradun, India mail.guptaankur@gmail.com.
[Ti] Title:Calcified Spleen and Gallstones.
[So] Source:N Engl J Med;378(4):380, 2018 Jan 25.
[Is] ISSN:1533-4406
[Cp] Country of publication:United States
[La] Language:eng
[Mh] MeSH terms primary: Calcinosis/diagnostic imaging
Gallstones/diagnostic imaging
Splenic Diseases/diagnostic imaging
[Mh] MeSH terms secundary: Adult
Calcinosis/complications
Gallstones/complications
Hepatitis C, Chronic/complications
Humans
Male
Radiography
Spleen/diagnostic imaging
Splenic Diseases/complications
Tomography, X-Ray Computed
beta-Thalassemia/complications
[Pt] Publication type:CASE REPORTS; JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180208
[Lr] Last revision date:180208
[Js] Journal subset:AIM; IM
[Da] Date of entry for processing:180125
[St] Status:MEDLINE
[do] DOI:10.1056/NEJMicm1703915

  8 / 8953 MEDLINE  
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[PMID]: 28450766
[Au] Autor:Vincent O; Oluwaseyi B; James B; Saidat L
[Ad] Address:Haematology and Blood Transfusion Science Department, University of Lagos, Nigeria.
[Ti] Title:Coinheritance of B-Thalassemia and Sickle Cell Anaemia in Southwestern Nigeria.
[So] Source:Ethiop J Health Sci;26(6):517-522, 2016 Nov.
[Is] ISSN:2413-7170
[Cp] Country of publication:Ethiopia
[La] Language:eng
[Ab] Abstract:BACKGROUND: Genes for haemoglobin S are found in high frequencies in Nigeria. However, there is little information on beta thalassemia in sickle cell anaemia in this population. The clinical presentation of HbS- ß thalassemia is enormously variable, ranging from an asymptomatic state to a severe disorder similar to homozygous sickle cell disease. MATERIALS AND METHODS: Haemoglobin A and HbF were determined in sickle cell anaemia patients attending LAUTECH Teaching Hospital, Osogbo, by elution after electrophoresis and alkaline denaturation methods respectively. Haematological parameters were estimated using Sysmex KX-21N and percentage target cells using Leishman's staining technique. RESULTS: Exactly 6% f the SCA patients were found to have elevated HbA (>3.3%) and HbF (>1.3%). These patients also had normal erythrocyte indices, increased platelet count, a significantly higher HCT and an increased % target cell. CONCLUSION: These findings confirm that the frequency of beta thalassaemia in sickle cell patients in Nigeria is higher than previously thought. It is therefore important to consider the possibility of this variant in patients with sickle cell anaemia since their course may differ from that of patients with homozygous sickle cell anaemia.
[Mh] MeSH terms primary: Anemia, Sickle Cell/epidemiology
Anemia, Sickle Cell/genetics
beta-Thalassemia/epidemiology
beta-Thalassemia/genetics
[Mh] MeSH terms secundary: Cross-Sectional Studies
Erythrocyte Indices
Female
Fetal Hemoglobin/analysis
Hematocrit
Hemoglobin A2/analysis
Humans
Male
Nigeria/epidemiology
Platelet Count
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:9034-53-1 (Hemoglobin A2); 9034-63-3 (Fetal Hemoglobin)
[Em] Entry month:1802
[Cu] Class update date: 180205
[Lr] Last revision date:180205
[Js] Journal subset:IM
[Da] Date of entry for processing:170429
[St] Status:MEDLINE

  9 / 8953 MEDLINE  
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[PMID]: 28467346
[Au] Autor:Soliman AT; De Sanctis V; Yassin M; Wagdy M; Soliman N
[Ad] Address:. vdesanctis@libero.it.
[Ti] Title:Chronic anemia and thyroid function.
[So] Source:Acta Biomed;88(1):119-127, 2017 Apr 28.
[Is] ISSN:0392-4203
[Cp] Country of publication:Italy
[La] Language:eng
[Ab] Abstract:Anaemia is a global public health problem affecting both developing and developed countries with major consequences for human health as well as social and economic development. It occurs at all stages of the life cycle, but is more prevalent in pregnant women and young children. Iron deficiency anaemia (IDA) impairs thyroid metabolism in animals and human and may negatively affect growth and develpment of children. On the other hand both overt and subclinical hypothyroidism are associated with anemia and adding iron to thyroxine therapy improves both conditions compared to thyroxine therapy alone. In addition patients with chronic hemolytic anemia requiring repeated blood transfusion have high prevalence of hypothalamic-pituitary thyroid axis. Both primary hypothyroidism and central hypothyroidism occur in these patients with increasing prevalence with age, severity of the anemia and higher ferritin concentration denoting poor chelation.  Proper blood transfusion and intensive chelation appears to prevent deterioration of thyroid function and in many cases can reverse thyroid pathology. Physicians treating these forms of anemia should be aware of thyroid disorders in these patients for early screening, prevention and proper management of any thyroid dysfunction.
[Mh] MeSH terms primary: Anemia, Iron-Deficiency/complications
Hypothyroidism/etiology
[Mh] MeSH terms secundary: Anemia, Iron-Deficiency/therapy
Anemia, Sickle Cell/complications
Anemia, Sickle Cell/therapy
Animals
Blood Transfusion
Chelation Therapy
Dietary Supplements
Humans
Hypothyroidism/therapy
Iron/therapeutic use
beta-Thalassemia/complications
beta-Thalassemia/therapy
[Pt] Publication type:JOURNAL ARTICLE; REVIEW
[Nm] Name of substance:E1UOL152H7 (Iron)
[Em] Entry month:1801
[Cu] Class update date: 180125
[Lr] Last revision date:180125
[Js] Journal subset:IM
[Da] Date of entry for processing:170504
[St] Status:MEDLINE
[do] DOI:10.23750/abm.v88i1.6048

  10 / 8953 MEDLINE  
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[PMID]: 29200160
[Au] Autor:Gomber S; Dabas A; Bagmar S; Madhu SV
[Ad] Address:Departments of Pediatrics.
[Ti] Title:Glucose Homeostasis and Effect of Chelation on ß Cell Function in Children With ß-Thalassemia Major.
[So] Source:J Pediatr Hematol Oncol;40(1):56-59, 2018 Jan.
[Is] ISSN:1536-3678
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:OBJECTIVE: To assess the prevalence of impaired glucose tolerance in ß-thalassemia major and correlate it with chelation therapy. MATERIALS AND METHODS: Sixty-seven subjects with ß-thalassemia major, aged 1 to 20 years, were enrolled in our prospective cohort. Clinical details were recorded. Baseline oral glucose tolerance test, serum insulin, C peptide, and insulin resistance were measured. The biochemical profile was repeated after 6 months. RESULTS: The mean age of subjects was 7.43±4.48 years. Eight (11.9%) subjects had impaired fasting glucose, 7 (10.4%) had impaired glucose tolerance, and 1 (1.4%) subject had diabetes at baseline. Subjects with abnormal glucose profile had longer disease duration (95% confidence interval [CI] of difference=-6.64 to -0.68; P=0.019) and higher fasting blood glucose (95% CI of difference=-32.1 to -10.5; P=0.001) and serum ferritin (95% CI of difference=-219.8 to -3.4; P=0.001) than normoglycemic subjects. Insulin resistance and serum ferritin showed significant increase at 6 months (P<0.001 and P=0.001, respectively). Patients on deferiprone alone significantly improved glucose homeostasis on follow-up than those on desferrioxamine or combination therapy of desferrioxamine and deferiprone (P<0.05). CONCLUSIONS: Prolonged disease duration and higher serum ferritin adversely affects glucose homeostasis in thalassemic children. Deferiprone was the most effective chelator to improve glucose homeostasis in chronically transfused thalassemics.
[Mh] MeSH terms primary: Blood Glucose/physiology
Chelation Therapy
Deferoxamine/therapeutic use
Glucose Intolerance/drug therapy
Homeostasis/drug effects
Pyridones/therapeutic use
beta-Thalassemia/complications
[Mh] MeSH terms secundary: Adolescent
Blood Glucose/drug effects
Child
Child, Preschool
Deferoxamine/pharmacology
Female
Ferritins/blood
Glucose Intolerance/etiology
Glucose Intolerance/physiopathology
Humans
Infant
Insulin Resistance
Iron Chelating Agents/pharmacology
Iron Chelating Agents/therapeutic use
Iron Overload/drug therapy
Iron Overload/etiology
Male
Prospective Studies
Pyridones/pharmacology
Young Adult
beta-Thalassemia/blood
beta-Thalassemia/metabolism
beta-Thalassemia/therapy
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (Blood Glucose); 0 (Iron Chelating Agents); 0 (Pyridones); 2BTY8KH53L (deferiprone); 9007-73-2 (Ferritins); J06Y7MXW4D (Deferoxamine)
[Em] Entry month:1801
[Cu] Class update date: 180112
[Lr] Last revision date:180112
[Js] Journal subset:IM
[Da] Date of entry for processing:171205
[St] Status:MEDLINE
[do] DOI:10.1097/MPH.0000000000001043


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