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[PMID]:29318368
[Au] Autor:Mirlohi MS; Yaghooti H; Shirali S; Aminasnafi A; Olapour S
[Ad] Endereço:Hyperlipidemia Research Center, School of Allied Medical Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
[Ti] Título: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] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo: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] Termos MeSH primário: Transfusão de Sangue
Produtos Finais de Glicação Avançada/sangue
Sobrecarga de Ferro/etiologia
Estresse Oxidativo
Reação Transfusional/fisiopatologia
Talassemia beta/sangue
[Mh] Termos MeSH secundário: Adolescente
Adulto
Biomarcadores/sangue
Terapia por Quelação/efeitos adversos
Terapia Combinada/efeitos adversos
Estudos Transversais
Desferroxamina/uso terapêutico
Feminino
Seres Humanos
Irã (Geográfico)
Sobrecarga de Ferro/prevenção & controle
Masculino
Piridonas/uso terapêutico
Receptores Depuradores Classe E/sangue
Adulto Jovem
Talassemia beta/terapia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Glycation End Products, Advanced); 0 (OLR1 protein, human); 0 (Pyridones); 0 (Scavenger Receptors, Class E); 2BTY8KH53L (deferiprone); J06Y7MXW4D (Deferoxamine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180111
[St] Status:MEDLINE
[do] DOI:10.1007/s00277-017-3223-3


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[PMID]:29384977
[Au] Autor:Zou DM; Rong DD; Zhao H; Su L; Sun WL
[Ad] Endereço:Department of Hematology.
[Ti] Título:Improvement of chronic hepatitis B by iron chelation therapy in a patient with iron overload: A case report.
[So] Source:Medicine (Baltimore);96(52):e9566, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: This report describes seroconversion of hepatitis B surface antigen (HBsAg) in a patient with marked iron overload caused by chronic hepatitis B (CHB) after receiving iron chelation therapy and discusses the role of iron chelation therapy in CHB. PATIENT CONCERNS: Increased serum ferritin level for 2 months. DIAGNOSIS: Secondary iron overload and CHB. INTERVENTION: To relieve iron load of the body, the patient underwent regular phlebotomy therapy and deferoxamine (DFO) therapy. During the therapy, serum ferritin and hepatitis B virus (HBV) were monitored and the iron concentration of the liver and heart were followed by T2* of magnetic resonance imaging (MRI) scan. OUTCOMES: Serum ferritin gradually decreased. Approximately 1 year after the therapy, HBsAg turned persistently negative. LESSONS: Iron chelation therapy may attenuate HBV infection.
[Mh] Termos MeSH primário: Terapia por Quelação/métodos
Desferroxamina/uso terapêutico
Hepatite B Crônica/complicações
Sobrecarga de Ferro/complicações
Sobrecarga de Ferro/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Ferritinas/sangue
Antígenos de Superfície da Hepatite B/imunologia
Seres Humanos
Sobrecarga de Ferro/terapia
Masculino
Flebotomia/métodos
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hepatitis B Surface Antigens); 9007-73-2 (Ferritins); J06Y7MXW4D (Deferoxamine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180201
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009566


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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] Endereço:a Fondazione per la Ricerca Farmacologica Gianni Benzi Onlus , Valenzano ( BA ), Italy.
[Ti] Título: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] País de publicação:England
[La] Idioma:eng
[Ab] Resumo: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] Termos MeSH primário: Transfusão de Sangue/métodos
Terapia por Quelação/métodos
Talassemia beta/complicações
[Mh] Termos MeSH secundário: Adolescente
Adulto
Criança
Feminino
Seres Humanos
Modelos Logísticos
Masculino
Adulto Jovem
Talassemia beta/terapia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1080/03007995.2017.1326890


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[PMID]:28467346
[Au] Autor:Soliman AT; De Sanctis V; Yassin M; Wagdy M; Soliman N
[Ad] Endereço:. vdesanctis@libero.it.
[Ti] Título:Chronic anemia and thyroid function.
[So] Source:Acta Biomed;88(1):119-127, 2017 Apr 28.
[Is] ISSN:0392-4203
[Cp] País de publicação:Italy
[La] Idioma:eng
[Ab] Resumo: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] Termos MeSH primário: Anemia Ferropriva/complicações
Hipotireoidismo/etiologia
[Mh] Termos MeSH secundário: Anemia Ferropriva/terapia
Anemia Falciforme/complicações
Anemia Falciforme/terapia
Animais
Transfusão de Sangue
Terapia por Quelação
Suplementos Nutricionais
Seres Humanos
Hipotireoidismo/terapia
Ferro/uso terapêutico
Talassemia beta/complicações
Talassemia beta/terapia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
E1UOL152H7 (Iron)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180125
[Lr] Data última revisão:
180125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.23750/abm.v88i1.6048


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[PMID]:29200160
[Au] Autor:Gomber S; Dabas A; Bagmar S; Madhu SV
[Ad] Endereço:Departments of Pediatrics.
[Ti] Título: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] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo: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] Termos MeSH primário: Glicemia/fisiologia
Terapia por Quelação
Desferroxamina/uso terapêutico
Intolerância à Glucose/tratamento farmacológico
Homeostase/efeitos dos fármacos
Piridonas/uso terapêutico
Talassemia beta/complicações
[Mh] Termos MeSH secundário: Adolescente
Glicemia/efeitos dos fármacos
Criança
Pré-Escolar
Desferroxamina/farmacologia
Feminino
Ferritinas/sangue
Intolerância à Glucose/etiologia
Intolerância à Glucose/fisiopatologia
Seres Humanos
Lactente
Resistência à Insulina
Quelantes de Ferro/farmacologia
Quelantes de Ferro/uso terapêutico
Sobrecarga de Ferro/tratamento farmacológico
Sobrecarga de Ferro/etiologia
Masculino
Estudos Prospectivos
Piridonas/farmacologia
Adulto Jovem
Talassemia beta/sangue
Talassemia beta/metabolismo
Talassemia beta/terapia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Blood Glucose); 0 (Iron Chelating Agents); 0 (Pyridones); 2BTY8KH53L (deferiprone); 9007-73-2 (Ferritins); J06Y7MXW4D (Deferoxamine)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180112
[Lr] Data última revisão:
180112
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171205
[St] Status:MEDLINE
[do] DOI:10.1097/MPH.0000000000001043


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[PMID]:29224648
[Au] Autor:Issa OM; Roberts R; Mark DB; Boineau R; Goertz C; Rosenberg Y; Lewis EF; Guarneri E; Drisko J; Magaziner A; Lee KL; Lamas GA
[Ad] Endereço:Columbia University Division of Cardiology at Mount Sinai Medical Center, Miami Beach, FL.
[Ti] Título:Effect of high-dose oral multivitamins and minerals in participants not treated with statins in the randomized Trial to Assess Chelation Therapy (TACT).
[So] Source:Am Heart J;195:70-77, 2018 Jan.
[Is] ISSN:1097-6744
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:IMPORTANCE: In a prespecified subgroup analysis of participants not on statin therapy at baseline in the TACT, a high-dose complex oral multivitamins and multimineral regimen was found to have a large unexpected benefit compared with placebo. The regimen tested was substantially different from any vitamin regimen tested in prior clinical trials. OBJECTIVE: To explore these results, we performed detailed additional analyses of participants not on statins at enrollment in TACT. DESIGN: TACT was a factorial trial testing chelation treatments and a 28-component high-dose oral multivitamins and multiminerals regimen versus placebo in post-myocardial infarction (MI) patients 50 years or older. PARTICIPANTS: There were 460 (27%) of 1,708 TACT participants not taking statins at baseline, 224 (49%) were in the active vitamin group and 236 (51%) were in the placebo group. SETTING: Patients were enrolled at 134 sites around the United States and Canada. INTERVENTION: Daily high-dose oral multivitamins and multiminerals (6 tablets, active or placebo). MAIN OUTCOME: The primary end point of TACT was time to the first occurrence of any component of the composite end point: all-cause mortality, MI, stroke, coronary revascularization, or hospitalization for angina. RESULTS: The primary end point occurred in 137 nonstatin participants (30%), of which 51 (23%) of 224 were in the active group and 86 (36%) of 236 were taking placebo (hazard ratio, 0.62; 95% confidence interval, 0.44-0.87; P=.006). Results in the key TACT secondary end point, a combination of cardiovascular mortality, stroke, or recurrent MI, was consistent in favoring the active vitamin group (hazard ratio, 0.46; 95% confidence interval, 0.28-0.75; P=.002). Multiple end point analyses were consistent with these results. CONCLUSION AND RELEVANCE: High-dose oral multivitamin and multimineral supplementation seem to decrease combined cardiac events in a stable, post-MI population not taking statin therapy at baseline. These unexpected findings are being retested in the ongoing TACT2.
[Mh] Termos MeSH primário: Terapia por Quelação/métodos
Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem
Minerais/administração & dosagem
Infarto do Miocárdio/tratamento farmacológico
Vitaminas/administração & dosagem
[Mh] Termos MeSH secundário: Administração Oral
Idoso
Relação Dose-Resposta a Droga
Método Duplo-Cego
Quimioterapia Combinada
Feminino
Seguimentos
Seres Humanos
Masculino
Meia-Idade
Estudos Retrospectivos
Fatores de Tempo
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors); 0 (Minerals); 0 (Vitamins)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171215
[Lr] Data última revisão:
171215
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171212
[St] Status:MEDLINE


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[PMID]:28875336
[Au] Autor:Maira D; Cassinerio E; Marcon A; Mancarella M; Fraquelli M; Pedrotti P; Cappellini MD
[Ad] Endereço:Rare Disease Center, Department of Medicine and Medical Specialities, Ca' Granda Foundation IRCCS Ospedale Maggiore Policlinico, University of Milan, Milan, Italy. diletta.maira@gmail.com.
[Ti] Título:Progression of liver fibrosis can be controlled by adequate chelation in transfusion-dependent thalassemia (TDT).
[So] Source:Ann Hematol;96(11):1931-1936, 2017 Nov.
[Is] ISSN:1432-0584
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:A substantial proportion of patients with transfusion-dependent beta-thalassemia major suffer from chronic liver disease. Iron overload resulting from repeated transfusions and HCV infection has been implicated in the development of liver fibrosis. Hepatic siderosis and fibrosis were assessed in 99 transfusion-dependent thalassemia (TDT) patients using transient elastography (TE) and liver iron concentration (LIC) assessed by T2*MRI at baseline and after 4 years. Data were analyzed retrospectively. At baseline, the overall mean liver stiffness measurement (LSM) was 7.4 ± 3.2 kPa and the mean LIC was 4.81 ± 3.82 mg/g dw (n = 99). Data available at 4 ± 1.5 years showed a significant reduction in LSM (6.6 ± 3.2 kPa, p 0.017) and hepatic siderosis measured by LIC (3.65 ± 3.45 mg/g dw, p 0.001). This result was confirmed when considering patients with iron overload at the time of the first measurement (n = 41) and subjects treated with a stable dose of deferasirox over the entire period of observation (n = 39). A reduction of LSM, yet not statistically significant, was achieved in patients on combined deferoxamine + deferiprone, while the group on deferoxamine (n = 11) remained stable over time. HCV-RNA positivity was found in 33 patients at T0, 20 of which were treated during the observation period. Patients who underwent anti-HCV therapy showed a more evident reduction in LSM (9 ± 3 vs 7 ± 3.1 kPa, p 0.016). Adequate chelation therapy is mandatory in order to prevent liver disease progression in TDT. Patients could benefit from regular non-invasive assessment of liver fibrosis by TE to indirectly monitor treatment adequacy and therapeutic compliance.
[Mh] Termos MeSH primário: Transfusão de Sangue/tendências
Quelantes de Ferro/uso terapêutico
Cirrose Hepática/diagnóstico por imagem
Cirrose Hepática/terapia
Talassemia/diagnóstico por imagem
Talassemia/terapia
[Mh] Termos MeSH secundário: Adulto
Terapia por Quelação/tendências
Estudos de Coortes
Progressão da Doença
Feminino
Seres Humanos
Cirrose Hepática/epidemiologia
Imagem por Ressonância Magnética/tendências
Masculino
Estudos Retrospectivos
Talassemia/epidemiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Iron Chelating Agents)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171027
[Lr] Data última revisão:
171027
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170907
[St] Status:MEDLINE
[do] DOI:10.1007/s00277-017-3120-9


  8 / 1311 MEDLINE  
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[PMID]:28701428
[Au] Autor:Carter M; Abdi A; Naz F; Thabet F; Vyas A
[Ad] Endereço:Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing, Michigan.
[Ti] Título:A Mercury Toxicity Case Complicated by Hyponatremia and Abnormal Endocrinological Test Results.
[So] Source:Pediatrics;140(2), 2017 Aug.
[Is] ISSN:1098-4275
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mercury (Hg) poisoning is considered a rare disease by the National Institutes of Health and the diagnosis can present great challenges to clinicians. Children who are exposed to Hg can present with a wide variety of symptoms, including acrodynia, tremor, excessive salivation, and psychiatric symptoms, including insomnia. However, endocrinologic manifestations from Hg exposure are less well known. This is a case report of a 12-year-old boy who presented with body rash, irritability, insomnia, and profuse sweating after returning from a summer camp. The child was initially managed in the outpatient setting, and the investigation was mainly targeted toward infectious etiology, including Rocky Mountain spotted fever and Lyme disease. He was eventually admitted to the hospital with altered mental status and was noted to have hyponatremia with serum sodium of 121 mEq/L. Thyroid studies also revealed elevated free thyroxine levels in the presence of normal triiodothyronine and thyrotropin. The patient developed hypertension and tachycardia, and was found to have elevated 24-hour vanillylmandelic acid and metanephrines. Finally, heavy metal measurements revealed a blood Hg level that was greater than the reference values of 0 to 9 ng/mL. Chelation treatment with 2,3-dimercaptopropane-1-sulfonate was subsequently initiated and over a period of 8 months his symptoms resolved and his thyroid function test returned to normal. This case highlights some of the challenges commonly encountered in identifying Hg exposure. More importantly, it illustrates that exposure to Hg should be considered in children who present with the symptoms and abnormal endocrinologic test results described in this report.
[Mh] Termos MeSH primário: Hipertireoxinemia/diagnóstico
Hiponatremia/diagnóstico
Intoxicação por Mercúrio/diagnóstico
Metanefrina/sangue
Doenças Raras
Ácido Vanilmandélico/sangue
[Mh] Termos MeSH secundário: Terapia por Quelação
Criança
Diagnóstico Diferencial
Seres Humanos
Hipertireoxinemia/etiologia
Hiponatremia/etiologia
Masculino
Intoxicação por Mercúrio/tratamento farmacológico
Admissão do Paciente
Unitiol/uso terapêutico
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
4076-02-2 (Unithiol); 5001-33-2 (Metanephrine); 55-10-7 (Vanilmandelic Acid)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170828
[Lr] Data última revisão:
170828
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170714
[St] Status:MEDLINE


  9 / 1311 MEDLINE  
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[PMID]:28689036
[Au] Autor:Arenas IA; Navas-Acien A; Ergui I; Lamas GA
[Ad] Endereço:The Columbia University Division of Cardiology at Mount Sinai Medical Center, Miami Beach, FL, USA.
[Ti] Título:Enhanced vasculotoxic metal excretion in post-myocardial infarction patients following a single edetate disodium-based infusion.
[So] Source:Environ Res;158:443-449, 2017 10.
[Is] ISSN:1096-0953
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Toxic metals have been associated with cardiovascular mortality and morbidity. We have hypothesized that enhanced excretion of vasculotoxic metals might explain the positive results of the Trial to Assess Chelation Therapy (TACT). The purpose of this study was to determine whether a single infusion of the edetate disodium- based infusion used in TACT led to enhanced excretion of toxic metals known to be associated with cardiovascular events. METHODS: Twenty six patients (post-MI, age > 50 years, serum creatinine ≤ 2.0mg/dL) were enrolled in this open-label study. Urinary levels of 20 toxic metals normalized to urinary creatinine concentrations were measured at baseline in overnight urine collections, for 6h following a placebo infusion of 500mL normal saline and 1.2% dextrose, and for 6h following a 3g edetate disodium-based infusion. Self-reported metal exposure, smoking status, food frequency, occupational history, drinking water source, housing and hobbies were collected at baseline by a metal exposure questionnaire. RESULTS: The mean age was 65 years (range 51-81 years). All patients were male. 50% had diabetes mellitus and 58% were former smokers. Mean (SD) serum creatinine was 0.95 (0.31) mg/dL. Toxic metals were detected in the baseline urine of >80% of patients. After placebo infusion there were no significant changes in total urinary metal levels. After edetate infusion, total urinary metal level increased by 71% compared to baseline (1500 vs. 2580µg/g creatinine; P<0.0001). The effect of edetate was particularly large for lead (3835% increase) and cadmium (633% increase). CONCLUSIONS: Edetate disodium-based infusions markedly enhanced the urinary excretion of lead and cadmium, toxic metals with established epidemiologic evidence and mechanisms linking them to coronary and vascular events.
[Mh] Termos MeSH primário: Quelantes de Cálcio/farmacologia
Terapia por Quelação
Ácido Edético/farmacologia
Poluentes Ambientais/urina
Metais/urina
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Estudos Transversais
Dieta
Florida
Seres Humanos
Estilo de Vida
Masculino
Meia-Idade
Infarto do Miocárdio/epidemiologia
Infarto do Miocárdio/terapia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Calcium Chelating Agents); 0 (Environmental Pollutants); 0 (Metals); 9G34HU7RV0 (Edetic Acid)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171120
[Lr] Data última revisão:
171120
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170710
[St] Status:MEDLINE


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[PMID]:28677895
[Au] Autor:Leitch HA; Parmar A; Wells RA; Chodirker L; Zhu N; Nevill TJ; Yee KWL; Leber B; Keating MM; Sabloff M; St Hilaire E; Kumar R; Delage R; Geddes M; Storring JM; Kew A; Shamy A; Elemary M; Lenis M; Mamedov A; Ivo J; Francis J; Zhang L; Buckstein R
[Ad] Endereço:Hematology, St. Paul's Hospital and the University of British Columbia, Vancouver, BC, Canada.
[Ti] Título:Overall survival in lower IPSS risk MDS by receipt of iron chelation therapy, adjusting for patient-related factors and measuring from time of first red blood cell transfusion dependence: an MDS-CAN analysis.
[So] Source:Br J Haematol;179(1):83-97, 2017 Oct.
[Is] ISSN:1365-2141
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Analyses suggest iron overload in red blood cell (RBC) transfusion-dependent (TD) patients with myleodysplastic syndrome (MDS) portends inferior overall survival (OS) that is attenuated by iron chelation therapy (ICT) but may be biassed by unbalanced patient-related factors. The Canadian MDS Registry prospectively measures frailty, comorbidity and disability. We analysed OS by receipt of ICT, adjusting for these patient-related factors. TD International Prognostic Scoring System (IPSS) low and intermediate-1 risk MDS, at RBC TD, were included. Predictive factors for OS were determined. A matched pair analysis considering age, revised IPSS, TD severity, time from MDS diagnosis to TD, and receipt of disease-modifying agents was conducted. Of 239 patients, 83 received ICT; frailty, comorbidity and disability did not differ from non-ICT patients. Median OS from TD was superior in ICT patients (5·2 vs. 2·1 years; P < 0·0001). By multivariate analysis, not receiving ICT independently predicted inferior OS, (hazard ratio for death 2·0, P = 0·03). In matched pair analysis, OS remained superior for ICT patients (P = 0·02). In this prospective, non-randomized analysis, receiving ICT was associated with superior OS in lower IPSS risk MDS, adjusting for age, frailty, comorbidity, disability, revised IPSS, TD severity, time to TD and receiving disease-modifying agents. This provides additional evidence that ICT may confer clinical benefit.
[Mh] Termos MeSH primário: Transfusão de Eritrócitos/efeitos adversos
Quelantes de Ferro/uso terapêutico
Sobrecarga de Ferro/tratamento farmacológico
Síndromes Mielodisplásicas/mortalidade
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Canadá/epidemiologia
Causas de Morte
Terapia por Quelação
Comorbidade
Feminino
Transplante de Células-Tronco Hematopoéticas
Seres Humanos
Sobrecarga de Ferro/sangue
Sobrecarga de Ferro/epidemiologia
Sobrecarga de Ferro/etiologia
Masculino
Meia-Idade
Síndromes Mielodisplásicas/complicações
Síndromes Mielodisplásicas/epidemiologia
Síndromes Mielodisplásicas/terapia
Prognóstico
Sistema de Registros
Risco
Análise de Sobrevida
Transplante Homólogo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Iron Chelating Agents)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171009
[Lr] Data última revisão:
171009
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170706
[St] Status:MEDLINE
[do] DOI:10.1111/bjh.14825



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