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1.
Artigo em Inglês | MEDLINE | ID: mdl-38832436

RESUMO

BACKGROUND: Hemoglobin disorders such as thalassemia major have created an economic burden on the health care system. Iron chelation therapy (ICT) is the most expensive cost component in patients with thalassemia. ICT was administered to reduce the toxic effects of iron overload. This study aims to compare the costs of iron chelators as monotherapy in patients with thalassemia major in Indonesia, specifically in Cipto Faculty of Medicine, Universit. METHODS: This is a retrospective analytical observational study. Data were collected from the thalassemia registry from 2016 to 2019. Patients' age, gender, type of thalassemia, and type of iron chelation were recorded. Complications and total annual costs were evaluated. All thalassemia patients aged ≥2 years who were only receiving monotherapy ICT and had no history of therapy switching were eligible. We excluded subjects who moved out to other facilities or lost to follow-up. RESULTS: From a total of 256 subjects, 249 subjects were included. The median age is 28 years old. Both sexes were represented equally. As many as 96.8% of subjects have thalassemia beta. Deferiprone was the most common iron chelator used (86.7%). Complications were observed in the subjects based on 4-year data collection; most of them were cardiomyopathy, diabetes mellitus, delayed puberty, and malnutrition (P=0.422; P=0.867; P=0.004; and P=0.125, respectively). Deferiprone had a lower mean annual cost of USD 3581 than deferasirox, which had a cost of USD 6004. CONCLUSIONS: Cardiomyopathy, diabetes mellitus, delayed puberty, and malnutrition were the most common complications found in the study. This study showed that deferiprone should be taken as consideration as a drug of choice to treat iron overload in thalassemia provided by Indonesian national health insurance which is less costly despite the probability of complications found after the treatment was given. Further investigations are required to evaluate contributing factors of complications in thalassemia.

2.
Pediatr Gastroenterol Hepatol Nutr ; 26(2): 116-126, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36950058

RESUMO

Purpose: This study aimed to evaluate the prevalence and risk factors of infant dyschezia as well as pediatrician awareness regarding this disease in Indonesia. Methods: This is a two-part cross-sectional study, which was divided into study A and B. Study A: Parents whose infants were under 9 months old and attended well-baby clinics were recruited at two randomly selected primary health centers. Parents also provided information on the infant's previous medical history, and socio-demographic and family details. The Rome IV criteria was translated and validated to be used for diagnosis of infant dyschezia. Study B: Randomly selected pediatricians were surveyed by using a questionnaire to evaluate their knowledge regarding infant dyschezia. Results: The prevalence of infant dyschezia based on the result of this study was 11.8%. Three risk factors had a significant relationship with infant dyschezia i.e., the number of children in the family (odds ratio [OR], 5.619; 95% confidence interval [CI], 2.194-14.390; p<0.001), complementary food diet (OR, 4.238; 95% CI, 1.902-9.443; p<0.001), and social-emotional disturbance (OR, 5.670; 95% CI, 2.550-12.609; p<0.001). The percentage of pediatricians correctly diagnosed infant dyschezia was 71.5%. Most pediatricians agreed that they did not perform any diagnostic testing (79.7%) and only provided education in cases of infant dyschezia (58.5%). Conclusion: The prevalence of infant dyschezia identified in our study was higher than that in other neighboring Asian countries, with the highest prevalence observed in infants 7-9 months old. Being an only child, receiving complementary food diet, and sociao-emotional disturbances were significant risk factors of infant dyschezia.

3.
PLoS One ; 18(1): e0280401, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36638135

RESUMO

Beta thalassemia major (TM) is a common hereditary disease in Indonesia. Iron overload due to regular transfusion may induce myocardial iron deposition leading to electrophysiological dysfunction and functional disorders of the heart. Ventricular arrhythmia is one of the most common causes of sudden cardiac death in thalassemia patients. This cross-sectional study of 62 TM patients aged 10-32 years in Cipto Mangunkusumo General Hospital was done to assess their electrophysiological properties and heart rate variability, including 24- hour Holter monitoring, signal averaged electrocardiogram (SAECG) for detection of ventricular late potential (VLP), and determination of heart rate variability (HRV). We also assessed their 12-lead ECG parameters, such as P wave, QRS complex, QT/ QTc interval, QRS dispersion, and QT/ QTc dispersion. Iron overload was defined by T2-star magnetic resonance (MR-T2*) values of less than 20 ms or ferritin level greater than 2500 ng/mL. Subjects were grouped accordingly. There were significant differences of QTc dispersion (p = 0.026) and deceleration capacity (p = 0.007) between MR-T2* groups. Multivariate analysis showed an inverse correlation between QTc dispersion and MR-T2* values. There was a proportional correlation between heart rate deceleration capacity in the low MR-T2* group (p = 0.058) and the high ferritin group (p = 0.007). No VLPs were detectable in any patients. In conclusion, prolonged QTc dispersion and decreased heart rate deceleration capacity were significantly correlated with greater odds of iron overload among patients with Thalassemia major.


Assuntos
Sobrecarga de Ferro , Talassemia beta , Humanos , Talassemia beta/complicações , Frequência Cardíaca , Estudos Transversais , Indonésia/epidemiologia , Sobrecarga de Ferro/diagnóstico , Ferritinas
4.
Anemia ; 2022: 3572986, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35573052

RESUMO

Background: ß-Thalassemia has a very wide clinical variation, depending on the severity of the patient's condition. Individuals with ß-thalassemia traits are usually asymptomatic; however, laboratory examination will show mild anemia with microcytic hypochromic erythrocytes morphology with wide variation depending on the genotype. This study was conducted to determine the reference value of hematological parameters and hemoglobin (Hb) analysis based on the phenotype of ß-thalassemia (ß 0 and ß +) and determine the differences of hematological characteristics between the two phenotypes. Methods: This cross-sectional study was conducted by evaluating the hematological parameters and Hb analysis of the ß-thalassemia trait in the family of thalassemia patient population. The subjects were divided into ß 0 and ß +. The subject with normal Hb analysis with or without iron deficiency was excluded. Results: A total of 203 subjects with thalassemia traits were included from the families of thalassemia patients, consisting of 101 subjects with ß 0-thalassemia, 82 subjects with ß +-thalassemia, and the mutation had not been found in 20 subjects. There was a relationship in the mean/median of hematological parameters, HbA2 and HbF, between ß 0-thalassemia and ß +-thalassemia (P < 0.05). ROC for each hematological parameter, HbA2 and HbF, showed that the highest diagnostic value based on the area under the curve was mean corpuscular hemoglobin (MCH) (0.900) and mean corpuscular volume (MCV) (0.898). The cutoff point of MCH for ß 0-thalassemia trait was ≤20.5 pg (sensitivity 85%, specificity 90%) and MCV was ≤66.8 fL (sensitivity 87%, specificity 87%). Conclusion: MCH values can be used as a screening tool for predicting ß 0-thalassemia in the relatives of thalassemia patients in the South Sumatra population.

5.
BMJ Open ; 11(12): e054736, 2021 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-34862299

RESUMO

INTRODUCTION: Thalassaemia is an inherited blood disorder, for which definitive treatments remain largely inaccessible. The recommended approach to reduce the disease burden is by prevention through screening. Currently, the implementation of thalassaemia preventive measures is poorly regulated in Indonesia. Thalassaemia prevention and education are best targeted to the youth, but information on their awareness towards thalassaemia is limited. This study aims to investigate the knowledge, attitude and practice (KAP) towards thalassaemia among Indonesian youth. METHODS: This observational study took place between January and May 2021. An online questionnaire was disseminated to Indonesian youth aged 15-24. Eligible respondents included carriers, unaffected individuals and individuals with unknown carrier status. The questionnaire comprised 28 questions to assess KAP. A cut-off of 75% was used to categorise participant's KAP into poor or negative and good or positive. Descriptive statistics, χ2 test, logistic regression and Pearson correlation were performed for data analysis. RESULTS: A total of 906 responses were gathered, and 878 were analysed. Most respondents had poor knowledge (62.1%), positive attitude (83.3%) and poor practice (54.4%) towards thalassaemia. The results implied that respondents had limited understanding regarding the types of thalassaemia and the difference between asymptomatic carriers and individuals without the thalassaemia trait. Many (82.6%) believed they were not carrying thalassaemia trait despite the fact that most (95.7%) never got tested. Age, education, gender, residence and family income were key factors that correlated with or predicted the youth's KAP towards thalassaemia. Older respondents and women were more likely to have good KAP. CONCLUSION: Thalassaemia screening targeted to the youth is urgently needed, and future interventions must consider sociodemographic factors that may affect how they perceive the disease. Social media appeals to the youth as an important source of information, but school, parents and health professionals should also be involved in delivering education about thalassaemia.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Talassemia , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , Indonésia/epidemiologia , Inquéritos e Questionários , Talassemia/prevenção & controle , Adulto Jovem
6.
Clin Exp Pediatr ; 63(8): 314-320, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32668823

RESUMO

BACKGROUND: The accumulation of unpaired α-globin chains in patients with ß-thalassemia major may clinically create ineffective erythropoiesis, hemolysis, and chronic anemia. Multiple blood transfusions and iron overload cause cellular oxidative damage. However, α-tocopherol, an antioxidant, is a potent scavenger of lipid radicals in the membranes of red blood cells (RBCs) of patients with ß-thalassemia major. PURPOSE: To evaluate the effects of α-tocopherol on hemolysis and oxidative stress markers on the RBC membranes of patients with ß-thalassemia major. METHODS: Forty subjects included in this randomized controlled trial were allocated to the placebo and α-tocopherol groups. Doses of α-tocopherol were based on Institute of Medicine recommendations: 4-8 years old, 200 mg/day; 9-13 years old, 400 mg/day; 14-18 years old, 600 mg/day. Hemolysis, oxidative stress, and antioxidant variables were evaluated before and after 4-week α-tocopherol or placebo treatment, performed before blood transfusions. RESULTS: Significant enhancements in plasma haptoglobin were noted in the α-tocopherol group (3.01 mg/dL; range, 0.60-42.42 mg/dL; P=0.021). However, there was no significant intergroup difference in osmotic fragility test results; hemopexin, malondialdehyde, reduced glutathione (GSH), or oxidized glutathione (GSSG) levels; or GSH/GSSG ratio. CONCLUSION: Use of α-tocopherol could indirectly improve hemolysis and haptoglobin levels. However, it played no significant role in oxidative stress or as an endogen antioxidant marker in ß-thalassemia major.

7.
Biol Blood Marrow Transplant ; 26(6): 1106-1112, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31931116

RESUMO

Patients with severe thalassemia commonly have a survival that is significantly shorter than that of the general population. Allogeneic hematopoietic stem cell transplantation (allo-SCT) is the only established treatment that is potentially curative, but it is limited by the availability of donors and the medical condition of the patient. To expand the donor pool to include haploidentical related donors, we introduced a program consisting of a pharmacologic pretransplant immune suppression phase (PTIS) and 2 courses of dexamethasone and fludarabine, followed by pretransplant conditioning with fludarabine-i.v. busulfan and post-transplant graft-versus-host disease (GVHD) prophylaxis with cyclophosphamide, tacrolimus, and mycophenolate mofetil. We transplanted 83 consecutive transfusion-dependent patients with thalassemia (median age, 12 years; range, 1 to 28 years) with a minimum follow-up of 6 months (median, 15 months; range, 7 to 53 months); the 3-year projected overall and event-free survival is over 96%, and there have been no secondary graft failures. Of the first 31 patients, we had 2 graft failures, both of them occurring in patients with extremely high titers of anti-donor-specific HLA antibodies (anti-DSAs), but after adjusting the PTIS to include bortezomib and rituximab for patients with high titers of anti-DSAs and using pharmacologic dose guidance for busulfan, we had no graft failures in the last 52 patients. Six (7%) of 83 patients developed severe GVHD. We conclude that this is a safe and efficacious approach to allogeneic SCT in thalassemia, yielding results comparable to those available for patients with fully matched donors.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Talassemia , Bussulfano/uso terapêutico , Criança , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Talassemia/terapia , Condicionamento Pré-Transplante
8.
Drug Res (Stuttg) ; 69(4): 234-240, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30189460

RESUMO

BACKGROUND: The leaves, fruit peels, and bark of mango trees (Mangifera indica L) contain mangiferin as an active compound with known anti-oxidative and iron chelating properties. This study aims to evaluate the benefits of mangiferin in the management of iron overload. METHODS: Thirty rats were divided into five groups: normal control, rats with iron overload, and rats with iron overload treated with oral mangiferin doses of 50, 100, or 200 mg/kg BW, respectively. The iron overload in this rat model was induced by means of 15 mg intraperitoneal iron dextran, twice a week for 4 weeks. Plasma mangiferin was measured using high performance liquid chromatography, plasma ferritin by using enzyme linked immunosorbent assay, and iron contents of plasma, urine, and tissues by using atomic absorbance spectrophotometry. RESULTS: Plasma mangiferin concentration at doses of 50, 100, or 200 mg/kg BW were 416.10±112.04, 310.55±134.18, and 450.11±165.99 ng/mL, respectively. At 50 mg/kg BW, mangiferin significantly decreased plasma ferritin levels (from 7051.14±1368.24 to 5543.80±1225.53 ng/mL, (p=0.037). Mangiferin also showed tendency to increase urinary iron excretion and to decrease cardiac and hepatic iron accumulation. CONCLUSION: In our model, oral administration of mangiferin showed non-linear pharmacokinetics and low bioavailability. At a dose of 50 mg/kg BW, mangiferin decreased plasma ferritin levels significantly. Mangiferin did not prevent the increase of plasma iron, although it exerted tendency to increase urinary iron excretion and to decrease iron accumulation in liver and heart.


Assuntos
Sobrecarga de Ferro/tratamento farmacológico , Xantonas/farmacologia , Animais , Modelos Animais de Doenças , Ferritinas/sangue , Frutas/química , Ferro/sangue , Quelantes de Ferro/farmacologia , Sobrecarga de Ferro/sangue , Complexo Ferro-Dextran/farmacologia , Masculino , Mangifera/química , Oxirredução/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta/química , Ratos , Ratos Sprague-Dawley
9.
Acta Med Indones ; 50(3): 230-236, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30333273

RESUMO

BACKGROUND: routine blood transfusion in transfusion-dependent-thalassemia (TDT) causes iron accumulation in various organ. Serum markers of iron overload, serum ferritin and transferrin saturation, are sensitive but not specific. MRI T2-star (T2*) is valuable for detecting iron level in organs. This study aimed to explore the degree of iron overload in various organs, iron deposition difference between children and adults, also its correlation with serum marker of iron overload. METHODS: this was a cross-sectional study of TDT patients who had been evaluated by MRI T2* examination in Cipto Mangunkusumo Hospital from 2014 to 2018. RESULTS: a total of 546 subjects was included in this study. The number of subjects between children and adults was almost equal. Most of subjects had normal cardiac iron deposition. The difference of cardiac iron overload between children and adults was significant (p=0.009). Liver evaluation showed that most of subjects had moderate to severe iron overload. This difference between children and adults was significant (p=0.017). Pancreas evaluation showed that either children or adults mostly had mild pancreatic iron overload. Analysis of T2* showed that pancreatic iron deposition progressed with increasing age. Serum ferritin had weak correlation with heart T2* MRI, moderate correlation with pancreas and liver T2* MRI. Relationship between transferrin saturation and T2* MRI was extremely weak. CONCLUSION: cardiac and hepatic iron deposition between children and adults differ significantly. Liver has the greatest iron overload, followed by pancreas and heart. Iron deposition in liver and pancreas has been started from earlier age. Pancreatic iron deposition rises with increasing age. Serum ferritin and transferrin saturation should not be used solely to predict iron overload in various organs. We suggest that MRI evaluation must be conducted at least once to assess iron deposition in organs.


Assuntos
Transfusão de Sangue , Sobrecarga de Ferro/diagnóstico , Imageamento por Ressonância Magnética , Talassemia/terapia , Adolescente , Adulto , Criança , Estudos Transversais , Feminino , Ferritinas/sangue , Humanos , Sobrecarga de Ferro/etiologia , Fígado/metabolismo , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Miocárdio/metabolismo , Miocárdio/patologia , Talassemia/complicações , Adulto Jovem
10.
Acta Med Indones ; 50(2): 168-176, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29950538

RESUMO

BACKGROUND: there are currently three iron chelator readily available for patients Indonesia; deferiprone/DFP (branded as Ferriprox), deferasirox/DFX (branded as Exjade) and deferoxamine/DFO (branded as Desferal). This study aims to determine which iron chelator is the most efficient in reducing cardiac and hepatic iron overload (measured by means of T2* MRI). METHODS: journal search with determined MeSH term was done in PubMed and Scopus. Studies that looked upon thalassemia major patient in all ages with usage of monotherapy iron chelation and its effect on myocardial T2* MRI and/or liver T2* MRI was included. Appraisal of studies was done using Oxford's CEBM appraisal tools and Joanna Brigs Institute critical appraisal tools. RESULTS: total of 11 studies with grand total of 611 samples were included. Mean T2* MRI value or (when available) mean changes in T2* MRI value after usage of specific iron chelator was gained from all the studies included. Comparison study and individual studies shows better control and increase of myocardial T2* MRI in those with DFP, and of liver T2* in those with good adherence to DFO chelation. CONCLUSION: DFP is superior in controlling or reducing myocardial iron load (as proven by mT2* MRI) and DFO had better capabilities in controlling or reducing hepatic iron load (as proven by liver T2* MRI). Studies with longer observation and larger samples is needed to see a significant changes of T2* MRI in DFX.


Assuntos
Benzoatos/uso terapêutico , Desferroxamina/uso terapêutico , Piridonas/uso terapêutico , Talassemia/diagnóstico por imagem , Talassemia/tratamento farmacológico , Triazóis/uso terapêutico , Criança , Deferasirox , Deferiprona , Quimioterapia Combinada , Coração/diagnóstico por imagem , Humanos , Indonésia , Sobrecarga de Ferro/etiologia , Sobrecarga de Ferro/prevenção & controle , Fígado/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino
12.
Hematology ; 22(8): 501-507, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28218005

RESUMO

OBJECTIVES: Recent advancements have promoted the use of T2* magnetic resonance imaging (MRI) in the non-invasive detection of iron overload in various organs for thalassemia major patients. This study aims to determine the iron load in the heart and liver of patients with thalassemia major using T2* MRI and to evaluate its correlation with serum ferritin level and iron chelation therapy. METHODS: This cross-sectional study included 162 subjects diagnosed with thalassemia major, who were classified into acceptable, mild, moderate, or severe cardiac and hepatic iron overload following their T2* MRI results, respectively, and these were correlated to their serum ferritin levels and iron chelation therapy. RESULTS: The study found that 85.2% of the subjects had normal cardiac iron stores. In contrast, 70.4% of the subjects had severe liver iron overload. A significant but weak correlation (r = -0.28) was found between cardiac T2* MRI and serum ferritin, and a slightly more significant correlation (r = 0.37) was found between liver iron concentration (LIC) and serum ferritin. DISCUSSION: The findings of this study are consistent with several other studies, which show that patients generally manifest with liver iron overload prior to cardiac iron overload. Moreover, iron accumulation demonstrated by T2* MRI results also show a significant correlation to serum ferritin levels. CONCLUSION: This is the first study of its kind conducted in Indonesia, which supports the fact that T2* MRI is undoubtedly valuable in the early detection of cardiac and hepatic iron overload in thalassemia major patients.


Assuntos
Sobrecarga de Ferro/diagnóstico , Sobrecarga de Ferro/etiologia , Fígado/metabolismo , Fígado/patologia , Imageamento por Ressonância Magnética , Miocárdio/metabolismo , Miocárdio/patologia , Talassemia beta/complicações , Terapia por Quelação , Estudos Transversais , Ecocardiografia , Feminino , Ferritinas/sangue , Testes de Função Cardíaca , Humanos , Ferro/metabolismo , Sobrecarga de Ferro/tratamento farmacológico , Masculino
13.
Hum Genet ; 127(3): 303-14, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20183929

RESUMO

b-Thalassemia/HbE disease is clinically variable. In searching for genetic factors modifying the disease severity, patients were selected based on their disease severities, and a genome-wide association study (GWAS) was performed. Genotyping was conducted with the Illumina Human 610-Quad BeadChips array using DNAs from 618 Thai b0-thalassemia/HbE patients who were classified as 383 severe and 235 mild phenotypes by a validated scoring system. Twenty-three SNPs in three independent genes/regions were identified as being significantly associated with the disease severity. The highest association was observed with SNPs in the b-globin gene cluster (chr.11p15), and rs2071348 of the HBBP1 gene revealed the most significant association [P = 2.96 9 10(-13), odds ratio (OR) = 4.33 (95% confidence interval (CI), 2.74-6.84)]. The second was identified in the intergenic region between the HBS1L and MYB genes (chr.6q23), among which rs9376092 was the most significant [P = 2.36 9 10(-10), OR = 3.07 (95% CI, 2.16-4.38)]. The third region was located in the BCL11A gene (chr.2p16.1), and rs766432 showed the most significant association [P = 5.87 9 10-10, OR = 3.06 (95% CI, 2.15-4.37)]. All three loci were replicated in an independent cohort of 174 Indonesian patients. The associations to fetal hemoglobin levels were also observed with SNPs on these three regions. Our data indicate that several genetic loci act in concert to influence HbF levels of beta(0)-thalassemia/HbE patients. This study revealed that all the three reported loci and the alpha-globin gene locus are the best and common predictors of the disease severity in beta-thalassemia.


Assuntos
Hemoglobina E/genética , Polimorfismo de Nucleotídeo Único , Índice de Gravidade de Doença , Talassemia beta/genética , Adolescente , Adulto , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Frequência do Gene , Estudo de Associação Genômica Ampla , Humanos , Masculino , Fenótipo , Adulto Jovem , alfa-Globinas/genética , Globinas beta/genética , Talassemia beta/complicações , Talassemia beta/patologia
14.
Clin Appl Thromb Hemost ; 14(3): 346-51, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18160592

RESUMO

Thromboembolic events and hypercoagulable state have been reported in patients with thalassemia. As platelets play an important role in the pathogenesis of thrombosis, the authors aimed to find the pattern of changes in platelet count, function and activation, and evidence of coagulation activation in patients with thalassemia major in Indonesia. A total of 31 patients with splenectomized and 35 patients with nonsplenectomized thalassemia major were enrolled in this study. Platelet count, platelet aggregation, beta-thromboglobulin, and D-dimer levels were measured. All measured parameters were significantly higher in splenectomized than in nonsplenectomized patients. beta-thromboglobulin level was increased, but D-dimer level was within normal range. The authors concluded that there was an increase in platelet activation in patients with beta-thalassemia major. Platelet activation was higher in splenectomized than in nonsplenectomized patients.


Assuntos
Ativação Plaquetária , Agregação Plaquetária , Talassemia beta/sangue , Adolescente , Adulto , Criança , Estudos Transversais , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Indonésia , Masculino , Contagem de Plaquetas , Fatores de Risco , Esplenectomia , Tromboembolia/sangue , Tromboembolia/etiologia , Talassemia beta/complicações , Talassemia beta/cirurgia , beta-Tromboglobulina/metabolismo
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