Ana Martins - Academia.edu (original) (raw)
Papers by Ana Martins
Lancet, Jan 25, 2015
The mainstay of treatment for Gaucher's disease type 1 is alternate-week infusion of enzyme r... more The mainstay of treatment for Gaucher's disease type 1 is alternate-week infusion of enzyme replacement therapy (ERT). We investigated whether patients stable on such treatment would remain so after switching to oral eliglustat, a selective inhibitor of glucosylceramide synthase. In this phase 3, randomised, multinational, open-label, non-inferiority trial, we enrolled adults (aged ≥18 years) who had received ERT for 3 years or more for Gaucher's disease. Patients were randomly allocated 2:1 at 39 clinics (stratified by ERT dose; block sizes of four; computer-generated centrally) to receive either oral eliglustat or imiglucerase infusions for 12 months. Participants and investigators were aware of treatment assignment, but the central reader who assessed organ volumes was masked. The composite primary efficacy endpoint was percentage of patients whose haematological variables and organ volumes remained stable for 12 months (ie, haemoglobin decrease not more than 15 g/L, plat...
The Journal of pediatrics, 2009
Gene, 2015
Pompe disease is an autosomal recessive disorder linked to GAA gene that leads to a multi-system ... more Pompe disease is an autosomal recessive disorder linked to GAA gene that leads to a multi-system intralysosomal accumulation of glycogen. Mutation identification in the GAA gene can be very important for early diagnosis, correlation between genotype-phenotype and therapeutic intervention. For this purpose, peripheral blood from 57 individuals susceptible to Pompe disease was collected and all exons of GAA gene were amplified; the sequences and the mutations were analyzed in silico to predict possible impact on the structure and function of the human protein. In this study, 46 individuals presented 33 alterations in the GAA gene sequence, among which five (c.547-67C>G, c.547-39T>G, p.R437H, p.L641V and p.L705P) have not been previously described in the literature. The alterations in the coding region included 15 missense mutations, three nonsense mutations and one deletion. One insertion and other 12 single base changes were found in the non-coding region. The mutation p.G611D was found in homozygosis in a one-year-old child, who presented low levels of GAA activity, hypotonia and hypertrophic cardiomyopathy. Two patients presented the new mutation p.L705P in association with c.-32-13T>G. They had low levels of GAA activity and developed late onset Pompe disease. In our study, we observed alterations in the GAA gene originating from Asians, African-Americans and Caucasians, highlighting the high heterogeneity of the Brazilian population. Considering that Pompe disease studies are not very common in Brazil, this study will help to better understand the potential pathogenic role of each change in the GAA gene. Furthermore, a precise and early molecular analysis improves genetic counseling besides allowing for a more efficient treatment in potential candidates.
Molecular Genetics and Metabolism, 2015
Objectives. Baseline data from the Morquio A Clinical Assessment Program (MorCAP) revealed that i... more Objectives. Baseline data from the Morquio A Clinical Assessment Program (MorCAP) revealed that individuals with Morquio A syndrome show substantial impairment in multiple domains including endurance and respiratory function (Harmatz et al, Mol Genet Metab, 2013). Here, 1-and 2-year longitudinal endurance and respiratory function data are presented.
Grammaticalization and Parametric Variation, 2005
Page 1. Clitic placement, VP-ellipsis and scrambling in Romance 1 Ana Maria Martins (University o... more Page 1. Clitic placement, VP-ellipsis and scrambling in Romance 1 Ana Maria Martins (University of Lisbon) 1. Introduction My goal in this paper will be to account for variation and change with respect to clitic placement, VP-ellipsis ...
Parameter Theory and Linguistic Change, 2012
Genetics and Molecular Biology, 2014
This review aims to provide clinicians in Latin America with the most current information on the ... more This review aims to provide clinicians in Latin America with the most current information on the clinical aspects, diagnosis, and management of Hunter syndrome, a serious and progressive disease for which specific treatment is available. Hunter syndrome is a genetic disorder where iduronate-2-sulfatase (I2S), an enzyme that degrades glycosaminoglycans, is absent or deficient. Clinical manifestations vary widely in severity and involve multiple organs and tissues. An attenuated and a severe phenotype are recognized depending on the degree of cognitive impairment. Early diagnosis is vital for disease management. Clinical signs common to children with Hunter syndrome include inguinal hernia, frequent ear and respiratory infections, facial dysmorphisms, macrocephaly, bone dysplasia, short stature, sleep apnea, and behavior problems. Diagnosis is based on screening urinary glycosaminoglycans and confirmation by measuring I2S activity and analyzing I2S gene mutations. Idursulfase (recombinant I2S) (Elaprase ® , Shire) enzyme replacement therapy (ERT), designed to address the underlying enzyme deficiency, is approved treatment and improves walking capacity and respiratory function, and reduces spleen and liver size and urinary glycosaminoglycan levels. Additional measures, responding to the multi-organ manifestations, such as abdominal/inguinal hernia repair, carpal tunnel surgery, and cardiac valve replacement, should also be considered. Investigational treatment options such as intrathecal ERT are active areas of research, and bone marrow transplantation is in clinical practice. Communication among care providers, social workers, patients and families is essential to inform and guide their decisions, establish realistic expectations, and assess patients' responses.
Probus, 2000
An Error Occurred Setting Your User Cookie. This site uses cookies to improve performance. If you... more An Error Occurred Setting Your User Cookie. This site uses cookies to improve performance. If your browser does not accept cookies, you cannot view this site. Setting Your Browser to Accept Cookies. There are many reasons why a cookie could not be set correctly. ...
Molecular Genetics and Metabolism, 2009
Recombinant human alpha-l-iduronidase (Aldurazyme), laronidase) is approved as an enzyme replacem... more Recombinant human alpha-l-iduronidase (Aldurazyme), laronidase) is approved as an enzyme replacement therapy to treat the lysosomal storage disorder, mucopolysaccharidosis type I (MPS I) at a dose of 0.58 mg/kg by once-weekly intravenous infusion. To assess whether alternate dosing regimens might provide a better reduction in lysosomal storage, a 26-week, randomized, open-label, multinational dose-optimization trial was conducted. The pharmacodynamic effect and safety of the approved laronidase dose was compared to three alternative regimens (1.2mg/kg every 2 weeks; 1.2mg/kg every week; 1.8 mg/kg every 2 weeks) among 33 MPS I patients. The four treatment regimens showed no significant differences in the reduction of urinary glycosaminoglycan excretion or liver volume. Laronidase had an acceptable safety profile in all dose regimen groups. Infusion-associated reactions were the most common drug-related adverse events across dose regimens (by patient incidence), and included pyrexia (21%), vomiting (15%), rash (15%), and urticaria (12%). Patients in the approved dose group had the lowest incidence of drug-related adverse events (38% vs. 63-75%) and infusion-associated reactions (25% vs. 25-63%). There was one death: a patient with acute bronchitis died of respiratory failure 6h after completing the first laronidase infusion. The approved 0.58 mg/kg/week laronidase dose regimen provided near-maximal reductions in glycosaminoglycan storage and the best benefit-to-risk ratio. The 1.2mg/kg every 2 weeks regimen may be an acceptable alternative for patients with difficulty receiving weekly infusions, but the long-term effects of this regimen are unknown.
The Journal of Pediatrics, 2009
RefDoc, THE reference in scientific document supply / Refdoc, la référence en fourniture de docum... more RefDoc, THE reference in scientific document supply / Refdoc, la référence en fourniture de documents scientifiques ...
The Journal of Pediatrics, 2009
The Journal of Pediatrics, 2009
... Martins AM, Valadares ER, Porta G, Coelho J, Semionato Filho J, Pianovski MA, Kerstenetzky MS... more ... Martins AM, Valadares ER, Porta G, Coelho J, Semionato Filho J, Pianovski MA, Kerstenetzky MS, Montoril Mde F, Aranda PC, Pires RF, Mota RM, Bortolheiro TC; Brazilian Study Group on Gaucher Disease and other Lysosomal Storage Diseases. ...
Journal of Organometallic Chemistry, 2004
The synthesis of [TiInd(NCtBu2)Cl2] and the applications of [TiCp′(NCtBu2)Cl2] (Cp′=Ind, Cp*, C... more The synthesis of [TiInd(NCtBu2)Cl2] and the applications of [TiCp′(NCtBu2)Cl2] (Cp′=Ind, Cp*, Cp) as ethylene and propylene homopolymerisation catalysts, as well as its behaviour as catalysts of ethylene and 10-undecen-1-ol copolymerisation are described. The optimisation of the catalytic reactions showed that all compounds are very active homopolymerisation catalysts, particularly [TiInd(NCtBu2)Cl2] that gives 123.37×106 g/(molTi [E] h) and 50.77×106 g/(molTi [P] h)
Journal of Inherited Metabolic Disease, 2008
Rev. Assoc. Med. …, 2010
Giugliani, Roberto; Federhen, Andressa; Muñoz Rojas, Maria Verónica; Vieira, Taiane Alves; Artiga... more Giugliani, Roberto; Federhen, Andressa; Muñoz Rojas, Maria Verónica; Vieira, Taiane Alves; Artigalás, Osvaldo; Pinto, Louise Lapagesse Carmargo; Azevedo, Ana Cecília; Acosta, Angelina Xavier; Bomfim, Carmem; Lourenço, Charles Marques; Kim, Chong Ae; ...
Rev. Bras. Hematol. …, 2003
Martins AM et al Rev. bras. hematol. hemoter. 2003;25(2):89-95 Artigo/Article Palavras-chave: Doe... more Martins AM et al Rev. bras. hematol. hemoter. 2003;25(2):89-95 Artigo/Article Palavras-chave: Doença de Gaucher; doenças de depósito; Brasil. Tratamento da Doença de Gaucher.p65 02/07/2003, 20:14 89 Rev. bras. hematol. hemoter. 2003;25(2):89-95.
Lancet, Jan 25, 2015
The mainstay of treatment for Gaucher's disease type 1 is alternate-week infusion of enzyme r... more The mainstay of treatment for Gaucher's disease type 1 is alternate-week infusion of enzyme replacement therapy (ERT). We investigated whether patients stable on such treatment would remain so after switching to oral eliglustat, a selective inhibitor of glucosylceramide synthase. In this phase 3, randomised, multinational, open-label, non-inferiority trial, we enrolled adults (aged ≥18 years) who had received ERT for 3 years or more for Gaucher's disease. Patients were randomly allocated 2:1 at 39 clinics (stratified by ERT dose; block sizes of four; computer-generated centrally) to receive either oral eliglustat or imiglucerase infusions for 12 months. Participants and investigators were aware of treatment assignment, but the central reader who assessed organ volumes was masked. The composite primary efficacy endpoint was percentage of patients whose haematological variables and organ volumes remained stable for 12 months (ie, haemoglobin decrease not more than 15 g/L, plat...
The Journal of pediatrics, 2009
Gene, 2015
Pompe disease is an autosomal recessive disorder linked to GAA gene that leads to a multi-system ... more Pompe disease is an autosomal recessive disorder linked to GAA gene that leads to a multi-system intralysosomal accumulation of glycogen. Mutation identification in the GAA gene can be very important for early diagnosis, correlation between genotype-phenotype and therapeutic intervention. For this purpose, peripheral blood from 57 individuals susceptible to Pompe disease was collected and all exons of GAA gene were amplified; the sequences and the mutations were analyzed in silico to predict possible impact on the structure and function of the human protein. In this study, 46 individuals presented 33 alterations in the GAA gene sequence, among which five (c.547-67C>G, c.547-39T>G, p.R437H, p.L641V and p.L705P) have not been previously described in the literature. The alterations in the coding region included 15 missense mutations, three nonsense mutations and one deletion. One insertion and other 12 single base changes were found in the non-coding region. The mutation p.G611D was found in homozygosis in a one-year-old child, who presented low levels of GAA activity, hypotonia and hypertrophic cardiomyopathy. Two patients presented the new mutation p.L705P in association with c.-32-13T>G. They had low levels of GAA activity and developed late onset Pompe disease. In our study, we observed alterations in the GAA gene originating from Asians, African-Americans and Caucasians, highlighting the high heterogeneity of the Brazilian population. Considering that Pompe disease studies are not very common in Brazil, this study will help to better understand the potential pathogenic role of each change in the GAA gene. Furthermore, a precise and early molecular analysis improves genetic counseling besides allowing for a more efficient treatment in potential candidates.
Molecular Genetics and Metabolism, 2015
Objectives. Baseline data from the Morquio A Clinical Assessment Program (MorCAP) revealed that i... more Objectives. Baseline data from the Morquio A Clinical Assessment Program (MorCAP) revealed that individuals with Morquio A syndrome show substantial impairment in multiple domains including endurance and respiratory function (Harmatz et al, Mol Genet Metab, 2013). Here, 1-and 2-year longitudinal endurance and respiratory function data are presented.
Grammaticalization and Parametric Variation, 2005
Page 1. Clitic placement, VP-ellipsis and scrambling in Romance 1 Ana Maria Martins (University o... more Page 1. Clitic placement, VP-ellipsis and scrambling in Romance 1 Ana Maria Martins (University of Lisbon) 1. Introduction My goal in this paper will be to account for variation and change with respect to clitic placement, VP-ellipsis ...
Parameter Theory and Linguistic Change, 2012
Genetics and Molecular Biology, 2014
This review aims to provide clinicians in Latin America with the most current information on the ... more This review aims to provide clinicians in Latin America with the most current information on the clinical aspects, diagnosis, and management of Hunter syndrome, a serious and progressive disease for which specific treatment is available. Hunter syndrome is a genetic disorder where iduronate-2-sulfatase (I2S), an enzyme that degrades glycosaminoglycans, is absent or deficient. Clinical manifestations vary widely in severity and involve multiple organs and tissues. An attenuated and a severe phenotype are recognized depending on the degree of cognitive impairment. Early diagnosis is vital for disease management. Clinical signs common to children with Hunter syndrome include inguinal hernia, frequent ear and respiratory infections, facial dysmorphisms, macrocephaly, bone dysplasia, short stature, sleep apnea, and behavior problems. Diagnosis is based on screening urinary glycosaminoglycans and confirmation by measuring I2S activity and analyzing I2S gene mutations. Idursulfase (recombinant I2S) (Elaprase ® , Shire) enzyme replacement therapy (ERT), designed to address the underlying enzyme deficiency, is approved treatment and improves walking capacity and respiratory function, and reduces spleen and liver size and urinary glycosaminoglycan levels. Additional measures, responding to the multi-organ manifestations, such as abdominal/inguinal hernia repair, carpal tunnel surgery, and cardiac valve replacement, should also be considered. Investigational treatment options such as intrathecal ERT are active areas of research, and bone marrow transplantation is in clinical practice. Communication among care providers, social workers, patients and families is essential to inform and guide their decisions, establish realistic expectations, and assess patients' responses.
Probus, 2000
An Error Occurred Setting Your User Cookie. This site uses cookies to improve performance. If you... more An Error Occurred Setting Your User Cookie. This site uses cookies to improve performance. If your browser does not accept cookies, you cannot view this site. Setting Your Browser to Accept Cookies. There are many reasons why a cookie could not be set correctly. ...
Molecular Genetics and Metabolism, 2009
Recombinant human alpha-l-iduronidase (Aldurazyme), laronidase) is approved as an enzyme replacem... more Recombinant human alpha-l-iduronidase (Aldurazyme), laronidase) is approved as an enzyme replacement therapy to treat the lysosomal storage disorder, mucopolysaccharidosis type I (MPS I) at a dose of 0.58 mg/kg by once-weekly intravenous infusion. To assess whether alternate dosing regimens might provide a better reduction in lysosomal storage, a 26-week, randomized, open-label, multinational dose-optimization trial was conducted. The pharmacodynamic effect and safety of the approved laronidase dose was compared to three alternative regimens (1.2mg/kg every 2 weeks; 1.2mg/kg every week; 1.8 mg/kg every 2 weeks) among 33 MPS I patients. The four treatment regimens showed no significant differences in the reduction of urinary glycosaminoglycan excretion or liver volume. Laronidase had an acceptable safety profile in all dose regimen groups. Infusion-associated reactions were the most common drug-related adverse events across dose regimens (by patient incidence), and included pyrexia (21%), vomiting (15%), rash (15%), and urticaria (12%). Patients in the approved dose group had the lowest incidence of drug-related adverse events (38% vs. 63-75%) and infusion-associated reactions (25% vs. 25-63%). There was one death: a patient with acute bronchitis died of respiratory failure 6h after completing the first laronidase infusion. The approved 0.58 mg/kg/week laronidase dose regimen provided near-maximal reductions in glycosaminoglycan storage and the best benefit-to-risk ratio. The 1.2mg/kg every 2 weeks regimen may be an acceptable alternative for patients with difficulty receiving weekly infusions, but the long-term effects of this regimen are unknown.
The Journal of Pediatrics, 2009
RefDoc, THE reference in scientific document supply / Refdoc, la référence en fourniture de docum... more RefDoc, THE reference in scientific document supply / Refdoc, la référence en fourniture de documents scientifiques ...
The Journal of Pediatrics, 2009
The Journal of Pediatrics, 2009
... Martins AM, Valadares ER, Porta G, Coelho J, Semionato Filho J, Pianovski MA, Kerstenetzky MS... more ... Martins AM, Valadares ER, Porta G, Coelho J, Semionato Filho J, Pianovski MA, Kerstenetzky MS, Montoril Mde F, Aranda PC, Pires RF, Mota RM, Bortolheiro TC; Brazilian Study Group on Gaucher Disease and other Lysosomal Storage Diseases. ...
Journal of Organometallic Chemistry, 2004
The synthesis of [TiInd(NCtBu2)Cl2] and the applications of [TiCp′(NCtBu2)Cl2] (Cp′=Ind, Cp*, C... more The synthesis of [TiInd(NCtBu2)Cl2] and the applications of [TiCp′(NCtBu2)Cl2] (Cp′=Ind, Cp*, Cp) as ethylene and propylene homopolymerisation catalysts, as well as its behaviour as catalysts of ethylene and 10-undecen-1-ol copolymerisation are described. The optimisation of the catalytic reactions showed that all compounds are very active homopolymerisation catalysts, particularly [TiInd(NCtBu2)Cl2] that gives 123.37×106 g/(molTi [E] h) and 50.77×106 g/(molTi [P] h)
Journal of Inherited Metabolic Disease, 2008
Rev. Assoc. Med. …, 2010
Giugliani, Roberto; Federhen, Andressa; Muñoz Rojas, Maria Verónica; Vieira, Taiane Alves; Artiga... more Giugliani, Roberto; Federhen, Andressa; Muñoz Rojas, Maria Verónica; Vieira, Taiane Alves; Artigalás, Osvaldo; Pinto, Louise Lapagesse Carmargo; Azevedo, Ana Cecília; Acosta, Angelina Xavier; Bomfim, Carmem; Lourenço, Charles Marques; Kim, Chong Ae; ...
Rev. Bras. Hematol. …, 2003
Martins AM et al Rev. bras. hematol. hemoter. 2003;25(2):89-95 Artigo/Article Palavras-chave: Doe... more Martins AM et al Rev. bras. hematol. hemoter. 2003;25(2):89-95 Artigo/Article Palavras-chave: Doença de Gaucher; doenças de depósito; Brasil. Tratamento da Doença de Gaucher.p65 02/07/2003, 20:14 89 Rev. bras. hematol. hemoter. 2003;25(2):89-95.