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1.
Rev. clín. esp. (Ed. impr.) ; 223(1): 10-16, ene. 2023.
Artigo em Espanhol | IBECS | ID: ibc-214304

RESUMO

Antecedentes y objetivo Los servicios de consultoría en ética clínica (CEC) surgen de los comités de ética para la asistencia sanitaria (CEAS) para atender conflictos éticos en tiempo real. Nuestro objetivo es conocer la percepción de utilidad de la CEC entre los profesionales sanitarios tras un año de su creación, así como evaluar los cambios de tendencia en el uso de la CEC y de los CEAS entre 2015 y 2021. Material y método Estudio observacional transversal mediante una encuesta estandarizada a los profesionales sanitarios de un hospital terciario urbano. Se compararon estos resultados con los de una encuesta idéntica realizada sobre la misma población en 2015. Resultados Participaron 213 profesionales (edad media 44 ± 11 años, 69% mujeres). Los profesionales conocían más la existencia de los CEAS que la CEC (94 vs. 61%; p<0,001). Un total de 45 encuestados (21%) habían consultado a la CEC desde su puesta en marcha; el 95% de ellos reconocían la utilidad de la consulta. Los facultativos conocían y utilizaban más la CEC que otros grupos profesionales. El grado de conocimiento sobre los CEAS en 2021 aumentó significativamente respecto a 2015 (94 vs. 76%; p<0,001). Se identificaron como áreas de mejora la necesidad de una mayor difusión del servicio, garantizar recursos institucionales para su mantenimiento y fomentar mayor participación de distintos profesionales. Conclusiones En los últimos años ha aumentado el conocimiento de los CEAS y de la CEC entre los profesionales sanitarios quienes consideran a la CEC útil para la atención de problemas éticos cotidianos (AU)


Background and objective Clinical ethics consultation services (CEC) have arisen from healthcare ethics committees (HEC) to address ethical conflicts in real-time. Our aim was to determine the perception of usefulness of a CEC service among healthcare workers one year after its creation as well as to assess changes in trends in the use of the CEC and HEC between 2015 and 2021. Material and method This observational, cross-sectional study was based on a standardized survey of healthcare workers at an urban tertiary care hospital. The results were also compared to those from an identical survey conducted in the same population in 2015. Results A total of 213 professionals participated (mean age 44±11 years, 69% women). The professionals were more familiar with the HEC than the CEC service (94 vs. 61%; p<0.001). Forty-five individuals (21%) had consulted the CEC since its implementation; 95% of them found the consultation useful. Physicians knew about and used the CEC more than other groups of professionals. The degree of knowledge of the HEC increased significantly by 2021 compared to 2015 (94 vs. 76%; p<0.001). Some areas for improvement identified were the need for greater dissemination of the service, guaranteeing institutional resources to maintain the service, and encouraging greater participation from different professional groups. Conclusions Knowledge of the institutional HEC and CEC services has increased in recent years among healthcare workers, who considered the CEC service to be useful for addressing ethical conflicts in daily practice (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Percepção Social , Pessoal de Saúde , Comitês de Ética Clínica , Estudos Transversais
2.
Rev Clin Esp (Barc) ; 223(1): 10-16, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36528057

RESUMO

BACKGROUND AND OBJECTIVE: Clinical ethics consultation services (CEC) have arisen from Healthcare Ethics Committees (HEC) to address ethical conflicts in real-time. Our aim was to determine the perception of usefulness of a CEC service among healthcare workers one year after its creation as well as to assess changes in trends in the use of the CEC and HEC between 2015 and 2021. MATERIALS AND METHODS: This observational, cross-sectional study was based on a standardized survey of healthcare workers at an urban tertiary care hospital. The results were also compared to those from an identical survey conducted in the same population in 2015. RESULTS: A total of 213 professionals participated (mean age 44 ± 11 years, 69% women). The professionals were more familiar with the HEC than the CEC service (94% vs 61%; p < 0.001). Forty-five individuals (21%) had consulted the CEC since its implementation; 95% of them found the consultation useful. Physicians knew about and used the CEC more than other groups of professionals. The degree of knowledge of the HEC increased significantly by 2021 compared to 2015 (94% v. 76%; p < 0.001). Some areas for improvement identified were the need for greater dissemination of the service, guaranteeing institutional resources to maintain the service, and encouraging greater participation from different professional groups. CONCLUSIONS: Knowledge of the institutional HEC and CEC services has increased in recent years among healthcare workers, who considered the CEC service to be useful for addressing ethical conflicts in daily practice.


Assuntos
Consultoria Ética , Médicos , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Masculino , Estudos Transversais , Atenção à Saúde , Percepção
3.
Rev. clín. esp. (Ed. impr.) ; 222(10): 593-598, dic. 2022. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-212779

RESUMO

Introducción La consultoría en ética clínica (CEC) es un modelo útil de asesoría ética, pero con escasa implantación en Europa. En el presente artículo se comparte la experiencia de uno de los primeros servicios de consultoría ética en España. Material y métodos Estudio observacional retrospectivo de todas las consultas recibidas por el servicio de CEC del Hospital Universitario de La Princesa (Madrid, España) entre el 1 de septiembre de 2019 y el 31 de agosto de 2021. Se analizaron variables demográficas, logísticas y éticas de los casos. Resultados Se analizaron 63 casos, en los que se identificaron un total de 124 conflictos éticos. El 41% (n=26) de las consultas eran de carácter urgente y el 38% (n=24), preferentes. La evaluación inicial se realizó en menos de 24horas en 50 casos (79%). El servicio que consultó con mayor frecuencia fue Medicina Intensiva (9; 14%). Los medios de contacto preferidos fueron el busca (36; 57%), el sistema electrónico de historia clínica (13; 21%) o la conversación directa con el equipo consultor (7; 11%). Los problemas éticos más comunes estaban relacionados con la adecuación de medidas terapéuticas (24; 19%), el rechazo del tratamiento (19; 15%), la comunicación con el paciente o su familia (29; 23%) o la competencia del paciente (13; 11%). Conclusiones Los servicios de CEC proporcionan una asistencia rápida y eficiente para la resolución de problemas éticos en la práctica habitual. Su implementación en España es factible (AU)


Introduction Clinical ethics consultation services (CEC) are useful model for ethical counselling, albeit with scarce implementation in European countries. This article shares the experience of one of the first ethics consultation services in Spain. Materials and methods This work is a retrospective, observational study of all consultations received by the CEC service at La Princesa University Hospital (Madrid, Spain) from September 1, 2019 to August 31, 2021. The demographic, logistic, and ethical variables of the cases were analyzed. Results A total of 63 cases were analyzed in which a total of 124 ethical conflicts were identified. Forty-one percent of the cases (n=26) were emergency consultations and 38% (n=24) were preferential inquiries. An initial evaluation was performed with 24hours in 50 cases (79%). The department that consulted most often was the Intensive Care Unit (9; 14%). The preferred contact methods were via pager (36; 57%), the electronic medical record system (13; 21%), or direct conversations with consulting team (7; 11%). The most common ethical conflicts were those related to the adequacy of treatment measures (24; 19%), refusal of treatment (19; 15%), communication with the patient or his/her family (29; 23%), or the patient's capacity (13; 11%). Conclusion CEC services provide quick, efficient assistance for resolving ethical problems in daily practice. Their implementation in Spain is feasible (AU)


Assuntos
Humanos , Consultoria Ética/estatística & dados numéricos , Bioética , Hospitais Universitários/ética , Estudos Retrospectivos , Espanha
4.
Rev Clin Esp (Barc) ; 222(10): 593-598, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36427658

RESUMO

INTRODUCTION: Clinical ethics consultation services (CEC) are useful model for ethical counselling, albeit with scarce implementation in European countries. This article shares the experience of one of the first ethics consultation services in Spain. MATERIALS AND METHODS: This work is a retrospective, observational study of all consultations received by the CEC service at La Princesa University Hospital (Madrid, Spain) from September 1, 2019 to August 31, 2021. The demographic, logistic, and ethical variables of the cases were analyzed. RESULTS: A total of 63 cases were analyzed in which a total of 124 ethical conflicts were identified. Forty-one percent of the cases (n = 26) were emergency consultations and 38% (n = 24) were preferential inquiries. An initial evaluation was performed with 24 h in 50 cases (79%). The department that consulted most often was the Intensive Care Unit (9; 14%). The preferred contact methods were via pager (36; 57%), the electronic medical record system (13; 21%), or direct conversations with consulting team (7; 11%). The most common ethical conflicts were those related to the adequacy of treatment measures (24; 19%), refusal of treatment (19; 15%), communication with the patient or his/her family (29; 23%), or the patient's capacity (13; 11%). CONCLUSION: CEC services provide quick, efficient assistance for resolving ethical problems in daily practice. Their implementation in Spain is feasible.


Assuntos
Consultoria Ética , Humanos , Feminino , Masculino , Estudos Retrospectivos , Atenção à Saúde , Comunicação , Hospitais Universitários
5.
Materials (Basel) ; 15(15)2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35955263

RESUMO

Metal matrix syntactic foams (MMSF) are advanced cellular materials constituted by a system of a minimum of two phases, in which a dispersion of hollow particles is embedded by a continuous metal matrix. The incorporation of porous fillers favors the development of low-density materials with exceptional behavior for damping vibrations, impacts, and blast effects, shielding acoustic, thermal, and electromagnetic energies. There are three main techniques to produce them: infiltration casting technique (ICT), stir casting technique (SCT), and powder metallurgy technique (P/M). The first two techniques are used for embedding filler into lower melting point metallic matrices than fillers, in contrast to P/M. The present study demonstrates the feasibility of producing MMSF with components of similar melting points by ICT. The fillers were synthesized in-situ with aluminum and a natural foaming agent from wastes of Spanish white marble quarries. These novel aluminum syntactic foams (ASF) were mechanically characterized following the ISO-13314 and exhibited a porosity, plateau stress, and energy absorption capacity of 41%, 37.65 MPa, 8.62 MJ/m3 (at 35% of densification), respectively. These properties are slightly superior to equal porosity LECA ASF, making these novel ASF suitable for the same applications as LECA-ASF.

6.
SAR QSAR Environ Res ; 31(9): 677-695, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32854545

RESUMO

A set of 23 steroidal 1,2,4,5-tetraoxane analogues were studied using quantum-chemical method (B3LYP/6-31 G*) and multivariate analyses (PCA, HCA, KNN and SIMCA) in order to calculate the properties and correlate them with antimalarial activity (log RA) against Plasmodium falciparum clone D-6 from Sierra Leone. PCA results indicated 99.94% of the total variance and it was possible to divide the compounds into two classes: less and more active. Descriptors responsible for separating were: highest occupied molecular orbital energy (HOMO), bond length (O1-O2), Mulliken electronegativity (χ) and Bond information content (BIC0). We use HCA, KNN and SIMCA to explain relationships between molecular properties and biological activity of a training set and to predict antimalarial activity (log RA) of 13 compounds (#24-36) with unknown biological activity. We apply molecular docking simulations to identify intermolecular interactions with a selected biological target. The results obtained in multivariate analysis aided in the understanding of the activity of the new compound's design (#24-36). Thus, through chemometric analyses and docking molecular study, we propose theoretical synthetic routes for the most promising compounds 28, 30, 32 and 36 that can proceed to synthesis steps and in vitro and in vivo assays.


Assuntos
Antimaláricos/química , Desenho de Fármacos , Plasmodium falciparum/efeitos dos fármacos , Tetraoxanos/química , Simulação de Acoplamento Molecular , Relação Quantitativa Estrutura-Atividade
7.
Neurologia (Engl Ed) ; 35(8): 543-550, 2020 Oct.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29279256

RESUMO

INTRODUCTION: Neurology is one of the medical specialties offered each year to residency training candidates. This project analyses the data associated with candidates choosing neurology residency programmes in recent years. METHODS: Data related to specialty selection were obtained from official reports by the Spanish Ministry of Health, Social Services, and Equality. Information was collected on several characteristics of teaching centres: availability of stroke units, endovascular intervention, national reference clinics for neurology, specific on-call shifts for neurology residents, and links with medical schools or national research networks. RESULTS: The median selection list position of candidates selecting neurology training has been higher year on year; neurology was among the 4 most popular residency programmes in 2016. Potential residents were mainly female, Spanish, and had good academic results. The median number of hospitals with higher numbers of beds, endovascular intervention, stroke units, and national reference clinics for neurology is significantly lower. This is also true when centers are analysed by presence of specific on-call shifts for neurology residents and association with medical schools or national research networks. The centres selected by candidates with the highest median selection list position in 2012-2016 were the Clínico San Carlos, 12 de Octubre, and Vall d'Hebron university hospitals. CONCLUSIONS: Neurology has gradually improved in residency selection choices and is now one of the 4 most popular options. Potential residents prefer larger centres which are more demanding in terms of patient care and which perform more research activity.


Assuntos
Medicina/estatística & dados numéricos , Neurologia/educação , Educação Médica , Feminino , Hospitais de Ensino , Humanos , Internato e Residência , Masculino , Faculdades de Medicina , Espanha
8.
Rev Clin Esp (Barc) ; 220(5): 275-281, 2020.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31761414

RESUMO

OBJECTIVES: Although the reasons are unknown, the prevalence of arterial hypertension and atherosclerotic cardiovascular events in the adult population with Down syndrome (SD) is anecdotal. To better understand this finding, we evaluated the haemodynamic characteristics of a cohort of adults with SD. METHODS: We conducted a cross-sectional study of adults with SD recruited consecutively from the outpatient clinics of an internal medicine department between June and November 2018. We collected demographic, clinical and laboratory variables and employed a thoracic bioimpedance device (HOTMAN® System) for the haemodynamic measures. Outpatient blood pressure monitoring (OBPM) was conducted on a subgroup of participants. RESULTS: Twenty-six participants (mean age, 45±11years) participated in the study (50% men). The sample's mean blood pressure (BP) was 109/69±11/9mmHg, with a mean heart rate of 60±12bpm. None of the participants had hypertension. The predominant haemodynamic profile consisted of normal dynamism (65%), normal BP (96%), hypochronotropism (46%), normal inotropism (50%) and hypervolaemia (54%), with normal peripheral vascular resistance values (58%). Twelve participants underwent OBPM (46%). The mean 24-h systolic BP, diastolic BP, mean BP and mean heart rate were 105±11mmHg, 67±11mmHg, 80±11mmHg and 61±6bpm, respectively. CONCLUSIONS: The most common haemodynamic profile observed in adults with SD consisted of hypochronotropism and hypervolaemia, with normal values for peripheral vascular resistance and optimal mean BP values. There were no participants with hypertension in our sample.

9.
Psychoneuroendocrinology ; 72: 47-53, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27343726

RESUMO

Gaze following is a basic building block of social behavior that has been observed in multiple species, including primates. The absence of gaze following is associated with abnormal development of social cognition, such as in autism spectrum disorders (ASD). Some social deficits in ASD, including the failure to look at eyes and the inability to recognize facial expressions, are ameliorated by intranasal administration of oxytocin (IN-OT). Here we tested the hypothesis that IN-OT might enhance social processes that require active engagement with a social partner, such as gaze following. Alternatively, IN-OT may only enhance the perceptual salience of the eyes, and may not modify behavioral responses to social signals. To test this hypothesis, we presented four monkeys with videos of conspecifics displaying natural behaviors. Each video was viewed multiple times before and after the monkeys received intranasally either 50 IU of OT or saline. We found that despite a gradual decrease in attention to the repeated viewing of the same videos (habituation), IN-OT consistently increased the frequency of gaze following saccades. Further analysis confirmed that these behaviors did not occur randomly, but rather predictably in response to the same segments of the videos. These findings suggest that in response to more naturalistic social stimuli IN-OT enhances the propensity to interact with a social partner rather than merely elevating the perceptual salience of the eyes. In light of these findings, gaze following may serve as a metric for pro-social effects of oxytocin that target social action more than social perception.


Assuntos
Movimentos Oculares/fisiologia , Macaca mulatta/fisiologia , Neuropeptídeos/farmacologia , Ocitocina/farmacologia , Percepção Social , Percepção Visual/fisiologia , Animais , Masculino , Neuropeptídeos/administração & dosagem , Ocitocina/administração & dosagem
10.
Clin Transl Oncol ; 16(4): 386-94, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23907291

RESUMO

BACKGROUND: Breast cancer subtypes can be identified by genomic testing or pathology-based approximations. However, these classifications are not equivalent and the clinical relevance of both classifications needs to be fully explored. METHODS: Ninety-four patients were randomized to neoadjuvant single agent doxorubicin or docetaxel. Tumor subtype was assessed by pathology-based classification and by gene expression using the PAM50 plus the claudin-low predictor (CLP). Kappa Cohen's coefficient (κ) was used to test the agreement between methods. Multivariate Cox proportional hazards analyses were used to determine the significance of each methodology in the prediction of prognosis. Likelihood ratio statistics of both classifications were evaluated. RESULTS: The agreement between pathology-based classification and PAM50 was moderate [κ = 0.551, 95 % confidence interval (95 % CI) 0.467-0.641]. Tumor subtype assessed by both classifications were prognostic for overall survival (OS) and relapse-free survival (P < 0.05). However, PAM50 + CLP provided more prognostic information, in terms of OS, than the pathology-based classification (P < 0.05). Patients with triple negative tumors as well as basal-like tumors had worse OS when first treated with doxorubicin (HR = 5.98, 95 % CI 1.25-28.67, and HR = 5.02, 95 % CI 0.96-26.38, respectively). However, claudin-low tumors did not show significant differences in OS according to neoadjuvant treatment branch. Indeed, we found that claudin-low tumors treated with pre-operative doxorubicin had significantly better OS than basal-like tumors treated with neoadjuvant doxorubicin (adjusted HR = 0.16, 95 % CI 0.04-0.69, P = 0.014). CONCLUSIONS: The assignment of tumor subtype can differ depending on the methodology, which might have implications on patient's management and therapy selection.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Terapia Neoadjuvante/métodos , Adulto , Idoso , Antineoplásicos/uso terapêutico , Neoplasias da Mama/mortalidade , Docetaxel , Doxorrubicina/uso terapêutico , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Modelos de Riscos Proporcionais , Taxoides/uso terapêutico
11.
Q J Nucl Med Mol Imaging ; 58(1): 66-73, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24104854

RESUMO

AIM: Classical prognostic and predictive factors serve to predict outcome and response to neoadjuvant treatment in stage II and III breast cancer. The purpose is to determine the relation between the SUVmax of the locoregional disease with these classical prognostic factors. METHODS: A prospective study including 43 stage II and III breast cancer patients was performed. In all the patients, two 18F-FDG PET-CT studies were performed before and after neoadjuvant chemotherapy. After this treatment, surgery and adjuvant treatment were carried out. To combine the information of the locoregional disease, the SUVmax of the lesion (tumor or abnormal lymphnodes) with the highest uptake was used. SUVmax and prognostic factors were studied with the Kruskal-Wallis non-parametric test and with the Mann-Whitney U. RESULTS: A statistically significant association between elevated SUVmax value and absence of estrogen receptors (ER) expression (16 vs.. 10; P<0.019) was found. Locorregional disease with positive HER2 phenotype had a statistically significant SUVmax value greater than Luminal A (estrogen and/or progesterone positive receptors with Ki67<15%) and B (estrogen and/or progesterone positive receptors with Ki67≥to 15%) (13.4 vs. 7.9 and 8.9; P<0.022 and P<0.024, respectively). Triple negative phenotype disease had higher SUVmax than Luminal A and B (15.4; P<0.030 and P<0.038). Positive correlation between the percentage of the Ki67 Proliferation Index and SUVmax (P<0.007) was demonstrated. High grade disease had a higher SUVmax than low grade (P<0.004). CONCLUSION: Locorregional SUVmax is associated to prognostic and predictive factors and reaffirms the utility of PET-CT as a tool in the common clinical practice.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/diagnóstico , Fluordesoxiglucose F18 , Estadiamento de Neoplasias/métodos , Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Neoplasias da Mama/terapia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Antígeno Ki-67/metabolismo , Pessoa de Meia-Idade , Modelos Estatísticos , Terapia Neoadjuvante/métodos , Fenobarbital/química , Prognóstico , Estudos Prospectivos , Compostos Radiofarmacêuticos , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Resultado do Tratamento
12.
Ann Oncol ; 24(3): 655-61, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23104719

RESUMO

BACKGROUND: Measurement of residual disease following neoadjuvant chemotherapy that accurately predicts long-term survival in locally advanced breast cancer (LABC) is an essential requirement for clinical trials development. Several methods to assess tumor response have been described. However, the agreement between methods and correlation with survival in independent cohorts has not been reported. PATIENTS AND METHODS: We report survival and tumor response according to the measurement of residual breast cancer burden (RCB), the Miller and Payne classification and the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, in 151 LABC patients. Kappa Cohen's coefficient (К) was used to test the agreement between methods. We assessed the correlation between the treatment outcome and overall survival (OS) and relapse-free survival (RFS) by calculating Harrell's C-statistic (c). RESULTS: The agreement between Miller and Payne classification and RCB classes was very high (К = 0.82). In contrast, we found a moderate-to-fair agreement between the Miller and Payne classification and RECIST criteria (К = 0.52) and RCB classes and RECIST criteria (К = 0.38). The adjusted C-statistic to predict OS for RCB index (0.77) and RCB classes (0.75) was superior to that of RECIST criteria (0.69) (P = 0.007 and P = 0.035, respectively). Also, RCB index (c = 0.71), RCB classes (c = 0.71) and Miller and Payne classification (c = 0.67) predicted better RFS than RECIST criteria (c = 0.61) (P = 0.005, P = 0.006 and P = 0.028, respectively). CONCLUSIONS: The pathological assessment of tumor response might provide stronger prognostic information in LABC patients.


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Doxorrubicina/uso terapêutico , Taxoides/uso terapêutico , Adulto , Idoso , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/patologia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Docetaxel , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasia Residual , Modelos de Riscos Proporcionais , Resultado do Tratamento , Carga Tumoral
15.
Ann Oncol ; 23(7): 1750-6, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22052985

RESUMO

BACKGROUND: Identification of predicting factors for anthracyclines-based chemotherapy remains a clinical challenge. Glutathione S-transferase (GSTs) enzymes detoxify chemotherapy drugs and their metabolites. Several polymorphisms in GST genes result in reduced or no activity of the enzymes. Specifically, GSTM1 and GSTT1 genes are polymorphically deleted, the polymorphism GSTP1 c.313A>G (rs1695) determines the amino acid substitution Ile105Val, where the Val-containing enzyme has reduced activity. Also, GSTA1*B allele has reduced levels of GSTA1 enzyme. Several polymorphisms in GSTs have been associated with differences in survival for cancer patients treated with chemotherapy. PATIENTS AND METHODS: We genotyped a total of five polymorphisms in GSTM1, GSTT1, GSTP1 and GSTA1 genes in 159 patients with locally advanced breast cancer, treated with single-agent doxorubicin or docetaxel (Taxotere). Gene expression microarrays were performed in 67 breast tumor samples. We correlate this data with treatment outcome. RESULTS: In multivariate analysis, patients homozygous GG for GSTP1 c.313A>G SNP had a lower risk of chemoresistance when treated with doxorubicin (odds ratio 0.106; confidence interval 0.012-0.898; P=0.040). No association was found in the docetaxel arm. Also, we found that GSTP1 expression varied significantly among breast cancer molecular subtypes. CONCLUSIONS: GSTP1 may constitute another tool contributing to individualized anthracycline-based therapy.


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Neoplasias da Mama/genética , Doxorrubicina/uso terapêutico , Glutationa S-Transferase pi/genética , Polimorfismo de Nucleotídeo Único , Taxoides/uso terapêutico , Adulto , Idoso , Antibióticos Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/enzimologia , Docetaxel , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Expressão Gênica , Estudos de Associação Genética , Genótipo , Glutationa Transferase/genética , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Análise de Sequência de DNA , Deleção de Sequência , Taxoides/farmacologia , Resultado do Tratamento
16.
Breast Cancer Res Treat ; 128(1): 127-36, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21465170

RESUMO

UNLABELLED: Taxanes and anthracyclines improve the outcome of early breast cancer, although the benefit is limited to a small proportion of patients and are toxic. We prospectively looked for predictors of response to these drugs. EXPERIMENTAL DESIGN: Four cycles of doxorubicin (75 mg/m²) or docetaxel (100 mg/m²) were compared as presurgical chemotherapy for breast cancer. Biomarkers were determined by immunohistochemistry and fluorescent in situ hybridization using prechemotherapy core biopsies. Tumors were also classified into one of the molecular intrinsic subtypes using an immunohistochemical panel of five biomarkers and genomic profiles. Single genes and intrinsic subtypes were correlated with response to doxorubicin versus docetaxel. Among the 204 evaluable patients, significant predictors of sensitivity in multivariate analysis were low topo2a expression and ER-negative status for doxorubicin and small tumor size and ER-negative status for docetaxel. Predictors of resistance in multivariate analysis were triple-negative status (ER/PgR/HER2 negative by IHC/FISH) for doxorubicin, and high TNM stage for docetaxel. Triple-negative tumors were associated with topo2a overexpression more than the other subtypes. In 94 patients with gene expression profiles, docetaxel was superior to doxorubicin in the basal-like subtype (good pathological response rate - PCR + class I of 56 vs. 0%; P = 0.034); no significant differences were observed in the other subtypes when comparing these two drugs. Low topo2a expression and ER-negative status were predictors of response to doxorubicin, while small tumor size and ER-negative status predicted response to docetaxel. Docetaxel was superior to doxorubicin in triple-negative/basal-like tumors, while no significant differences were seen in the remaining intrinsic subtypes.


Assuntos
Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Carcinoma Lobular/genética , Doxorrubicina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Genes Neoplásicos , Taxoides/uso terapêutico , Adulto , Idoso , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Lobular/tratamento farmacológico , DNA Topoisomerases Tipo II/genética , DNA Topoisomerases Tipo II/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Docetaxel , Feminino , Expressão Gênica , Perfilação da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Resultado do Tratamento
17.
Rev. senol. patol. mamar. (Ed. impr.) ; 23(5): 189-194, nov.-dic. 2010. tab
Artigo em Espanhol | IBECS | ID: ibc-85958

RESUMO

Objetivos: Determinar si la punción con colorante mejora los resultados de la biopsia del ganglio centinela. Material y métodos: Ciento cincuenta casos de carcinoma invasor de la mama fueron sometidos a biopsia del ganglio centinela mediante técnica combinada, para determinar si la punción con colorante es rentable. Se realizó inyección subareolar indérmica de una dosis de 0,4 mCi de radioisótopico el día previo a la cirugía. Se practicó gammagrafía en todos los casos. La inyección intraparenquimatosa de 4 cc. de colorante se realizó 20 minutos antes de la cirugía, y se siguió de masaje mamario. Resultados: La tasa de migración fue 92,3% para el radioisótopo y 75% para el colorante (p = 0,01). La media de ganglios resecados fue mayor para la técnica con colorante: 2,6 vs. 1,2 (p = 0,02). No se observaron diferencias en la tasa de falsos negativos (0,2 vs. 0,4) ni en el valor predictivo negativo. La precisión diagnóstica fue mayor para el radioisótopo (90,3% vs. 75% (p = 0,001). El mismo resultado se obtuvo para el porcentaje de éxito técnico (92,3 vs. 75% (0,001)). Conclusiones: La punción con colorante no añade información a la realizada con radioisótopo. A pesar de que la técnica se debe adaptar a las necesidades del centro y a las habilidades del cirujano, una vez superada la curva de validación la técnica radioisotópica por sí misma aporta suficiente información, con menor morbilidad y coste(AU)


Objetives: To determine whether blue dye enhances sentinel node biopsy detection. Material and methods: One hundred fifty hundred consecutive cases of breast cancer were submitted to sentinel node biopsy by combined technique in order to analyze if vital blue was cost-efective. Radioisotope dose was 0,4 mCi of Tc, subareolar intradermic inyection, the day before surgery. Gammagraphy was performed in every case. Colorant was methylene blue, 4 cc administered by intraparenchimatous inyection in upper-outer quadrant 20 minutes previous to surgery, followed by breast massagge. Results: Migration rate was 92.3% for radioisotope and 75% for colorant (p = 0.01). Mean number of nodes excised was higher for colorant: 2,6 vs. 1,2 (p = 0.02). False negative rate showed no difference (0.2 vs. 0.4) nor did negative predictive value. Accuracy to staging (True neg+ true pos./total) was higher for technecium (90.3% vs. 75% (p = 0.001) and so happenned with percentage of technical success (total- no migration): 92.3% vs. 75% (0.001). Conclusions: Colorant did no add any information concerning axillary status. More nodes had to be excised, and bigger incisions were made to achieve direct visualization. Accuracy to stage the lesion and percentage of technical success were higher with radioisotope after the learning curve is achieved and blue injection can be spared(AU)


Assuntos
Humanos , Feminino , Neoplasias da Mama/diagnóstico , Biópsia de Linfonodo Sentinela/tendências , Carcinoma/complicações , Carcinoma/diagnóstico , Radioisótopos , Azul de Metileno , Estudos Prospectivos , Avaliação de Resultado de Intervenções Terapêuticas/métodos
18.
Rev. senol. patol. mamar. (Ed. impr.) ; 23(4): 168-172, ago.-oct. 2010. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-85953

RESUMO

La importancia en la detección de la amplificación del gen HER2 es esencial en el cáncer de mama puesto que estas pacientes no responden a los tratamientos de quimioterapia y hormonales convencionales. La determinación del HER2 tiene un papel crucial como diana terapéutica del trastuzumab. A continuación discutiremos la efectividad y utilidad clínica de la técnica hibridación in situ fluorescente (FISH), la hibridación in situ cromogénica (CISH) y la hibridación in situ cromogénica con plata (SISH), como métodos usados para el estudio del gen HER2 en la selección correcta de las pacientes con cáncer de mama, que son candidatas a recibir trastuzumab(AU)


The importance of determining HER2 status lays on the fact that breast cancer patients with HER2 amplification are more reluctant to conventional chemotherapy and hormonal treatments. Thus the HER2 analysis is an essential requisite to determine which patients are eligible to be treated with trastuzumab. The aim of this article is reviewing the effectiveness and clinical utility of HER 2 diagnostic test with fluorescence in situ hybridization (FISH), chromogenic in situ hybridization (CISH) and silver chromogenic in situ hybridization (SISH) to correctly select breast cancer patients who are candidates to be treated with trastuzumab(AU)


Assuntos
Humanos , Feminino , Hibridização In Situ/métodos , Receptor ErbB-2/administração & dosagem , Receptor ErbB-2/análise , Neoplasias da Mama/diagnóstico , Citogenética/métodos , Análise Citogenética/instrumentação , Hibridização In Situ/tendências , Hibridização In Situ , Genes erbB-2 , Corantes Fluorescentes
19.
Rev. senol. patol. mamar. (Ed. impr.) ; 19(2): 70-72, abr.-jun. 2006. ilus
Artigo em Es | IBECS | ID: ibc-050348

RESUMO

El dermatofibrosarcoma protuberans (DFSP) es un tumor rarode la piel, localmente agresivo con elevado rango de recidivas ybaja incidencia de metástasis a distancia. Puede originarse comouna pequeña lesión asintomática y pasar desapercibido. La extirpacióncon amplios márgenes ha sido el tratamiento de elecciónaunque la cirugía micrográfica de Mohs puede ser el mejor tratamiento.Se presenta un paciente con un dermatofibrosarcomaprotuberans mamario y se revisa la literatura


Dermatofibrosarcoma protuberans is an uncommon tumorof the dermis (DFSP) is a locally agressive tumor with a highrecurrence rate but rare systemic metastasis. It may start as asmall asymtomatic lesion, which is likely ignored. Surgical excisionwith wide margins has been considered the standardtherapy though Mohs micrographic surgery may be the besttreatment option. We study the case of a man with DFSP inthe breast. Literature is also reviewed


Assuntos
Masculino , Adulto , Humanos , Dermatofibrossarcoma/diagnóstico , Dermatofibrossarcoma/cirurgia , Mama/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/cirurgia , Mastectomia Subcutânea , Recidiva Local de Neoplasia
20.
Br J Neurosurg ; 19(2): 192-7, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16120527

RESUMO

Cerebral solitary Langerhans cell histiocytosis (LCH) is a very uncommon condition. We describe two new cases: a 30-year-old man with seizures and a tumour in the left frontal lobe, which was composed of a polymorphic infiltrate with a predominance of histiocytes and eosinophils; and a 65-year-old man with headaches and dysarthria, with a left parietal tumour, which showed a diffuse proliferation of histiocytic cells and areas of necrosis. In both cases, the histiocytes were strongly positive for S-100 and CD1a, and Birbeck's granules were demonstrated by electron microscopy in the first case. Both patients underwent a complete excision of their lesions. The second patient received additional postoperative radiotherapy. They were asymptomatic after 26 and 27 months, respectively. It seems that cerebral solitary LCH is a clinicopathological entity with a good outcome. Only 15 cases of this rare process have been previously reported in the English literature.


Assuntos
Histiocitose de Células de Langerhans/patologia , Adulto , Idoso , Antígenos CD1/metabolismo , Grânulos Citoplasmáticos/ultraestrutura , Histiocitose de Células de Langerhans/metabolismo , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Masculino , Microscopia Eletrônica , Proteínas S100/metabolismo , Resultado do Tratamento
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