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Artigo em Inglês | MEDLINE | ID: mdl-34533295


OBJECTIVE: The aim of this study was to examine the effectiveness of a school-based gamification strategy to prevent childhood obesity. METHODS: Schools were randomized in Santiago, Chile, between March and May 2018 to control or to receive a nutrition and physical activity intervention using a gamification strategy (i.e., the use of points, levels, and rewards) to achieve healthy challenges. The intervention was delivered for 7 months and participants were assessed at 4 and 7 months. Primary outcomes were mean difference in BMI z score and waist circumference (WC) between trial arms at 7 months. Secondary outcomes were mean difference in BMI and systolic and diastolic blood pressure between trial arms at 7 months.  RESULTS: A total of 24 schools (5 controls) and 2,197 students (653 controls) were analyzed. Mean BMI z score was lower in the intervention arm compared with control (adjusted mean difference -0.133, 95% CI: -0.25 to -0.01), whereas no evidence of reduction in WC was found. Mean BMI and systolic blood pressure were lower in the intervention arm compared with control. No evidence of reduction in diastolic blood pressure was found. CONCLUSIONS: The multicomponent intervention was effective in preventing obesity but not in reducing WC. Gamification is a potentially powerful tool to increase the effectiveness of school-based interventions to prevent obesity.

J Cancer Res Ther ; 17(2): 547-550, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34121706


Purpose: Health emergency due to COVID-19 started in Uruguay on March 13, 2020; our mastology unit tried to ensure adequate oncological care, and protect patients from the virus infection and complications. Objective: To assess the health care activities in the "peak" of the pandemic during 3 months. Materials and Methods: we collected data from the electronic health record. Results: There were a total of 293 medical appointments from 131 patients (221 face-to-face), that decreased by 16.7% compared to the same period in 2019 (352 appointments). The medical appointments were scheduled to evaluate the continuity of systemic treatment or modifications (95 patients; 72.5%), follow-up (17; 12.9%), first-time consultation (12; 9.1%), and assess paraclinical studies (7; 5.3%). The patients were on hormone therapy (81 patients; 74%), chemotherapy (CT) (21; 19%), and anti-HER2 therapies (9; 8%). New twenty treatments were initiated. Of the 14 patients that were on adjuvant/neoadjuvant CT, 9 (64.3%) continued with the same regimen with the addition of prophylactic granulocyte-colony-stimulating factors (G-CSF), and 5 (35.7%), who were receiving weekly paclitaxel, continued the treatment with no changes. Of the seven patients that were on palliative CT, 2 (28.5%) continued the treatment with the addition of G-CSF, 3 (42.8%) continued with weekly capecitabine or paclitaxel with no treatment changes, and 2 (28.5%) changed their treatment regimen (a less myelosuppressive regimen was selected for one and due to progression of the disease in the other patient). The ninety patients who were receiving adjuvant, neoadjuvant, or palliative criteria hormone therapy and/or anti-HER2 therapies, continued the treatment with no changes. Conclusions: The evidence suggests that, although medical appointments decreased by approximately 17%, we could maintain healthcare activities, continued most of the treatments while the most modified was CT with G-CSF to avoid myelosuppression.

Neoplasias da Mama/tratamento farmacológico , COVID-19/epidemiologia , Continuidade da Assistência ao Paciente/estatística & dados numéricos , Atenção à Saúde/estatística & dados numéricos , Oncologia/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Medula Óssea/efeitos dos fármacos , Neoplasias da Mama/complicações , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , COVID-19/transmissão , Controle de Doenças Transmissíveis/normas , Continuidade da Assistência ao Paciente/organização & administração , Atenção à Saúde/organização & administração , Atenção à Saúde/normas , Registros Eletrônicos de Saúde/estatística & dados numéricos , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Hematopoese/efeitos dos fármacos , Hematopoese/imunologia , Humanos , Oncologia/organização & administração , Oncologia/normas , Pessoa de Meia-Idade , Pandemias/prevenção & controle , Encaminhamento e Consulta/normas , Encaminhamento e Consulta/estatística & dados numéricos , Estudos Retrospectivos , Telemedicina/organização & administração , Telemedicina/normas , Telemedicina/estatística & dados numéricos , Triagem/organização & administração , Triagem/normas , Uruguai/epidemiologia
Rev. méd. Urug ; 36(1): 49-58, mar. 2020. tab, graf
Artigo em Espanhol | LILACS, BNUY | ID: biblio-1094226


Resumen: Las mutaciones de BRCA1 son raras en el cáncer de mama (CM) esporádico; sin embargo, su expresión a nivel tumoral se encuentra disminuida o ausente en 30%-50% de los casos. Objetivo: valorar la expresión tumoral de BRCA1 por inmunohistoquímica (IHQ) en mujeres uruguayas diagnosticadas de CM antes de los 40 años. Material y método: se incluyeron pacientes diagnosticadas de CM antes de los 40 años. Se utilizaron los anticuerpos monoclonales anti-BRCA1 MS110 contra el extremo N-terminal y GLK-2 contra el extremo C-terminal. Se calculó la sobrevida global (SVG) y la sobrevida libre de enfermedad (SVLE), para la construcción de las curvas se utilizó el método de Kaplan-Meier y la diferencia de sobrevida se evaluó mediante el test de log rank. Resultados: se incluyeron 40 pacientes, la SVG y la SVLE a cinco años fueron de 73% y 60% respectivamente. La expresión de BRCA1 mediante GLK-2 fue <10% en 16 de las 40 pacientes (40%). La SVG y la SVLE a cinco años para las pacientes con expresión <10% fue de 56% vs 85% para las pacientes con expresión >10% (p=0,015) y de 40% vs 72% (p=0,034) respectivamente. La expresión de BRCA1 mediante MS110 fue <10% en 11 de las 40 pacientes (27,5%). No se encontraron diferencias en la SVG ni en la SVLE a cinco años con este marcador. Conclusión: la pérdida de la expresión tumoral de BRCA1 determinada mediante GLK-2 se encontró en el 40% de las pacientes incluidas y se asoció a una menor SVG y SVLE, por lo que podría tener un valor pronóstico desfavorable en estas pacientes.

Summary: BRCA1 mutations are rare in sporadic breast cancer (CM), however their expression at the tumor level is diminished or absent in 30-50% of cases. Objective: to assess the tumor expression of BRCA1 using immunohistochemistry (IHC) in Uruguayan women diagnosed with BC before the age of 40 years. Material and methods: patients diagnosed with BC before the age of 40 between. The antibodies used were anti BRCA1 MS110 monoclonal antibodies against the N-terminal end and GLK-2 against the C-terminal. Overall survival (OS) and disease free survival (DFS) were calculated; the curves were developed using the Kaplan-Meier method and the difference in survival was evaluated through the log rank test. Results: the average age of the 40 patients included was 36 years. The 5-year OS and DFS were 73% and 60% respectively. The expression of BRCA1 with GLK-2 was <10% in 16 of the 40 patients included (40%). The 5-year OS and DFS for patients with <10% expression was 56% vs. 85% for patients with >10% (p=0.015) and 40% vs. 72% (p = 0.034) respectively. The expression of BRCA1 by MS110 was <10% in 11 of the 40 patients included (27.5%). No differences were found in the 5-year OS or DFS based on the expression of this marker. Conclusion: The loss of BRCA1 expression using GLK-2, which suggests the presence of a truncated protein, was associated with a statistically significantly lower OS and DFS, that the decrease in the BRCA1 protein as determined by GLK2 has an unfavorable prognostic value for young patients with BC.

Resumo: As mutações de BRCA1 são raras no câncer de mama (CM) esporádico; no entanto sua expressão no nível tumoral está diminuída ou ausente em 30-50% dos casos. Objetivo: avaliar a expressão tumoral de BRCA1 por imuno-histoquímica (IHQ) em mulheres uruguaias com diagnóstico de CM antes dos 40 anos. Material e métodos: foram incluídas pacientes com diagnóstico de CM antes dos 40 anos. Foram utilizados anticorpos monoclonais anti BRCA1 MS110 contra o extremo N-terminal e GLK-2 contra o extremo C-terminal. A sobrevida global (SVG) e a sobrevida livre de enfermidade (SVLE) foram calculadas; o método de Kaplan-Meier foi utilizado para a construção das curvas e a diferença de sobrevida foi avaliada usando o teste de log-rank. Resultados: foram incluídas 40 pacientes; a SVG e a SVLE aos 5 anos foram 73% e 60% respectivamente. A expressão de BRCA1 mediante GLK-2 foi <10% em 16 das 40 pacientes (40 %). A SVG e a SVLE aos 5 anos para as pacientes com expressão £10% foi 56% vs. 85% para as pacientes com expressão >10% (p=0,015) e 40% vs. 72% (p=0,034) respectivamente. A expressão de BRCA1 mediante MS110 foi =10% em 11 das 40 pacientes (27,5%). Não foram encontradas diferenças na SVG nem na SVLE aos 5 anos com este marcador. Conclusão: foi encontrada perda da expressão tumoral de BRCA1 determinada por GLK-2 em 40% das pacientes incluídas e foi associada a uma menor SVG e SVLE, o que poderia ter um valor prognóstico desfavorável nestas pacientes.

Humanos , Feminino , Adulto , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/metabolismo , Proteína BRCA1/análise
JCO Glob Oncol ; 6: 217-223, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32045546


PURPOSE: Trastuzumab has shown an overall survival (OS) benefit in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC), in both the adjuvant and the metastatic setting. We assessed the effectiveness of trastuzumab in patients treated in daily practice according to national treatment coverage protocols and compared our results with those reported by randomized clinical trials. These coverage protocols included patient selection criteria similar to those of those clinical trials and were developed by the Uruguayan National Resource Fund (FNR), the agency that has funded these prescriptions for more than a decade. PATIENTS AND METHODS: We included all patients with HER2-positive BC treated with trastuzumab under FNR coverage approved between January 1, 2006, and December 31, 2016. The source of data was the FNR database, and primary outcome was OS, analyzed through Cox proportional hazards regression analysis. RESULTS: A total of 1,944 women were included: 1,085 women (55.8%) were postmenopausal and 1,240 (63.7%) had HER2 and hormone receptor-positive BC. Trastuzumab was administered as adjuvant therapy to 1,233 patients (63.5%), of whom 154 also received it as a neoadjuvant treatment. Three hundred nineteen patients (16.4%) received trastuzumab for advanced disease. Five-year OS in the adjuvant setting was 86.4% (95% CI, 84.0% to 88.7%). The median survival of patients with advanced BC was 25.1 months (95% CI, 10.1 to 42.5 months). CONCLUSION: Our survival results are not inferior to those reported in clinical trials, in both adjuvant and advanced settings. Importantly, these results support the relevance and the feasibility of treating patients in routine practice, following coverage protocols based on patient selection criteria and methods supported by positive clinical trials. In addition, these results favor quality and appropriate access to BC treatment in our country.

FEBS J ; 286(19): 3909-3925, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31162791


Trypanosoma cruzi is the causative agent of Chagas disease. The only two drugs accepted for the treatment of this infection are benznidazole and nifurtimox, which are of limited use in the predominant chronic phase. On the search for new drugs, the intracellular Ca2+ regulation has been postulated as a possible target, due to differences found between host cells and the parasite. The mechanisms involved in the intracellular Ca2+ regulation of T. cruzi have been partially elucidated. However, nothing is known about a putative channel responsible for the Ca2+ entry into this parasite. In contrast, in Leishmania spp., a closely related hemoflagelate, a sphingosine-activated plasma membrane Ca2+ channel has been recently described. The latter resembles the L-type voltage-gated Ca2+ channel present in humans, but with distinct characteristics. This channel is one of the main targets concerning the mechanism of action of miltefosine, the unique oral drug approved against leishmaniasis. In the present work, we describe for the first time, the electrophysiological characterization of a sphingosine-activated Ca2+ channel of T. cruzi by reconstituting plasma membrane vesicles into giant liposomes and patch clamp. This channel shares some characteristic as activation by Bay K8644 and inhibition by channel blockers such as nifedipine. However, the T. cruzi channel differs from the L-type VGCC in its activation by sphingosine and/or miltefosine. Albeit the conductance for each, Ba2+ , Ca2+ and Sr2+ was similar, the parasite channel appears not to be voltage dependent. A gene that presents homology in critical amino acids with its human ortholog Ca2+ channel was identified.

Canais de Cálcio/fisiologia , Esfingosina/fisiologia , Trypanosoma cruzi/fisiologia , Animais , Antiprotozoários/farmacologia , Cálcio/metabolismo , Canais de Cálcio/efeitos dos fármacos , Transporte de Íons , Fosforilcolina/análogos & derivados , Fosforilcolina/farmacologia
Rev. urug. cardiol ; 34(1): 85-107, abr. 2019. tab
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-991650


resumen está disponible en el texto completo

Summary: Background: trastuzumab-induced cardiac dysfunction is a manifestation of cardiotoxicity, usually reversible, transient and dose independent. Its early detection by transthoracic echocardiogram allows the modification of therapeutic schemes and the initiation of cardioprotective drugs. Objective: to evaluate the presence of trastuzumab cardiotoxicity manifested as left ventricular dysfunction assessed by transthoracic echocardiogram and its evolution with trastuzumab suspension and initiation of cardioprotective drugs. Material and methods: observational study; case series. We retrospectively selected patients who started treatment with trastuzumab for breast cancer, with at least 5 consecutive transthoracic echocardiograms and who met trastuzumab-induced cardiac dysfunction criteria defined as the relative reduction of the left ventricular ejection fraction > 10% with respect to the baseline, with final value <53%. Age, stage of the disease, cardiovascular risk factors , number of trastuzumab cycles, exposure time, left ventricular ejection fraction, reduction percentage and time to normalization were recorded. Left ventricular ejection fraction was calculated by the Simpson method. The numerical variables are expressed as median and range. Results: of a total of 43 patients at risk of trastuzumab-induced cardiac dysfunction, during the period 2014-2017, results of the eight cases that met the inclusion criteria are shown. All were asymptomatic. Baseline left ventricular ejection fraction was: 63% (55-65), at the time of trastuzumab-induced cardiac dysfunction: 49% (45-52) and percentage of decrease: 22.5% (16.1 -26.2). All the patients temporarily suspended trastuzumab and they initiated enalapril (losartan if there was intolerance) and carvedilol. Left ventricular ejection fraction normalization occurred in all patients. The time between ventricular dysfunction and normalization of left ventricular ejection fraction was 49.5 days (28-166). The ventricular dysfunction appeared early in 2 patients (cycles 5 and 6 of trastuzumab) and in the rest, between cycles 10 and 15. The patients with early manifestation had a delayed recovery of left ventricular ejection fraction (119 and 166 days respectively). After normalization of ventricular dysfunction, all patients restarted treatment with trastuzumab while maintaining cardioprotective treatment. Conclusions: in this number of cases, we observed two different patterns of trastuzumab-induced cardiac dysfunction, one with earlier manifestation and greater delay in left ventricular ejection fraction recovery. Cardiac dysfunction was reversible and all patients could continue treatment. It is the intention of the working group to continue investigating on this topic through observational cohort and randomized clinical studies to analyze the risk factors for the development of trastuzumab-induced cardiac dysfunction, as well as eventual preventive measures.

Resumo: Introdução: a disfunção ventricular devida ao trastuzumab é uma manifestação de cardiotoxicidade com lesão geralmente reversível, transitória e dose independente. Sua detecção precoce pelo ecocardiograma transtorácico permite a modificação de esquemas terapêuticos e o início de drogas cardioprotetoras. Objetivo: avaliar a presença de cardiotoxicidade do trastuzumab manifestada como disfunção do ventrículo esquerdo no ecocardiograma transtorácido e sua evolução frente à suspensão do trastuzumab e início de drogas cardioprotetoras. Material e métodos: estudo observacional; série de casos. Selecionamos retrospectivamente pacientes que iniciaram o tratamento com trastuzumab para câncer de mama, com pelo menos 5 ecocardiogramas consecutivos e que preencheram os critérios do disfunção do ventrículo esquerdo definidos como a redução relativa da fração de ejeção >10% em comparação com linha de base, com valor final: <53%. Idade, estágio da doença, fatores de risco cardiovascular , número de ciclos de trastuzumab, tempo de exposição, fração de ejeção, percentual de redução e tempo para normalização foram registrados. A fração de ejeção foi calculada pelo método de Simpson. As variáveis numéricas são expressas como mediana e intervalo. Resultados: de um total de 43 pacientes em risco de disfunção ventricular, durante o período de 2014-2017, os resultados dos oito casos que preencheram os critérios de inclusão são mostrados. Os pacientes eram assintomáticos na área cardiovascular. Linha de base de fração de ejeção: 63% (55-65), quando disfunção ventricular: 49% (45-52), e declínio percentual: 22,5% (16,1-26,2). Todos suspenderam temporariamente o trastuzumab e iniciaram o enalapril (losartan se houve intolerância) e carvedilol. A normalização da fração de ejeção ocorreu em todos os pacientes. O tempo entre o disfunção ventricular e a normalização foi de 49,5 dias (28-166). O disfunção ventricular é expressa em ciclos 5 e 6 de trastuzumab em 2 pacientes e no resto entre os ciclos 10 e 15. Os pacientes com manifestação precoce levaram mais tempo para se recuperar (119 e 166 dias, respectivamente). Após a normalização da fração de ejeção o tratamento com trastuzumab continuou mais o tratamento cardioprotetor. Conclusões: nesta série de casos, observamos dois padrões diferentes de disfunção ventricular devida ao trastuzumab, um mais precose e com mais atraso na recuperação da fração de ejeção do ventrículo esquerdo. A disfunção ventricular devida ao trastuzumab foi reversível e todos os pacientes puderam continuar o tratamento. É a intenção do grupo de trabalho para continuar investigando através de estudos de coorte observacionais e ensaios clínicos randomizados para analisar os fatores de risco para o desenvolvimento de disfunção ventricular devida ao trastuzumab e possíveis medidas preventivas.

Rev. luna azul ; 49(0): 220-240, 2019. tab, ilus
Artigo em Espanhol | LILACS | ID: biblio-1121058


Los humedales representan una transición entre un ambiente terrestre y acuático, constituyéndose como uno de los sistemas naturales más importantes debido a sus múltiples funciones; no obstante, a pesar de su importancia, representan uno de los ecosistemas más vulnerables. Los humedales de la costa de la región de Coquimbo-Chile configuran un sistema dinámico con gran presencia de biodiversidad en un área con predominio semi-árido. En este contexto, resulta importante acercarse a un mayor conocimiento de estos sistemas con el fin de promover su conservación y/o restauración, siendo una fundamental herramienta las experiencias educativas. Objetivo. Determinar cómo es percibido el futuro del humedal "El Culebrón" por estudiantes de enseñanza media a través del desarrollo de escenarios cualitativos. Materiales y métodos. Se generó inicialmente un conjunto de escenarios a partir de una proyección de 10 años, los cuales fueron reinterpretados mediante el software NVIVO9. Resultados. El análisis permitió diferenciar cuatro escenarios: "responsabilidad social", "cambio climático", "crecimiento de lo natural" y "urbanización". Conclusiones. Se puede inferir un futuro amenazante de los humedales desde la perspectiva percibida por los estudiantes debido a la interacción de impulsores de cambio indirectos, entre los que se destacan elementos naturales (cambio climático y eventos extremos) cambios demográficos (urbanización) y culturales (conciencia ambiental precaria o insuficiente)

Wetlands represent a transition between a terrestrial and aquatic environment, becoming one of the most important natural systems due to their multiple functions. However, despite their importance, they represent one of the most vulnerable ecosystems. The wetlands of the coast of the Coquimbo Region, Chile, form a dynamic system with a large presence of biodiversity in an area with semi-arid predominance. In this context, it is important to approach a greater knowledge of these systems to promote their conservation and/or restoration, educational experiences being a fundamental tool. Objective: to determine how the future of "El Culebrón" wetland is perceived by middle school students, through the development of qualitative scenarios. Materials and methods: A set of scenarios was initially generated from a 10-year projection, which were reinterpreted using NVIVO9 software. Results: the analysis allowed to differentiate four scenarios: "social responsibility", "climate change", "natural growth" and "urbanization". Conclusions: a threatening future of wetlands can be inferred from the perspective perceived by students due to the interaction of indirect drivers of change, among which natural elements (climate change and extreme events), demographic elements (urbanization) and cultural changes (poor or insufficient environmental awareness) stand out.

Humanos , Educação em Saúde Ambiental , Mudança Climática , Chile , Áreas Alagadas
Rev. Urug. med. Interna ; 3(3): 20-26, oct. 2018. tab
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1092344


Resumen: El síndrome de Li-Fraumeni (SLF) es una enfermedad hereditaria autosómica dominante con elevada penetrancia, que se caracteriza por la aparición precoz de múltiples tumores en un individuo y una marcada agregación familiar. Aproximadamente el 70% de los pacientes que cumplen criterios clínicos para su diagnóstico son portadores de la mutación germinal del gen TP53 localizado en el cromosoma 17p13. El gen TP53 es un supresor tumoral que cumple una importante función en el control de la estabilidad genómica. Se estima que el riesgo de desarrollar cáncer es del 50 % para las mujeres a los 31 años de edad y para los hombres a los 46 años y cerca del 100 % para ambos sexos a los 70 años. El curso clínico de la enfermedad es similar que en pacientes sin SLF a excepción de la edad más temprana al diagnóstico. Presentamos el caso de una paciente de 31 años a la que se diagnostica un condrosarcoma pelviano tratado con cirugía y al momento de la recidiva, aproximadamente 8 meses después, un cáncer de mama localizado. En otro miembro de su familia se había identificado la mutación 375G>C en el gen TP53 mediante secuenciación Sanger, la cual fue detectada posteriormente en nuestra paciente. Se discuten aspectos particulares del manejo como la minimización de la exposición a la radioterapia (por reportes de tumores malignos en zonas irradiadas) y el especial manejo de la repercusión del diagnóstico a nivel de los otros integrantes de la familia.

Abstract: The Li-Fraumeni syndrome (SLF) is a highly penetrant condition with an autosomal dominant inheritance pattern, characterized by an early onset of multiple tumors in a subject and a marked familial occurrence. About 70 % of patients meeting clinical criteria for diagnosis of the disease carry the germline mutation of TP53 gene located in chromosome 17p13. TP53 is a tumor suppressor gene known for its major role in genome stability control. It has been estimated that risk of cancer development is 50 % for women at the age of 31 and for men at the age of 46 and nearly 100 % for both men and women at 70 years of age. Except at earlier ages of diagnosis, the clinical course of the disease for healthy patients and for patients suffering SLF shows similarities. We present the case of a 31-year-old patient diagnosed both with pelvic chondrosarcoma treated surgically and localized breast cancer during relapse, about 8 months later. By Sanger sequencing, mutation 375G>C had been identified in TP53 gene in another family member, and said mutation was later detected in our patient. We discuss particular aspects of treatment procedures, such as minimizing radiotherapy exposure (due to reports of malignancies in radiated areas) and the special management of diagnosis implications for other family members.

Resumo: A síndrome de Li-Fraumeni (SLF) é uma doença hereditária autorexistente dominante com pena de penetração, que caracteriza a aparição precoz de múltiplos tumores em um indivíduo e uma coletânea familiar. Aproximadamente o 70% dos pacientes com critérios clínicos para o diagnóstico em crianças portadores da mutação germinal do gen TP53 localizado no cromosoma 17p13. El gen TP53 é um tumor tumoral que cumple uma função importante no controle da estabilização genómica. Se estima que o riesgo do desengate faz dos 50% para as mulheres aos 31 anos de idade e para os 40 anos e cerca de 100% para ambos os sexos aos 70 anos. O curso clínico da doença é semelhante ao que ocorre com a SLF a exceção da doença mais tem sido diagnosticada. Presentamos o caso de um paciente de 31 años que diagnostica um paciente de pélvico com relato ao momento da recidiva, aproximadamente 8 meses depois, em um lugar de mama próximo. En otio miembro de la familia se habiocuident to the mutación 375G> C en el gen TP53 por secuenciación Sanger, a cual fue detectada em recente paciente. A discussão foi feita sobre os aspectos do tratamento com a minimização da exposição à radioterapia (por tumores malignos em zonas irradiadas) e o especial manejo da repercussão do diagnóstico a nível dos otros integrantes da familia

Toxicon ; 151: 37-46, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-29959967


Bactridine 2 (Bact-2) is an antibacterial toxin from Tityus discrepans venom which modifies isoforms 1.2, 1.4 and 1.6 voltage-dependent sodium (Nav) channels. Bactridine-induced Na+ outflow in Yersinia enterocolitica was blocked by amiloride, suggesting that Bact-2 effect was mediated by an amiloride sensitive sodium channel. In this study we show that Bact-2 increases also an outward rectifying current in rat dorsal root ganglia (DRG) sensory neurons; therefore, the nature of the outward rectifying currents was characterized and then the effect of Bact-2 on these currents was studied. These currents are enhanced by amiloride, are decreased by Na+ when an outward pH gradient is present and its reversal potential coincides with that of a Cl-/H+ exchanger, suggesting that rectifying currents are produced by the electrogenic Cl-/H+ exchanger modulated by the Na+/H+ antiporter. Bact-2 also leads to an increase of the outward currents in a similar way to the produced by the inhibition of the Na+/H+ exchanger. Additionally, the subsequent application of Bact-2 after blocking the Na+/H+ exchanger does not produce any further effect, suggesting that Bact-2 modifies the outward current by modulating the activity of the Na+/H+ exchanger. The effect of Bact-2 on pHi regulation was determined using the pH indicator BCECF. The results show that the Na+/H+ exchanger is blocked by amiloride and Na+ free solutions and is modulated by Bact-2 in a similar way as cariporide. This study validates that besides Nav channels, Bact-2 modulates the activity of the Na+/H+ exchanger.

Gânglios Espinais/citologia , Neurônios/efeitos dos fármacos , Venenos de Escorpião/química , Trocadores de Sódio-Hidrogênio/antagonistas & inibidores , Trocadores de Sódio-Hidrogênio/metabolismo , Amilorida , Animais , Antiporters/metabolismo , Fenômenos Eletrofisiológicos/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Masculino , Ratos , Ratos Sprague-Dawley , Escorpiões/fisiologia , Sódio , Zinco
Neuroscience ; 376: 204-223, 2018 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-29555037


Collapsin Response Mediator Protein 2 (CRMP2) is an intracellular protein involved in axon and dendrite growth and specification. In this study, CRMP2 was identified in a conditioned media derived from degenerated sciatic nerves (CM). On cultured rat hippocampal neurons, acute extracellular application of CM or partially purified recombinant CRMP2 produced an increase in cytoplasmic calcium. The increase in cytoplasmic calcium was mostly mediated through NMDA receptors, with a minor contribution of N-type VDCC, and it was maintained as long as CM was present. By using live-labeling of CRMP2, Ca2+ channel binding domain 3 (CBD3) peptide derived from CRMP2, and recombinant CRMP2, we demonstrated that that this effect was mediated by an action on the extracellular side of the NMDA receptor. This is the first report of an extracellular action of CRMP2. Prolonged exposure to extracellular CRMP2, may contribute to neuronal calcium dysregulation and neuronal damage.

Cálcio/metabolismo , Fármacos do Sistema Nervoso Central/administração & dosagem , Citoplasma/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intercelular/administração & dosagem , Proteínas do Tecido Nervoso/administração & dosagem , Receptores de N-Metil-D-Aspartato/metabolismo , Animais , Cátions Bivalentes/metabolismo , Células Cultivadas , Fármacos do Sistema Nervoso Central/isolamento & purificação , Meios de Cultivo Condicionados , Citoplasma/metabolismo , Espaço Extracelular , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Camundongos , Simulação de Acoplamento Molecular , Proteínas do Tecido Nervoso/isolamento & purificação , Proteínas do Tecido Nervoso/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Nervo Óptico/metabolismo , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Proteínas Recombinantes/administração & dosagem , Nervo Isquiático/metabolismo
Rev. argent. mastología ; 36(131): 38-49, jul. 2017. tab
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1127627


Objetivo Evaluar la validez de la ecografía axilar (ea) con punción citológica para indicar linfadenectomía axilar en pacientes con cáncer de mama, dentro del marco de los criterios propuestos por el estudio acosog Z0011. Material y método Estudio prospectivo, descriptivo. Se presentan los resultados del análisis de 123 pacientes con diagnóstico de cáncer de mama pertenecientes a la Unidad de Mastología del Hospital Español de Montevideo (Uruguay). En todas las pacientes se evaluó la axila con ecografía y, cuando existían ganglios sospechosos, se procedió a realizar punción con aguja fina. Cuando esta modalidad resultó positiva, en todas las pacientes se realizó linfadenectomía axilar de inicio. Cuantificamos la carga tumoral axilar de estas pacientes y analizamos la indicación de linfadenectomía axilar dentro del marco de propuestas del acozog Z0011. Resultados Los resultados obtenidos para predecir alta carga tumoral fueron los siguientes: porcentaje de verdaderos positivos (vp) 88,88%; porcentaje de falsos negativos (fn) 32%; sensibilidad (s) 80%; especificidad 80,95%; valor predictivo positivo (vpp) 88,89%; valor predictivo negativo (vpn) 68%; cociente de probabilidad positivo 4,20; cociente de probabilidad negativo 0,25; pacientes correctamente diagnosticados 80,33%. Discusión Desde hace varios años, la ecografía axilar con punción citológica ha demostrado elevada especificidad para predecir metástasis ganglionares. Publicaciones recientes afirman que la positividad de esta modalidad de estudio evidencia alta carga tumoral axilar y que, por lo tanto, se debe excluir a la paciente de las conductas conservadoras sobre la axila propuestas por el estudio acosog Z0011. Conclusiones Nuestros resultados concuerdan con la literatura internacional: la ecografía axilar con punción citológica es una metodología de elevada especificidad para predecir alta carga tumoral axilar. Esta metodología permite individualizar a aquellas pacientes que deben ser tratadas de inicio con linfadenectomía axilar, inclusive bajo los nuevos postulados del acosog Z0011

Objectives Evaluate the validity of ultrasound-guided fine needle aspiration (ugfna) of lymph nodes to determine axillary lymphadenectomy in patients with breast cancer, following the criteria proposed by acosog Z0011. Materials and method A prospective descriptive design was utilized. We present the analysis and results of 123 patients who were treated in the Unidad de Mastología at Hospital Español in Montevideo (Uruguay). All patients underwent axillary ultrasonography in order to evaluate lymphnodes. When suspicious lymph nodes were found, ugfna was performed. Patients who's ugfna yielded positive results were subjected to immediate axillary lymphadenectomy. We then quantified tumoral load and analyzed it according to the guidelines proposed by acosog Z0011. Results The following results were obtained for predicting tumoral load: True Positive Value of 88.88%; False Negative Value of 32%; Sensitivity of 80%; Specificity of 80.95%; Positive Predictive Value of 88.89%; Negative Predictive Value of 68%; Positive Likelihood Ratio of 4.20; Negative Likelihood Ratio of 0.25; accurately diagnosed patients 80.33%. Discussion ugfna has shown to have elevated specificity when predicting lymph node metastases. Recent investigations have shown that positive results of ugfna of lymph nodes determines elevated tumoral load; therefore, conservative treatment proposed by acosog Z0011 should not be followed. Conclusions Our results are comparable to research published internationally. ugfna is a method which has high specificity for the prediction of elevated axillary lymph node tumoral load. ugfna allows the tailoring of treatment for patients which must be treated initially with axillary lymphadenectomy, even under the new evidence put forth by acosog Z0011.

Humanos , Feminino , Neoplasias da Mama , Ultrassonografia , Metástase Neoplásica
Rev. méd. Urug ; 33(2): 94-101, Jun. 2017.
Artigo em Espanhol | LILACS | ID: biblio-859972


Introducción: en Uruguay el cáncer de mama (CM) es la principal causa de muerte por esta afección en la mujer. Aproximadamente 5,4% de los casos se diagnostican en menores de 40 años, es decir, en mujeres en edad reproductiva y laboralmente activas. Objetivo: investigar la frecuencia, características clínico-patológicas y evolución de pacientes uruguayas diagnosticadas con CM antes de los 40 años y su sobrevida de acuerdo al subtipo biológico. Material y método: se recolectaron datos relacionados con las características clínico-patológicas y la evolución de pacientes menores de 40 años tratadas por CM en el período comprendido entre el 1º de enero de 2006 y 31 de diciembre de 2012 asistidas en las instituciones participantes. Se calculó la sobrevida global (SVG) y la sobrevida libre de enfermedad (SVLE) para todas las pacientes, globalmente, y según el subtipo biológico. Resultados: se incluyeron 107 pacientes; edad mediana: 35 años (rango 24 a 39 años); las características clínico-patológicas fueron: carcinoma ductal: 89,7%; GH 2-3: 93,5%; estadio: II-III: 75%; metástasis axilares: 57%; HER2- RE/RP+ 53%; HER2+ 24,5%, y triple negativas (TN) 22,5%. El 17% de las pacientes presentaron antecedentes familiares (AF) significativos y la totalidad realizaron los tratamientos según pautas vigentes. La SVG y la SVLE a cinco años para la totalidad de las pacientes fueron 79% y 72%, respectivamente. La SVG y la SVLE fueron 97% y 90%, respectivamente, para las pacientes ER/PR+/HER2-; de 54% y 49% para las HER2+, y de 60% y 20% para las TN. Las curvas de SVLE fueron similares para las pacientes TN y HER2+, mientras que las pacientes ER/PR+/HER2- tuvieron una mayor SVG y SVLE (Log Rank, p < 0,0001). Conclusiones: las pacientes uruguayas diagnosticadas de CM antes de los 40 años incluidas tuvieron una SVG y una SVLE menor a la reportada en pacientes de la población general y de mayor rango etario. Si bien la peor evolución se ha vinculado al retraso en el diagnóstico, la mayoría de nuestras pacientes fueron diagnosticadas en estadios localizados y la totalidad realizó los tratamientos según las pautas vigentes. Por otra parte, la proporción de subtipos desfavorables (TN y HER2+) fue mayor a lo reportado para mujeres de todas las edades con CM, por lo que su peor evolución podría estar relacionada con el perfil biológico.

Introduction: In Uruguay, breast cancer is the main cause of death for this condition. Approximately 5.4% of cases are diagnosed in women younger than 40 years old, in other words, in women in their reproductive age, when they may be part of the labor force. Objective: To investigate the frequency, clinical and pathological characteristics and evolution of Uruguayan patients who are diagnosed with breast cancer before they are 40 years old, and their survival according to the biological sub-type. Method: the data in connection with the clinical and pathological characteristics and the evolution of patients was collected for women younger than 40 years old who had been treated for breast cancer at the participating institutions between January 1, 20016 and December 31, 2012. Global survival and disease-free survival was calculated for all patients, globally and according to the biological sub-type. Results: 107 students were included in the study; median age: 35 years old, range (24 to 39 years old); clinical and pathological characteristics: ductal carcinoma: 89.7%; Grade 2-3: 93.5%; stage II-III: 75% axillary metastasis: 57%; HER2- ER/PR 53%; HER"+ 24.5% and triple negative 22.5%. 17% of patients evidenced significant family history, and all of them were treated according to protocols in force. Global survival and disease free-survival after five years was 79% and 72% respectively. Global survival and disease free-survival was 97% and 90% respectively for patients RE/RP+/HER2-; of 54% and 49% for HER2+, and of 60% and 20% for triple negative. Disease-free survival curves were similar for patients triple negative and HER2+, whereas patients RE/RP+/HER2-evidenced a greater global survival and disease-free survival (Log Rank, p ? 0,0001). Conclusions: Uruguayan patients diagnosed with breast cancer before the age of 40 years old included in the study evidenced a lower global survival and disease free-survival rate than that reported for patients of the general population and older than 40 years old. In spite of the fact that the worse evolution has been associated to delays in diagnostic, most patients were diagnosed in the localized stage and all of them were treated according to protocols in force. Likewise, the proportion of the unfavorable sub-types (triple negative and HER2+) was greater than that reported for women of all ages with breast cancer. Thus, the worse evolution could be associated with the biological profile.

Introdução: no Uruguai o câncer de mama (CM) é a principal causa de morte das mulheres por este tipo de patologia. Aproximadamente 5,4% dos casos são diagnosticados em mulheres com menos de 40 anos, ou seja, mulheres em idade reprodutiva e economicamente ativas. Objetivo: pesquisar a frequência, características clínico-patológicas e evolução de pacientes uruguaias diagnosticadas com CM antes dos 40 anos e sua sobrevida de acordo com o subtipo biológico. Material e método: foram coletados dados relacionados com as características clínico-patológicas e a evolução de pacientes com menos de 40 anos tratadas por CM no período 1º de janeiro de 2006 - 31 de dezembro de 2012 atendidas nas instituições participantes. A sobrevida global (SVG) e a sobrevida livre de doença (SVLE) foi calculada para todas as pacientes, e segundo o subtipo biológico. Resultados: 107 pacientes foram incluídas com idade mediana 35 anos (intervalo 24 a 39 anos); as características clínico-patológicas foram: carcinoma ductal: 89,7%; GH 2-3: 93,5%; estadio: II-III: 75%; comprometimento axilar: 57%; HER2- RE/RP+ 53%; HER2+ 24,5%, e triplo negativo (TN) 22,5%. 17% das pacientes apresentavam antecedentes familiares (AF) significativos e todas foram tratadas observando-se as pautas vigentes. A SVG e a SVLE aos cinco anos para o total de pacientes foram 79% e 72%, respectivamente. A SVG e a SVLE foram 97% e 90%, respectivamente, para as pacientes ER/PR+/HER2-; 54% e 49% para as HER2+, e 60% e 20% para as TN. As curvas de SVLE foram similares para as pacientes TN e HER2+, porém as pacientes ER/PR+/HER2- apresentaram SVG e SVLE maiores (Log Rank, p ? 0,0001). Conclusões: as pacientes uruguaias diagnosticadas com CM antes dos 40 anos incluídas neste estudo apresentaram SVG e SVLE menores às registradas para pacientes da população em geral e com idades superiores. Embora a pior evolução esteja vinculada ao diagnóstico tardio, a maioria das pacientes estudadas foi diagnosticada em estádios localizados e todas receberam tratamento de acordo com as pautas vigentes. Por outra lado, a proporção de subtipos desfavoráveis (TN y HER2+) foi maior ao informado para mulheres de todas as idades com CM, por isso uma pior evolução poderia estar relacionada com o perfil biológico.

Adulto , Neoplasias da Mama , Sobrevida , Mulheres , Adulto Jovem
Arch. med. interna (Montevideo) ; 37(3): 109-113, nov. 2015. ilus, tab
Artigo em Espanhol | LILACS-Express | LILACS | ID: lil-770754


RESUMEN: Objetivo: Valorar la frecuencia y severidad de la cardiotoxicidad inducida por Trastuzumab (TTZ) en pacientes portadoras de cáncer de mama (CM) HER 2 positivo, asistidas en los Servicios de Oncología del Hospital de Clínicas y de la Asociación Española Primera en Salud. Métodos: Estudio observacional retrospectivo, que incluyó pacientes del Hospital de Clínicas y de la Asociación Española diagnosticadas de CM HER 2 positivo, que recibieron tratamiento con TTZ entre enero de 2007 y diciembre de 2013. Resultados: Se incluyeron 69 pacientes, la mayoría de las cuales tuvieron CM localizado, y cuya media de edad fue 50,1 años. 27% de las pacientes presentó cardiotoxicidad, y el 26% de éstas desarrolló insuficiencia cardíaca sintomática; todas recibieron tratamiento médico adecuado, siendo la insuficiencia cardíaca reversible en la mayoría de los casos. Conclusiones: La frecuencia de cardiotoxicidad observada en el estudio fue del 27 % (IC 95 %: 16,27; 38,8). Con las limitaciones propias del estudio, éste permite verificar similitudes con otras poblaciones reportadas, variando la frecuencia entre 3,7 y 34 %. Sin embargo, la proporción de pacientes que presentaron insuficiencia cardíaca sintomática (7%) fue algo superior a la reportada en la literatura, que es del 4%. La cardiotoxicidad fue reversible en la mayoría de las pacientes.

ABSTRACT: Objective: To evaluate the frequency and severity of Trastuzumab-induced cardiotoxicity in HER2 positive breast cancer (BC) patients assisted in Oncologic Services of the Hospital de Clínicas and Asociación Española Primera en Salud. Methods: Retrospective observational study of HER2 positive BC patients from Hospital de Clínicas and Asociación Española under systemic therapy with Trastuzumab (TTZ) from January 2007 to December 2013. Results: The study included 69 patients, most were early BC, mean age was 50,1 years . 27% of the patients developed cardiotoxicity and 26 % of them developed symptomatic heart failure. All patients received adequate medical treatment and the most instances were reversible Conclusions: The frequency of cardiotoxicity observed in the study was 27% (IC 95 %: 16,27; 38,8). With the limitations of the study, it can verify reported similarities with other populations, oscillating frequency between 3.7 and 34%. However, the proportion of patients who had symptomatic heart failure (7%) was higher than that reported in the literatura wich is 4%. Cardiotoxicity was reversible in most patients.

Front Cell Neurosci ; 9: 364, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26441535


Several reports have shown that a sciatic nerve conditioned media (CM) causes neuronal-like differentiation in PC12 cells. This differentiation is featured by neurite outgrowth, which are exclusively dendrites, without axon or sodium current induction. In previous studies, our group reported that the CM supplemented with a generic inhibitor for tyrosine kinase receptors (k252a) enhanced the CM-induced morphological differentiation upregulating neurite outgrowth, axonal formation and sodium current elicitation. Sodium currents were also induced by depletion of endogenous precursor of nerve growth factorr (proNGF) from the CM (pNGFd-CM). Given that sodium currents, neurite outgrowth and axon specification are important features of neuronal differentiation, in the current manuscript, first we investigated if proNGF was hindering the full PC12 cell neuronal-like differentiation. Second, we studied the effects of exogenous wild type (pNGFwt) and mutated (pNGFmut) proNGF isoforms over sodium currents and whether or not their addition to the pNGFd-CM would prevent sodium current elicitation. Third, we investigated if proNGF was exerting its negative regulation through the sortilin receptor, and for this, the proNGF action was blocked with neurotensin (NT), a factor known to compete with proNGF for sortilin. Thereby, here we show that pNGFd-CM enhanced cell differentiation, cell proportion with long neurites, total neurite length, induced axonal formation and sodium current elicitation. Interestingly, treatment of PC12 cells with wild type or mutated proNGF isoforms elicited sodium currents. Supplementing pNGFd-CM with pNGFmut reduced 35% the sodium currents. On the other hand, pNGFd-CM+pNGFwt induced larger sodium currents than pNGFd-CM. Finally, treatments with CM supplemented with NT showed that sortilin was mediating proNGF negative regulation, since its blocking induced similar effects than the pNGFd-CM treatment. Altogether, our results suggest that proNGF within the CM, is one of the main inhibitors of full neuronal differentiation, acting through sortilin receptor.

Rev. méd. Urug ; 31(3): 165-171, set. 2015. tab
Artigo em Espanhol | LILACS | ID: lil-763424


Introducción: el cáncer de mama (CM) es el cáncer más frecuente en la mujer uruguaya, cada año se registran unos 1.840 casos nuevos y unas 660 mujeres mueren como consecuencia de esta enfermedad. Con el fin de mejorar la calidad de la asistencia de las pacientes portadoras de patología mamaria se creó la Unidad Docente Asistencial de Mastología (UDAM) en el año 2009. Objetivo: valorar la calidad de la asistencia en la UDAM del Hospital de Clínicas. Material y método: estudio observacional, retrospectivo, que incluyó a las pacientes diagnosticadas y tratadas por CM en una UDAM desde junio de 2009 hasta junio de 2014. Para valorar la calidad de la asistencia se utilizaron los indicadores propuestos por la Sociedad Europea de Mastología (EUSOMA) en 2010. Resultados: se incluyeron 115 pacientes tratadas por CM; la mediana de edad fue de 63 años, la mayoría de las pacientes tuvieron CM limitados a la mama o axila, receptores hormonales (RRHH) positivos / HER2 negativos. Se cumplieron los criterios de calidad relacionados con el diagnóstico preoperatorio, informe anatomopatológico, tratamiento quirúrgico, radiante y oncológico. Sin embargo, en el 40% de los casos el intervalo de tiempo entre el diagnóstico y el primer tratamiento oncológico fue superior a seis semanas. Conclusiones: la atención recibida por las pacientes asistidas en nuestra UDAM en el período de referencia cumplió con la mayoría de los indicadores propuestos por EUSOMA. Se destaca la necesidad de mejorar el tiempo de espera entre el diagnóstico y el primer tratamiento oncológico.

Introduction: breast cancer is the most frequent types of cancer in Uruguayan women. Every year there are 1,840 new cases and around 660 women die from this disease. The Mastology Teaching Unit was created in 2009 to improve the quality of assistance in patients with breast cancer. Objective: to evaluate the quality of assistance at the Mastology Teaching Unit of the University Hospital. Method: observational, retrospective study that included women diagnosed and treated for breast cancer in a Mastology Teaching Unit from June 2009 through June, 2014. In order to evaluate the quality of assistance the indicators suggested by the European Society of Mastology in 2010 were used. Results: 115 patients treated for breast cancer were included in the study. Average age was 63 years old, most patients had breast cancer limited in the breast or armpit, (RRHH) positive hormonal receptors, HER2 negative. The quality criteria associated to preoperative diagnosis, pathology analysis, surgical treatment, radiotherapy and oncologic treatment were met. However, in 40% of cases the time interval between diagnosis and the first oncologic treatment was over six weeks. Conclusions: care received by patients seen at the Mastology Unit during the referred period met most indicators suggested by the European Society of Mastology. The need to improve the waiting time between diagnosis and the first oncologic treatment is emphasized.

Introdução: no Uruguai o câncer de mama (CM) é o tipo mais frequente na mulher; a cada ano aproximadamente 1.840 casos novos são registrados e 660 mulheres morrem como consequência desta patologia. Buscando melhorar a qualidade da assistência prestada às pacientes portadoras desta patologia mamaria, em 2009, foi criada a Unidade Docente Assistencial de Mastologia (UDAM). Objetivo: avaliar a qualidade da assistência na UDAM do Hospital de Clínicas. Material e método: estudo observacional, retrospectivo, incluindo as pacientes diagnosticadas e tratadas por CM na UDAM no período junho de 2009 - junho de 2014. Para avaliar a qualidade da assistência foram utilizados os indicadores propostos em 2010 pela Sociedade Europeia de Mastologia (EUSOMA). Resultados: foram incluídas 115 pacientes tratadas por CM; a mediana de idade foi 63 anos; a maioria das pacientes apresentaram CM limitados a mama ou axila, receptores hormonais (RRHH) positivos / HER2 negativos. Os critérios de qualidade relacionados com diagnóstico pré-operatório, laudo anatomopatológico, tratamento cirúrgico, radiante e oncológico foram observados. No entanto, em 40% dos casos o intervalo de tempo entre o diagnóstico e o primeiro tratamento oncológico foi superior a seis semanas. Conclusões: a atenção recebida pelas pacientes assistidas na UDAM no período de estudo cumpriu com a maioria dos indicadores propostos pela EUSOMA. Destaca-se a necessidade de melhorar o tempo de espera entre o diagnóstico e o primeiro tratamento oncológico.

Humanos , Neoplasias da Mama , Hospitais de Ensino , Qualidade da Assistência à Saúde
Toxicon ; 90: 124-33, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25111201


This paper presents the first study of chicken IgY pharmacokinetics (PK) in rabbits. We measured IgY blood serum concentrations using a specific high sensitivity ELISA method. The fast initial component observed when studying horse Fab, F(ab')2 or IgG was absent from IgY PK. During the first 80 min of observation there was only a single slow exponential decay, which sped up afterward to the point that IgY became undetectable after 216 h of observation; due to this time course, PK parameters were determined with trapezoidal integration. The most significant IgY pharmacokinetic parameters determined were (all presented as medians and their 95% confidence interval): Area Under the Curve = 183.8 (135.2, 221.5) mg·h·L(-1); Distribution volume of the central compartment·[Body Weight (BW)](-1) = 46.0 (21.7, 70.3) mL·kg(-1); Distribution volume in steady state·BW(-1) = 56.8 (44.4, 68.5) mLkg(-1); Mean Residence Time = 40.1 (33.6, 48.5) h; Total plasma clearance·BW(-1) = 1.44 (1.15, 1.66) mL·h(-1)·kg(-1). Anti IgY IgG titers determined by ELISA increased steadily after 72 h, and reached 2560 (1920, 5760) dilution(-1) at 264 h; anti-chicken IgG concentrations rose up to 3.19 (2.31, 6.17) µg/mL in 264 h. Our results show that IgY PK lacks the fast initial decay observed in other PK studies using horse IgG, F(ab')2 or Fab, remains in the body 39.0 (28.7, 47.2) % much as IgG and is ≈3 times more immunogenic that horse IgG in rabbits.

Antivenenos/sangue , Imunoglobulinas/sangue , Animais , Antivenenos/uso terapêutico , Ensaio de Imunoadsorção Enzimática , Cavalos , Imunoglobulinas/uso terapêutico , Coelhos
Rev. chil. infectol ; 30(6): 585-590, dic. 2013. graf, tab
Artigo em Espanhol | LILACS | ID: lil-701703


Introduction: Monitoring PK/PD of vancomycin with basal and peak serum levels and the area under the curve of drug exposure 24 h/MIC (ABC 24 h/MIC) could optimize the management of children. Objective: To study the PK of vancomycin in children hospitalized in the Pediatric Intensive Care Unit (PICU), assessing PK/PD parameters withABC24 h/MIC. Methods: Retrospective, descriptive study in the PICU (Hospital Luis Calvo Mackenna) between January 2008-March 2010. We included children < 18 years who required antimicrobial treatment with vancomycin for suspected/confirmed staphylococcal infection using a dose of 40 mg/k/day. Plasmatic levels were performed one hour postinfusion and 30 min prior to the next dose. The following PK/PD parameters were calculated: vancomycin clearance, elimination rate constant, volume of distribution, half-life (T1/2) and ABC 24 h/ MIC. Results: We enrolled eighty-four children. According to ABC 24 h/MIC obtained, 54% (45/84) of children reached an optimal level (> 400 mg*hr/L). Based on the traditional PK/PD parameters, 49% of cases (41/84) presented a basal level of vancomycin in the therapeutic range (5-15 μg/mL) and of those, only 39% (16/41) had a ABC 24 h/MIC over 400 mg*h/L. Discussion: Based on our results, children admitted to PICU could be exposed to sub therapeutic doses of vancomycin. We recommend to implement tailored antimicrobial treatment monitoring vancomycin PK/PD parameters.

Introducción: El monitoreo farmacocinético-farmacodinámico (PK/PD) de vancomicina podría optimizar el manejo de niños que reciben vancomicina y se encuentran en shock séptico grave. Objetivo: Estudiar PK/PD de vancomicina en niños hospitalizados en una unidad de paciente crítico, relacionando parámetros farmacocinéticos (PFC) tradicionales con ABC 24 h/CIM. Material y Método: Estudio retrospectivo, descriptivo, en la Unidad de Paciente Crítico Pediátrico (UPCP) del Hospital Luis Calvo Mackenna en el período enero de 2008 - marzo de 2010. Se incluyeron niños < 18 años tratados con vancomicina por sospecha/confirmación de infección estafilocóccica y recibieron dosis de 40 mg/kg/día. Se midieron concentraciones plasmáticas pico y basales. Los PFC calculados fueron realizados con software de farmacocinética TDMS®. Resultados: Se enrolaron 84 niños. En relación del parámetro ABC 24h/CIM obtenido, 54% (45/84) de los niños alcanzaron niveles óptimos (> 400 mg*h/L). Del análisis por PFC tradicionales, 49% de los casos (41/84) presentó concentraciones basales de vancomicina en rango terapéutico (5-15 μg/mL) y de ellos, sólo 39% (16/41) presentó un ABC 24 h/CIM > 400 mg*h/L. Todos los pacientes con concentraciones basales > 15 μg/mL alcanzan un ABC 24 h/CIM > 400 mg*h/L. Discusión: Los pacientes pediátricos que ingresan a la UPCP podrían estar expuestos a dosis sub-terapéuticas de vancomicina. Es recomendable individualizar el tratamiento de vancomicina utilizando monitoreo con parámetros PK/PD.

Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Antibacterianos/farmacocinética , Infecções Estafilocócicas/sangue , Vancomicina/farmacocinética , Área Sob a Curva , Antibacterianos/uso terapêutico , Unidades de Terapia Intensiva , Unidades de Terapia Intensiva Pediátrica , Estudos Retrospectivos , Infecções Estafilocócicas/tratamento farmacológico , Vancomicina/uso terapêutico
Endosc Ultrasound ; 2(4): 208-18, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24949398


OBJECTIVE: Endoscopic ultrasound (EUS) has become an important imaging modality for the diagnosis, staging and treatment of gastrointestinal disorders. However, no official data exists regarding clinical EUS practice in Latin America (LA). This study assessed current EUS practice and training. PATIENTS AND METHODS: A direct mail survey questionnaire was sent to 268 Capítulo Latino Americano de Ultrasonido Endoscópico members between August 2012 and January 2013. The questionnaire was sent out in English, Spanish and Portuguese languages and was available through the following site: Responses were requested only from physicians who perform EUS. RESULTS: A total of 70 LA physicians answered the questionnaire until January 2013. Most of the participants were under 42 years of age (53%) and 80% were men. Most participants (45.7%) perform EUS in Brazil, 53% work in a private hospital. The majority (70%) also perform endoscopic retrograde cholangiopancreatography. A total 42% had performed EUS for 2 years or less and 22.7% for 11 years or more. Only 10% performed more than 5000 EUS. The most common indication was an evaluation of pancreatic-biliary-ampullary lesions. Regarding training, 48.6% had more than 6 months of dedicated hands-on EUS and 37% think that at least 6 months of formal training is necessary to acquire competence. Furthermore, 64% think that more than 50 procedures for pancreatic-biliary lesions are necessary. CONCLUSION: This survey provides insight into the status of EUS in LA. EUS is performed mostly by young endoscopists in LA. Diagnostic upper EUS is the most common EUS procedure. Most endosonographers believe that formal training is necessary to acquire competence.

Rev Chilena Infectol ; 30(6): 585-90, 2013 Dec.
Artigo em Espanhol | MEDLINE | ID: mdl-24522298


INTRODUCTION: Monitoring PK/PD of vancomycin with basal and peak serum levels and the area under the curve of drug exposure 24 h/MIC (ABC 24 h/MIC) could optimize the management of children. OBJECTIVE: To study the PK of vancomycin in children hospitalized in the Pediatric Intensive Care Unit (PICU), assessing PK/PD parameters withABC24 h/MIC. METHODS: Retrospective, descriptive study in the PICU (Hospital Luis Calvo Mackenna) between January 2008-March 2010. We included children < 18 years who required antimicrobial treatment with vancomycin for suspected/confirmed staphylococcal infection using a dose of 40 mg/k/day. Plasmatic levels were performed one hour postinfusion and 30 min prior to the next dose. The following PK/PD parameters were calculated: vancomycin clearance, elimination rate constant, volume of distribution, half-life (T1/2) and ABC 24 h/ MIC. RESULTS: We enrolled eighty-four children. According to ABC 24 h/MIC obtained, 54% (45/84) of children reached an optimal level (> 400 mg*hr/L). Based on the traditional PK/PD parameters, 49% of cases (41/84) presented a basal level of vancomycin in the therapeutic range (5-15 µg/mL) and of those, only 39% (16/41) had a ABC 24 h/MIC over 400 mg*h/L. DISCUSSION: Based on our results, children admitted to PICU could be exposed to sub therapeutic doses of vancomycin. We recommend to implement tailored antimicrobial treatment monitoring vancomycin PK/PD parameters.

Antibacterianos/farmacocinética , Infecções Estafilocócicas/sangue , Vancomicina/farmacocinética , Adolescente , Antibacterianos/uso terapêutico , Área Sob a Curva , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Unidades de Terapia Intensiva , Unidades de Terapia Intensiva Pediátrica , Masculino , Estudos Retrospectivos , Infecções Estafilocócicas/tratamento farmacológico , Vancomicina/uso terapêutico
Arch. med. interna (Montevideo) ; 34(3): 88-90, dic. 2012. ilus
Artigo em Espanhol | LILACS-Express | LILACS | ID: lil-754121


Resumen: Arch Med Interna 2012 - 34(3):88-90 La enfermedad de Paget mamaria es una manifestación cutánea poco frecuente del cáncer de mama, representando del 1 al 3% de estos tumores. La forma clínica clásica de presentación es través de una lesión eritematosa y descamante que involucra pezón y areola y que ocasionalmente puede producir secreción por el pezón o retracción del mismo. La búsqueda de un carcinoma subyacente es primordial para una correcta decisión terapéutica y condiciona el pronóstico de las pacientes. Presentamos el caso de una paciente de 58 años que consulta por una lesión que involucra pezón y aréola derechos de 3 años de evolución. Se realizó la evaluación imagenológica mediante mamografía y resonancia magnética (RM) mamaria y posteriormente la biopsia de la misma, diagnosticándose una enfermedad de Paget y realizándose el tratamiento correspondiente.

Mammary Paget’s disease is a rare manifestation of breast cancer,accounting for 1 to 3% of these tumors. The classic clinical presentation is is throug desquamative and erythematous lesion that involves nipple and areola, an occasionally can cause nipple discharge or nipple retraction. The search for an underlying carcinoma is essential for correct therapeutic decision and determines the prognosis of patients. We report a 58 years patient who presented with a lesion that involved right nipple and areola . Imaging evaluation was performed with mammography and breast Magnetic Resonance Imaging (MRI) . Biopsy of the clinical lesion was performed. Paget disease was diagnosed, performing the corresponding treatment.