Durable Complete Responses in Metastatic Colorectal Cancer Treated with Chemotherapy Alone

Background/Purpose: The median survival for patients with metastatic colorectal cancer (mCRC) has progressively increased over the past decades. Since the introduction of 5-fluorouracil (5-FU)-based chemotherapy, followed by hepatic resection of metastases, and more recently the adoption of newer chemotherapeutic regimens associated with targeted therapy, the gains are getting more substantial. Despite the recognition of the potential for long-term survival after surgical resection of metastatic disease, long-term survival data to determine the potential curative role of chemotherapy alone is lacking. Methods: We performed a retrospective review of 2751 patients who presented with mCRC at The MD Anderson Cancer Center from 1990 through 2003. Patients alive at 5 years who achieved complete response with chemotherapy and were not submitted to any surgical or interventional procedures directed to the metastatic sites were included in the analysis. Results: The 5-year overall survival rate for all patients with mCRC during this period was 10.8%. Among these long-term survivors, 2.2% achieved a sustained complete response after chemotherapy (all 6 with fluoropyrimidines and 2 with irinotecan) as the only treatment modality and were without evidence of disease until the last follow-up visit (median of 10.3 years). This number corresponds to 0.24% (6 of 2541) of all patients with mCRC included in this review. Conclusion: Cure with chemotherapy alone is possible for a very small number of patients with metastatic colorectal cancer. Improved therapies are increasing complete response rates, but the impact of modern chemotherapy on durable complete responses will require additional follow up.

Characterization of the Biocompatible Magnetic Colloid on the Basis of Fe(3)O(4) Nanoparticles Coated with Dextran, Used as Contrast Agent in Magnetic Resonance Imaging

The magnetic resonance imaging contrast agent, the so-called Endorem (TM) colloidal suspension on the basis of superparamagnetic iron oxide nanoparticles (mean diameter of 5.5 nm) coated with dextran, were characterized on the basis of several measurement techniques to determine the parameters of their most important physical and chemical properties. It is assumed that each nanoparticle is consisted of Fe(3)O(4) monodomain and it was observed that its oxidation to gamma-Fe(2)O(3) occurs at 253.1 degrees C. The Mossbauer spectroscopy have shown a superparamagnetic behavior of the magnetic nanoparticles. The Magnetic Resonance results show an increase of the relaxation times T(1), T(2), and T(2)* with decreasing concentration of iron oxide nanoparticles. The relaxation effects of SPIONs contrast agents are influenced by their local concentration as well as the applied field strength and the environment in which these agents interact with surrounding protons. The proton relaxation rates presented a linear behavior with concentration. The measured values of thermooptic coefficient partial derivative n/partial derivative T, thermal conductivity K, optical birefringence Delta n(0), nonlinear refractive index n(2), nonlinear absorption beta` and third-order nonlinear susceptibility vertical bar chi((3))vertical bar are also reported.

Characterization of Superparamagnetic Iron Oxide Coated with Silicone Used as Contrast Agent for Magnetic Resonance Image for the Gastrointestinal Tract

The present work is a report of the characterization of superparamagnetic iron oxide nanoparticles coated with silicone used as a contrast agent in magnetic resonance imaging of the gastrointestinal tract. The hydrodynamic size of the contrast agent is 281.2 rim, where it was determined by transmission electron microscopy and a Fe(3)O(4) crystalline structure was identified by X-ray diffraction, also confirmed by Mossbauer Spectroscopy. The blocking temperature of 190 K was determined from magnetic measurements based on the Zero Field Cooled and Field Cooled methods. The hysteresis loops were measured at different temperatures below and above the blocking temperature. Ferromagnetic resonance analysis indicated the superparamagnetic nature of the nanoparticles and a strong temperature dependence of the peak-to-peak linewidth Delta H(pp), giromagnetic factor g, number of spins N(S) and relaxation time T(2) were observed. This behavior can be attributed to an increase in the superexchange interaction.

In Vitro Phototoxicity of Liposomes and Nanocapsules Containing Chloroaluminum Phthalocyanine on Human Melanoma Cell Line

In this study, the photodynamic action of liposomes (LP) and nanocapsules (NC) containing Chloroaluminum phthalocyanine (CIAIPc), on the human melanoma cell (WM 1552C), was assessed. The light source was setup at 672 nm, which corresponds to the maximum absorption wavelength of the CIAIPc. Both colloidal carriers presented size in nanometric scale as well as negative zeta potential. The cellular damage was light dose dependent ranging from 30% of cell death at 70 mJ.cm(-2) to 90% of death at 700 mJ.cm(-2). However, the photocytotoxic effect of LP at 70 mJ.cm(-2) was slightly more efficient to induce cellular death than NC formulation. At 140 mJ.cm(-2), and 700 mJ.cm(-2) both nanocarriers were equally efficient to induce cellular damage. Therefore, in the present work, the maximum phototoxic effect was obtained with 700 mJ.cm(-2) of light dose, in combination with 0.29 mu g.mL(-1) of CIAIPc encapsulated into LP and NC. The cells were also positive to annexin V, after the PDT treatment with LP and NC, showing that one of the mechanisms of cellular death involved is apoptosis. In summary, the potential of LP and NC as a drug delivery system, in Photodynamic Therapy (PDT) against melanoma, has been confirmed using a lower concentration of the photosensitizer and lower light doses than that applied in current protocols. This is an innovative proposal to treat melanoma cell lines that until now have not received the benefit of the PDT protocol for treatment.

Autologous non-myeloablative haemopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: a phase I/II study

Background Autologous non-myeloablative haemopoietic stem cell transplantation is a method to deliver intense immune suppression. We evaluated the safety and clinical outcome of autologous non-myeloablative haemopoietic stem cell transplantation in patients with retapsing-remitting multiple sclerosis (MS) who had not responded to treatment with interferon beta. Methods Eligible patients had relapsing-remitting MS, attended Northwestern Memorial Hospital, and despite treatment with interferon beta had had two corticosteroid-treated relapses within the previous 12 months, or one relapse and gadolinium-enhancing lesions seen on MRI and separate from the relapse. Peripheral blood haemopoietic stem cells were mobilised with 2 g per m(2) cyclophosphamide and 10 mu g per kg per day filgrastim. The conditioning regimen for the haemopoietic stem cells was 200 mg per kg cyclophosphamide and either 20 mg alemtuzumab or 6 mg per kg rabbit antithymocyte globulin. Primary outcomes were progression-free survival and reversal of neurological disability at 3 years post-transplantation. We also sought to investigate the safety and tolerability of autologous non-myeloablative haemopoietic stem cell transplantation. Findings Between January 2003, and February, 2005, 21 patients were treated. Engraftment of white blood cells and platelets was on median day 9 (range day 8-11) and patients were discharged from hospital on mean day 11 (range day 8-13). One patient had diarrhoea due to Clostridium difficile and two patients had dermatomal zoster. Two of the 17 patients receiving alemtuzumab developed late immune thrombocytopenic purpura that remitted with standard therapy. 17 of 21 patients (81%) improved by at least 1 point on the Kurtzke expanded disability status scale (EDSS), and five patients (24%) relapsed but achieved remission after further immunosuppression. After a mean of 37 months (range 24-48 months), all patients were free from progression (no deterioration in EDSS score), and 16 were free of relapses. Significant improvements were noted in neurological disability, as determined by EDSS score (p<0.0001), neurological rating scale score (p=0.0001), paced auditory serial addition test (p=0.014), 25-foot walk (p<0.0001), and quality of life, as measured with the short form-36 (SF-36) questionnaire (p<0.0001). Interpretation Non-myeloablative autologous haemopoietic stem cell transplantation in patients with relapsing-remitting MS reverses neurological deficits, but these results need to be confirmed in a randomised trial.

Detection of Clonal Immunoglobulin and T-Cell Receptor Gene Rearrangements in Childhood Acute Lymphoblastic Leukemia Using a Low-Cost PCR Strategy

Background Imunoglobulin (Ig) and T cell receptor (TCR) gene rearrangements function as specific markers for minimal residual disease (MRD) which is one of the best predictors of outcome in childhood acute lymphoblastic leukemia (ALL) We recently reported on the prognostic value of MRD during the induction of remission through a simplified PCR method Here we report on gene rearrangement frequencies and offer guidelines for the application of the technique Procedure Two hundred thirty three children had DNA extracted from bone marrow Ig and TCR gene rearrangements were amplified using consensus primers and conventional PCR PCR products were submitted to homo/heteroduplex analysis A computer program was designed to define combinations of targets for clonal detection using a minimum set of primers and reactions Results At least one clonal marker could be detected in 98% of the patients and two markers in approximately 80% The most commonly rear ringed genes in precursor B cell ALL were IgH (75%) TCRD (59%) IgK (55%), and TCRG (54%) The most commonly rearranged genes for TALL were TCRG (100%) and TCRD (24%) The sensitivity of primers was limited to the detection of 1 leukemic cell among 100 normal cells Conclusions We propose that eight PCR reactions per ALL subtype would allow for the detection of two markers in most cases In addition these reactions ire suitable for MRD monitoring especially when aiming the selection of patients with high MRD levels (>= 10(-2)) at the end of induction therapy Such an approach would be very useful in centers with limited financial resources Pediatr Blood Cancer 2010 55 1278-1286 (C) 2010 Wiley Liss Inc

Distinct tumor suppressor mechanisms evolve in rodent species that differ in size and lifespan

Large, long-lived species experience more lifetime cell divisions and hence a greater risk of spontaneous tumor formation than smaller, short-lived species. Large, long-lived species are thus expected to evolve more elaborate tumor suppressor systems. In previous work, we showed that telomerase activity coevolves with body mass, but not lifespan, in rodents: telomerase activity is repressed in the somatic tissues of large rodent species but remains active in small ones. Without telomerase activity, the telomeres of replicating cells become progressively shorter until, at some critical length, cells stop dividing. Our findings therefore suggested that repression of telomerase activity mitigates the increased risk of cancer in larger-bodied species but not necessarily longer-lived ones. These findings imply that other tumor suppressor mechanisms must mitigate increased cancer risk in long-lived species. Here, we examined the proliferation of fibroblasts from 15 rodent species with diverse body sizes and lifespans. We show that, consistent with repressed telomerase activity, fibroblasts from large rodents undergo replicative senescence accompanied by telomere shortening and overexpression of p16(Ink4a) and p21(Cip1/Waf1) cycline-dependent kinase inhibitors. Interestingly, small rodents with different lifespans show a striking difference: cells from small shorter-lived species display continuous rapid proliferation, whereas cells from small long-lived species display continuous slow proliferation. We hypothesize that cells of small long-lived rodents, lacking replicative senescence, have evolved alternative tumor-suppressor mechanisms that prevent inappropriate cell division in vivo and slow cell growth in vitro. Thus, large-bodied species and small but long-lived species have evolved distinct tumor suppressor mechanisms.

Mudan??a de paradigma na presta????o de servi??os pela Receita Federal do Brasil

A Receita Federal do Brasil (RFB) instituiu o Servi??o Interativo de Atendimento Virtual, com o objetivo de propiciar atendimento aos contribuintes de forma interativa, por interm??dio da internet, com o uso de certificados digitais. Esse servi??o preconiza a disponibiliza????o de op????es de atendimento, que, em virtude do sigilo fiscal, eram disponibilizados somente nas unidades da RFB, o que obrigava o comparecimento dos contribuintes a elas. A implanta????o dessas op????es de atendimento vem promovendo a melhoria da seguran??a e da qualidade dos servi??os prestados aos contribuintes, aumentando a comodidade de acesso e a rapidez na resolu????o de problemas, reduzindo as filas existentes em diversas unidades da RFB, reduzindo os custos na presta????o de servi??os e no uso deles, al??m de possibilitar melhor aloca????o de m??o-de-obra

Rela????o indiv??duo e institui????o total: socializa????o, controles e coes??o internos em uma organiza????o policial

O artigo analisa os resultados de uma pesquisa realizada com 1.322 indiv??duos pertencentes ?? Pol??cia Militar de Minas Gerais. ?? luz das discuss??es de Goffman, Foulcalt e Etzioni, buscou-se verificar a inser????o dos servidores na institui????o, sua percep????o quanto ao aparato de controle institucional e os conflitos resultantes da intera????o entre superior e subordinado. Concluiu-se que reformas ocorridas ap??s a eclos??o de greve na institui????o em 1997 ainda s??o t??midas diante do aparato de socializa????o existente e do distanciamento entre oficiais e pra??as. Assim, ?? necess??ria a revis??o dos mecanismos de socializa????o e coer????o, para que a organiza????o policial avance na consecu????o de seus objetivos e d?? respostas efetivas ??s necessidades dos atores envolvidos, a si pr??pria e ?? sociedade.

Necessidades de informa????o e compet??ncias informacionais no setor p??blico: um estudo de caso

O texto apresenta parte do referencial te??rico de pesquisa de doutorado, que buscou estabelecer rela????es te??ricas e pr??ticas entre as necessidades de informa????o de uma determinada atividade e as compet??ncias informacionais desenvolvidas para atend??-las. A premissa da pesquisa foi que a atividade estudada, a supervis??o indireta de institui????es financeiras, era intensiva em informa????o e poderia ser estudada como atividade informacional, a partir do uso de par??metros informacionais. Os par??metros utilizados nos modelos te??ricos foram o ciclo e a tecnologia da informa????o e os contextos de comunica????o da informa????o. A pesquisa emp??rica se iniciou com a identifica????o dos fatores cr??ticos de sucesso da atividade, visando a posterior mapeamento das necessidades de informa????o e das compet??ncias dos profissionais supervisores. Os resultados obtidos e sua an??lise permitiram relacionar os fatores cr??ticos de sucesso da atividade ??s necessidades de informa????o dos profissionais de supervis??o indireta e ??s suas compet??ncias informacionais.

Sambas de Marias e Socorros : conversas entre a vida que pede passagem e o Programa de Proteção a Vitímas e Testemunhas Ameaçadas - PROVITA

Esta pesquisa foi realizada a partir da experiência da pesquisadora como psicóloga no Programa de Proteção a Vítimas e Testemunhas Ameaçadas do Espírito Santo – PROVITA/ES. O trabalho foi produzido a partir de encontros com os usuários e profissionais da política de proteção e pesquisa nos documentos internos do PROVITA/ES. Teve como foco a análise das práticas que constituem o que esse programa compreende enquanto proteção à testemunha ameaçada e os efeitos que tais práticas produzem quando se encontram com a vida singular dos sujeitos protegidos. Os diários de campo produzidos pela pesquisadora, antes e ao longo do processo de pesquisa, foram importante material de análise e permitiram aparecer não somente os modos de funcionamento da instituição, como as resistências e escapes dos profissionais e usuários da política. Colocar em análise esses modos de funcionamento tem o objetivo de produzir novas práticas que abarquem as miudezas da vida e as diferentes histórias dos sujeitos protegidos.

Comportamento agronômico de progênies F4 de cafeeiros oriundos do cruzamento entre os cultivares Mundo Novo e Catuaí

A espécie Coffea arabica L é cultivada em todas as regiões cafeeiras do Estado de Minas Gerais, com predominância dos cultivares Catuaí e Mundo Novo, por seu vigor vegetativo, alto potencial produtivo e boa qualidade de bebida. Visando a identificar e selecionar progênies de cafeeiro com boas características agronômicas, foi instalado e conduzido um experimento na Fazenda Experimental da EPAMIG, no município de Três Pontas, MG. Foram avaliadas 39 progênies na 4ª geração de autofecundação, após o 2º retrocruzamento entre 'Catuaí' e 'Mundo Novo' (genitor recorrente), desenvolvidas pelo programa de melhoramento genético da Epamig. Os cultivares Catuaí Vermelho MG 99, Rubi MG 1192 e Acaiá Cerrado MG 1474 foram utilizados como testemunhas. Foram analisadas as características: produção de café beneficiado em sc.ha-1 de oito safras (1998/1999 a 2005/2006), vigor vegetativo, percentagem de frutos chochos e classificação quanto à peneira. Ficou evidente que existe variabilidade genética dentro do grupo de progênies estudadas. As maiores produtividades foram encontradas na sétima e oitava colheita. As progênies 1189-9-80-1 e 1189-9-80-3 apresentaram melhor desempenho, em todas as características avaliadas e serão selecionadas para futuros trabalhos de melhoramento genético, sendo lançadas como cultivar ou utilizadas em hibridações.

Superprodução, purificação e caracterização parcial de complexos proteína-polissacáridos inovadores a partir de estirpes de basidiomicetos

O presente trabalho teve como objectivo o estudo de meios de cultura, tendo em vista a superprodução de complexos proteína-polissacáridos, intracelulares e extracelulares, a partir dos basidiomicetos Pleurotus ostreatus e Lentinula edodes. O meio de cultura suplementado com soro de leite apresentou diversas vantagens para a obtenção dessas macromoléculas biológicas, face aos restantes meios analisados, pelo que foi seleccionado para a produção em fermentador de laboratório em regime descontínuo. O crescimento da cultura foi efectuado a 28°C, 200 rpm e durante 10 dias, e as produtividades de complexos proteína-polissacáridos obtidas para o Pleurotus ostreatus foram de 0,008 ± 8,12 x 10-5 g/(L.dia) e de 0,324 ± 0,005 g/(L.dia), para os complexos precipitados a partir da biomassa e do caldo de fermentação, respectivamente. Posteriormente, os complexos intracelulares e extracelulares foram purificados por cromatografia de filtração em gel e parcialmente caracterizados, revelando concentrações de polissacáridos superiores à concentração proteica, pseudo-actividade de superóxido dismutase, e valores de Mr entre 64 e 9 000kDa. As amostras de complexos proteína-polissacáridos foram caracterizadas por HPLC e apresentaram picos de UV e IR com tempos de retenção de aproximadamente 6 e 12 minutos, respectivamente. Após hidrólise ácida, os complexos heteropolissacáridos obtidos apresentaram na sua constituição glucose, ramnose e arabinose. Adicionalmente, a análise dos complexos proteína-polissacáridos por FT-IR revelou bandas de absorção características destas macromoleculas biológicas, designadamente, a 846,5; 1032,3; 1186,4; 1471,0; 1648,8; 2739,6 e 3419,3 cm-1 para o Pleurotus ostreatus e 862,3; 1044,1; 1474,9; 1644,8; 2372,0; 2992,5; e 3415,4 cm-1 para Lentinula edodes.

Análise da concordância da codificação de causa básica de óbito por acidentes de trânsito

OBJETIVO: Avaliar a concordância de informações pesquisadas sobre causa básica de óbito por acidente de trânsito e compará-las com as codificações feitas a partir das Declarações de Óbitos. MATERIAL E MÉTODO: Foram estudados 50 óbitos por acidentes de trânsito ocorridos em 5 hospitais de Belo Horizonte, MG.Com base nas informações obtidas através de questionário procedeu-se à codificação da causa básica dos óbitos. A seguir foi feita análise de concordância entre esta classificação e a registrada na Declaração do Óbito. RESULTADOS: Foi calculado o Kappa (0,124) com intervalo de confiança 95% (-0,1533 - 0,4022), sendo considerada uma baixa concordância. Os dados mostraram também uma subclassificação de óbitos por acidentes de trânsito, uma vez que 32% dos 50 óbitos estudados foram codificados como acidentes não especificados (E928.9). CONCLUSÃO: Concluiu-se pela necessidade de haver maior esforço na melhoria do preenchimento da Declaração de Óbito pelos médicos legistas que realizam as necrópsias em mortes por acidentes de trânsito.

Preliminary results of a study of magnetic properties in the Foum-Zguid dyke (Morocco)

This work focuses on the study of flow and propagation of magma using rock magnetic analyses along sections across the thick Jurassic dyke of Foum-Zguid (Southern Morocco). Thermomagnetic data show that Ti-poor titanomagnetite is the main magnetic carrier. Petrographic analysis shows that the main Ti phase (ilmenite) occurs either as lamellae within spinel (center of the dyke) or as isolated grains (dyke margin). Bulk magnetic properties display distinct behavior according to the distance to the dyke margin; grain size of the main magnetic carrier decreases towards the center of the dyke, while the natural remanent magnetization and the bulk magnetic susceptibility increase. Only the magnetic susceptibility ellipsoid close to the dyke margin corresponds to that usually found in thin dykes, with the magnetic foliation sub parallel to dyke margins. Maximum principal axis is in most cases either parallel or perpendicular to the intersection between the planes of magnetic foliation and dyke wall. Moreover, when this axis is perpendicular to the intersection it is associated with a more oblate magnetic susceptibility ellipsoid shape, indicating the presence of complex magnetic fabrics. The studied magnetic properties show that, in this 100 m wide thick dyke, flow structures related with dyke propagation are only preserved close to the quickly cooled dyke margins.