A single nucleotide deletion at the C1 inhibitor gene as the cause of hereditary angioedema: insights from a Brazilian family

Background: Hereditary angioedema is an autosomal dominant disease characterized by episodes of subcutaneous and submucosal edema. It is caused by deficiency of the C1 inhibitor protein, leading to elevated levels of bradykinin. More than 200 mutations in C1 inhibitor gene have been reported. The aim of this study was to analyze clinical features of a large family with an index case of hereditary angioedema and to determine the disease-causing mutation in this family. Methods: Family pedigree was constructed with 275 individuals distributed in five generations. One hundred and sixty-five subjects were interviewed and investigated for mutation at the C1 inhibitor gene. Subjects reporting a history of recurrent episodes of angioedema and/or abdominal pain attacks underwent evaluation for hereditary angioedema. Results: We have identified a novel mutation at the C1 inhibitor gene, c.351delC, which is a single-nucleotide deletion of a cytosine on exon 3, resulting in frameshift with premature stop codon. Sequencing analysis of the hypothetical truncated C1 inhibitor protein allowed us to conclude that, if transcription occurs, this protein has no biological activity. Twenty-eight members of the family fulfilled diagnostic criteria for hereditary angioedema and all of them presented the c.351delC mutation. Variation in clinical presentation and severity of disease was observed among these patients. One hundred and thirty-seven subjects without hereditary angioedema did not have the c.351delC mutation. Conclusion: The present study provides definitive evidence to link a novel genetic mutation to the development of hereditary angioedema in patients from a Brazilian family.

Temporal distribution of trauma deaths: Quality of trauma care in a developing country

Background: Examination of the epidemiology and timing of trauma deaths has been deemed a useful method to evaluate the quality of trauma care. Objective: The purpose of this study was to evaluate the quality of trauma care in a regional trauma system and in a university hospital in Brazil by comparing the timing of deaths in the studied prehospital and in-hospital settings to those published for trauma systems in other areas. Methods: We analyzed the National Health Minister`s System of Deaths Information for the prehospital mortality and we retrospectively collected the demographics, timelines, and trauma severity scores of all in-hospital patients who died after admission through the Emergency Unit of Hospital das Clinicas de Ribeirao Preto between 2000 and 2001. Results. During the study period, there were 787 trauma fatalities in the city: 448 (56.9%) died in the prehospital setting and 339 (43.1%) died after being admitted to a medical facility. In 2 years, 238 trauma deaths occurred in the studied hospital, and we found a complete clinical set of data for 224 of these patients. The majority of deaths in the prehospital setting were caused by penetrating injuries (66.7%), whereas in-hospital mortality was mainly because of blunt traumas (59.1%). The largest number of in-hospital deaths occurred beyond 72 hours of stay (107 patients-47%). Conclusions: The region studied showed some deficiencies in prehospital and in-hospitals settings, in particular in the critical care and short-term follow-up of trauma patients when compared with the literature. Particularly, the late mortality may be related to training and human resources deficiency. Based on the timeline of trauma deaths, we can suggest that the studied region needs improvements in the prehospital trauma system and in hospital critical care.

Systemic lupus erythematosus: Association with KIR and SLC11A1 polymorphisms, ethnic predisposition and influence in clinical manifestations at onset revealed by ancestry genetic markers in an urban Brazilian population

Systemic lupus erythematosus (SLE) is an autoimmune disorder of the connective tissue with a wide and heterogeneous spectrum of manifestations, with renal and neurological involvement usually related to worse prognosis. SLE more frequently affects females of reproductive age, and a high prevalence and renal manifestation seem to be associated with non-European ethnicity. The present study aims to investigate candidate loci to SLE predisposition and evaluate the influence of ethnic ancestry in the disease risk and clinical phenotypic heterogeneity of lupus at onset. Samples represented by 111 patients and 345 controls, originated from the city of Belem, located in the Northern Region of Brazil, were investigated for polymorphisms in HLA-G, HLA-C, SLC11A1, MTHFR, CASP8 and 15 KIR genes, in addition to 89 Amerindian samples genotyped for SLC11A1. We also investigated 48 insertion/deletion ancestry markers to characterize individual African, European and Amerindian ancestry proportions in the samples. Predisposition to SLE was associated with GTGT deletion at the SLC11A1 3`UTR, presence of KIR2DS2 +/KIR2DS5 +/KIR3DS1 + profile, increased number of stimulatory KIR genes, and European and Amerindian ancestries. The ancestry analysis ruled out ethnic differences between controls and patients as the source of the observed associations. Moreover, the African ancestry was associated with renal manifestations. Lupus (2011) 20, 265-273.

Co-Expression of Leptin and Oestrogen Receptors in the Preoptic-Hypothalamic Area

The interaction between the reproductive axis and energy balance suggests that leptin acts as a possible mediator. This hormone acts in the regulation of metabolism, feeding behaviour and reproduction. Animals homozygous for the gene `ob` (ob/ob) are obese and infertile, and these effects are reversed after systemic administration of leptin. Thus, the present study aimed to determine: (i) whether cells that express leptin also express oestrogen receptors of type-alpha (ER-alpha) or -beta (ER-beta) in the medial preoptic area (MPOA) and in the arcuate (ARC), dorsomedial (DMH) and ventromedial hypothalamic nucleus and (ii) whether there is change in the gene and protein expression of leptin in these brain areas in ovariectomised (OVX) animals when oestrogen-primed. Wistar female rats with normal oestrous cycles or ovariectomised oestrogen-primed or vehicle (oil)-primed were utilised. To determine whether there was a co-expression, immunofluorescence was utilised for double staining. Confocal microscopy was used to confirm the co-expression. The technique of real-time polymerase chain reaction and western blotting were employed to analyse gene and protein expression, respectively. The results obtained showed co-expression of leptin and ER-alpha in the MPOA and in the DMH, as well as leptin and ER-beta in the MPOA, DMH and ARC. However, we did not detect leptin in the MPOA, ARC and DMH using western blotting and there was no statistical difference in leptin gene expression in the MPOA, DMH, ARC, pituitary or adipose tissue between OVX rats treated with oestrogen or vehicle. In conclusion, the results obtained in the present study confirm that the brain is also a source of leptin and reveal co-expression of oestrogen receptors and leptin in the same cells from areas related to reproductive function and feeding behaviour. Although these data corroborate the previous evidence obtained concerning the interaction between the action of brain leptin and reproductive function, the physiological relevance of this interaction remains uncertain and additional studies are necessary to elucidate the exact role of central leptin.

Evaluating Australia's National Medicines Policy using geographical mapping

Background: There has been a proliferation of quality use of medicines activities in Australia since the 1990s. However, knowledge of the nature and extent of these activities was lacking. A mechanism was required to map the activities to enable their coordination. Aims: To develop a geographical mapping facility as an evaluative tool to assist the planning and implementation of Australia's policy on the quality use of medicines. Methods: A web-based database incorporating geographical mapping software was developed. Quality use of medicines projects implemented across the country was identified from project listings funded by the Quality Use of Medicines Evaluation Program, the National Health and Medical Research Council, Mental Health Strategy, Rural Health Support, Education and Training Program, the Healthy Seniors Initiative, the General Practice Evaluation Program and the Drug Utilisation Evaluation Network. In addition, projects were identified through direct mail to persons working in the field. Results: The Quality Use of Medicines Mapping Project (QUMMP) was developed, providing a Web-based database that can be continuously updated. This database showed the distribution of quality use of medicines activities by: (i) geographical region, (ii) project type, (iii) target group, (iv) stakeholder involvement, (v) funding body and (vi) evaluation method. At September 2001, the database included 901 projects. Sixty-two per cent of projects had been conducted in Australian capital cities, where approximately 63% of the population reside. Distribution of projects varied between States. In Western Australia and Queensland, 36 and 73 projects had been conducted, respectively, representing approximately two projects per 100 000 people. By comparison, in South Australia and Tasmania approximately seven projects per 100 000 people were recorded, with six per 100 000 people in Victoria and three per 100 000 people in New South Wales. Rural and remote areas of the country had more limited project activity. Conclusions: The mapping of projects by geographical location enabled easy identification of high and low activity areas. Analysis of the types of projects undertaken in each region enabled identification of target groups that had not been involved or services that had not yet been developed. This served as a powerful tool for policy planning and implementation and will be used to support the continued implementation of Australia's policy on the quality use of medicines.

Which aspects of socio-economic status are related to health in mid-aged and older women?

A population-based study was conducted to validate gender- and age-specific indexes of socio-economic status (SES) and to investigate the associations between these indexes and a range of health outcomes in 2 age cohorts of women. Data from 11,637 women aged 45 to 50 and 9,5 10 women aged 70 to 75 were analyzed. Confirmatory factor analysis produced four domains of SES among the mid-aged cohort (employment, family unit, education, and migration) and four domains among the older cohort (family unit, income, education, and migration). Overall, the results supported the factor structures derived from another population-based study (Australian Bureau of Statistics, 1995), reinforcing the argument that SES domains differ across age groups. In general, the findings also supported the hypotheses that women with low SES would have poorer health outcomes than higher SES women, and that the magnitude of these effects would differ according to the specific SES domain and by age group, with fewer and smaller differences observed among older women. The main exception was that in the older cohort, the education domain was significantly associated with specific health conditions. Results suggest that relations between SES and health are highly complex and vary by age, SES domain, and the health outcome under study.

Men's perceived health needs

Cross-sectional survey data describing health priorities and needs perceived by men and women living in Newcastle, Australia are compared and contrasted with national health policies. The highest prevalence of felt needs for men were stress (13 percent), cost of medical care (10 percent) and money problems (9 percent); while stress (16 percent), overweight (16 percent) and money problems (15 percent) were highest for women. These contrast with the 2000 National Health Priorities of cancer. mental health, injury, cardiovascular health, diabetes and asthma. We conclude that men's perceived unmet health needs are similar to those of women; while sharing some commonalities, they also differ from health professional priorities. Incorporating felt needs into health service planning and delivery is a critical unmet challenge for government planners.

Aboriginal and Torres Strait Islander health research and the conduct of longitudinal studies: issues for debate

The National Health and Medical Research Council, Research Agenda Working Group (RAWG), and the literature on Indigenous health have identified the need to fill gaps in descriptive data on Aboriginal and Torres Strait Islander health and noted both the lack of research with urban populations and the need for longitudinal studies. This paper presents some of the broad ethical and methodological challenges associated with longitudinal research in Indigenous health and focuses particularly on national studies and studies in urban areas. Our goal is to advance debate in the public health arena about the application of ethical guidelines and the conduct of longitudinal studies in Aboriginal and Torres Strait Islander communities. We encourage others to offer their experiences in this field.

A trajet??ria dos programas de transfer??ncia de renda no Brasil: o impacto da vari??vel federativa

Neste trabalho, analisa-se a trajet??ria dos programas de transfer??ncia de renda no sistema de prote????o social brasileiro, procurando demonstrar como algumas quest??es federativas t??m afetado decisivamente a sua implementa????o, desde as primeiras iniciativas subnacionais at?? a ado????o de programas nacionais com clara interface intergovernamental. O argumento central ?? que o modelo federativo influenciou diretamente o desenvolvimento dos programas de transfer??ncia de renda no Brasil, sendo determinante para o seu bom desempenho.

Mecanismos de sustentabilidade das pol??ticas de vigil??ncia sanit??ria: um olhar sobre a Anvisa

Este artigo pretende ser uma colabora????o para o debate na ??rea de gest??o estrat??gica da sa??de, com foco na vigil??ncia sanit??ria. Nele buscou-se compreender as configura????es organizacionais que viabilizam (maior) ades??o ?? formula????o de estrat??gias em uma ag??ncia reguladora, a Ag??ncia Nacional de Vigil??ncia Sanit??ria (Anvisa). Foram consultados documentos da Anvisa dispon??veis ao p??blico na Internet, al??m de documentos internos nos arquivos da ??rea de planejamento da Ag??ncia. Foram analisados dois momentos de planejamento estrat??gico da Ag??ncia, ?? luz dos aspectos relacionados aos conceitos de poder e cultura, da configura????o organizacional, al??m das formas de controle sobre as ag??ncias reguladoras. Conclui-se que mecanismos que refor??am a transpar??ncia institucional levam ao sucesso de uma formula????o estrat??gica e ?? maior sustentabilidade das pol??ticas.

Gest??o do conhecimento em organiza????es p??blicas de sa??de no Brasil: diagn??stico de pr??ticas

As organiza????es p??blicas e privadas vivem diante de um cen??rio complexo, em que os fatores econ??micos e sociais de alcance mundial s??o respons??veis pela sua reestrutura????o. Nesse contexto, a Gest??o do Conhecimento (GC) se torna um valioso instrumento estrat??gico para a vida das pessoas e das organiza????es a que pertencem. A cria????o e a implanta????o de processos que gerem, armazenem, gerenciem e disseminem o conhecimento representam o mais novo desafio a ser enfrentado pelas organiza????es. O estudo realizado junto a Centros de Pesquisa Cl??nica (unidades vinculadas principalmente a Hospitais Universit??rios) e organiza????es p??blicas de sa??de integrantes do Programa Nacional de Gest??o P??blica e Desburocratiza????o (GESP??BLICA) tem como objetivo verificar como o tema GC est?? sendo tratado. O artigo identifica as pr??ticas de GC empregadas pelas organiza????es de sa??de abrangidas pelo estudo e sugere recomenda????es para uma dissemina????o mais eficaz do Modelo de Excel??ncia em Gest??o P??blica.

A presen??a do Estado no setor sa??de no Brasil

O artigo analisa, de forma introdut??ria, as mudan??as na pol??tica na ??rea de sa??de no Brasil. A partir de uma breve retomada de alguns estudos que discutem o papel do Estado na provis??o, financiamento e regula????o do setor sa??de, a autora procura estabelecer pontes ou interfaces entre estes modelos te??ricos e o processo hist??rico mais recente, que deu origem ao Sistema ??nico de Sa??de ??? SUS. Finalmente, a autora discute o que mudou e o que ainda permanece, e se mant??m como tra??o caracter??stico do sistema de sa??de brasileiro.

Sistema ??nico de Sa??de: a busca do entendimento de seus princ??pios e sistemas de valores para profissionais do servi??o p??blico

No per??odo de 2004 a 2008, o Minist??rio da Sa??de, conveniado com institui????es de ensino superior, ofereceu aos servidores dos n??cleos estaduais da sa??de um curso de especializa????o sobre Planejamento Estrat??gico e Pol??ticas P??blicas com o objetivo de informar, esclarecer e discutir o Sistema ??nico de Sa??de (SUS). A pesquisa discute esse programa educacional enquanto estrat??gia de mudan??a de cultura organizacional no Sistema ??nico de Sa??de. Dois dos principais focos do programa educacional foram a compreens??o dos pressupostos filos??ficos do SUS pelos funcion??rios do Minist??rio da Sa??de e a transforma????o do conhecimento t??cito dos servidores em conhecimento sistematizado via elabora????o de monografias, na perspectiva da incorpora????o de uma nova vis??o sobre o SUS. Foi utilizada abordagem metodol??gica quali-quantitativa, com uso de question??rios, entrevistas e grupos focais com os 636 respondentes que participaram do curso. A an??lise dos resultados considerou a avalia????o que os servidores/alunos faziam do curso, suas expectativas, suas necessidades de reconhecimento do trabalho e de satisfa????o pessoal, e a monografia realizada. Os resultados indicam a ocorr??ncia de aprendizagem e sensibiliza????o para as mudan??as; no entanto, no n??vel individual fatores organizacionais como a participa????o, comunica????o, reconhecimento de compet??ncias e pr??ticas de Recursos Humanos foram mencionados como entraves para o aprendizado e modifica????o da cultura organizacional. Conclui-se que os processos de aprendizagem desenvolvidos pela organiza????o devem ser processos continuados e n??o estrat??gias de a????o pontuais.

Saúde, trabalho e processos de subjetivação nas escolas

Neste artigo se discute o conceito de subjetividade utilizado nas práticas de saúde. Parte-se da tese de que a concepção de subjetividade predominante no pensamento dos trabalhadores no campo da saúde não está em sintonia com valores e pressupostos de renovação de conceitos e práticas, neste âmbito, na atualidade. Defende-se o caráter processual e coletivo dos processos de produção de subjetividade, contra o caráter individualista, apriorístico e objetificado prevalente nas práticas em psicologia e campos afins. Desdobra-se desta reflexão a defesa das transformações dessas práticas tendo como norte as articulações entre gestão no trabalho e processos de subjetivação, com base nos pressupostos teórico-filosóficos da obra de M. Foucault e na ergologia de linhagem francesa. Nessa direção de análise, afirma-se a importância de se pesquisar as articulações entre organização do trabalho, produção de saúde-doença e processos de subjetivação em curso. O foco das análises é a escola pública.

Os processos de formação na Política Nacional de Humanização : a experiência de um curso para gestores e trabalhadores da atenção básica em saúde

Este artigo tem como objetivo relatar a experiência de um curso de formação da Política Nacional de Humanização voltado para gestores e trabalhadores da atenção básica de um município no estado do Rio de Janeiro. O curso visou a formação de apoiadores institucionais capazes de fomentar rede no Sistema Único de Saúde (SUS), promover mudanças e consolidação nos modos de atenção e de gestão dos serviços. Como referencial metodológico, buscou-se um modo de "formação-intervenção" que fosse baseado em práticas concretas de intervenção dos trabalhadores nos processos de trabalho em saúde. O curso envolveu quarenta participantes, gestores e trabalhadores de nível médio e superior, ligados à atenção básica, oriundos da Estratégia de Saúde da Família e de Unidades de Saúde. Como resultados destacam-se ações de co-gestão no formato de reuniões com os usuários para o compartilhamento de decisões relativas ao serviço; implementação de acolhimento, com intervenções que garantam o acesso do usuário ao serviço; e de clínica ampliada, com discussões em equipe dos casos clínicos; e ações no campo da saúde do trabalhador, como efeito das discussões dos processos de trabalho nas equipes multiprofissionais.