GWAS in Breast Cancer

Breast cancer is the most diagnosed cancer in women, and the second cause of cancer-related deaths among women worldwide. It is expected that more than 240,000 new cases and 40,450 deaths related to the disease will occur in 2016. It is well known that inherited genetic variants are drivers for breast cancer development. There are many mechanisms through which germline genetic variation affects prognosis, such as BRCA1 and BRCA2 genes, which account for approximately 20% of the increased hereditary risks. Therefore, it is evident that the genetic pathways that underlie cancer development are complex in which networks of multiple alleles confer disease susceptibility and risks. Global analyses through genome-wide association studies (GWAS) have revealed several loci across the genome are associated with the breast cancer. This chapter compiles all breast GWAS released since 2007, year of the first article published in this area, and discuss the future directions of this field. Currently, hundreds of genetic markers are linked to breast cancer, and understanding the underlying mechanisms of these variants might lead to the discover of biomarkers and targets for therapy in patients

Lamivudine therapy for hepatitis B in renal transplantation

Antiviral therapies are associated with an increased risk of acute rejection in transplant patients. The aim of the present study was to evaluate the efficacy and safety of lamivudine therapy for hepatitis B virus (HBV) infection in renal transplant patients. Six patients were included in this study. They received 150 mg/day of lamivudine during a follow-up period of 24 months. The laboratory tests monitored were HBV DNA, HBsAg, HBeAg, ALT, gamma-GT, serum creatinine and blood cyclosporine levels. The HBV DNA became undetectable in four patients as early as in the third month of treatment. After six months, the viral load was also negative in the other two patients, and remained so until 18 months of follow-up. The medication was well tolerated with no major side effects. Lamivudine was safe and effective in blocking HBV replication in renal transplant patients without any apparent increase in the risk of graft failure for the 24-month period of study

O poder da caneta: a Medida Provisória no processo legislativo estadual

A Medida Provisória (MP) brasileira é um dos instrumentos legislativos mais poderosos nas mãos do Presidente da República para alterar unilateralmente o status quo. Apesar de o judiciário ter reconhecido a competência dos governadores para instituir e adotar a MP, esta existe apenas em seis estados. O artigo procura explicar a não adoção deste instrumento legislativo pela maioria dos estados. Enfatiza-se a escassa ou marginal relevância que é dada à MP pelo governador nos seis casos que a adotaram. Defende-se, aqui, que os governadores, diferentemente dos presidentes, não necessitam de mais um instrumento legislativo ou da ampliação da delegação de prerrogativas legislativas para garantir sua agenda frente a seus respectivos legislativos, já que com ou sem poder de decreto estadual os governadores controlariam a já limitada agenda decisória nos estados.<br>The Brazilian Provisional Measure (MP) is one of the most powerful legislative instruments in the hands of the President to unilaterally change the status quo. Although the judiciary (STF) has recognized the competence of Governors to establish and adopt the MP only six states attribute the prerogative to edit MP until 2010. This article seeks to explain the non-adoption of this legislative instrument by most states emphasizing the low or marginal relevance that is given to the MP by the Governor in the six cases that adopted it. It is argued here that the Governors, unlike Presidents, do not require another legislative instrument or expanding the delegation of legislative powers to ensure their legislative agenda forward their respective State Legislative Assemblies, because with or without decree power the State Governors would control the limited decisional agenda in the states

Causas e prognóstico da insuficiência renal aguda hospitalar em pacientes idosos Causes and prognosis of acute renal failure in elderly patients

OBJETIVOS: O objetivo deste estudo foi analisar as causas e o prognóstico de pacientes idosos (>70 anos de idade) com IRA tratados em nosso Serviço. CASUÍSTICA E MÉTODOS: Dos 361 pacientes adultos e portadores de IRA, atendidos em nosso serviço no período de janeiro/95 a dezembro/96, acompanhamos 130 pacientes (36%) com idade superior a 70 anos (média de 76,0 &plusmn; 4,7 anos, variando de 70 a 94 anos). Destes, 84 (65%) eram do sexo masculino e 66 (51%) estavam no pós-operatório de cirurgias diversas. Os dados foram obtidos através de formulários padronizados usados no Serviço. RESULTADOS: As causas mais freqüentes foram: isquêmicas 48 (38%), sepsis 40 (31%), nefrotóxicas 46 (35%) e obstrutivas 10 (7,7%); em outros 14 (11%) foram diagnosticados mais de um agente causal. IRA não-oligúrica ocorreu em 81 pacientes (62,8%) e em 50 pacientes (39%) houve necessidade de diálise. A mortalidade na população com idade abaixo de 70 anos foi 43% e nos idosos 53,1%, não havendo diferença estatística entre os grupos (p=0,085). A mortalidade foi maior (p<0,0001) nos pacientes idosos oligúricos (86%) do que nos idosos não-oligúricos (32%); maior em casos de IRA cirúrgica (66,7%) do que em IRA de origem médica (41,8%), e em pacientes internados em UTI (69%) do que nos internados em enfermaria (17%). O número de óbitos também foi maior (p<0,0001) no grupo que necessitou de diálise (84%) do que nos não dialisados (33%). CONCLUSÃO: Concluímos que o percentual de pacientes idosos com IRA é elevado; apresentaram mortalidade ao redor de 50%, não superior ao observado na população mais jovem; oligúria, cirurgia, necessidade de tratamento em UTI e necessidade de diálise foram fatores de prognóstico desfavorável nesta casuística.<br>The prolonged life span of populations is the obvious reason for an increasing proportion of elderly patients with acute renal failure (ARF). The role of age as a factor indicative of a poor prognosis is a matter of controversy. OBJECTIVE: To evaluate this role we have analyzed the final outcome of elderly patients with ARF treated in our Nephrology Service. MATERIAL AND METHODS: Among 361 ARF cases prospectively studied during a two-year period (January 1995 to December 1996), 130 (36%) occurred in patients over 70 years of age. Etiology, clinical course and prognosis were analyzed. The average age was 76.0 &plusmn; 4.7 years, varying from 70 to 94 years; 84 patients (65%) were male, and surgical causes accounted for 51% of geriatric ARF. RESULTS: The most frequent causes were: ischemic (volume depletion, arterial hypotension, and/or low cardiac output) in 48 patients (38%), sepsis in 40 (312%), nephrotoxic drugs in 46 (35%) and obstructive abnormalities in 10 (7.7%); in other 14 (11%) they were diagnosed more than a causal agent. Oliguria was present in 37.2% (81 patients), and dialysis was needed in 50 patients (39%). The mortality in the population with age below 70 years was 43% and in the elderly patients was 53.8%; total mortality was similar in both groups of patients (p=0.085). Oliguria, need for dialysis, presence of surgical causes of ARF, and ARF acquired within the intensive care unit were associated with poor prognosis in elderly group. CONCLUSION: We concluded that the percentile of elderly patients with ARF is elevated; they presented mortality about of 50%, and this is not superior to the observed in the youngest population; oliguria, dialysis need, ICU cares and surgery are factors of unfavorable prognostic in these patients