Neoadjuvant chemoradiotherapy with or without panitumumab in patients with wild-type KRAS, locally advanced rectal cancer (LARC): a randomized, multicenter, phase II trial SAKK 41/07.

BACKGROUND: We conducted a randomized, phase II, multicenter study to evaluate the anti-epidermal growth factor receptor (EGFR) mAb panitumumab (P) in combination with chemoradiotherapy (CRT) with standard-dose capecitabine as neoadjuvant treatment for wild-type KRAS locally advanced rectal cancer (LARC). PATIENTS AND METHODS: Patients with wild-type KRAS, T3-4 and/or N+ LARC were randomly assigned to receive CRT with or without P (6 mg/kg). The primary end-point was pathological near-complete or complete tumor response (pNC/CR), defined as grade 3 (pNCR) or 4 (pCR) histological regression by Dworak classification (DC). RESULTS: Forty of 68 patients were randomly assigned to P + CRT and 28 to CRT. pNC/CR was achieved in 21 patients (53%) treated with P + CRT [95% confidence interval (CI) 36%-69%] versus 9 patients (32%) treated with CRT alone (95% CI: 16%-52%). pCR was achieved in 4 (10%) and 5 (18%) patients, and pNCR in 17 (43%) and 4 (14%) patients. In immunohistochemical analysis, most DC 3 cells were not apoptotic. The most common grade ≥3 toxic effects in the P + CRT/CRT arm were diarrhea (10%/6%) and anastomotic leakage (15%/4%). CONCLUSIONS: The addition of panitumumab to neoadjuvant CRT in patients with KRAS wild-type LARC resulted in a high pNC/CR rate, mostly grade 3 DC. The results of both treatment arms exceeded prespecified thresholds. The addition of panitumumab increased toxicity.

Malaltia de Still de l’adult, revisió de 41 casos

Es descriuen les manifestacions clíniques, radiològiques, pronòstic i tractament de 41 pacients amb malaltia de Still de l’adult provinents de dos hospitals universitaris de Barcelona. La presentació clínica més freqüent va ser la poliartritis febril. El curs de la malaltia va ser monocíclic en el 44% dels pacients, policíclic en el 26% i crònic articular en el 30%. Els AINE o AAS van controlar la malaltia en el 19.5% i dosis altes de glucocorticoides en el 73%; el 48,7% van requerir algun immunosupressor addicional i al 17% se’ls va haver d’afegir tractament biològic per al control de la malaltia.

Prevalence of acute toxoplasmosis infection among 41,112 pregnant women and the mother-to-child transmission rate in a public hospital in South Brazil

Untreated acute toxoplasmosis among pregnant women can lead to serious sequelae among newborns, including neurological impairment and blindness. In Brazil, the risk of congenital toxoplasmosis (CTox) has not been fully evaluated. Our aim was to evaluate trends in acute toxoplasmosis prevalence from 1998-2005, the incidence of CTox and the rate of mother-to-child transmission (MTCT). A cross-sectional study was undertaken to dentify patients who fit the criteria for acute toxoplasmosis during pregnancy. Exposed newborns were included in a historical cohort, with a median follow-up time of 11 months, to establish definite diagnosis of CTox. Diagnoses for acute infection in pregnancy and CTox were based on European Research Network on Congenital Toxoplasmosis criteria. In 41,112 pregnant women, the prevalence of acute toxoplasmosis was 4.8/1,000 women. The birth prevalence of CTox was 0.6/1,000 newborns [95% confidence interval (CI): 0.4-0.9]. During the follow-up study, 12 additional cases were detected, increasing the CTox rate to 0.9/1,000 newborns (95% CI: 0.6-1.3). Among the 200 newborns exposed to Toxoplasma gondii,there were 37 babies presenting diagnostic criteria of CTox, leading to an MTCT rate of 18.5% (95% CI: 13.4-24.6%). The additional cases identified during follow-up reinforce the need for serological monitoring during the first year of life, even in the absence of evidence of congenital infection at birth.

Infection kinetics of human adenovirus serotype 41 in HEK 293 cells

The purpose of this work was to acquire an overview of the infectious cycle of HAdV-41 in permissive HEK 293 cells and compare it to that observed with the prototype of the genus, Human adenovirus C HAdV-2. HEK 293 cells were infected with each virus separately and were harvested every 12 h for seven days. Infection kinetics were analysed using confocal and electronic microscopy. The results show that, when properly cultivated, HAdV-41 was not fastidious. It had a longer multiplication cycle, which resulted in the release of complete viral particles and viral stocks reached high titres. After 60 h of infection, the export of viral proteins from the infected cell to the extracellular milieu was observed, with a pattern similar to that previously described for HAdV-2 penton-base trafficking after 30 h of infection. HAdV-41 had a non-lytic cycle and the infection spread from the first infected cell to its neighbours. The release process of the viral particles is unknown. The results observed for HAdV-41 infection in HEK 293 cells show how different this virus is from the prototype HAdV-2 and provides information for the development of this vector for use in gene therapy.

Drugs Associated with Hepatotoxicity and their Reporting Frequency of Liver Adverse Events in VigiBase (TM) Unified List Based on International Collaborative Work

BACKGROUND Challenges exist in the clinical diagnosis of drug-induced liver injury (DILI) and in obtaining information on hepatotoxicity in humans. OBJECTIVE (i) To develop a unified list that combines drugs incriminated in well vetted or adjudicated DILI cases from many recognized sources and drugs that have been subjected to serious regulatory actions due to hepatotoxicity; and (ii) to supplement the drug list with data on reporting frequencies of liver events in the WHO individual case safety report database (VigiBase). DATA SOURCES AND EXTRACTION (i) Drugs identified as causes of DILI at three major DILI registries; (ii) drugs identified as causes of drug-induced acute liver failure (ALF) in six different data sources, including major ALF registries and previously published ALF studies; and (iii) drugs identified as being subjected to serious governmental regulatory actions due to their hepatotoxicity in Europe or the US were collected. The reporting frequency of adverse events was determined using VigiBase, computed as Empirical Bayes Geometric Mean (EBGM) with 90% confidence interval for two customized terms, 'overall liver injury' and 'ALF'. EBGM of >or=2 was considered a disproportional increase in reporting frequency. The identified drugs were then characterized in terms of regional divergence, published case reports, serious regulatory actions, and reporting frequency of 'overall liver injury' and 'ALF' calculated from VigiBase. DATA SYNTHESIS After excluding herbs, supplements and alternative medicines, a total of 385 individual drugs were identified; 319 drugs were identified in the three DILI registries, 107 from the six ALF registries (or studies) and 47 drugs that were subjected to suspension or withdrawal in the US or Europe due to their hepatotoxicity. The identified drugs varied significantly between Spain, the US and Sweden. Of the 319 drugs identified in the DILI registries of adjudicated cases, 93.4% were found in published case reports, 1.9% were suspended or withdrawn due to hepatotoxicity and 25.7% were also identified in the ALF registries/studies. In VigiBase, 30.4% of the 319 drugs were associated with disproportionally higher reporting frequency of 'overall liver injury' and 83.1% were associated with at least one reported case of ALF. CONCLUSIONS This newly developed list of drugs associated with hepatotoxicity and the multifaceted analysis on hepatotoxicity will aid in causality assessment and clinical diagnosis of DILI and will provide a basis for further characterization of hepatotoxicity.

BAY 41-2272 activates host defence against local and disseminated Candida albicans infections

In our previous study, we have found that 5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridine-3-yl]-pyrimidin-4-ylamine (BAY 41-2272), a guanylate cyclase agonist, activates human monocytes and the THP-1 cell line to produce the superoxide anion, increasing in vitro microbicidal activity, suggesting that this drug can be used to modulate immune functioning in primary immunodeficiency patients. In the present work, we investigated the potential of the in vivo administration of BAY 41-2272 for the treatment of Candida albicans and Staphylococcus aureus infections introduced via intraperitoneal and subcutaneous inoculation. We found that intraperitoneal treatment with BAY 41-2272 markedly increased macrophage-dependent cell influx to the peritoneum in addition to macrophage functions, such as spreading, zymosan particle phagocytosis and nitric oxide and phorbol myristate acetate-stimulated hydrogen peroxide production. Treatment with BAY 41-2272 was highly effective in reducing the death rate due to intraperitoneal inoculation of C. albicans, but not S. aureus. However, we found that in vitro stimulation of peritoneal macrophages with BAY 41-2272 markedly increased microbicidal activities against both pathogens. Our results show that the prevention of death by the treatment of C. albicans-infected mice with BAY 41-2272 might occur primarily by the modulation of the host immune response through macrophage activation.

Educação em saúde ao ostomizado: um estudo bibliométrico

Este trabalho objetivou identificar a produção científica sobre orientação ao ostomizado, publicada entre 1970 e 2004 e classificá-la segundo quantidade, cronologia de publicação, função exercida pelos autores, procedência, tipo, assunto, origem e palavras-chave; utilizando a metodologia bibliométrica. As 27 publicações foram coletadas no banco de dados DEDALUS, nas bases de dados LILACS, MEDLINE e de uma docente da EEUSP (referência nacional em ostomia). No total, 19 são nacionais, oito internacionais e escritas principalmente por enfermeiros e estomaterapeutas. Os tipos são: dissertações, teses, folhetos, livros e artigos. A procedência dos materiais é da academia, laboratorial e hospitalar. A década de noventa é a que concentra o maior número de trabalhos nesta área temática. Todos têm como finalidade elevar a auto-estima dos pacientes para fazê-los sentir que, mesmo com uma ostomia, eles podem levar uma vida normal. Assim, o estudo mostrou que a enfermeira como educadora de um ostomizado deve conhecer tais publicações para melhorar a assistência.

Sentimentos e experiências na vida das mulheres com câncer de mama

Identificar os sentimentos e as experiências relacionados ao câncer de mama torna-se importante para que as pessoas de seu convívio social compreendam essa etapa da vida da mulher. Uma revisão da literatura foi realizada buscando identificar quais são os pensamentos e os sentimentos mais comuns experimentados pelas mulheres depois do diagnóstico de câncer de mama. Foi realizada por meio de busca bibliográfica no LILACS e MEDLINE, e as palavras-chave utilizadas foram: breast, câncer, feeling, female, representações, sentimentos. Conteúdos do câncer foram abordados, como o significado da doença e suas implicações para a vida emocional e social da mulher. Concluiu-se que as experiências relacionadas ao câncer de mama têm um âmbito muito individual, tendo representações diferenciadas para cada mulher.

O Índex de Katz na avaliação da funcionalidade dos idosos

Com o crescente aumento do número de idosos, cresce, também, a necessidade de utilização de instrumentos de avaliação funcional. Tal utilização, no entanto, deve ser comparável entre os diversos estudos e diferentes realidades. O Índex de Independência nas Atividades de Vida Diária (AVD), desenvolvido por Sidney Katz, é um dos instrumentos mais antigos e também dos mais citados na literatura nacional e internacional. Diferentes publicações têm mostrado, no entanto, versões modificadas do referido instrumento, dificultando aos leitores sua correta utilização. Este estudo teve por objetivo traçar o histórico do desenvolvimento, evolução e correta utilização do Índex de Independência nas Atividades de Vida Diária de Katz, bem como as modificações e adaptações desenvolvidas, com a anuência do autor, no transcorrer do tempo, de forma a contribuir para a uniformização das informações das pesquisas relacionadas à avaliação funcional em gerontologia.

Aspectos da comunicação da enfermeira com o deficiente auditivo

Indivíduos com limitação auditiva têm seu processo comunicativo prejudicado. Procurou-se explorar aspectos da comunicação da enfermeira com os deficientes auditivos. Estudo descritivo-exploratório, realizado em hospitais de Fortaleza de maio a junho de 2004 mediante entrevistas abertas analisadas qualitativamente. As enfermeiras percebem que é difícil a comunicação com o deficiente auditivo, embora algumas tenham desempenho satisfatório. Nesse processo, algumas referem utilizar tanto a comunicação não verbal, por mímica e leitura labial, como a comunicação verbal oral e escrita. Outras utilizam o acompanhante, quebrando o sigilo da consulta. Para aperfeiçoar a comunicação, sugerese o preparo profissional na graduação e cursos de LIBRAS. Conforme se conclui, existe dificuldade da enfermeira ao se comunicar com o deficiente auditivo.