Molecular detection of EGFRvIII-positive cells in the peripheral blood of breast cancer patients.

The aim of this study is to evaluate epidermal growth factor receptor variant III, EGFRvIII, a cancer specific mutant, as a possible marker for the diagnosis of breast cancer occult systemic disease. EGFRvIII mRNA was identified by an RT-nested PCR with a high sensitivity. In 102 women studied, the mutant was detected in the peripheral blood of 30% of 33 low risk, early stage patients, in 56% of 18 patients selected for neoadjuvant chemotherapy, in 63.6% of 11 patients with disseminated disease and 0% of 40 control women. In low risk, early stage patients, the presence of one or more tumour characteristics predicting recurrence such as the absence of oestrogen receptors and the presence of ERBB2 or histologic grades G2/G3 was significantly associated with EFGRvIII detection (p<0.05). EGFRvIII mRNA has characteristics to be a useful marker for the diagnosis of occult systemic disease in breast cancer. Follow-up studies will evaluate its clinical value as a decision criterion for systemic therapy.

Use of the sensitive/less-sensitive (detuned) EIA strategy for targeting genetic analysis of HIV-1 to recently infected blood donors.

OBJECTIVE: To corroborate the validity of the recently developed sensitive/less sensitive (S/LS) dual enzyme immunoassay (EIA) strategy for the detection of recently infected individuals and to genetically analyze recently transmitted strains of HIV-1 in a US blood donor population. DESIGN: The S/LS EIA strategy was used to identify 33 recently infected subjects among 281 enrolled HIV-1 seropositive blood donors (from a total of 410 HIV-1 infected subjects identified from 5 230 463 blood donations screened by participating US blood centers in 1995-1996). METHODS: We analysed three host response and viral characteristics were associated with recent HIV-1 infection: rapidly increasing EIA optical density (OD) values, genetically homogeneous env gene quasispecies, and putative non-syncytium inducing env V3 loop sequences. The drug resistance genotypes of the recently transmitted strains were determined by DNA sequencing. RESULTS: Increasing EIA OD values, clonal HIV-1 quasispecies and V3 loop sequences with inferred NSI phenotypes were generally detected in LS EIA non-reactive samples. Thirty-two subtype B and one CRF02_AG recombinant HIV-1 were detected. Genetic evidence for drug resistance to zidovudine (K70R) and non-nucleoside analog reverse transcriptase inhibitors (V108I) was detected in one strain each, and three other strains showed the presence of accessory protease inhibitor resistance mutations. CONCLUSIONS: Immunologic and virologic results further substantiate the validity of the S/LS EIA strategy for the detection of recent infections and illustrate its use for targeting molecular and epidemiological investigations to incident cases identified from large cross-sectional screening programs, rather than the more costly and logistically difficult longitudinal studies.

Analysis of the protease sequences of HIV-1 infected individuals after Indinavir monotherapy.

BACKGROUND: Protease inhibitors (PI) are an important HIV-1 treatment tool. The HIV-1 genetic diversity as a result of antiretroviral exposure is a potential barrier to successful antiretroviral therapy. OBJECTIVES: To describe the impact of the selective pressure of the PI Indinavir in the protease region of the pol gene of HIV-1. STUDY DESIGN: We have examined the extent of protease sequence heterogeneity in previously antiretroviral drug naive HIV-1 infected individuals receiving Indinavir as monotherapy for at least 48 weeks. RESULTS: Analysis based on the consensus of this group of sequences showed regions with higher and lower polymorphism. The degree of genetic variation was greater in regions less critical for the structure and function of the enzyme. To investigate the selective pressure imposed by drug therapy, we have analyzed the rate of synonymous (ds) and nonsynonymous (dn) substitutions. The three critical regions for enzyme activity showed ds/dn ratio >1. whereas other regions had ds/dn ratio <1. The detected amino acid mutations had a trend to be conservative, thus maintaining the physical chemical amino acid characteristics. Phylogenetic analysis established the presence of subtype B (n=38), subtype F (n=9), and B/F recombinants within the protease region of pol gene (n=3). More prevalent detected mutations, thought to contribute to antiretroviral resistance, were L63P (42%), L10I (35%), M36I (30%), V82A/T/F (26%). CONCLUSIONS: A great deal of predicted cross-resistance between PIs was observed. Out of the 50 individuals, 34% were considered to have major mutations to Indinavir, and 66% had minor or no mutations to Indinavir. Viral loads were significantly higher among patients with major mutations, compared with patients minor/no mutations, although no differences in the CD4 counts were found. The viral load at baseline and nadir (week 4) was able to predict the group of individuals with greater chances of selecting drug resistance related mutations.

Risk factors for human papillomavirus infection among women in Portugal: the CLEOPATRE Portugal Study.

OBJECTIVE: To investigate demographic, socioeconomic, lifestyle, and medical factors that might predispose women to cervical human papillomavirus (HPV) infection. METHOD: A cross-sectional population-based study was performed. Women aged 18-64 years who attended selected obstetrics and gynecology or sexually transmitted disease (STD) clinics in mainland Portugal between February 2008 and March 2009 were recruited, according to an age-stratified sampling strategy. Liquid-based cytology samples were analyzed centrally for HPV genotype and for cytologic features. Univariate and multivariate logistic regression analyses identified risk factors for HPV infection. RESULTS: Among the 2326 women evaluated, the crude prevalence of HPV infection was 19.4%. Lifetime number of sexual partners was a strong predictor of HPV infection (odds ratio 5.44 for 5-10 partners versus 1 partner; P<0.001). Other risk factors were young age (particularly among women aged 20-24 years; P<0.001); country of birth other than mainland Portugal (P=0.002); education up to secondary school level (P=0.010); smoking history (≤ 10 years; P=0.004); and any STD in the past 12 months (P=0.052). CONCLUSION: Data from the present study may aid identification of women at increased risk of HPV infection and target prevention strategies. TRIAL REGISTRATION: National Commission of Data Protection (CNPD) registration number 5346/2007; Sanofi Pasteur MSD study number HPV-E05.

[Bibliometry of cancer in Portugal: 1997 to 2006]. / Bibliometria do cancro em Portugal: 1997 a 2006.

INTRODUCTION: the scientific production of Portuguese institutions in the specific field Oncology during a 10 year period (1997-2006) was evaluated. The contribution of national authors to the international scientific production was verified. This enabled to assess and quantify the importance of authors, departments, institutions and scientific investigations. MATERIAL AND METHODS: Using version 2006 of Web of Science, section Science Citation Index, a database of literature references which enables analysis of citations, and also the Journal Citation Reports (tools produced by ISI Thomson Scientific), a quantitative and qualitative analysis of the Portuguese scientific production on cancer between 1997 to 2006 was performed. RESULTS: during the studied period, 1.384 articles were published in scientific journals with given impact factor, which obtained a total of 16.484 citations, corresponding to a mean of 11.91 citations per article. Between 1997 and 2006 an increase of 214% was noticed in the national scientific production in the selected field. Ten authors represent 46% of the produced documents. The majority of published articles were performed by Universities, being Oporto University the one with highest contribution. Co-authorship is the rule in the production of articles and Portugal is no exception. Articles with international collaboration where those which obtained the highest citation rate. The Portuguese contribution to the international scientific production in the field of Oncology in the studied period was of 0.21%. CONCLUSIONS: Bibliometric analysis is a reliable tool to evaluate the development and quality of scientific production. A growing visibility of investigation in this area was observed. This conclusion is based on the increase in the number of articles published in international journals of recognized reputation. National authors publish few articles, but they select high standard journals.

[Breast pathology: evaluation of the Portuguese scientific activity based on bibliometric indicators]. / Patologia mamária: avaliação da actividade científica nacional através de indicadores bibliométricos (1995 Julho 2005).

INTRODUCTION AND OBJECTIVES: The bibliometric analysis of the Portuguese scientific production in the field of breast pathology since 1995 to date (July 2005) provides an overview on the developed scientific activity on this subject and allows the characterisation of some relevant features as well as its evolution along the studied period. MATERIAL AND METHODS: Documents collected, reflecting the national scientific production in the field of breast pathology between 1995 and July 2005 in 3 databases, Medline (with search interface PubMed), Science Citation Index and Index of the Portuguese medical journals were studied. We applied quantitative and qualitative bibliometric indicators to the found number of articles and the journals where they were published. The quantitative indicators based on the number of published articles illustrate Portugal's position in the area of breast pathology within the international scientific community; further, it also allows the identification of the participation of the different institutions and national bodies, allocated by geographic areas, in scientific production as well as the establishment of international collaboration. Qualitative indicators were used to investigate the influence, and the impact of the scientific production. These are indicators based on the journal classification where the articles were published and also the citations they received. The number of citations obtained by the articles collected in the performed search, was determined, based on the Science Citation Index and the Impact Factor (IF) of the journals, which is annually published in the Journal Citation Reports (JCR). In spite of all its constraints, it is difficult not to accept the opinion that the Impact Factor is today one of the few means (if not the sole one) which enables an assessment of the influence of a journal in the international scientific community. RESULTS: During the evaluated period, the Portuguese scientific production in the selected area showed an increase of 200%. We analysed 348 documents (232 published in the selected international Databases and 16 in the national Database. We noticed that articles published by one single author are very rare, n=6 and that co-authorship is the most common way of publishing. The distribution of article production is as follows: 59% in the North Zone, 26% in the South Zone and 15% in the Central Zone of the country. The national institutions with a higher rate of publishing in renowned international journals are IPATIMUP, IPO Porto and IPO Lisboa. The institutions which publish the larger number of papers in Portuguese journals are Hospitals and Health Centres. The international journals selected by the national scientists present a high impact factor. In the whole of the 232 articles selected in the international databases, 81 have not received any citation and 120 obtained a total of 1.856 citations. It should be noted that the more recent articles have not yet received citations. The articles resulting from international collaboration, were those receiving an higher rate of citations. CONCLUSIONS: An increase of the investigation in breast pathology is observed, this being illustrated by the increase in the number of articles published in well-recognized international journals. It is also noticed a trend to publish in journals with a higher impact factor as well as an increasing role of co-authorship and international collaboration.