Amfenac increases the radiosensitivity of uveal melanoma cell lines

Purpose To evaluate the proliferation rates of five human uveal melanoma (UM) cell lines after treatment with amfenac, a cyclooxygenase (COX)-2 inhibitor, and subsequent radiation exposure.Methods Five human UM cell lines (92.1, SP6.5, MKT-BR, OCM-1, and UW-1) and one human fibroblast cell line (BJ) were incubated with amfenac. Treated and non-treated cell lines were then exposed to various doses of gamma radiation: 0, 2, 4, 6, and 8 Gy. Sulphorhodamine-B assay was used to assess proliferation rates 48 h post-radiation.Results Treatment of UM cell lines with amfenac prior to radiation led to a marked reduction in proliferation rates. This difference was statistically significant in all cell lines at every radiation dose (P < 0.005), with the exception of 92.1 at 2 Gy (P=0.157). Fibroblasts treated with amfenac showed significantly higher proliferation rates after 2 and 8 Gy, with no significant differences at 0, 4, and 6 Gy.Conclusions the radiosensitivity of UM cell lines was increased by the administration of amfenac, the active metabolite of nepafenac. There appears to be a radioprotective effect of amfenac on human fibroblasts. the topical administration of nepafenac may decrease tumour recurrence and radiation-induced complications while broadening the indications for radiotherapy by treating larger tumours.McGill Univ, Dept Ophthalmol & Pathol, Ctr Hlth, Montreal, PQ H3A 2B4, CanadaHenry C Witelson Ocular Pathol Lab, Montreal, PQ H3A 2B4, CanadaUniversidade Federal de São Paulo, UNIFESP EPM, Dept Ophthalmol, São Paulo, BrazilUniversidade Federal de São Paulo, UNIFESP EPM, Dept Ophthalmol, São Paulo, BrazilWeb of Scienc

Use of the Internet for health information by physicians for patient care in a teaching hospital in Ibadan, Nigeria

BACKGROUND: The Internet is the world's largest network of information, communication and services. Although the Internet is widely used in medicine and has made significant impact in research, training and patient care, few studies had explored the extent to which Nigerian physicians use Internet resources for patient care. The objective of this study was to assess physicians' use of the Internet for health information for patient care. METHOD: 172 physicians at the University College hospital (UCH) Ibadan, Nigeria; completed a 31-item, anonymous, standardized questionnaire. The Epi-Info software was used for data analysis. RESULTS: The mean age of the respondents was 31.95 years (SD 4.94). Virtually all (98%) the respondents had used the Internet; 76% accessed it from cyber cafes. E-mail was the most commonly used Internet service (64%). Ninety percent of the respondents reported they had obtained information from the Internet for patient care; of this number, 76.2% had searched a database. The database most recently searched was MEDLINE/PubMed in 99% of cases. Only 7% of the respondents had ever searched the Cochrane Library. More than half (58.1%) perceived they had no confidence to download full-text articles from online sources such as the Health Internetwork Access to Research Initiative (HINARI). Multiple barriers to increased use of the Internet were identified including poor availability of broadband (fast connection speed) Internet access, lack of information searching skills, cost of access and information overload. CONCLUSION: Physicians' use of the Internet for health information for patient care was widespread but use of evidenced-based medicine resources such as Cochrane Library, Up-to-date and Clinical Evidence was minimal. Awareness and training in the use of EBM resources for patient care is needed. Introduction of EBM in the teaching curriculum will enhance the use of EBM resources by physicians for patient care

Predicting gene promoter methylation in non-small-cell lung cancer by evaluating sputum and serum

The use of 5-methylcytosine demethylating agents in conjunction with inhibitors of histone deacetylation may offer a new therapeutic strategy for lung cancer. Monitoring the efficacy of gene demethylating treatment directly within the tumour may be difficult due to tumour location. This study determined the positive and negative predictive values of sputum and serum for detecting gene methylation in primary lung cancer. A panel of eight genes was evaluated by comparing methylation detected in the primary tumour biopsy to serum and sputum obtained from 72 patients with Stage III lung cancer. The prevalence for methylation of the eight genes in sputum (21–43%) approximated to that seen in tumours, but was 0.7–4.3-fold greater than detected in serum. Sputum was superior to serum in classifying the methylation status of genes in the tumour biopsy. The positive predictive value of the top four genes (p16, DAPK, PAX5 β, and GATA5) was 44–72% with a negative predictive value for these genes ⩾70%. The highest specificity was seen for the p16 gene, and this was associated with a odds ratio of six for methylation in the tumour when this gene was methylated in sputum. In contrast, for serum, the individual sensitivity for all genes was 6–27%. Evaluating the combined effect of methylation of at least one of the four most significant genes in sputum increased the positive predictive value to 86%. These studies demonstrate that sputum can be used effectively as a surrogate for tumour tissue to predict the methylation status of advanced lung cancer where biopsy is not feasible

Three-Dimensional Structure of the Enveloped Bacteriophage Φ12: An Incomplete T = 13 Lattice Is Superposed on an Enclosed T = 1 Shell

BACKGROUND:Bacteriophage phi12 is a member of the Cystoviridae, a unique group of lipid containing membrane enveloped bacteriophages that infect the bacterial plant pathogen Pseudomonas syringae pv. phaseolicola. The genomes of the virus species contain three double-stranded (dsRNA) segments, and the virus capsid itself is organized in multiple protein shells. The segmented dsRNA genome, the multi-layered arrangement of the capsid and the overall viral replication scheme make the Cystoviridae similar to the Reoviridae. METHODOLOGY/PRINCIPAL FINDINGS:We present structural studies of cystovirus phi12 obtained using cryo-electron microscopy and image processing techniques. We have collected images of isolated phi12 virions and generated reconstructions of both the entire particles and the polymerase complex (PC). We find that in the nucleocapsid (NC), the phi12 P8 protein is organized on an incomplete T = 13 icosahedral lattice where the symmetry axes of the T = 13 layer and the enclosed T = 1 layer of the PC superpose. This is the same general protein-component organization found in phi6 NC's but the detailed structure of the entire phi12 P8 layer is distinct from that found in the best classified cystovirus species phi6. In the reconstruction of the NC, the P8 layer includes protein density surrounding the hexamers of P4 that sit at the 5-fold vertices of the icosahedral lattice. We believe these novel features correspond to dimers of protein P7. CONCLUSIONS/SIGNIFICANCE:In conclusion, we have determined that the phi12 NC surface is composed of an incomplete T = 13 P8 layer forming a net-like configuration. The significance of this finding in regard to cystovirus assembly is that vacancies in the lattice could have the potential to accommodate additional viral proteins that are required for RNA packaging and synthesis

Characterization of a potent and highly unusual minimally enhancing antibody directed against dengue virus

Dengue virus is a major pathogen and severe infections can lead to life threatening dengue hemorrhagic fever (DHF). Dengue exists as four serotypes and DHF is often associated with secondary heterologous infections. Antibody dependent enhancement (ADE) may drive higher virus loads in these secondary infections, and is purported to result from antibodies that recognize dengue but fail to fully neutralize. We have characterized two antibodies, 2C8 and 3H5, which bind to the envelope protein. 3H5 is highly unusual as it is both potently neutralizing, but promotes little if any ADE, whereas 2C8 has strong capacity to promote ADE. We show that 3H5 shows resilient binding in endosomal pH conditions and neutralizes at low occupancy. Immune complexes of 3H5 and dengue virus do not efficiently interact with Fcγ receptors, which we propose is due to the binding mode of 3H5 and which constitutes the primary mechanism of how ADE is avoided

Risk of persistent high-grade squamous intraepithelial lesion after electrosurgical excisional treatment with positive margins: a meta-analysis

CONTEXT AND OBJECTIVE: Even if precursor lesions of cervical cancer are properly treated, there is a risk of persistence or recurrence. The aim here was to quantify the risks of persistence of high-grade intraepithelial squamous lesions, one and two years after cervical electrosurgical excisional treatment with positive margins. DESIGN AND SETTING: Systematic review of the literature and meta-analysis at Instituto Fernandes Figueira. METHODS: This meta-analysis was on studies published between January 1989 and July 2009 that were identified in Medline, Scopus, Embase, Cochrane, SciELO, Lilacs, Adolec, Medcarib, Paho, Wholis, Popline, ISI Web of Science and Sigle. Articles were selected if they were cohort studies on electrosurgical excisional treatment of high-grade squamous intraepithelial lesions with a minimum follow-up of one year, a histopathological outcome of persistence of these lesions and a small risk of bias. RESULTS: The search identified 7,066 articles and another 21 in the reference lists of these papers. After applying the selection and exclusion criteria, only four articles were found to have extractable data. The risk of persistence of high-grade intraepithelial lesions after one year was 11.36 times greater (95% confidence interval, CI: 5.529-23.379, P < 0.0001) in patients with positive margins and after two years, was four times greater (95% CI: 0.996-16.164), although without statistical significance. CONCLUSION: This meta-analysis confirms the importance of positive margins as an indicator of incomplete treatment after the first year of follow-up and highlights the need for appropriately chosen electrosurgical techniques based on disease location and extent, with close surveillance of these patients

Development and evaluation of an instrument for the critical appraisal of randomized controlled trials of natural products

<p>Abstract</p> <p>Background</p> <p>The efficacy of natural products (NPs) is being evaluated using randomized controlled trials (RCTs) with increasing frequency, yet a search of the literature did not identify a widely accepted critical appraisal instrument developed specifically for use with NPs. The purpose of this project was to develop and evaluate a critical appraisal instrument that is sufficiently rigorous to be used in evaluating RCTs of conventional medicines, and also has a section specific for use with single entity NPs, including herbs and natural sourced chemicals.</p> <p>Methods</p> <p>Three phases of the project included: 1) using experts and a Delphi process to reach consensus on a list of items essential in describing the identity of an NP; 2) compiling a list of non-NP items important for evaluating the quality of an RCT using systematic review methodology to identify published instruments and then compiling item categories that were part of a validated instrument and/or had empirical evidence to support their inclusion and 3) conducting a field test to compare the new instrument to a published instrument for usefulness in evaluating the quality of 3 RCTs of a NP and in applying results to practice.</p> <p>Results</p> <p>Two Delphi rounds resulted in a list of 15 items essential in describing NPs. Seventeen item categories fitting inclusion criteria were identified from published instruments for conventional medicines. The new assessment instrument was assembled based on content of the two lists and the addition of a Reviewer's Conclusion section. The field test of the new instrument showed good criterion validity. Participants found it useful in translating evidence from RCTs to practice.</p> <p>Conclusion</p> <p>A new instrument for the critical appraisal of RCTs of NPs was developed and tested. The instrument is distinct from other available assessment instruments for RCTs of NPs in its systematic development and validation. The instrument is ready to be used by pharmacy students, health care practitioners and academics and will continue to be refined as required.</p