Gene expression profiling of tumour epithelial and stromal compartments during breast cancer progression

The progression of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) marks a critical step in the evolution of breast cancer. There is some evidence to suggest that dynamic interactions between the neoplastic cells and the tumour microenvironment play an important role. Using the whole-genome cDNA-mediated annealing, selection, extension and ligation assay (WG-DASL, Illumina), we performed gene expression profiling on 87 formalin-fixed paraffin-embedded (FFPE) samples from 17 patients consisting of matched IDC, DCIS and three types of stroma: IDC-S (<3 mm from IDC), DCIS-S (<3 mm from DCIS) and breast cancer associated-normal stroma (BC-NS; >10 mm from IDC or DCIS). Differential gene expression analysis was validated by quantitative real time-PCR, immunohistochemistry and immunofluorescence. The expression of several genes was down-regulated in stroma from cancer patients relative to normal stroma from reduction mammoplasties. In contrast, neoplastic epithelium underwent more gene expression changes during progression, including down regulation of SFRP1. In particular, we observed that molecules related to extracellular matrix (ECM) remodelling (e.g. COL11A1, COL5A2 and MMP13) were differentially expressed between DCIS and IDC. COL11A1 was overexpressed in IDC relative to DCIS and was expressed by both the epithelial and stromal compartments but was enriched in invading neoplastic epithelial cells. The contributions of both the epithelial and stromal compartments to the clinically important scenario of progression from DCIS to IDC. Gene expression profiles, we identified differential expression of genes related to ECM remodelling, and specifically the elevated expression of genes such as COL11A1, COL5A2 and MMP13 in epithelial cells of IDC. We propose that these expression changes could be involved in facilitating the transition from in situ disease to invasive cancer and may thus mark a critical point in disease development.     

Absolute risk of venous and arterial thromboembolism in thrombophilic families is not increased by high thrombin-activatable fibrinolysis inhibitor (TAFI) levels

High levels of thrombin-activatable fibrinolysis inhibitor (TAFI) are a supposed risk factor for thrombosis. However, results from previous studies are conflicting. We assessed the absolute risk of venous and arterial thromboembolism in subjects with high TAFI levels (>126 U/dl) versus subjects with normal levels, and the contribution of other concomitant thrombophilic defects. Relatives from four identical cohort studies in families with either deficiencies of antithrombin, protein C or protein S, prothrombin 20210A, high factor VIII levels, or hyperhomocysteinemia were pooled. Probands were excluded. Of 1,940 relatives, 187 had high TAFI levels. Annual incidences of venous thromboembolism were 0.23% in relatives with high TAFI levels versus 0.26% in relatives with normal TAFI levels (adjusted relative risk [RR] 0.8; 95% confidence interval [CI], 0.5-1.3). For arterial thrombosis these were 0.31% versus 0.23% (adjusted RR 1.4; 95% CI, 0.9-2.2). High levels of factor VIII, IX and XI were observed more frequently in relatives with high TAFI levels. Only high factor VIII levels were associated with an increased risk of venous and arterial thrombosis, independently of TAFI levels. None of these concomitant defects showed interaction with high TAFI levels. High TAFI levels were not associated with an increased risk of venous and arterial thromboembolism in thrombophilic families.     

Absconding: A review of the literature 1996-2008

Absconding is a significant problem with potential for harm to patients or the general public. The consequences of absconding include physical harm, prolonged treatment time, and substantial economic costs. The aim of this systematic literature review is to synthesize quality literature about absconding from psychiatric facilities, identify gaps in knowledge, and make recommendations for practice. An electronic search yielded 39 journal articles that met the review criteria. Findings demonstrate that a single definition of absconding remains elusive, making the prevalence of absconding difficult to establish. Absconding events are multifactorial, with environmental, psychosocial, and organic aspects. Negative consequences exist including violence, aggression, and self-neglect and harm to self and others. Papers are clustered around the following themes: harm and risk, absconder profiles, absconding rates, and perceptions of nurses and patients. Nursing interventions designed to decrease absconding have been implemented with success, but only in a few studies and in Australia, none have been reported in the literature to date. Further research is required to identify appropriate nursing-based interventions that may prove useful in reducing the risk of absconding.     

Economic and cultural correlates of cannabis use among mid-adolescents in 31 countries

AIMS: To examine cannabis use among mid-adolescents in 31 countries and associations with per-capita personal consumer expenditure (PCE), unemployment, peer factors and national rates of cannabis use in 1999. DESIGN, PARTICIPANTS AND MEASUREMENT: Nationally representative, self-report, classroom survey with 22 223 male and 24 900 female 15-year-olds. Country characteristics were derived from publicly available economic databases and previously conducted cross-national surveys on substance use. FINDINGS: Cannabis use appears to be normative among mid-adolescents in North America and several countries in Europe. The life-time prevalence of cannabis use was 26% among males and 15% among females and was lowest for males and females in the former Yugoslav Republic (TFYR) of Macedonia: 2.5% and to 2.5%, respectively; and highest for males in Switzerland (49.1%) and in Greenland for females (47.0%). The highest prevalence of frequent cannabis use (more than 40 times in life-time) was seen in Canada for males (14.2%) and in the United States for females (5.5%). Overall, life-time prevalence and frequent use are associated with PCE, perceived availability of cannabis (peer culture) and the presence of communities of older cannabis users (drug climate). CONCLUSIONS: As PCE increases, cannabis use may be expected to increase and gender differences decrease. Cross-national comparable policy measures should be developed and evaluated to examine which harm reduction strategies are most effective.     

Pre-dialysis education and patient choice

The discussion was initiated by a paper on the influence of a pre-dialysis education programme on the mode of renal replacement therapy by Goovaerts et al (NDT 2005). Barriers to the uptake of self-care treatment modalities, including late referral, limited availability of treatment options, reimbursement, support from staff and families, the requirement for a helper and the length of the training programmes for home haemodialysis (HD) were discussed by 21 participants from 12 countries. The 'take-home' messages from the discussion were that to optimise the uptake of self-care modalities, renal units should try to ensure the all patients who are able to choose are fully informed before starting dialysis, even if they are referred to the unit very late. Offering a wide range of treatment options to new patients, and allowing (or encouraging) home HD without a helper, may also increase the number of patients who start and stay on a self-care modality. It should be possible to provide an acceptable level of training, without compromising on safety, within 3 weeks if the patient is confident with needling.     

Axial STIR MRI: a faster method for confirming femoral head reduction in DDH

Purpose  Non-concentric reduction of the femoral head within the acetabulum is detrimental to its delicate cartilaginous structure and may result in a growth disturbance. Successful relocation of the dislocated femoral head depends on subtle clinical findings and radiography. The combination of a dislocated femoral head and a severely dysplastic acetabulum can result in a clinical examination that is unhelpful in confirming reduction under anaesthesia. In cases where uncertainty existed regarding head reduction in a spica cast, we performed axial short inversion time inversion recovery (STIR) and axial proton density magnetic resonance imaging (MRI) scans. We retrospectively reviewed the efficiency and accuracy of MRI in confirming femoral head location after closed reduction and spica application in eight children. Methods  One hundred and fifty-three cases of developmental dysplasia were treated with examination under anaesthesia and spica application in our unit over a 3-year period. Eight cases where MRI scanning was performed were identified. Before application of the spica cast, we used radiographic screening to assess the stability of the reduction. Absence of the ossific nucleus within the femoral head made confirmation of the location with the image intensifier unreliable. To confirm concentric femoral head location after closed reduction and spica application, we performed an MRI scan in the immediate post-anaesthesia period. Results  All scans were performed within 30 min of application of the spica, and the average time for each scan was 5 min. All eight children who had MRI post-application of the spica had concentric reduction of the femoral head. MRI allowed three-dimensional appreciation of the acetabulum and femoral head. Use of the axial STIR images allows accurate assessment of the cartilaginous ossific nucleus. All patients were discharged the same afternoon and followed up as outpatients. No patient in our group required contrast arthrography. Conclusion  While not indicated in all cases of femoral head dislocation, MRI is useful to confirm concentric reduction of the femoral head in a dysplastic acetabulum when examination under anaesthesia and radiographic screening have been uncertain. In our series, 1 in 20 cases needed MRI. This is a reliable, non-invasive method confirming definite reduction of the femoral head prior to discharge in all of our patients. In this initial series, all patients had axial and coronal STIR and proton density MRI. We now only use axial STIR images because they provide adequate information regarding the position of the femoral head relative to the acetabulum.     

Socio-demographic variations in perspectives on cardiovascular disease and associated risk factors.

Coronary heart disease (CHD) rates in Ireland are very high but little is known about attitudes to the disease. Qualitative attitudinal data were collected in focus group settings from 74 individuals across socio-demographic categories in order to assess knowledge of and attitudes to CHD and associated risk factors. Focus group questions were derived from group deconstruction of constructs from the Health Belief Model, Theory of Planned Behaviour, Protection Motivation Theory and Social Learning Theory. Participants were drawn from the personnel lists of local government and a health authority hospital. Eight types of groups were constructed according to the various permutations of the three variables: age, gender and occupational group. Analyses revealed good knowledge levels about risk factors among participants. However, participants exhibited mixed loci of control and low motivation to change behaviours. Men generally were less motivated to change than women; older men thought it too late and younger ones too soon. Though white and blue collar groups' views were similar, the discussion in white collar groups was more varied. Participants were sceptical about apparently contradictory medical advice which undermined motivation to change. The data complement earlier work and suggest preventative initiatives should be more focused.     

A restricted access material for rapid analysis of [11C]-labeled radiopharmaceuticals and their metabolites in plasma

IntroductionAnalysis of the radioactive components in plasma taken during positron emission tomography (PET) measurements is often vital for the correct quantification of the PET data. The described high-performance liquid chromatography (HPLC) method has been developed to provide a fast, sensitive and robust method for the measurement of plasma samples from PET studies using [¹¹C]-labeled radiopharmaceuticals.MethodsUnadulterated plasma samples were analyzed directly, following a simple filtration, by the use of a small extraction column, containing a restricted access material, combined with a monolithic analysis column in a column-switching HPLC system.ResultsUp to 4 ml of plasma was analyzed by this method within 4.5–7 min in a fully automated process. Because of the rapid analysis, a large number of samples could be analyzed during a 90-min PET scan. The extraction column could be used for analysis of up to 500 ml of plasma before replacement was required.ConclusionsThe described method is fast and robust and the large sample volumes allow for accurate determination of the radioactive components in plasma even at 90 min after injection of a [¹¹C]-labeled radiopharmaceutical.