Urological referral of asymptomatic men in general practice in England

The Prostate Cancer Risk Management Programme (PCRMP) launched in November 2002 provides guidelines for general practitioners (GPs) on age-specific prostate-specific antigen (PSA) cutoff levels in asymptomatic men. The impact of the PCRMP on GP referrals is unknown. This study investigates whether there was a change in the proportion of asymptomatic men with raised PSA levels (⩾3 ng ml−1) who were referred to urologists since the launch of the guidelines. Sixty-nine general practices in four areas of England and the main pathology laboratory in each area, which had participated in our previous research, were asked to provide data. Forty-eight practices (70%) provided retrospective data on urological referrals in men who had a PSA test taken in the periods 1 December 2001 to 31 May 2002 (pre-launch) and 1 December 2003 to 31 May 2004 (post-launch). Data on referrals were completed for 709 (79%) out of 898 and 1040 (90%) out of 1157 raised records pre- and post-launch, respectively. The percentage of men with raised PSA levels who were asymptomatic was similar in both time periods (19–20%) and the proportion referred to urologists according to the PCRMP guidelines did not increase significantly over time (24% pre-launch and 29% post-launch, P=0.42). The referral rate was lower than expected if the guidelines had been followed. The influence of the guidelines seems to have been low. At the time of data collection, 56% (112 out of 200) of GP partners reported that they were aware of receiving the PCRMP pack. To ensure future, effective implementation of guidelines requires evaluation

Actin binding to WH2 domains regulates nuclear import of the multifunctional actin regulator JMY

© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Molecular Biology of the Cell 23 (2012): 853-863, doi:10.1091/mbc.E11-12-0992.Junction-mediating and regulatory protein (JMY) is a regulator of both transcription and actin filament assembly. In response to DNA damage, JMY accumulates in the nucleus and promotes p53-dependent apoptosis. JMY's actin-regulatory activity relies on a cluster of three actin-binding Wiskott–Aldrich syndrome protein homology 2 (WH2) domains that nucleate filaments directly and also promote nucleation activity of the Arp2/3 complex. In addition to these activities, we find that the WH2 cluster overlaps an atypical, bipartite nuclear localization sequence (NLS) and controls JMY's subcellular localization. Actin monomers bound to the WH2 domains block binding of importins to the NLS and prevent nuclear import of JMY. Mutations that impair actin binding, or cellular perturbations that induce actin filament assembly and decrease the concentration of monomeric actin in the cytoplasm, cause JMY to accumulate in the nucleus. DNA damage induces both cytoplasmic actin polymerization and nuclear import of JMY, and we find that damage-induced nuclear localization of JMY requires both the WH2/NLS region and importin β. On the basis of our results, we propose that actin assembly regulates nuclear import of JMY in response to DNA damage.This work was supported by grants from the National Institutes of Health, an American Heart Association Predoctoral Fellowship (J.B.Z.), the Robert Day Allen Fellowship Fund (J.B.Z.), and a National Science Foundation Predoctoral Fellowship (B.B.)

Prostate specific antigen testing policy worldwide varies greatly and seems not to be in accordance with guidelines: a systematic review

<p>Abstract</p> <p>Background</p> <p>Prostate specific antigen (PSA) testing is widely used, but guidelines on follow-up are unclear.</p> <p>Methods</p> <p>We performed a systematic review of the literature to determine follow-up policy after PSA testing by general practitioners (GPs) and non-urologic hospitalists, the use of a cut-off value for this policy, the reasons for repeating a PSA test after an initial normal result, the existence of a general cut-off value below which a PSA result is considered normal, and the time frame for repeating a test.</p> <p><it>Data sources</it>. MEDLINE, Embase, PsychInfo and the Cochrane library from January 1950 until May 2011.</p> <p><it>Study eligibility criteria</it>. Studies describing follow-up policy by GPs or non-urologic hospitalists after a primary PSA test, excluding urologists and patients with prostate cancer. Studies written in Dutch, English, French, German, Italian or Spanish were included. Excluded were studies describing follow-up policy by urologists and follow-up of patients with prostate cancer. The quality of each study was structurally assessed.</p> <p>Results</p> <p>Fifteen articles met the inclusion criteria. Three studies were of high quality. Follow-up differed greatly both after a normal and an abnormal PSA test result. Only one study described the reasons for not performing follow-up after an abnormal PSA result.</p> <p>Conclusions</p> <p>Based on the available literature, we cannot adequately assess physicians’ follow-up policy after a primary PSA test. Follow-up after a normal or raised PSA test by GPs and non-urologic hospitalists seems to a large extent not in accordance with the guidelines.</p