In this cohort presenting with acute urinary retention related to benign prostatic hyperplasia and receiving alpha-blockers before a trial without catheter, intravesical prostatic protrusion appears to strongly predict the outcome of a trial without catheter. A trial without catheter is more likely to fail in patients with intravesical prostatic protrusion larger than 10 mm.
Nitric oxide-donating non-steroidal anti-inflammatory drugs are safer than traditional NSAIDs and inhibit the growth of prostate cancer cells with greater potency than NSAIDs. In vivo, prostate cancer deposits are found in a hypoxic environment which induces resistance to chemotherapy. The aim of this study was to assess the effects and mechanism of action of a NO-NSAID called NOsulindac on the PC-3 prostate cancer cell line under hypoxic conditions. NO-sulindac was found to have pro-apoptotic, cytotoxic, and anti-invasive effect on PC-3 cells under normoxia and hypoxia. NO-sulindac was significantly more cytotoxic than sulindac at all oxygen levels. The sulindac/linker and NO-releasing subunits both contributed to the cytotoxic effects of NO-sulindac. Resistance of PC-3 cells to NO-sulindac was induced as the oxygen concentration declined. Hypoxia-induced chemoresistance was reversed by knocking-down hypoxia-inducible factor-1a (HIF-1a) mRNA using RNAi. Nuclear HIF-1a levels were upregulated at 0.2% oxygen but reduced by treatment with NO-sulindac, as was Akt phosphorylation. NO-sulindac treatment of hypoxic PC-3 cells transfected with a reporter construct, downregulated activation of the hypoxia response element (HRE) promoter. Co-transfection of PC-3 cells with the HRE promoter reporter construct and myrAkt (constitutively active Akt) plasmids reversed the NO-sulindac induced reduction in HRE activation. Real-time polymerase chain reaction analysis of hypoxic, NO-sulindac treated PC-3 cells showed downregulation of lysyl oxidase and carbonic anhydrase IX mRNA expression. Collectively, these novel findings demonstrate that NO-sulindac directly inhibits the hypoxia response of PC-3 prostate cancer cells by inhibiting HIF-1a translation via the Akt signalling pathway. The ability of NO-sulindac to inhibit tumour adaption to hypoxia has considerable relevance to the future management of prostate cancer with the same cellular properties as PC-3. ' 2008 Wiley-Liss, Inc.Key words: hypoxia; prostate cancer; nitric oxide donors; NONSAIDs; AktIn Western Europe and North America, prostate cancer is the commonest cancer and the second most common cause of cancer death in men. In the United Kingdom, prostate cancer accounts for 23% of all new male cancer diagnoses and 13% of male cancerrelated deaths. 1 Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit tumourigenesis in a variety of cancers. [2][3][4] In vitro studies have shown that conventional NSAIDs, at physiological achievable doses, inhibit the proliferation of immortalised human prostate cancer cells. 5 Additionally, meta-analyses of observational studies of men taking regular NSAIDs have reported statistically significant reductions in risk of prostate cancer. 6,7 However, conventional NSAIDs have several side-effects, particularly gastrointestinal bleeding, which limit their use in elderly patients with prostate cancer. In an attempt to reduce the side-effects of traditional NSAIDs, cyclooxygenase-2 inhibitors and nitric oxide (NO • )-donating non-steroidal...
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The management of female genital trauma is complex and should be performed by a well-trained team of health care professionals. It is important to remember that many female genital injuries will cause not just physical injury, but also significant psychological and emotional distress that may lead on to future physical dysfunction. The approach of any health care professional in the immediate diagnosis and management of females with a genital injury must be aimed at getting the best and most appropriate care to the patient as soon as possible. It is also important to remember that many of these injuries are the result of crimes and careful documentation is required so as not to remove or invalidate evidence that may later be required by the courts. This article is aimed at non-specialist healthcare providers who may find themselves faced with a female genital trauma patient. It will cover the range of injuries and conditions that should be expected and describes the treatment that should be given for the best possible physical and psychological outcomes. At all times it should be remembered that the patient should be assessed and resuscitated in accordance with recognised ATLS protocols.
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