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Camilleri M.,Mayo Medical School | Drossman D.A.,Drossman Gastroenterology PLLC | Becker G.,Albert Ludwigs University of Freiburg | Webster L.R.,PRA Health science | And 2 more authors.
Neurogastroenterology and Motility | Year: 2014

Background: Opioids are effective for acute and chronic pain conditions, but their use is associated with often difficult-to-manage constipation and other gastrointestinal (GI) effects due to effects on peripheral μ-opioid receptors in the gut. The mechanism of opioid-induced constipation (OIC) differs from that of functional constipation (FC), and OIC may not respond as well to most first-line treatments for FC. The impact of OIC on quality of life (QoL) induces some patients to decrease or stop their opioid therapy to relieve or avoid constipation. Purpose: At a roundtable meeting on OIC, a working group developed a consensus definition for OIC diagnosis across disciplines and reviewed current OIC treatments and the potential of treatments in development. By consensus, OIC is defined as follows: 'A change when initiating opioid therapy from baseline bowel habits that is characterized by any of the following: reduced bowel movement frequency, development or worsening of straining to pass bowel movements, a sense of incomplete rectal evacuation, or harder stool consistency'. The working group noted the prior validation of a patient response outcome and end point for clinical trials and recommended future efforts to create treatment guidelines and QoL measures specific for OIC. Details from the working group's discussion and consensus recommendations for patient care and research are presented in this article. © 2014 John Wiley & Sons Ltd. Source


Ismail M.,University of Surrey | Morgan R.,University of Surrey | Harrington K.,The Institute of Cancer Research | Davies J.,The Royal Surrey County Hospital | Pandha H.,University of Surrey
Cryobiology | Year: 2010

Tumour cryotherapy has been described as both immunostimulatory and immunoinhibitory in previous studies. However, previous studies have not accurately reproduced the precise conditions of current clinical cryotherapy. The objective of this study is to assess the immunological effects of cryotreated whole tumour cells on dendritic cells (DC) maturation and function using an. in vitro model. Prostate cancer cells were cooled using Endocare cryo-system to mimic temperatures achieved during clinical cryotherapy. Human DC were prepared from cluster of differentiation (CD) 14 monocytes and matured with lipopolysaccharide (LPS). Cryotreated cancer cells were added to DC on day 3. On day 7, DC were harvested and phenotyped. Cytokine gene expression was assessed using real time quantitative polymerase chain reaction (RT-PCR). Functional activity of DC was assessed in allogenic mixed lymphocyte reaction (MLR) and the molecular changes using gene microarray technology. There was statistically significant upregulation of costimulatory molecules and maturation markers (CD86, CD83, CD80 and CL II) in DC loaded with cryotreated whole tumour cells compared to both control DC and DC matured with LPS ( P< 0.001). There was a significant increase in stimulatory cytokines gene expression (IL-2, IL-12, IL-15, IL-18 and IFN-γ). However, IL-10 and TGF-β expression reduced significantly. The effect of different freezing temperature was equal. cDNA microarray analysis showed upregulation of interleukin 1 (IL-1) and cycline dependent kinase inhibitor 1A (CDKN1A (p21) and downregulation of Caspase 8 and BCL2. Overall, our findings suggest that the effect of cryotherapy is generally stimulatory to DC which may enhance anti-tumour effects. Therefore, the combination of cryotherapy and DC vaccine may represent a novel method to increase the efficacy of cryotherapy especially at the peripheral zones of the prostate where cells are exposed to sub-lethal temperature. © 2010 Elsevier Inc. Source


O'Donnell T.,The National Orthopaedic Hospital | Hogan N.,Mount St. Annes | Solan M.,The Royal Surrey County Hospital | Stephens M.M.,The National Orthopaedic Hospital | Stephens M.M.,University College Dublin
Foot and Ankle Surgery | Year: 2010

Background: There are many procedures described for the correction of severe hallux valgus. This is the first to examine the role of a basal osteotomy with distal soft tissue release. Methods: 26 patients with severe hallux valgus underwent a basal chevron osteotomy with distal soft tissue release. All were reviewed at an average of 38 months. Results: The mean AOFAS score improved from 24 to 82 points (p<0.001). The IMA improved from an average of 23.90 to 130 (p<0.01). The HVA improved from an average of 490 to 170 (p<0.005). The correlation coefficient between the AOFAS score and various radiological angles was low (0.47). Conclusions: Good clinical outcomes in cases of severe hallux valgus can be achieved without full restoration of normal radiological values. Furthermore, a basal chevron osteotomy with a distal soft tissue release offers a high satisfaction rating with regards to both clinical and functional outcomes in the short to medium-term. Level of evidence: Level IV - Case series. © 2009 European Foot and Ankle Society. Source


Di Palma S.,The Royal Surrey County Hospital | Di Palma S.,University of Surrey
Head and Neck Pathology | Year: 2013

Carcinoma ex pleomorphic adenoma (CXPA) is a broad category of carcinomas of the salivary glands which includes at least 2 clinically relevant categories; one is referred here as early CXPA (ECXPA), the other as widely invasive CXPA. The former includes several histological patterns ranging from non-invasive/in situ/intraductal/intratubular, early invasive/extratubular/intracapsular and extracapsular (up to 6 mm). The latter includes any CXPA with invasion of >6 mm. The clinical behaviour of ECXPA is not aggressive and tends to overlap that of a pleomorphic adenoma (PA) which makes the histological report of carcinoma contradictory. These early malignant changes in PA are known since the 1970s but it has been the use of immunohistochemical and molecular genetic analysis for HER-2 and TP53 gene in the last decade that has clarified the genuine malignant nature of the cells. HER-2 and TP53 gene and protein are involved in the early stages of malignant transformation of PA. Moreover the immunohistochemical over-expression HER-2, p53 protein and Mib-1 proliferation marker may be useful markers to identify malignant areas in PA. © 2013 Springer Science+Business Media New York. Source


Banks L.,Kings College | Kirk-Bayley J.,The Royal Surrey County Hospital
Journal of the Intensive Care Society | Year: 2014

There are concerns about the safety of hydroxyethyl starch (HES) solutions for intensive care patients regarding possible increased mortality and increased incidence of renal impairment with associated morbidity. This large trial showed no change in primary outcome related to mortality, but an increased relative risk of 21% for the use of renal replacement therapy. © The Intensive Care Society 2014. Source

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