Leicester General Hospital

About: Leicester General Hospital is a healthcare organization based out in Leicester, United Kingdom. It is known for research contribution in the topics: Population & Transplantation. The organization has 2481 authors who have published 3034 publications receiving 107437 citations.

Expression of nuclear Notch3 in pancreatic adenocarcinomas is associated with adverse clinical features, and correlates with the expression of STAT3 and phosphorylated Akt.

Abstract: Background and Objectives Reactivation of the Notch signalling pathway occurs in a range of human malignancies. Previous research suggests that Notch3 is expressed in pancreatic adenocarcinomas, but neither cellular location nor association with clinical parameters has been described. The relationship between Notch3, clinical endpoints, and other proteins with potential to interact with Notch was therefore examined. Methods An immunohistochemical study was performed on human pancreatic adenocarcinoma (n = 23) and normal pancreas (n = 12), to assess expression of Notch3, cyclin D1, pAkt, STAT3 and pSTAT3. Immunohistochemical data were then correlated with clinicopathological characteristics. Results Notch3 was significantly overexpressed in the cytoplasm of 73.9% of tumours. Nuclear expression was not observed in normal pancreatic ductal tissue, but was noted in 43.5% of tumours. No tumour expressing nuclear Notch3 was resectable. There were significant correlations between expression and intracellular location of Notch3 and each of STAT3, pSTAT3 and pAkt, but not cyclin D1. Conclusion The presence of Notch3 in tumour nuclei is likely to represent functional activation of the protein, and is clearly linked to a more aggressive tumour phenotype. The correlation with STAT3, pSTAT3 and pAkt expression has not previously been described and the concurrent intracellular localisation of these proteins suggests a functional relationship between them. J. Surg. Oncol. 2008;97:63–68. © 2007 Wiley-Liss, Inc.

Randomized clinical trial of metronidazole ointment versus placebo in perianal Crohn's disease

Abstract: Background: The potential for metronidazole 10 per cent ointment to exert therapeutic benefit in perianal Crohn's disease, while minimizing the adverse effects found with oral metronidazole, was evaluated in a randomized placebo-controlled study. Methods: Subjects with perianal Crohn's disease were randomized to metronidazole 10 per cent ointment, 0.7 g applied perianally three times daily, or placebo ointment. The Perianal Crohn's Disease Activity Index (PCDAI) was scored at baseline and after 4 weeks of treatment. Perianal pain was assessed on a visual analogue scale. Results: Seventy-four subjects (33 metronidazole, 41 placebo) were evaluated. The mean(s.e.m.) reduction in PCDAI score at 4 weeks was 2.4(0.5) in the metronidazole group and 2·2(0·4) in the placebo group (P = 0.660). More subjects in the metronidazole group than the placebo group showed a reduction in PCDAI score of at least 5 points (10 of 27 versus 4 of 34; P = 0·031). Perianal discharge was reduced significantly in metronidazole-treated subjects (P = 0.012). A greater reduction in perianal pain was seen in the metronidazole group, which approached statistical significance (P = 0.059). No serious adverse events were reported. Conclusion: Metronidazole 10 per cent ointment was not effective in the reduction of PDCAI score, but some secondary outcomes showed improvement suggestive of a treatment effect. It is well tolerated, with minimal adverse effects, and has potential as treatment for pain and discharge associated with perianal Crohn's disease. Registration number: NCT00509639 (http://www.clinicaltrials.gov).

Analysis of factors associated with complications following renal transplant needle core biopsy

Abstract: Objective To determine factors associated with complications in patients undergoing renal transplant biopsy. Patients and methods A total of 210 consecutive renal transplant patients biopsied for acute graft dysfunction or as part of a long term surveillance programme. Biopsies were performed under ultrasound control at two centres (Nottingham City and Leicester General Hospitals). Results Seventeen patients developed macroscopic haematuria following biopsy (8%). There were no graft losses. In cases where at least one biopsy core contained only renal medullary tissue, there was a significantly higher risk of a post-biopsy bleed (P < 0.001). Conclusion This study demonstrates that even with careful ultrasound guidance, renal transplant biopsy has an important complication rate. Every effort must be made to obtain very superficial biopsies which consist largely or exclusively of renal cortex.

Perineal reconstruction after extra-levator abdominoperineal excision (eLAPE): a systematic review

Abstract: Extra-levator abdominal perineal excision of rectum (eLAPE) for low rectal tumours is associated with a lower incidence of circumferential resection involvement. However, there is no consensus on the ideal technique for perineal reconstruction following eLAPE. We thereby conducted a 5-year review of perineal closure outcomes following eLAPE. A systematic review of the literature was conducted between 2006 and July 2012. Perineal wound healing and complications in the post-operative period were examined. Original data following eLAPE were found in 27 studies involving 963 individuals to inform a qualitative synthesis. Pooled analysis revealed that investigators most commonly employed either biomesh closure (12 studies, n = 149), myocutaneous flap closure (9 studies, n = 201) and primary closure (4, n = 578). The incidence of minor and major wound complications and perineal hernias across the latter groups was (27.5, 13.4 and 2.7 %), (29.4, 19.4 and 0 %) and (17.1, 6.4 and 1.2 %), respectively. Two studies utilised synthetic mesh closure (n = 4) and omentoplasty (n = 31). Objective assessment of wound healing was strikingly deficient across most studies, largely due to low level retrospective evidence lacking randomised controls. Modest cohort sizes with short follow-up data were evident due to the relative novelty of eLAPE. The paucity of high quality data, suggests that a prospective, randomised trial is needed to determine the ideal technique for perineal reconstruction following eLAPE.

Infertility, Obstetric and Gynaecological Problems in Coeliac Sprue

Abstract: There is now substantial evidence that coeliac sprue is associated with infertility both in men and women. In women it can also lead to delayed menarche, amenorrhoea, early menopause, recurrent abortions, and a reduced pregnancy rate. In men it can cause hypogonadism, immature secondary sex characteristics and reduce semen quality. The real mechanism by which coeliac sprue produces these changes is unclear, but factors such as malnutrition, iron, folate and zinc deficiencies have all been implicated. In addition in men gonadal dysfunction is believed to be due to reduced conversion of testosterone to dihydrotestosterone caused by low levels of 5 alpha-reductase in coeliac sprue. This leads to derangement of the hypothalamic-pituitary axis. Hyperprolactinaemia is seen in 25% of coeliac patients, which causes impotence and loss of libido. Gluten withdrawal and correction of deficient dietary elements can lead to a return of fertility both in men and women.