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.

The direct effects of diethylstilboestrol and nifedipine on the contractile responses of isolated human and rat detrusor muscles

Abstract: We have studied the direct effect of 2 mumol.l-1 diethylstilboestrol on isolated rat and human detrusor muscles. Diethylstilboestrol significantly reduced the amplitude of the contractile response of rat detrusor muscle to stimulation with acetylcholine, carbachol, electrical field stimulation, and 5-hydroxytryptamine. In isolated human bladder it also significantly reduced contractions stimulated with acetylcholine, carbachol, and electrical field stimulation. In depolarized rat detrusor muscle stimulated with different concentrations of calcium ions, the contractile responses were significantly reduced by the addition of diethylstilboestrol. Diethylstilboestrol also significantly reduced the amplitude of contractile response to potassium chloride. The inhibitory action of diethylstilboestrol was enhanced by the reduction of extracellular calcium ions, the maximum contractile response to acetylcholine, carbachol, and electrical field stimulation being reduced by a further 32%, 23%, and 45% respectively. Diethylstilboestrol did not have a significant effect on carbachol-induced contractions in depolarized rat detrusor muscle suspended in a calcium-free environment. Diethylstilboestrol was effective in blocking rat and human detrusor muscle contraction. The likely mechanism is a reduction of the influx of calcium ions into the cell during contraction rather than an effect on intracellular calcium release. These results give support for treating incontinent patients with drugs that block calcium ion uptake, and may suggest a further beneficial effect of oestrogen therapy in postmenopausal women.

Hypoxia and angiogenesis in pancreatic cancer

Abstract: Background: Pancreatic cancer remains one of the most lethal of all solid tumours of the gastrointestinal tract. It is characterized by late diagnosis, aggressive local invasion, early metastasis and resistance to chemoradiotherapy. Increasing knowledge regarding the molecular events behind the growth and invasion of pancreatic cancer may lead to new targets for intervention. Methods: A search of Pubmed and Medline databases was undertaken using the keywords pancreatic cancer, gastrointestinal cancer, hypoxia, angiogenesis and anti-angiogenesis therapy. Results: Hypoxia is the driving force behind angiogenesis in pancreatic cancers. Research into angiogenesis has shown many different sites that can be targeted by agents such as tyrosine kinase inhibitors. Conclusion: Anti-angiogenic therapy could be an important adjunct to conventional chemotherapy treatment of gastrointestinal neoplasia. Abbreviations: CA, carbonic anhydrase; 5-FU, 5-fluorouracil; HO, haem oxygenase; MAPK, mitogen-activated protein kinase; HIF-1, hypoxia-inducible factor-1; IGF, insulin-like growth factor; IL-6, interleukin-6; MVD, microvessel density; mRNA, messenger RNA; NRP-1, neuropilin-1; PD-ECGF, platelet-derived endothelial cell growth factor; PGF, placenta growth factor; TSP, thrombospondin; VEGFR, vascular endothelial growth factor receptor.

Influence of aspirin on early allograft thrombosis and chronic allograft nephropathy following renal transplantation.

Abstract: Background: Primary thrombosis and chronic allograft nephropathy are important causes of early and late graft loss, respectively, following renal transplantation. This study examined the potential for aspirin therapy to reduce these complications. Methods: A consecutive series of 105 cadaveric renal transplants treated with aspirin 150 mg daily for the first 3 months after transplantation was compared with an untreated historical control group (n = 121). Protocol needle-core biopsies were performed on all transplants in both groups at 1 week and 12 months after transplantation. Needle-core allograft biopsies were performed at 3, 6 and 12 months after transplantation, and serum creatinine was measured at each outpatient attendance for the duration of follow-up. Results: There was a significantly lower rate of primary allograft thrombosis in patients treated with aspirin (none of 105) compared with that in the control group (six (5 per cent) of 121; P = 0·03). There were no differences in renal function or 2-year allograft survival between the two groups. Aspirin-treated patients had a lower incidence of chronic allograft nephropathy at 1 year than controls although this did not reach statistical significance (16 versus 26 per cent; P = 0·075). There were no major bleeding complications in either group in association with peptic ulcer disease or following renal transplant biopsy. Conclusion: Aspirin reduced the rate of early graft thrombosis of renal transplants in this series but did not improve renal function or graft survival. A trend towards a lower rate of chronic allograft nephropathy was noted with aspirin treatment. These findings require confirmation in a prospective randomized trial. © 2001 British Journal of Surgery Society Ltd

Outcome after surgical resection for duodenal adenocarcinoma in the UK

Abstract: BackgroundFactors influencing long‐term outcome after surgical resection for duodenal adenocarcinoma are unclear.MethodsA prospectively created database was reviewed for patients undergoing surgery for duodenal adenocarcinoma in six UK hepatopancreaticobiliary centres from 2000 to 2013. Factors influencing overall survival and disease‐free survival (DFS) were identified by regression analysis.ResultsResection with curative intent was performed in 150 (84·3 per cent) of 178 patients. The postoperative morbidity rate for these patients was 40·0 per cent and the in‐hospital mortality rate was 3·3 per cent. Patients who underwent resection had a better median survival than those who had a palliative surgical procedure (84 versus 8 months; P < 0·001). The 1‐, 3‐ and 5‐year overall survival rates for patients who underwent resection were 83·9, 66·7 and 51·2 per cent respectively. Median DFS was 53 months, and 1‐ and 3‐year DFS rates were 80·8 and 56·5 per cent respectively. Multivariable analysis revealed that node status (hazard ratio 1·73, 95 per cent c.i. 1·07 to 2·79; P = 0·006) and lymphovascular invasion (hazard ratio 3·49, 1·83 to 6·64; P = 0·003) were associated with overall survival.ConclusionResection of duodenal adenocarcinoma in specialist centres is associated with good long‐term survival. Lymphovascular invasion and nodal metastases are independent prognostic indicators.

Recommendations for management of diabetes during Ramadan: update 2020, applying the principles of the ADA/EASD consensus

Abstract: Fasting the Holy month of Ramadan constitutes one of the five pillars of the Muslim faith. Although there is some evidence that intermittent fasting during Ramadan may be of benefit in losing weight and cardiometabolic risk factors, there is no strong evidence these benefits apply to people with diabetes. The American Diabetes Association/European Association for the Study of Diabetes consensus recommendations emphasize the importance of patient factors and comorbidities when choosing diabetes medications including the presence of comorbidities, atherosclerotic cardiovascular disease, heart failure, chronic kidney disease, hypoglycemia risk, weight issues and costs. Structured education and pre-Ramadan counseing are key components to successful management of patients with diabetes. These should cover important aspects like glycemic targets, self-monitoring of blood glucose, diet, physical activity including Taraweeh prayers, medication and dose adjustment, side effects and when to break the fast. The decision cycle adapted for the specific situation of Ramadan provides an aid for such an assessment. Children with type 1 diabetes should strongly be advised not to fast due to the high risk of acute complications such as hypoglycemia and probably diabetic ketoacidosis (DKA), although there is very little evidence that DKA is increased in Ramadan. Pregnant women with diabetes or gestational diabetes should be advised to avoid fasting because of possible negative maternal and fetal outcomes. Hypoglycemia is a common concern during Ramadan fasting. To prevent hypoglycemic and hyperglycemic events, we recommend the adoption of diabetes self-management education and support principles. The use of the emerging technology and continuous glucose monitoring during Ramadan could help to recognize hypoglycemic and hyperglycemic complications related to omission and/or medication adjustment during fasting; however, the cost represents a significant barrier.