Leicester Royal Infirmary

About: Leicester Royal Infirmary is a healthcare organization based out in Leicester, United Kingdom. It is known for research contribution in the topics: Population & Carotid endarterectomy. The organization has 5300 authors who have published 6204 publications receiving 208464 citations.

HDAC inhibitor confers radiosensitivity to prostate stem-like cells.

Abstract: Radiotherapy can be an effective treatment for prostate cancer, but radiorecurrent tumours do develop. Considering prostate cancer heterogeneity, we hypothesised that primitive stem-like cells may constitute the radiation-resistant fraction. Primary cultures were derived from patients undergoing resection for prostate cancer or benign prostatic hyperplasia. After short-term culture, three populations of cells were sorted, reflecting the prostate epithelial hierarchy, namely stem-like cells (SCs, α2β1integrinhi/CD133+), transit-amplifying (TA, α2β1integrinhi/CD133−) and committed basal (CB, α2β1integrinlo) cells. Radiosensitivity was measured by colony-forming efficiency (CFE) and DNA damage by comet assay and DNA damage foci quantification. Immunofluorescence and flow cytometry were used to measure heterochromatin. The HDAC (histone deacetylase) inhibitor Trichostatin A was used as a radiosensitiser. Stem-like cells had increased CFE post irradiation compared with the more differentiated cells (TA and CB). The SC population sustained fewer lethal double-strand breaks than either TA or CB cells, which correlated with SCs being less proliferative and having increased levels of heterochromatin. Finally, treatment with an HDAC inhibitor sensitised the SCs to radiation. Prostate SCs are more radioresistant than more differentiated cell populations. We suggest that the primitive cells survive radiation therapy and that pre-treatment with HDAC inhibitors may sensitise this resistant fraction.

Selection of Patients with Critical Limb Ischaemia for Femorodistal Vein Bypass

Abstract: The merits of an aggressive policy of distal reconstruction have been questioned by some observers. To determine the factors affecting graft patency and mortality, we analysed 78 consecutive infragenicular femorodistal vein grafts performed in 72 patients with critical limb ischaemia. The primary, primary assisted and secondary graft patency rates at 36 months were 29, 57 and 64%, respectively. The limb salvage and patient survival rates at 36 months were 67 and 74%, respectively. Univariate analysis (log-rank test) was performed to identify factors affecting graft patency, limb salvage and mortality at 1 month (perioperative) and 1 year. Independent variables of age, sex, diabetes, presentation, level of anastomosis and vein technique (reversed or in situ ) did not affect graft patency. The ankle systolic pressure did not predict graft patency but was an independent variable affecting mortality ( p = 0.047), as did diabetes ( p = 0.019). These results show that excellent limb salvage can be successfully achieved in severely ischaemic patients by adopting an aggressive approach to femorodistal bypass, and that age, gender and poor medical condition are not contraindications to femorodistal bypass. The difference between the primary and primary assisted patency rates in this series is dramatic and reflects the impact of a vein graft surveillance programme in preventing graft occlusion.

Metabolic outcomes in young children with type 1 diabetes differ between treatment centers: the Hvidoere Study in Young Children 2009†

Abstract: Objective: To investigate whether center differences in glycemic control are present in prepubertal children Research Design and Methods: This cross-sectional study involved 18 pediatric centers worldwide. All children, Results: A total of 1133 children participated (mean age: 8.0 +/- 2.1 y; females: 47.5%, mean diabetes duration: 3.8 +/- 2.1 y). HbA1c (overall mean: 8.0 +/- 1.0%; range: 7.3-8.9%) and severe hypoglycemia frequency (mean 21.7 events per 100 patient-years), but not DKA, differed significantly between centers (p Conclusions: Center differences in metabolic outcomes are present in children

Skeletal muscle degradation and nitrogen wasting in rats with chronic metabolic acidosis.

Abstract: 1. Chronic metabolic acidosis is associated with impaired growth and negative nitrogen balance, suggesting that it promotes endogenous protein catabolism. 2. Skeletal muscle is the major repository of body protein and is a potential target for stimuli of protein catabolism. 3. This study in vivo examines the effects of chronic metabolic acidosis on the relationship between growth, nitrogen disposal and skeletal muscle catabolism in the rat. 4. Growth, nitrogen utilization and acquisition of body mass were significantly impaired in acidotic animals compared with pair-fed controls. 5. Total nitrogen excretion was significantly increased in acidotic rats despite decreased urea production. The time course of this response to acidosis was synchronous with that of accelerated protein catabolism in skeletal muscle. 6. It is proposed that metabolic acidosis impairs growth by stimulating skeletal muscle protein catabolism. It is suggested that this forms part of a co-ordinated multi-organ homoeostatic response to acidosis, skeletal muscle and down-regulated urea production supplying the nitrogen required for renal ammoniagenesis.