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.

Five year results of a randomized trial of adjuvant 5-fluorouracil and levamisole in colorectal cancer.

Abstract: Following curative surgery for colorectal cancer 141 patients were randomized to receive a 6 month course of 5-fluorouracil (5FU) with or without postoperative levamisole or supportive treatment only. The patients have been followed up for a minimum of 5 years and 52 per cent of patients in the control group, 44 per cent of the 5FU group and 32 per cent of the 5FU/levamisole group have died of tumour recurrence. This represents a significant survival advantage in the patients receiving levamisole, even when other patient and tumour factors are allowed for.

The Fornix in Health and Disease: An Imaging Review

Abstract: Anatomy and function of the fornix are reviewed and examples of pathologic processes that affect it are discussed, with emphasis on the contribution of forniceal pathologic conditions to cognition in disease states.

Marimastat (BB2516): current status of development.

Abstract: Marimastat (BB-2516) is the first matrix metalloproteinase inhibitor to have entered clinical trials in the field of oncology. It has excellent bioavailability and has completed phase I and II trials. Phase I studies involved healthy volunteers who received short courses of marimastat; these were well tolerated. Symptoms experienced by many patients with various malignancies included severe joint and muscle pain which were debilitating in >60% of patients at doses >50 mg bid. These symptoms were reversible on discontinuation of the drug, and their incidence has been decreased by using marimastat 10 mg bid, the dose used in current studies. Phase II studies involved the use of serum tumor markers as surrogate indicators of antitumor activity. Six studies in colorectal, ovarian, and prostate cancer have been completed and pooled analysis has demonstrated a dose-dependent biological effect (as defined by the authors); 58% of patients respond at doses >50 mg bid. Effects on tumor markers were associated with increased survival. Small phase II studies have suggested potential activity in pancreatic and gastric cancer and have demonstrated the safety of combining cytotoxic chemotherapeutic agents with marimastat. Ongoing phase III studies are investigating the effects of marimastat in addition to chemotherapy in the treatment of small cell lung cancer and pancreatic and gastric carcinoma.

Mutation Analysis and Embryonic Expression of the HLXB9 Currarino Syndrome Gene

Abstract: The HLXB9 homeobox gene was recently identified as a locus for autosomal dominant Currarino syndrome, also known as hereditary sacral agenesis (HSA). This gene specifies a 403-amino acid protein containing a homeodomain preceded by a very highly conserved 82-amino acid domain of unknown function; the remainder of the protein is not well conserved. Here we report an extensive mutation survey that has identified mutations in the HLXB9 gene in 20 of 21 patients tested with familial Currarino syndrome. Mutations were also detected in two of seven sporadic Currarino syndrome patients; the remainder could be explained by undetected mosaicism for an HLXB9 mutation or by genetic heterogeneity in the sporadic patients. Of the mutations identified in the 22 index patients, 19 were intragenic and included 11 mutations that could lead to the introduction of a premature termination codon. The other eight mutations were missense mutations that were significantly clustered in the homeodomain, resulting, in each patient, in nonconservative substitution of a highly conserved amino acid. All of the intragenic mutations were associated with comparable phenotypes. The only genotype-phenotype correlation appeared to be the occurrence of developmental delay in the case of three patients with microdeletions. HLXB9 expression was analyzed during early human development in a period spanning Carnegie stages 12-21. Signal was detected in the basal plate of the spinal cord and hindbrain and in the pharynx, esophagus, stomach, and pancreas. Significant spatial and temporal expression differences were evident when compared with expression of the mouse Hlxb9 gene, which may partly explain the significant human-mouse differences in mutant phenotype.

Impaired glucose tolerance and fasting hyperglycaemia have different characteristics

Abstract: Summary Aims Use of the oral glucose tolerance test (OGTT) to define glucose intolerance in the general population may bias towards selection of those with insulin resistance. Beta cell function and insulin resistance markers were analysed in four groups: controls (n = 101); fasting hyperglycaemia (FH, n 45); impaired glucose tolerance; (IGT, n = 16) and those with features of both FH and IGT (‘Both’, n = 30). Methods Subjects underwent an OGTT. Plasma glucose, fasting lipid profiles, fasting, 30 and 120 min insulin were measured and beta cell function (% B) and insulin sensitivity (% S) assessed by homeostatic model assessment (HOMA) Results The FH group compared to controls had a significantly lower % B. The IGT group compared to controls had features of insulin resistance (higher body mass index (BMI), systolic blood pressure and 2 h insulin concentration). Subjects with ‘both’ IGT and FH had features of insulin resistance (higher BMI, systolic and diastolic blood pressure and triglyceride concentration) as well as beta cell dysfunction with a lower % B and 30 min insulin–glucose ratio compared to controls. There was a preponderance of males in this group. In all, 192 subjects' 30-min insulin concentration and incremental insulin response showed only a significantly negative correlation with fasting glucose concentration. In a linear regression analysis, a low 30-min insulin–glucose ratio was only a significant factor in the fasting glucose model. Thus, higher fasting glucose concentrations appear to be associated with beta cell dysfunction. However, HbA1 only showed a significant correlation with 120-min glucose, not fasting glucose concentration. Conclusions In those with milder degrees of glucose intolerance, FH is associated with beta cell dysfunction and those with IGT and a relatively ‘normal’ fasting glucose have features of the insulin resistance syndrome.