Glenfield Hospital

About: Glenfield Hospital is a healthcare organization based out in Leicester, United Kingdom. It is known for research contribution in the topics: Population & Extracorporeal membrane oxygenation. The organization has 1382 authors who have published 1812 publications receiving 99238 citations. The organization is also known as: Glenfield General Hospital.

Should acute scaphoid fractures be fixed? A randomized controlled trial.

Abstract: Background: With the proliferation of different fixation screws, there is an increasing trend to recommend early internal fixation of the broken scaphoid even if the fracture is not displaced. The benefits and risks of early fixation of scaphoid fractures have not been established. These were investigated in eighty-eight patients who were of working age with clearly defined minimally displaced or undisplaced bicortical fractures of the waist of the scaphoid. Methods: Patients who provided informed consent were randomized to treatment with early internal fixation with use of a Herbert screw without a cast (forty-four patients) or to nonoperative treatment for eight weeks with immobilization in a below-the-elbow plaster cast with the thumb left free (forty-four patients). The patients were evaluated at two, eight, twelve, twenty-six, and fifty-two weeks with respect to the severity of pain; tenderness; swelling; wrist movement; grip strength; and symptoms and disability, which were assessed with the Patient Evaluation Measure. In addition, radiographs were made and assessed at each visit. Results: No difference was detected between the groups with respect to age, sex, hand dominance, side of injury, mechanism of injury, or the occupation of the patients. The range of motion, score on the Patient Evaluation Measure, and grip strength were significantly better in the group managed operatively than in the group managed nonoperatively at the eight-week follow-up evaluation, which corresponded with the visit when the cast was removed in that group. Patients returned to work at five to six weeks after the injury in both groups. At twelve weeks, grip strength was better in patients who had had surgery. No significant difference was detected between the two groups with respect to any other outcome measure at any other time. Ten of the forty-four fractures treated nonoperatively had not healed radiographically at twelve weeks, and, as a consequence, the treatment was altered. Complications occurred in thirteen patients who had been managed operatively. All complications were minor, and ten were related to the scar. Conclusions: This study did not demonstrate a clear overall benefit of early fixation of acute scaphoid fractures beyond the decrease in the rate of a change in treatment because of a delayed union at twelve weeks. Early internal fixation of minimally displaced or nondisplaced fractures of the scaphoid waist, which would heal in a cast, could lead to overtreatment of a large proportion of such fractures, exposing such patients to avoidable surgical risk. Thus, we have adopted a program of so-called aggressive conservative treatment, whereby we carefully assess fracture-healing with plain radiographs, and computed tomography scans if necessary, after six to eight weeks of cast immobilization and recommend surgical fixation with or without bone-grafting at that time if a gap is identified at the fracture site. Such an approach should result in fracture union in over 95% of such patients. Level of Evidence: Therapeutic Level I. See Instructions to Authors for a complete description of levels of evidence.

Gene Expression Profiling Reveals Renin mRNA Overexpression in Human Hypertensive Kidneys and a Role for MicroRNAs

Abstract: The kidney has long been invoked in the etiology of essential hypertension. This could involve alterations in expression of specific genes and microRNAs (miRNAs). The aim of the present study was to identify, at the transcriptome-wide level, mRNAs and miRNAs that were differentially expressed between kidneys of 15 untreated hypertensive and 7 normotensive white male subjects of white European ancestry. By microarray technology we found 14 genes and 11 miRNAs that were differentially expressed in the medulla. We then selected and confirmed by real-time quantitative PCR expression differences for NR4A1, NR4A2, NR4A3, PER1, and SIK1 mRNAs and for the miRNAs hsa-miR-638 and hsa-let-7c. Luciferase reporter gene experiments in human kidney (HEK293) cells confirmed the predicted binding of hsa-let-7c to the 3' untranslated region of NR4A2 mRNA. In the renal cortex we found differential expression of 46 genes and 13 miRNAs. We then confirmed expression differences for AIFM1, AMBP, APOE, CD36, EFNB1, NDUFAF1, PRDX5, REN, RENBP, SLC13A1, STX4, and TNNT2 mRNAs and for miRNAs hsa-miR-21, hsa-miR-126, hsa-miR-181a, hsa-miR-196a, hsa-miR-451, hsa-miR-638, and hsa-miR-663. Functional experiments in HEK293 cells demonstrated that hsa-miR-663 can bind to the REN and APOE 3' untranslated regions and can regulate REN and APOE mRNA levels, whereas hsa-miR-181a regulated REN and AIFM1 mRNA. Our data demonstrated for the first time that miRNAs can regulate renin expression. The observed downregulation of 2 miRNAs in hypertension could explain the elevation in intrarenal renin mRNA. Renin, CD36, and other mRNAs, as well as miRNAs and associated pathways identified in the present study, provide novel insights into hypertension etiology.

Matrix Metalloproteinase 9 and the Epidermal Growth Factor Signal Pathway in Operable Non-Small Cell Lung Cancer

Abstract: Matrix metalloproteinase (MMP)-9 is an endopeptidase that digests basement membrane type IV collagen. Enhanced expression has been related to tumor progression both in vitro and in vivo. The control of MMP transcription is complex, but recently, epidermal growth factor receptor (EGFR) expression has been implicated in up-regulation of MMP-9 in tumor cells in vitro. Our objective was to evaluate the relationship between MMP-9 and EGFR expression in non-small cell lung cancer (NSCLC) and to assess the impact of expression on clinicopathological parameters and survival. This is a retrospective study of 169 patients who underwent resection for stage I-IIIa NSCLC with a postoperative survival >60 days. Minimum follow-up was 2 years. Standard avidin-biotin complex immunohistochemistry was performed on 4-microm paraffin-embedded sections from the tumor periphery using monoclonal antibodies to EGFR and MMP-9. MMP-9 was expressed in the tumor cells of 88 of 169 (52%) cases. EGFR expression was found in 94 of 169 (56%) cases [membranous, 55 of 169 (33%); cytoplasmic, 39 of 169 (23%)]. MMP-9 expression was associated with poor outcome in univariate (P = 0.0023) and multivariate (P = 0.027) analysis. Membranous, cytoplasmic, and overall EGFR expression were not associated with outcome (P = 0.13, 0.99, and 0.17, respectively). MMP-9 expression showed a strong correlation with EGFR expression (P < 0.0001) and EGFR membranous expression (P = 0.002) but not with cytoplasmic EGFR expression (P = 0.18). Co-expression of MMP-9 and EGFR (37%) conferred a worse prognosis (P = 0.0001). Subset analysis revealed only MMP-9 and membranous EGFR co-expression (22%) was associated with poor outcome (P = 0.0019). Our results show that a significant proportion of NSCLC tumors co-express MMP-9 and EGFR. The co-expression of these markers confers a poor prognosis. This finding suggests that EGFR signaling pathway may play an important role in the invasive behavior of NSCLC via specific up-regulation of MMP-9.

KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference

Abstract: Excessive alcohol consumption is a major public health problem worldwide. Although drinking habits are known to be inherited, few genes have been identified that are robustly linked to alcohol drinking. We conducted a genome-wide association metaanalysis and replication study among >105,000 individuals of European ancestry and identified β-Klotho (KLB) as a locus associated with alcohol consumption (rs11940694; P = 9.2 × 10−12). β-Klotho is an obligate coreceptor for the hormone FGF21, which is secreted from the liver and implicated in macronutrient preference in humans. We show that brain-specific β-Klotho KO mice have an increased alcohol preference and that FGF21 inhibits alcohol drinking by acting on the brain. These data suggest that a liver–brain endocrine axis may play an important role in the regulation of alcohol drinking behavior and provide a unique pharmacologic target for reducing alcohol consumption.