Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects.

Estimates from genome-wide association studies (GWAS) of unrelated individuals capture effects of inherited variation (direct effects), demography (population stratification, assortative mating) and relatives (indirect genetic effects). Family-based GWAS designs can control for demographic and indirect genetic effects, but large-scale family datasets have been lacking. We combined data from 178,086 siblings from 19 cohorts to generate population (between-family) and within-sibship (within-family) GWAS estimates for 25 phenotypes.

Verification and Validation of Digital Pathology (Whole Slide Imaging) for Primary Histopathological Diagnosis: All Wales Experience.

Aims: The study is aimed to verify Aperio AT2 scanner for reporting on the digital pathology platform (DP) and to validate the cohort of pathologists in the interpretation of DP for routine diagnostic histopathological services in Wales, United Kingdom.

Materials Methods And Results: This was a large multicenter study involving seven hospitals across Wales and unique with 22 (largest number) pathologists participating. 7491 slides from 3001 cases were scanned on Leica Aperio AT2 scanner and reported on digital workstations with Leica software of e-slide manager.

Role of the femorofemoral crossover graft in acute lower limb ischemia due to acute type B aortic dissection.

Acute limb ischemia due to type B aortic dissection is rare and continues to be a management challenge. A case series is presented here with the aim of assessing the outcomes of treatment with a femorofemoral crossover graft with or without thoracic stent graft insertion. This is a combined retrospective and prospective review of nine cases of acute lower limb ischemia secondary to acute type B aortic dissection.

Acute rupture of a fibromuscular dysplasia related renal artery aneurysm: emergency treatment with a covered stent.

We report the successful exclusion of a ruptured left renal artery aneurysm as a first presentation of fibromuscular dysplasia in a haemodynamically unstable 57-year-old man. The aneurysm was repaired in an emergency setting by deployment of a covered stent with a satisfactory result. Follow-up computed tomography confirmed successful exclusion of the aneurysm.

Preoperative consent: how to make sure your practice is legal--Part two.

The Mental Capacity Act 2005 (MCA) came into force in October 2007. This is now the keystone of the law regarding the assessment of capacity to consent and the treatment of those who lack capacity to consent for themselves. The first article in this two-part series (Corfield & Pomeroy 2008) covered preoperative consent: this article discusses the MCA (with accompanying relevant case law) in more detail by the use of illustrative examples and concentrates on issues that can arise once the patient is in the operating suite.

Preoperative consent: how to make sure your practice is legal--Part one.

Perioperative practitioners encounter consent issues constantly in their practice, both in terms of the main procedure listed and procedures they will undertake personally to enable the main procedure to be carried out safely. The law on consent has previously been governed by case (common) law but is now also partly governed by the Mental Capacity Act 2005 (MCA) (HMSO 2005). The onus is on practitioners to ensure that their practice is legal.

Non-attendance at the colorectal clinic: a prospective audit.

Introduction: Non-attendance in the out-patient department has financial costs for the NHS and clinical implications to the non-attender and those awaiting an appointment. The aim of this audit was to quantify the percentage of non-attenders at colorectal clinics in a UK teaching hospital, assess which factors affected attendance, establish why individuals fail to attend and to implement appropriate change.

Patients And Methods: The number of 'did-not-attend' patients was recorded initially for 686 appointments.

Alterations in the composition of the supramucosal defense barrier in relation to disease severity of ulcerative colitis.

Mucin glycoproteins and trefoil peptides play an important role in protection and repair of the gastrointestinal epithelium. This study investigates alterations in mucin and trefoil peptide gene expression and product localization in ulcerative colitis (UC). Product localization and message expression of mucin MUC1 to 6 and trefoil peptide TFF1 to 3 genes was analyzed in rectosigmoid tissue from a cohort of patients with active UC and compared with that of normal colorectal mucosa.

A rural emergency medical retrieval service: the first year.

Introduction: We describe the first year of operation of a rural emergency medical retrieval service (EMRS), staffed by emergency medicine and anaesthetic consultants and providing air based retrieval of critically ill and injured patients from general practitioner led community hospitals in rural west Scotland.

Methods: Data were collected on all patients referred to the service, both those subsequently transported and those where transport by the service was not indicated, for a period of 1 year from 1 October 2004 to 30 September 2005. Data collected included information on demographics, physiology, and medical interventions.

Abnormal subcellular distribution of mature MUC2 and de novo MUC5AC mucins in adenomas of the rectum: immunohistochemical detection using non-VNTR antibodies to MUC2 and MUC5AC peptide.

Anti-mucin variable number tandem repeat (VNTR) antibodies have been used previously to demonstrate the de novo presence of MUC5AC and MUC6 mucin in colorectal adenomas and increased synthesis of MUC2, the major secreted mucin in normal colorectal mucosa. Here we examined secreted mucins in tubular, tubulovillous and villous adenomas of the rectum using non-VNTR antibodies designed to assess mature mucin. Mucin gene messenger RNAs were detected by in situ hybridization.

Mucin gene expression in the ileoanal reservoir is altered and may be relevant to the risk of inflammation and dysplasia.

Background: Adaptive colonic phenotypic change of the ileal mucosa is a feature of the ileoanal reservoir (IAR) with time, as described by mucin glycoprotein and histological analysis. Mucin gene expression is altered in colorectal neoplasia and inflammatory bowel disease but little is known of its expression in the IAR.

Aims: To examine the changes in mucin gene expression contributing to mucosal protection of the IAR against a background of known changes occurring in inflammatory disease and colorectal neoplasia.

Mucin expression in the ileoanal reservoir reflects incomplete mucosal adaptation.

Restorative proctocolectomy is regarded as a standard surgical procedure for patients who require a proctocolectomy for ulcerative colitis and familial adenomatous polyposis. The ileal mucosa undergoes colonic phenotypic change with time, but the extent and relevance of these changes to the long-term safety of the ileoanal pouch are unclear. The aim of this study was to study the mucin biology of this adaptive process in order to assess its extent and possible impact on pouch safety.

Differential expression of the chromosome 11 mucin genes in colorectal cancer.

The four secretory mucin genes clustered on chromosome 11, MUC2, MUC5AC, MUC5B and MUC6, were screened in 37 patients with cancers in the left hemi-colon or rectum and 10 normal rectal controls. The mucin genes were detected by in situ hybridization using oligonucleotide probes to the variable number tandem repeat (VNTR) sequences, while the proteins were stained with non-VNTR (MUC2, MUC5AC and MUC5B) or VNTR (MUC6) antibodies. Low levels of MUC2 mRNA were detected in non-mucinous adenocarcinomas (5/27) while a higher proportion of mucinous carcinomas (4/9) was positive.

Coordinated localisation of mucins and trefoil peptides in the ulcer associated cell lineage and the gastrointestinal mucosa.

Background And Aims: Trefoil factor family (TFF) peptides and the chromosome 11p15.5 mucin glycoproteins are expressed and secreted in a site specific fashion along the length of the gastrointestinal tract. Evidence for coexpression of mucins and trefoil peptides has been suggested in numerous gastrointestinal mucosal pathologies.

Lack of mucin MUC5AC field change expression associated with tubulovillous and villous colorectal adenomas.

Background: MUC5AC is a secreted mucin aberrantly expressed by polypoid colorectal adenomas. It has been hypothesised that the "normal" surrounding colorectal mucosa expresses MUC5AC as a field change phenomenon that can be used to predict adenoma recurrence following resection.

Aim: To determine if there is a field change of de novo MUC5AC expression in histologically normal rectal mucosa adjacent to villous and tubulovillous adenomas, and thus whether MUC5AC expression can be used as a marker of early tumour recurrence.