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.

A Comprehensive Screen for TWIST Mutations in Patients with Craniosynostosis Identifies a New Microdeletion Syndrome of Chromosome Band 7p21.1

Abstract: Summary Mutations in the coding region of the TWIST gene (encoding a basic helix-loop-helix transcription factor) have been identified in some cases of Saethre-Chotzen syndrome. Haploinsufficiency appears to be the pathogenic mechanism involved. To investigate the possibility that complete deletions of the TWIST gene also contribute to this disorder, we have developed a comprehensive strategy to screen for coding-region mutations and for complete gene deletions. Heterozygous TWIST mutations were identified in 8 of 10 patients with Saethre-Chotzen syndrome and in 2 of 43 craniosynostosis patients with no clear diagnosis. In addition to six coding-region mutations, our strategy revealed four complete TWIST deletions, only one of which associated with a translocation was suspected on the basis of conventional cytogenetic analysis. This case and two interstitial deletions were detectable by analysis of polymorphic microsatellite loci, including a novel (CA) n locus 7.9 kb away from TWIST , combined with FISH; these deletions ranged in size from 3.5 Mb to >11.6 Mb. The remaining, much smaller deletion was detected by Southern blot analysis and removed 2,924 bp, with a 2-bp orphan sequence at the breakpoint. Significant learning difficulties were present in the three patients with megabase-sized deletions, which suggests that haploinsufficiency of genes neighboring TWIST contributes to developmental delay. Our results identify a new microdeletion disorder that maps to chromosome band 7p21.1 and that causes a significant proportion of Saethre-Chotzen syndrome.

Increased platelet depleted plasma 5-hydroxytryptamine concentration following meal ingestion in symptomatic female subjects with diarrhoea predominant irritable bowel syndrome.

Abstract: Background: Meal ingestion is often associated with exacerbation of gastrointestinal symptoms in subjects with irritable bowel syndrome (IBS). Furthermore, recent preliminary data suggest that 5-hydroxytryptamine (5-HT) concentration in platelet poor plasma is elevated following meal ingestion in some subjects with diarrhoea predominant IBS (d-IBS) compared with healthy subjects, although it is not known whether this is related to postprandial symptomatology. Aim: To expand on previous data by evaluating a larger number of subjects but also to assess plasma 5-hydroxyindole acetic acid (5-HIAA) concentrations, 5-HT turnover, platelet 5-HT stores, and any relationship to symptomatology. Methods: We assessed platelet depleted plasma 5-HT and 5-HIAA concentrations for two hours (60 minute intervals) under fasting conditions, and then for a further four hours (30 minute intervals) after a standard carbohydrate meal (457 kcal), together with fasting platelet 5-HT concentrations in 39 female subjects with d-IBS (aged 19–52 years; mean age 33) and 20 healthy female volunteers (aged 20–46 years, mean age 28). IBS symptomatology, in particular abdominal pain and bloating, and urgency to defecate were assessed throughout the study Results: When related to fasting levels, there was no statistically significant difference in postprandial plasma 5-HT concentrations between d-IBS and healthy subjects. However, when fasting levels were not taken into consideration, d-IBS subjects exhibited higher postprandial plasma 5-HT concentrations compared with healthy subjects (p=0.040). Furthermore, d-IBS subjects who exhibited postprandial symptomatology had higher levels of postprandial plasma 5-HT, whether assessed with respect to fasting baseline levels (p=0.069) or not (p=0.047), compared with d-IBS subjects who did not report postprandial symptomatology. This appeared to be associated with a concomitant increase in plasma 5-HIAA (p=0.161) but reduction in turnover (p=0.058). Lastly, d-IBS subjects had higher platelet concentrations of 5-HT than healthy subjects (p=0.009). Conclusions: These data suggest that postprandial symptomatology may be associated with increased platelet depleted plasma 5-HT concentrations in female subjects with d-IBS. In addition, the presence of increased platelet stores of 5-HT may act as a useful marker for the diagnosis and management of d-IBS.

Neonatal disease severity scoring systems.

Abstract: Illness severity scores have become widely used in neonatal intensive care. Primarily this has been to adjust the mortality observed in a particular hospital or population for the morbidity of their infants, and hence allow standardised comparisons to be performed. However, although risk correction has become relatively commonplace in relation to audit and research involving groups of infants, the use of such scores in giving prognostic information to parents, about their baby, has been much more limited. The strengths and weaknesses of the existing methods of disease severity correction in the newborn are presented in this review.

Screening for poststroke major depression: a meta-analysis of diagnostic validity studies

Abstract: Background Major depression is common in stroke patients and associated with increased rates of disability and mortality. Identifying depression may improve mental and physical health. The aim of this review was to determine the most accurate tool for detecting poststroke depression. Methods Seven databases were searched up to November 2012. Two authors selected studies using International Classification of Disease or Diagnostic and Statistical Manual diagnosis of depression as the reference standard. Two authors extracted data and assessed methodological quality. Included studies were synthesised using meta-analyses. Results A total of 24 included studies provided data on 2907 participants. The Center of Epidemiological Studies-Depression Scale (CESD) (sensitivity: 0.75; 95% CI 0.60 to 0.85; specificity: 0.88; 95% CI 0.71 to 0.95), the Hamilton Depression Rating Scale (HDRS) (sensitivity: 0.84; 95% CI 0.75 to 0.90; specificity:0.83; 95% CI 0.72 to 0.90) and the Patient Health Questionnaire (PHQ)-9 (sensitivity: 0.86; 95% CI 0.70 to 0.94; specificity: 0.79; 95% CI 0.60 to 0.90) appeared to be the optimal measures for screening measures. However, the clinical utility of all tools was modest for case-finding. Interpretation There are a number of possible instruments that may help in screening for poststroke depression but none are satisfactory for case-finding. Preliminary data suggests the CESD, HDRS or the PHQ-9 as the most promising options. Although it should be noted such scales should not be used in isolation but followed up with a more detailed clinical assessment. While there is promising data for the PHQ-2 in other populations, it performed less well than other measures.