St George's, University of London

About: St George's, University of London is a education organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Health care. The organization has 4953 authors who have published 11675 publications receiving 574153 citations. The organization is also known as: SGUL & St George's Hospital Medical School.

Mutations in FAM20C Are Associated with Lethal Osteosclerotic Bone Dysplasia (Raine Syndrome), Highlighting a Crucial Molecule in Bone Development

Abstract: The generation and homeostasis of bone tissue throughout development and maturity is controlled by the carefully balanced processes of bone formation and resorption. Disruption of this balance can give rise to a broad range of skeletal pathologies. Lethal osteosclerotic bone dysplasia (or, Raine syndrome) is an autosomal recessive disorder characterized by generalized osteosclerosis with periosteal bone formation and a distinctive facial phenotype. Affected individuals survive only days or weeks. We have identified and defined a chromosome 7 uniparental isodisomy and a 7p telomeric microdeletion in an affected subject. The extent of the deleted region at the 7p telomere was established by genotyping microsatellite markers across the telomeric region. The region is delimited by marker D7S2563 and contains five transcriptional units. Sequence analysis of FAM20C, located within the deleted region, in six additional affected subjects revealed four homozygous mutations and two compound heterozygotes. The identified mutations include four nonsynonymous base changes, all affecting evolutionarily conserved residues, and four splice-site changes that are predicted to have a detrimental effect on splicing. FAM20C is a member of the FAM20 family of secreted proteins, and its mouse orthologue (DMP4) has demonstrated calcium-binding properties; we also show by in situ hybridization its expression profile in mineralizing tissues during development. This study defines the causative role of FAM20C in this lethal osteosclerotic disorder and its crucial role in normal bone development.

Does outdoor air pollution induce new cases of asthma? Biological plausibility and evidence; a review.

Abstract: It is widely accepted that air pollution can exacerbate asthma in those who already have the condition. What is less clear is whether air pollution can contribute to the initiation of new cases of asthma. Mechanistic evidence from toxicological studies, together with recent information on genes that predispose towards the development of asthma, suggests that this is biologically plausible, particularly in the light of the current understanding of asthma as a complex disease with a variety of phenotypes. The epidemiological evidence for associations between ambient levels of air pollutants and asthma prevalence at a whole community level is unconvincing; meta-analysis confirms a lack of association. In contrast, a meta-analysis of cohort studies found an association between asthma incidence and within-community variations in air pollution (largely traffic dominated). Similarly, a systematic review suggests an association of asthma prevalence with exposure to traffic, although only in those living very close to heavily trafficked roads carrying a lot of trucks. Based on this evidence, the UK's Committee on the Medical Effects of Air Pollutants recently concluded that, overall, the evidence is consistent with the possibility that outdoor air pollution might play a role in causing asthma in susceptible individuals living very close to busy roads carrying a lot of truck traffic. Nonetheless, the effect on public health is unlikely to be large: air pollutants are likely to make only a small contribution, compared with other factors, in the development of asthma, and in only a small proportion of the population.

Trends in the prevalence of diagnosed atrial fibrillation, its treatment with anticoagulation and predictors of such treatment in UK primary care

Abstract: Objectives: To examine trends in the prevalence of diagnosed atrial fibrillation (AF), its treatment with oral anticoagulants between 1994 and 2003, and predictors of anticoagulant treatment in 2003. Methods: Analysis of electronic data from 131 general practices (about one million registered patients annually) contributing to the DIN-LINK database. Results: From 1994 to 2003 the prevalence of “active” AF rose from 0.78% to 1.31% in men and from 0.79% to 1.15% in women. The proportion of patients with AF taking anticoagulants rose from 25% to 53% in men and from 21% to 40% in women. Most others received antiplatelets. The likelihood of receiving anticoagulants was greater for men and with increasing stroke risk. It decreased sharply with age after 75 years. Socioeconomic status, urbanisation and region had no influence. Non-steroidal anti-inflammatory drugs, antiplatelet drugs and ulcer healing drugs were associated with reduced likelihood of receiving anticoagulants, as were peptic ulcers, chronic gut disorders, anaemias, psychoses and poor compliance. Anticoagulant treatment was associated with several cardiovascular co-morbidities and drugs, possibly due to secondary care treatment. Nevertheless, only 56.5% of patients at very high risk of stroke were taking anticoagulants in 2003, whereas 38.2% of patients at low risk of stroke received anticoagulants. Conclusions: This study confirms previously observed trends of increasing AF prevalence and warfarin treatment. Many patients who may benefit from anticoagulation still do not receive it, whereas others at lower risk of stroke do. The lower likelihood of women receiving anticoagulants is of particular concern.