St Thomas' Hospital

About: St Thomas' Hospital is a healthcare organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Pregnancy. The organization has 12105 authors who have published 15596 publications receiving 624309 citations. The organization is also known as: St Thomas's Hospital & St. Thomas's.

Comparison of Genome Screens for Two Independent Cohorts Provides Replication of Suggestive Linkage of Bone Mineral Density to 3p21 and 1p36

Abstract: Low bone mineral density (BMD) is a major risk factor for osteoporotic fracture. Studies of BMD in families and twins have shown that this trait is under strong genetic control. To identify regions of the genome that contain quantitative trait loci (QTL) for BMD, we performed independent genomewide screens, using two complementary study designs. We analyzed unselected nonidentical twin pairs (1,094 pedigrees) and highly selected, extremely discordant or concordant (EDAC) sib pairs (254 pedigrees). Nonparametric multipoint linkage (NPL) analyses were undertaken for lumbar spine and total-hip BMD in both cohorts and for whole-body BMD in the unselected twin pairs. The maximum evidence of linkage in the unselected twins (spine BMD, LOD 2.7) and the EDAC pedigrees (spine BMD, LOD 2.1) was observed at chromosome 3p21 (76 cM and 69 cM, respectively). These combined data indicate the presence, in this region, of a gene that regulates BMD. Furthermore, evidence of linkage in the twin cohort (whole-body BMD; LOD 2.4) at chromosome 1p36 (17 cM) supports previous findings of suggestive linkage to BMD in the region. Weaker evidence of linkage (LOD 1.0–2.3) in either cohort, but not both, indicates the locality of additional QTLs. These studies validate the use, in linkage analysis, of large cohorts of unselected twins phenotyped for multiple traits, and they highlight the importance of conducting genome scans in replicate populations as a prelude to positional cloning and gene discovery.

Posterior capsular opacification after cataract surgery.

Abstract: This is a review of the current status of clinical research on the prevention of posterior capsular opacification (PCO), which is now the commonest complication of cataract surgery occurring in up to 50% of patients by 2 to 3 years after the operation. PCO is caused by lens epithelial cells retained in the capsular bag following surgery which then proliferate, migrate and transform to myofibroblasts. Interest in the prevention of PCO has centred around surgical technique, pharmacological methods to remove or destroy lens epithelial cells and changes in intraocular lens material and design. Changes in surgical technique have little effect in prevention of PCO although a capsulorhexis size which lies on the optic diameter appears to be beneficial. Many different cytotoxic drugs and pharmacological agents have been used experimentally to prevent PCO but the problem has limited damage only to lens epithelial cells. So far, no method has been shown to be safe for clinical use. Current interest is centred once again on the intraocular lens itself, particularly the material that it is made from and changes in its edge profile.

Extracorporeal photopheresis (ECP) in the treatment of chronic graft-versus-host disease (GVHD)

Abstract: The aim of our study was to assess the efficacy of extracorporeal photopheresis (ECP) in chronic graft-versus-host disease (GVHD). Eleven patients with chronic cutaneous GVHD were studied. Four had mucosal involvement and five had pulmonary involvement. All had failed to improve on first- and second-line therapy. Three patients received ECP alone; the remainder continued to receive steroids and/or immunosuppressive therapy. Patients received ECP twice monthly for 4 months and then once monthly for 3 months. They were evaluated by serial skin scores, mucosal and skin photography, pulmonary function tests, biochemical and haematological parameters. Nine patients showed objective evidence of cutaneous improvement with a mean reduction in skin score of 48% overall. In the 10th patient, skin scores and oral involvement improved on twice monthly ECP but deteriorated when reduced to once monthly. The final patient died from renal failure secondary to cyclosporin toxicity. Two out of five patients with lung involvement showed a mild improvement in pulmonary function tests. Liver function tests were abnormal in five patients; they improved in one and deteriorated in three. All patients receiving concomitant immunosuppressive/steroid therapy were able to reduce drug dosages by trial completion. Our results indicate that ECP can benefit patients with cutaneous and mucosal chronic GVHD who have failed on first- and second-line therapies. The effect on the systemic manifestations of GVHD is less consistent.

Mapping the HLA association in Behcet's disease: A role for tumor necrosis factor polymorphisms?

Abstract: Objective. Experimental evidence suggests that inappropriate regulation of tumor necrosis factor α (TNFα) may play a role in the pathogenesis of Behcet's disease (BD). This is supported by recent reports high-lighting the efficacy of anti-TNFα agents in the treatment of this disease. The TNF gene is encoded in the class III region of the HLA complex adjacent to HLA-B. This genetic proximity to a gene that is already widely implicated in disease susceptibility led us to investigate the association between TNF promoter polymorphisms and susceptibility to BD. Methods. We studied 133 UK white Caucasoid patients with BD and 354 healthy controls. We attempted to dissect the contribution of individual polymorphisms in this gene-dense region by linkage disequilibrium mapping across 6 adjacent genes. Results. We report a novel association with the TNF promoter allele TNF-1031C. Subsequent analysis identified 2 extended HLA haplotypes associated with BD. One of them contained the previously recognized susceptibility gene HLA-B*51, while the other was defined by HLA-B*5701. Both of these haplotypes contained the TNF promoter polymorphism -1031C, an allele that was associated with disease even in individuals who did not carry either HLA-B*51 or HLA-B*5701. Conclusion. The TNF-1031C allele is independently associated with susceptibility to BD in Caucasoid patients. Further studies will be required to determine the functional effects of this polymorphism, its influence in disease pathogenesis, and its role in other ethnic groups.