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.

Antiphospholipid antibodies: A marker for thrombosis and recurrent abortion

Abstract: ConclusionConfirmatory evidence that aPL (the LA or aCL) are associated with an increased risk for arterial and venous thrombosis, recurrent spontaneous abortions, and fetal loss has led to increased laboratory requests for identification of these antibodies. Criteria for the definition of the APS is now well established. At present both the pathogenesis and the optimal management of the syndrome are uncertain. Treatment directed against the secondary thrombotic event is proving more successful than that directed against the underlying immunological abnormality. It is hoped that the results of various controlled therapeutic trials in the APS will indicate better ways of managing these difficult manifestations.

ANTIPHOSPHOLIPID ANTIBODIES AFFECT TROPHOBLAST GONADOTROPIN SECRETION AND INVASIVENESS BY BINDING DIRECTLY AND THROUGH ADHERED β2-GLYCOPROTEIN I

Abstract: Antiphospholipid antibodies (aPL) are associated with poor obstetric outcome, such as recurrent abortions, fetal death, growth retardation, and early preeclampsia (1). Passive transfer of whole immunoglobulin fractions from aPL-positive sera has been found to induce fetal loss and growth retardation in pregnant naive mice, suggesting a direct pathogenetic role (2–4). Although it has been assumed that aPL are directed against anionic PL, current advances in the field suggest that antibodies to PL-binding plasma proteins, such as β2-glycoprotein I (β2GPI), can be detected in standard aPL assays (5). Antibodies specific for β2GPI have been identified and found to be associated with the clinical manifestations of the antiphospholipid syndrome (APS) (6–22). The in vivo immunohistologic demonstration of β2GPI on trophoblast surfaces (23,24) and the induction of fetal loss by anti-β2GPI antibodies in experimental animal models (25,26) suggested a role of anti-β2GPI antibodies in fetal loss. Moreover, even murine and human aPL monoclonal antibodies (mAb) specifically reacting with anionic PL in the absence of any plasma cofactor have been shown to produce fetal loss, growth retardation, placental deposition, and necrosis in experimental animal models (3,27,28). Although experimental models have emphasized the role of thrombotic phenomena in placental tissue (4,27), studies in humans have shown that thrombotic events cannot account for all of the histopathologic findings in placentae from women with the APS (29,30). The possibility of direct villous and extravillous trophoblastic damage by aPL through the recognition of phosphatidylserine (PS) exposed during syncytium formation has been suggested (31). Reported direct effects of aPL on trophoblasts have included inhibition of the intercytotrophoblast fusion process (31), of human chorionic gonadotropin (hCG) or placental lactogen secretion (31,32), and/or of trophoblast invasiveness (31). Furthermore, whole IgG fractions from APS patient sera or xenogenic murine anti-PS mAb have been shown to displace annexin V from trophoblasts (and endothelial cell surfaces in the case of human IgG), thus creating conditions favorable to procoagulant state in vitro (31,33). The purpose of the present study was to investigate the in vitro ability of IgG from sera containing high levels of aPL to bind human trophoblast cells and to affect hCG secretion and invasiveness. Furthermore, to identify whether specific effects were related to individual antibody subpopulations, human mAb reacting with β2GPI or with anionic PL in the absence of any plasma cofactor were investigated for their ability to reproduce the binding to trophoblast cell membranes and the modulation of hormone secretion as well as invasiveness. From our results, it appears that trophoblast cells might represent one target for circulating aPL reacting with β2GPI and/or with “pure” anionic PL (whose binding is independent of any plasma cofactor) and that such antibodies affect trophoblast differentiation–related activities.

Retroversion of the acetabulum

Abstract: We describe a little-known variety of hip dysplasia, termed ‘acetabular retroversion’, in which the alignment of the mouth of the acetabulum does not face the normal anterolateral direction, but inclines more posterolaterally.The condition may be part of a complex dysplasia or a single entity. Other than its retroversion, the acetabulum is sited normally on the side wall of the pelvis, and its articular surface is of normal extent and configuration. The retroverted orientation may give rise to problems of impingement between the femoral neck and anterior acetabular edge.We define the clinical and radiological parameters and discuss pathological changes which may occur in the untreated condition. A technique of management is proposed.

British Association of Dermatologists guidelines for use of biological interventions in psoriasis 2005.

Abstract: Psoriasis is a common, persistent, relapsing inflammatory skin disease that can be associated with significant morbidity. Quality of life studies in psoriasis reveal a negative impact on patients comparable with that seen in cancer, arthritis and heart disease.1–5 Patients with severe disease constitute approximately 20–30% of all patients with psoriasis, often require systemic treatment, and represent a major economic burden to the Health Service. All standard systemic therapies for severe disease are associated with the potential for major long-term toxicity, many are expensive, and a proportion of patients has treatmentresistant disease.6 Biological therapies or ‘biologics’ describe agents designed to block specific molecular steps important in the pathogenesis of psoriasis and have emerged over the last 3–5 years as potentially valuable alternative therapeutic options. Currently, biological therapies for psoriasis comprise two main groups: (i) agents targeting the cytokine tumour necrosis factor (TNF)-a (e.g. etanercept, infliximab, adalimumab) and (ii) agents targeting T cells or antigen-presenting cells (e.g. efalizumab, alefacept). Two of these, etanercept (Enbrel) and efalizumab (Raptiva) were licensed in 2004 in the U.K. for patients with moderate to severe psoriasis.