Guy's and St Thomas' NHS Foundation Trust

About: Guy's and St Thomas' NHS Foundation Trust is a healthcare organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Medicine. The organization has 7686 authors who have published 9631 publications receiving 399353 citations. The organization is also known as: Guy's and St Thomas' National Health Service Foundation Trust & Guy's and St Thomas' National Health Service Trust.

Pregnancy and reproduction in autoimmune rheumatic diseases

Abstract: Despite evidence for the important role of oestrogens in the aetiology and pathophysiology of chronic immune/inflammatory diseases, the previous view of an unequivocal beneficial effect of oestrogens on RA compared with a detrimental effect on SLE has to be reconsidered. Likewise, the long-held belief that RA remits in the majority of pregnant patients has been challenged, and shows that only half of the patients experience significant improvement when objective disease activity measurements are applied. Pregnancies in patients with SLE are mostly successful when well planned and monitored interdisciplinarily, whereas a small proportion of women with APS still have adverse pregnancy outcomes in spite of the standard treatment. New prospective studies indicate better outcomes for pregnancies in women with rare diseases such as SSc and vasculitis. Fertility problems are not uncommon in patients with rheumatic disease and need to be considered in both genders. Necessary therapy, shortly before or during the pregnancy, demands taking into account the health of both mother and fetus. Long-term effects of drugs on offspring exposed in utero or during lactation is a new area under study as well as late effects of maternal rheumatic disease on children.

UK consensus on pregnancy in multiple sclerosis: ‘Association of British Neurologists’ guidelines

Abstract: Multiple sclerosis (MS) is more common in women than men and is most commonly diagnosed in early adulthood; thus, many patients will not have completed their families at the time of diagnosis. There is increasing awareness of the importance of early treatment in preventing long-term disability in MS. Delaying treatment until women with MS have completed their families can lead to the development of irreversible disability in at least some cases. It is therefore important to discuss family planning and pregnancy proactively. However, to date there is limited evidence to inform such discussions. We set out to develop consensus guidelines for the treatment of MS in pregnancy to encourage and facilitate discussions in this important area. The guidelines draw on available evidence from drug-specific pregnancy registers and published literature and have been scored by a panel of experts from a variety of disciplines using modified Delphi criteria. They cover prepregnancy counselling, management during pregnancy, delivery and anaesthetic options, postpartum advice and specific advice regarding currently licensed disease-modifying drugs. As the complexity and range of available disease-modifying drugs increase, further data gathering via a UK-wide MS pregnancy register is recommended.

Mechanisms of migraine as a chronic evolutive condition

Abstract: Understanding the mechanisms of migraine remains challenging as migraine is not a static disorder, and even in its episodic form migraine remains an “evolutive” chronic condition. Considerable progress has been made in elucidating the pathophysiological mechanisms of migraine, associated genetic factors that may influence susceptibility to the disease, and functional and anatomical changes during the progression of a migraine attack or the transformation of episodic to chronic migraine. Migraine is a life span neurological disorder that follows an evolutive age-dependent change in its prevalence and even clinical presentations. As a disorder, migraine involves recurrent intense head pain and associated unpleasant symptoms. Migraine attacks evolve over different phases with specific neural mechanisms and symptoms being involved during each phase. In some patients, migraine can be transformed into a chronic form with daily or almost daily headaches. The mechanisms behind this evolutive process remain unknown, but genetic and epigenetic factors, inflammatory processes and central sensitization may play an important role.

Features associated with epilepsy in the antiphospholipid syndrome

Abstract: OBJECTIVE: To assess the frequency of epilepsy in primary and secondary antiphospholipid syndrome (APS); to analyze the clinical and laboratory features characterizing those with epilepsy in a cohort of 538 patients with APS; and to find associated features that would suggest risk factors for epilepsy in APS. METHODS: We analyzed the clinical features of patients with APS who had epilepsy and compared them to the clinical features of non-epileptic APS patients. RESULTS: Of 538 APS patients, 46 (8.6%) had epilepsy. Epilepsy was more prevalent among APS secondary to systemic lupus erythematosus (SLE) compared to primary APS (13.7% vs 6%; p < 0.05). The patients with epilepsy had a higher prevalence of central nervous system (CNS) manifestations including focal ischemic events (strokes or transient ischemic events, 54.3% vs 24.6%; p < 0.0001) and amaurosis fugax (15.2% vs 4.9%; p < 0.05). APS patients with epilepsy had a higher frequency of valvular pathology (30.4% vs 14.6%; p < 0.01), thrombocytopenia (43.5% vs 25%; p < 0.05), and livedo reticularis (26.1% vs 11.5%; p < 0.01). The multivariate logistic regression analysis found CNS thromboembolic events as the most significant factor associated with epilepsy, with an odds ratio (OR) of 4.05 (95% confidence interval, CI: 2.05-8), followed by SLE (OR 1.4, 95% CI 1.2-4.7), and valvular vegetations (OR 2.87, 95% CI 1-8.27). CONCLUSION: Epilepsy is common in APS and most of the risk seems to be linked to vascular disease as manifested by extensive CNS involvement, valvulopathy, and livedo reticularis and to the presence of SLE. These factors, however, explain only part of the increased occurrence of epilepsy in APS and other causes such as direct immune interaction in the brain should be investigated.

Epitope specificity of monoclonal anti-beta 2-glycoprotein I antibodies derived from patients with the antiphospholipid syndrome.

Abstract: beta 2-Glycoprotein I (beta 2GPI) has been identified as a cofactor in the recognition of the phospholipid Ag cardiolipin (CL) by anticardiolipin Ab (aCL) purified from patients with autoimmune diseases. However, there is considerable controversy as to the exact nature of the epitopes to which these Abs are directed. mAb derived from patients with the antiphospholipid syndrome bound to CL only in the presence of beta 2GPI. Synthetic peptides that span the fifth C-terminal domain of beta 2GPI supported the binding of one of the mAbs to CL in a beta 2GPI-free system. These peptides possessed the phospholipid binding sequence Cys281-Lys-Asn-Lys-Glu-Lys-Lys-Cys288. Three of the mAbs bound to beta 2GPI that had been adsorbed on gamma-irradiated microtiter plates. Binding to beta 2GPI was inhibited in a dose-dependent manner by the peptides from the carboxyl-terminal end of beta 2GPI and soluble beta 2GPI, indicating that the mAb bound to peptides and beta 2GPI in free solution. Thus, mAbs derived from patients with the antiphospholipid syndrome have specificity for epitopes on the fifth domain of beta 2GPI. Our results support the idea that beta 2GPI acts as a primary Ag for these Abs.