London Bridge Hospital

About: London Bridge Hospital is a healthcare organization based out in London, United Kingdom. It is known for research contribution in the topics: Antiphospholipid syndrome & Systemic lupus erythematosus. The organization has 107 authors who have published 122 publications receiving 4523 citations.

Antiphospholipid syndrome, migraine and stroke

Abstract: It is over a quarter of a century since the description of the antiphospholipid (Hughes) syndrome (APS). This pro-thrombotic condition, characterized by the presence of antiphospholipid antibodies (aPL), results in an increased tendency to thrombosis and, in pregnancy, to recurrent miscarriage and other obstetric complications. Strikingly, APS can affect both veins and arteries, the latter leading, for example, to myocardial infarction and stroke. The brain appears to be particularly susceptible to the syndrome, with its attendant thrombosis and ischaemia, the neurological presentations ranging frommemory loss to movement disorders, from atypical multiple sclerosis to epilepsy. Additionally, some of these clinical associates of aPL may well have been under-recognizeduntil recently.Forexample, theassociationwith seizures (including temporal lobe epilepsy) first recognized in 1985, may well be substantial – a recent report suggesting that20%ofcasesof idiopathic teenage epilepsy were linked to aPL, for example. However, the two most important clinical neurological manifestations of Hughes syndrome are migraine and stroke. Migraine, in all its forms, is arguably the commonest clinical manifestation of the syndrome. Many Hughes syndrome patients presenting with thrombosis, transient ischaemic attacks (TIAs) or stroke at, say, the age of 40, give a history of severe headaches, often migrainous, dating back to childhood. Interestingly, there is often a family history of migraine, and a number of large family cohorts embracing migraine, APS and stroke are now being reported. Attempts at quantifying the prevalence of headache and migraine in Hughes syndrome (and in lupus) are limited by the well known difficulties in classification. This is doubly important as the links with cognitive impairment, in both lupus and in patients with antiphospholipid antibodies need clarification. For example, in a recent study of cognitive impairment in lupus, and its relationship to headache, Whitelaw and Spangenberg concluded that . . . ‘it is only APS (Hughes) syndrome which has been documented to produce impaired cognitive function in lupus’. The cause of the headache is uncertain. However, one of the most striking clinical observations is the often complete disappearance of the headaches when anticoagulation with heparin or warfarin is started, say, for a peripheral thrombosis, or with heparin prophylaxis in pregnancy. This observation has led to the use of a 2–3-week therapeutic trial of low-molecular-weight heparin in some cases of APS in which increasingly severe headaches are a feature. Stroke is now internationally recognized as an important manifestation of Hughes syndrome – the severity ranging from small TIAs to catastrophic fatal cerebral infarction. What is the relative contribution of Hughes syndrome to the huge medical social and economic problem of stroke? Published figures vary, ranging from 7% of all strokes to 41% in a major collaborative American stroke study. The latter study has, however, been criticised for a number of shortcomings, including the reliance on single aPL assessments. An important study from Rome found that in a younger population (under 45) a striking one in five of all strokes were associated with aPL. If such estimates are correct (and despite flaws in the standardization of aPL testing, clinical experience suggests that they are), then here we have a large group of individuals who, with a simple blood test, could be identified as being at risk of stroke and in whom preventative anti-aggregant or anticoagulant treatment could be instituted. Furthermore, a greater awareness of the fact that even on warfarin anticoagulation, patients with APS are at greater risk of thrombosis than from bleeding, would lead to more appropriate treatment. The discovery of the antiphospholipid syndrome has opened up new avenues for research in medicine and in epidemiology. Correspondence to: Graham Hughes, Head, The London Lupus Centre, London Bridge Hospital, London SE1 2PR, UK. Email: graham.hughes@hcaconsultant.co.uk

Gender‐based cardiometabolic risk evaluation in minority and non‐minority men grading the evidence of non‐traditional determinants of cardiovascular risk

Abstract: Evaluation of cardiometabolic risk has become vital in primary prevention of adverse vascular events (coronary artery disease, heart attack, stroke or congestive heart failure), particularly in younger middle-aged men (40-60 years old). To discern the prevalence of events in these men, clinicians often stratify cardiovascular risk and treat according to traditional Framingham risk criteria. Yet it is evident that the traditional Framingham risk assigned to intermediate- and low-risk men will miss several of these individuals deemed at high 'cardiometabolic risk', also known as residual cardiovascular risk. This review will elaborate the definition of cardiometabolic risk and apply the use of surrogate markers for cardiovascular risk stratification in men in addition to the traditional Framingham-based markers. It will utilise both gender non-specific and gender-specific determinants of cardiometabolic risk. Lastly, it will examine minority men's health and racial differences in these determinants of cardiovascular risk. This analysis includes an electronic literature search utilising PubMed, EMBASE and MEDLINE databases to clarify the level of evidence for the stepwise utility of novel biomarkers for cardiometabolic risk in the male patient. This manuscript generates discussion of the utility of markers of cardiometabolic risk stratification. The following questions are summarised: (i) Are there non-traditional tests that might define this risk better than traditional markers? (ii) Will treatment based on this risk assessment augment present risk stratification and lower cardiovascular risk? (iii) What is known regarding racial differences surrounding cardiometabolic risk assessment? Traditional risk factors including Framingham Risk Score underestimate the overall 10 year and lifetime risk for the intermediate-risk younger middle-aged men<60 years of age. This fact is especially true in the minority population. We have graded the evidence of non-gender specific and gender-specific markers of cardiometabolic risk, thereby, allowing greater clarification of risk in this population. The pragmatic use of these novel markers of cardiometabolic risk may help stratify those individuals at greater lifetime risk than that noted by the Framingham Risk Score.

Heparin, antiphospholipid antibodies and the brain

Abstract: One of the most striking observations in the clinical world of antiphospholipid syndrome (APS) is the dramatic and almost immediate improvement seen in many patients with neurological features such as headache, balance problems and memory loss, following the institution of low molecular weight (LMW) heparin treatment. From the earliest clinical descriptions of the syndrome, neurological involvement has been recognized as a common – indeed a central – feature. It was also noted that with anticoagulation treatment, many of those symptoms and signs, some of which had been present for months (for example chorea) or even years (epilepsy), rapidly improved. One of the problems facing clinicians dealing with APS patients is the limitation of treatment choices. Aspirin yes – but then what? Warfarin (Coumadin) poses a grave medical (and social) decision in a patient with worsening headache and concerns about stroke, yet with no previous thrombosis. Some lessons have been learnt from the management of APS in pregnancy. Those women on warfarin, usually changed to LMW heparin at the onset of pregnancy, are often free of cerebral symptoms for the whole eight to nine months of their pregnancy (and some assert that they are even better on LMW heparin than warfarin). Some years ago, in the absence of any more scientific guidance, we introduced a ‘heparin therapeutic trial’ for patients with increasing clinical APS problems despite anti-platelet therapy. This involved a two to three week course of LMW heparin (dalteparin/enoxaparin) with a clinical outcome defined by the patient. Placebo effects, certainly. But very often a decisive response. Such observations again focus on the pathogenesis and management of APS. Antibody mediated, undoubtedly, but is the brain pathology thrombotic, direct anti-neuronal attack, or predominantly vascular ‘sludging’? The rapid improvement in cognitive function, or in migraine severity when heparin is introduced, or on warfarin when the INR is carefully maintained at a higher level (e.g. 3.5–4) suggests that improvement in blood flow is important, though radiological and isotopic supporting evidence of this is scanty. At the present time, stroke and transverse myelitis are the two most feared neurological sequelae of antiphospholipid antibody (aPL) positivity – so much so that it remains an unfortunate fact that aPL testing is not yet routine in stroke screening. However, other non-stroke neurological features of APS are now widely recognized – balance problems, multiple sclerosis-like syndrome, deafness, anosmia, sleep disturbance. And, most prominent of all, memory loss There is little doubt that APS will become an important chapter in the broader field of neurology. Are there lessons for lupus? In lupus patients, many attempts have, over the years, been made to link particular antibodies to brain involvement – lymphocytotoxic antibodies, anti-NR2 and anti-ribosomal-P, for example. Most have proved disappointing as major diagnostic candidates. The link between brain pathology and aPL, however, appears to be more substantial, both in APS as well as in lupus. In a recent Italian multi-centre study of 959 lupus patients, the two items in the survey with the strongest link to neuropsychiatric involvement were anticardiolipin antibodies (p> 0.001) and lupus anticoagulant (p> 0.001). Thirty years ago, the pathogenesis of many nonfocal neuropsychiatric disorders in lupus was considered to involve both vascular and immune mechanisms. Much the same today. Correspondence to: GRV Hughes, London Lupus Centre, London Bridge Hospital, London SE1 2PR, UK Email: graham.hughes@hcaconsultant.co.uk Received 18 May 2012; accepted 21 May 2012

Clinical, functional and radiological outcomes of extracorporeal irradiation in limb salvage surgery for bone tumours

Abstract: AimsWe present a retrospective review of patients treated with extracorporeally irradiated allografts for primary and secondary bone tumours with the mid- and long-term survivorship and the functio...

A comparison of the transient hyperprolactinaemic stress response obtained using two different methods of analgesia for ultrasound-guided transvaginal oocyte retrieval

Abstract: Transient hyperprolactinaemia has been shown to accompany the procedure of oocyte retrieval under laparoscopic control. This study was concerned with establishing whether transvaginal oocyte retrieval was also associated with hyperprolactinaemia and whether the hyperprolactinaemic response was dependent on the method of anaesthesia/analgesia employed. Two distinct patterns were recorded. Oocyte retrieval under general anaesthesia was accompanied by a rapid rise in prolactin levels, which peaked after 40 min. Oocyte retrieval under intravenous sedation was associated with a slow rise in circulating prolactin concentrations. Significant differences in the prolactin rise between the general anaesthesia and sedation groups appeared within 10 min of the start of the procedure. It is concluded that although the surgical stress of oocyte recovery is associated with mild transient hyperprolactinaemia, most of the hyperprolactinaemic response is due to the anaesthetic.