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MacGregor E.A.,Blizard Institute of Cell and Molecular Science

Migraine is affected by fluctuating estrogen levels so it is not surprising that the perimenopause is a time of peak rate of change of migraine prevalence in women. Evidence supports estrogen 'withdrawal' as one of the important triggers of menstrual attacks of migraine without aura, while high levels are associated with migraine aura. This mini review addresses the issues of diagnosing migraine, treating the symptoms of migraine, and controlling co-morbid migraine and hot flushes with hormonal and non-hormonal options. Maintaining a stable estrogen environment is the most effective treatment for vasomotor symptoms and can also benefit estrogen-withdrawal migraine. Using only the lowest doses necessary to control symptoms minimizes the risk of unwanted side effects. Non-hormonal options for both conditions are limited but there is evidence of efficacy for fluoxetine and venflaxine, with less evidence for gabapentin. © 2011 Elsevier Ireland Ltd. All rights reserved. Source

MacDonald T.T.,Blizard Institute of Cell and Molecular Science | Monteleone I.,University of Rome Tor Vergata | Fantini M.C.,University of Rome Tor Vergata | Monteleone G.,University of Rome Tor Vergata

The gastrointestinal tract is the largest immune interface with the environment. Exposure to large numbers of dietary and microbial antigens requires complex and highly regulated immune responses by different mucosal cell types, which result in the induction and maintenance of intestinal homeostasis. Defects in this equilibrium can disrupt the homeostatic mechanisms and lead to chronic intestinal inflammation. We review the cell populations and mechanisms involved in the control of intestinal homeostasis and inflammation, focusing on inflammatory bowel diseases. We describe some aspects of gut immunity that could alter the delicate balance between inflammatory and tolerogenic responses and result in chronic gastrointestinal tract inflammation in patients. © 2011 AGA Institute. Source

Biddle A.,Queen Mary, University of London | Biddle A.,Blizard Institute of Cell and Molecular Science | Mackenzie I.C.,Queen Mary, University of London
Cancer and Metastasis Reviews

The majority of deaths from carcinoma are caused by secondary growths that result from tumour invasion and metastasis. The importance of epithelial-to-mesenchymal transition (EMT) as a driver of invasion and metastasis is increasingly recognised, and recent evidence has highlighted a link between EMT and the cancer stem cells that initiate and maintain tumours and have also been implicated in invasion and metastasis. Here, we review cancer stem cells and their link with EMT, and explore the importance of this link in metastasis and therapeutic resistance of tumours. We also discuss new evidence from our laboratory demonstrating that cancer stem cells display a remarkable phenotypic plasticity that enables them to switch between an epithelial phenotype that drives tumour growth and an EMT phenotype that drives metastasis. As successful therapies must eradicate cancer stem cells in all their guises, the identification of sub-types of cancer stem cells that display therapeutic resistance and phenotypic plasticity has important implications for the future design of therapeutic strategies. The ability to assay the responses of different cancer stem cell phenotypes in vitro holds promise for the rapid development of a new generation of targeted therapies that fulfil this objective. © 2012 Springer Science+Business Media, LLC. Source

MacGregor E.A.,St. Bartholomews Hospital | MacGregor E.A.,Blizard Institute of Cell and Molecular Science
Neurologic Clinics

Primary headaches are most common in women during their reproductive years and are affected by the hormonal fluctuations during pregnancy. Most headaches follow a benign course during pregnancy, although migraine is associated with increased risk of hypertensive disorders of pregnancy and stroke. Management of primary headaches during pregnancy is essentially similar to management in the nonpregnant state, with a few exceptions. This article reviews the epidemiology, prognosis, and management of primary headaches during pregnancy and lactation, and considers secondary headaches that are important to exclude. © 2012 Elsevier Inc. Source

Hawkes C.H.,Blizard Institute of Cell and Molecular Science
Multiple Sclerosis and Related Disorders

This review addresses several areas of contention related to the genetic theory for multiple sclerosis (MS). It is argued (a) that the concept of MS as a 'complex disease' has little value, (b) just because a disorder is found in multiple families, it is not necessarily genetically based, (c) although twin studies are claimed to show that MS is '30% genetically based' this concept derives from widely varying data, (d) although genome-wide association studies (GWAS) suggest the presence of several MS related genes this has yet to be proven, (e) monozygotic twins discordant for MS should have a different genetic sequence if the disorder has a genetic basis but data so far suggest this may not be correct and (f) epigenetics or epistasis are contentious topics and may not provide the answer. It is concluded that the role of genetics in MS etiology may be overstated and that attention should now be devoted to environmental causes. © 2012 Elsevier B.V. Source

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