Behan P.O.,University of Glasgow |
Behan P.O.,Glasgow Caledonian University |
Chaudhuri A.,Queens Hospital
Inflammopharmacology | Year: 2010
The literature for evidence of autoimmunity in multiple sclerosis (MS) is analysed critically. In contrast to the accepted theory, the human counterpart of the animal model experimental autoimmune demyelinating disease, experimental allergic encephalomyelitis (EAE), is not MS but a different demyelinating disorder, i.e. acute disseminated encephalomyelitis and acute haemorrhagic leucoencephalitis. Extrapolation of EAE research to MS has been guided largely by faith and a blind acceptance rather than sound, scientific rationale. No specific or sensitive immunological test exists that is diagnostic of MS despite the extensive application of modern technology. Immunosuppression has failed to have any consistent effect on prognosis or disease progression. The available data on MS immunotherapy are conflicting, at times contradictory and are based on findings in animals with EAE. They show predominantly a 30% effect in relapsing/remitting MS which suggests powerful placebo effect. Critical analysis of the epidemiological data shows no association with any specific autoimmune diseases, but does suggest that geographic factors and age at development posit an early onset possibly dependent on environmental influences. Certain neurological diseases are, however, found in association with MS, namely hypertrophic peripheral neuropathy, neurofibromatosis-1, cerebral glioma, glioblastoma multiforme and certain familial forms of narcolepsy. These share a common genetic influence possibly from genes on chromosome 17 affecting cell proliferation. A significant number of these disorders are of neural crest origin, the classical example being abnormalities of the Schwann cell. These and other data allow us to propose that MS is a developmental neural crest disorder, i.e. a cristopathy, implicating glial cell dysfunction with diffuse blood-brain barrier breakdown. The data on transcription factor SOX10 mutations in animals may explain these bizarre clinical associations with MS and the phenotypic variability of such alterations (Cossais et al. 2010). Research directed to the area of neural crest associations is likely to be rewarding. © 2010 Springer Basel AG.
Behan P.O.,University of Glasgow |
Chaudhuri A.,Queens Hospital
Multiple Sclerosis and Related Disorders | Year: 2014
Experimental allergic encephalomyelitis (EAE) is the commonest, readily induced, organspecific, autoimmune disorder of laboratory animals of its kind. It is an artificial disorder brought about by the immunisation of susceptible animals with brain antigens in complete Freunds adjuvant (CFA). Variations can be induced by altering the nature of the antigen and the conditions involving immunisation. Whilst it is often described as a demyelinating disease, in strict terms it is not, since the primary pathologic process is not demyelination but rather an encephalomyelitis that is immunologically induced. Rather, the prototype demyelinating disease is multiple sclerosis and its variants. In this paper, the central question we ask is whether the data gleaned from the EAE model contributes to our understanding of the pathological events in MS. Towards answering this, we describe the historical development of EAE and its hyperacute form, and discuss the findings studied extensively in the non-human primate which show that ordinary EAE is an exact model for ADEM in the human, and that the hyperacute form of EAE is represented by AHLE in the human. Additionally, we shall comment on the latest research on new variants of EAE, and explain our opinion regarding the use of EAE models in research aiming to understand the pathogenesis of multiple sclerosis. © 2014 Elsevier B.V.
Plataniotis G.A.,Queens Hospital |
Dale R.G.,Imperial College London
International Journal of Radiation Oncology Biology Physics | Year: 2014
Purpose To estimate the radiation equivalent of the chemotherapy contribution to observed complete response rates in published results of 1-phase radio-chemotherapy of muscle-invasive bladder cancer. Methods and Materials A standard logistic dose-response curve was fitted to data from radiation therapy-alone trials and then used as the platform from which to quantify the chemotherapy contribution in 1-phase radio-chemotherapy trials. Two possible mechanisms of chemotherapy effect were assumed (1) a fixed radiation-independent contribution to local control; or (2) a fixed degree of chemotherapy-induced radiosensitization. A combination of both mechanisms was also considered. Results The respective best-fit values of the independent chemotherapy-induced complete response (CCR) and radiosensitization (s) coefficients were 0.40 (95% confidence interval -0.07 to 0.87) and 1.30 (95% confidence interval 0.86-1.70). Independent chemotherapy effect was slightly favored by the analysis, and the derived CCR value was consistent with reports of pathologic complete response rates seen in neoadjuvant chemotherapy-alone treatments of muscle-invasive bladder cancer. The radiation equivalent of the CCR was 36.3 Gy. Conclusion Although the data points in the analyzed radio-chemotherapy studies are widely dispersed (largely on account of the diverse range of chemotherapy schedules used), it is nonetheless possible to fit plausible-looking response curves. The methodology used here is based on a standard technique for analyzing dose-response in radiation therapy-alone studies and is capable of application to other mixed-modality treatment combinations involving radiation therapy. © 2014 Elsevier Inc. All rights reserved.
Torres-Montaner A.,Queens Hospital
Critical Reviews in Oncology/Hematology | Year: 2011
It has been assumed for a long time that cancer originates in stem cells, the so-called stem cell theory of cancer origin. However, the origin of cancer in committed cells is becoming increasingly recognised. The author discusses accumulated data suggesting the preferential origin of cancer in committed cells. From histopathological, clinical and biological features, two broad tumour categories are here delineated according to the presumed cell stage of malignant transformation: common adult cancers and childhood/undifferentiated tumours corresponding to late and early stage origin, respectively. Higher cancer incidence in committed than stem cells, as well as other observations presented is consistent with the existence of an anti-cancer protective mechanism/s specific to stem cells postulated in a previous paper. Furthermore, two important carcinogenic pathways, the telomere attrition pathway and INK4a pathway, are expected to spare stem cells from direct cancer transformation. It is suggested that these two pathways are differentially involved in the two broad tumour categories delineated. © 2011 Elsevier Ireland Ltd.
McVeigh K.A.,Royal United Hospital |
Vakros G.,Queens Hospital
Clinical Ophthalmology | Year: 2015
Aim: In order to improve patient education, compliance, and administration of eye drops prescribed for patients suffering with glaucoma within a UK ophthalmology department, an eye drop chart (EDC) was designed, developed, and piloted with patients attending the glaucoma clinic over 1 month. Methods: A cross-sectional prospective pilot study of 25 patients using an administration aid and a self-reported questionnaire. Chi-square tests were used to compare responses pre- and postintervention. Results: Results demonstrated an impressive improvement in nine of eleven categories assessed regarding drop administration and compliance. Patients stating that they always wash their hands increased significantly from 64% (13 participants) to 92% (23 participants) (P=0.029), and those who always shake the bottle improved from 40% (10) to 84% (21) (P=0.001). Punctal occlusion techniques improved from 44% (11) to 72% (18) (P=0.015). Finally, patients who always discarded the bottle after 28 days of use rose from 68% to 92%, though the difference was not significant (P=0.09). Only the number of drops being administered to the eye and the length of time left between the application of drops remained relatively unchanged. Sixty-four percent reported finding EDC helpful or useful, 52% had positive responses when asked if they would continue using EDC, and 88% would recommend it to a friend. Conclusion: Although there are limitations to the data as they are subjective, descriptive, and limited to sample size of 25, the results of this pilot study have shown promise. The EDC appears to be a cost-effective way at improving patients’ use of topical ocular medications. © 2015 McVeigh and Vakros.