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Portsmouth, United Kingdom

Kam C.,Portsmouth Hospital NHS Trust | Balaratnam M.S.,University College London | Purves A.,Kings College | Mills K.R.,Kings College | And 7 more authors.
Muscle and Nerve | Year: 2011

The acronym CANOMAD encompasses chronic ataxic neuropathy combined with ophthalmoplegia, M protein, cold agglutinins, and anti-disialosyl antibodies. Herein we describe 2 patients presenting with progressive ataxic neuropathy who only developed ophthalmoplegia after a significant delay post-presentation, which in 1 case had features indicative of brainstem dysfunction. Both patients were found to have an IgM paraprotein and anti-disialosyl antibodies. They responded to treatment with intravenous immunoglobulin, thus illustrating the importance of diagnosing this condition. VC 2011 Wiley Periodicals, Inc. Source

Assomull R.G.,Cardiovascular Magnetic Resonance Unit | Assomull R.G.,Imperial College London | Shakespeare C.,Cardiovascular Magnetic Resonance Unit | Kalra P.R.,Portsmouth Hospital NHS Trust | And 16 more authors.
Circulation | Year: 2011

Background-: In patients presenting with new-onset heart failure of uncertain etiology, the role of coronary angiography (CA) is unclear. Although conventionally performed to differentiate underlying coronary artery disease from dilated cardiomyopathy, CA is associated with a risk of complications and may not detect an ischemic cause resulting from arterial recanalization or an embolic episode. In this study, we assessed the diagnostic accuracy of a cardiovascular magnetic resonance (CMR) protocol incorporating late gadolinium enhancement (LGE) and magnetic resonance CA as a noninvasive gatekeeper to CA in determining the etiology of heart failure in this subset of patients. Methods and Results-: One hundred twenty consecutive patients underwent CMR and CA. The etiology was ascribed by a consensus panel that used the results of the CMR scans. Similarly, a separate consensus group ascribed an underlying cause by using the results of CA. The diagnostic accuracy of both strategies was compared against a gold-standard panel that made a definitive judgment by reviewing all clinical data. The study was powered to show noninferiority between the 2 techniques. The sensitivity of 100%, specificity of 96%, and diagnostic accuracy of 97% for LGE-CMR were equivalent to CA (sensitivity, 93%; specificity, 96%; and diagnostic accuracy, 95%). As a gatekeeper to CA, LGE-CMR was also found to be a cheaper diagnostic strategy in a decision tree model when United Kingdom-based costs were assumed. The economic merits of this model would change, depending on the relative costs of LGE-CMR and CA in any specific healthcare system. Conclusion-: This study showed that LGE-CMR is a safe, clinically effective, and potentially economical gatekeeper to CA in patients presenting with heart failure of uncertain etiology. © 2011 American Heart Association. All rights reserved. Source

Pearl D.S.,Portsmouth Hospitals NHS Trust | Masoodi M.,MRC Human Nutrition Research | Masoodi M.,Nestle | Eiden M.,MRC Human Nutrition Research | And 10 more authors.
Journal of Crohn's and Colitis | Year: 2014

Background and Aims: The polyunsaturated fatty acids (PUFA) arachidonic acid (AA, n-6) and eicosapentaenoic acid (EPA, n-3) are precursors of eicosanoids and other lipid mediators which have critical roles in inflammation. The mediators formed from the different PUFA have different potencies. We hypothesised that metabolic changes associated with colonic mucosal inflammation would modify the bioavailability of the eicosanoid precursors AA and EPA. Methods: Colonic mucosa biopsies were obtained from patients with ulcerative colitis and from matched controls. Inflammation was graded endoscopically and histologically. Esterified and non-esterified fatty acids were determined within the biopsies using gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry, respectively. Results: Biopsy samples were collected from 69 UC patients (54 providing both inflamed and non-inflamed mucosa) and 69 controls. Inflamed mucosa had higher AA (p. <. 0.001) and lower EPA (p. <. 0.010) contents and a higher AA:EPA ratio (p. <. 0.001). Inflamed mucosa also had higher docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) and lower linoleic acid (LA) and α-linolenic acid (α-LNA) contents (all p. <. 0.001), compared to non-inflamed and controls. There were significant correlations between severity of inflammation and contents of AA, DPA and DHA (positive correlations) and of LA, α-LNA and EPA (negative correlations). Conclusions: Higher AA, AA:EPA ratio, DPA and DHA and lower LA, α-LNA and EPA are seen in inflamed mucosa in UC and correlate with severity of inflammation. This suggests an alteration in fatty acid metabolism in the inflamed gut mucosa, which may offer novel targets for intervention and should be considered if nutritional strategies are used. © 2013 European Crohn's and Colitis Organisation. Source

Masoodi M.,Nestle | Masoodi M.,Medical Research Council | Masoodi M.,University of Toronto | Pearl D.S.,Portsmouth Hospital NHS Trust | And 6 more authors.
PLoS ONE | Year: 2013

Objectives:Ulcerative colitis (UC) is a relapsing inflammatory disorder of unconfirmed aetiology, variable severity and clinical course, characterised by progressive histological inflammation and with elevation of eicosanoids which have a known pathophysiological role in inflammation. Therapeutic interventions targetting eicosanoids (5-aminosalicylates (ASA)) are effective first line and adjunctive treatments in mild-moderate UC for achieving and sustaining clinical remission. However, the variable clinical response to 5-ASA and frequent deterioration in response to cyclo-oxygenase (COX) inhibitors, has prompted an in depth simultaneous evaluation of multiple lipid mediators (including eicosanoids) within the inflammatory milieu in UC. We hypothesised that severity of inflammation is associated with alteration of lipid mediators, in relapsing UC.Design:Study was case-control design. Mucosal lipid mediators were determined by LC-MS/MS lipidomics analysis on mucosal biopsies taken from patients attending outpatients with relapsing UC. Univariate and multivariate statistical analyses were used to investigate the association of mucosal lipid mediators, with the disease state and severity graded histologically.Results:Levels of PGE2, PGD2, TXB2, 5-HETE, 11-HETE, 12-HETE and 15-HETE are significantly elevated in inflamed mucosa and correlate with severity of inflammation, determined using validated histological scoring systems.Conclusions:Our approach of capturing inflammatory mediator signature at different stages of UC by combining comprehensive lipidomics analysis and computational modelling could be used to classify and predict mild-moderate inflammation; however, predictive index is diminished in severe inflammation. This new technical approach could be developed to tailor drug treatments to patients with active UC, based on the mucosal lipid mediator profile. © 2013 Masoodi et al. Source

Shah R.,Yeovil District Hospital NHS Trust | Jones E.,University of Leicester | Vidart V.,University of Bristol | Kuppen P.J.K.,Leiden University | And 4 more authors.
Cancer Epidemiology Biomarkers and Prevention | Year: 2014

There is growing interest in early detection of colorectal cancer as current screening modalities lack compliance and specificity. This study systematically reviewed the literature to identify biomarkers for early detection of colorectal cancer and polyps. Literature searches were conducted for relevant papers since 2007. Human studies reporting on early detection of colorectal cancer and polyps using biomarkers were included. Methodologic quality was evaluated, and sensitivity, specificity, and the positive predictive value (PPV) were reported. The search strategy identified 3, 348 abstracts. A total of 44 papers, examining 67 different tumor markers, were included. Overall sensitivities for colorectal cancer detection by fecalDNAmarkers ranged from 53% to 87%. Combining fecal DNA markers increased the sensitivity of colorectal cancer and adenoma detection. Canine scent detection had a sensitivity of detecting colorectal cancer of 99% and specificity of 97%. The PPV of immunochemical fecal occult blood test (iFOBT) is 1.26%, compared with 0.31% for the current screening method of guaiac fecal occult blood test (gFOBT). A panel of serum protein biomarkers provides a sensitivity and specificity above 85% for all stages of colorectal cancer, and a PPV of 0.72%. Combinations of fecal and serum biomarkers produce higher sensitivities, specificities, and PPVs for early detection of colorectal cancer and adenomas. Further research is required to validate these biomarkers in a well-structured population-based study. © 2014 AACR. Source

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