tbuckley/cabot-search huggingface dataset:
Utility of Leukocyte Scanning in Osteomyelitis Complicating a Complex Fracture
Authors: M Solomon, S Macdessi, H van der Wall
Journal: Clinical Nuclear Medicine (2001)

SOLOMON, MICHAEL M.B.B.S., F.R.A.C.S., F.A.Orth.A.*; MACDESSI, SAMUEL M.B.B.S.*; VAN DER WALL, HANS M.B.B.S., Ph.D., F.R.A.C.P.† Author Information
Abstract 65: Regulation of KEAP1 expression by promoter methylation in malignant gliomas and association with patient's outcome
Authors: Raffaela Barbano, Lucia Anna Muscarella, Vincenzo D'Angelo, Massimiliano Copetti, Michelina Coco, Teresa Balsamo, Annamaria la Torre, Angelo Notarangelo, Michele Troiano, Salvatore Parisi, Nadia Icolaro, Domenico Catapano, Vanna Maria Valori, Fabio Pellegrini, Giuseppe Merla, Massimo Carella, Vito Michele Fazio, Paola Parrella
Journal: Cancer Research (2011)

Abstract The Keap1 (Kelch-like ECH-associated protein 1) protein tightly regulates the functions of Nrf2 (nuclear factor-erythroid 2-related factor 2) which plays a pivotal role in the cellular response to oxidative stress. Initial reports uncovered mutations in the KEAP1 gene in non-small cell lung cancer (NSCLC) leading to a permanent nrf2 activation. Mutations were often associated with loss of heterozigosity at the KEAP1 gene locus and promoter hypermethylation suggesting that biallelic inactivation is a common event in NSCLC. In this study, we sought to determine whether KEAP1 gene is epigenetically regulated in malignant gliomas and if promoter aberrant methylation may impact patient's outcome. We developed a Quantitative Methylation Specific PCR (QMSP) assay to analyze 86 malignant gliomas and 20 normal brain tissues. The discriminatory power of the assay was assessed by Receiving Operating Curve Characteristics (ROC) analysis. The AUC value of the curve was 0.823 (95%CI: 0.764-0.883) with an optimal cut off value of 0.133 yielding a 74% sensitivity (95%CI: 63%-82%) and an 85% specificity (95%CI: 64%-95%). Bisulfite sequencing analysis confirmed QMSP results and demonstrated a direct correlation between percentage of methylated CpGs and methylation levels (Spearman's Rho 0.929, P=0.003). Remarkably, a strong inverse correlation was observed between methylation levels and KEAP1 mRNA transcript in tumour tissue (Spearman's Rho -0.656 P=0.0001) and in a cell line before and after treatment with 2-deoxy-5 Azacytidine (P=0.003). RECPAM multivariate statistical analysis studying the interaction between MGMT and KEAP1 methylation in subjects treated with radiotherapy and temozolomide (n=70), identified three prognostic classes of glioma patients at different risk to progress. While simultaneous methylation of MGMT and KEAP1 promoters was associated with the lowest risk to progress, patients showing only MGMT methylation were the subgroup at the higher risk (HR 5.54, 95% CI 1.35-22.74). Our results indicate that that KEAP1 expression is frequently methylated in malignant gliomas and may represent a novel predictor of patient's outcome. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 65. doi:10.1158/1538-7445.AM2011-65
THU0110 The Effect of Subcutaneous (SC) Methotrexate (MTX) and Adalimumab (ADA) on Cytokine Profile in MTX-Naive Patients with Early Rheumatoid Arthritis (RA)
Authors: A.S. Avdeeva, A.A. Novikov, E.N. Aleksandrova, D.E. Karateev, E.L. Luchihina, E.L. Nasonov
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> To evaluate the changes in cytokine profile in MTX-naive patients (pts) with early RA during MTX and ADA+MTX therapy <h3>Methods</h3> Serum samples from 45 MTX-naive adults with early RA who received MTX (35 woman, mean age 53,5; 46-59,5 years, mean disease duration 7,0; 4,0-11,5 months, mean DAS 28 5,8; 4,9-6,4, RF positive-91%, anti-CCP positive-96%) were analyzed for selected markers of inflammation. The levels of IL-1b, IL-1Pa, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17, Eotaxin, FGF-basic, IFN-γ, IP-10, MCP-1, MIP-1α, MIP-1β, RANTES, TNF-α, VEGF (pg/ml) were tested by multiplex technology xMAP at baseline and weeks 12 and 24 <h3>Results</h3> After 3 months the efficacy of SC MTX have met the goal (EULAR response) in 23 (51%) of pts (not switching group). Switching to combination with ADA was required in 22 (49%) of pts (switching group). The relations between achievement of LDA or remission according to treatment regimens are shown in the table 1. In not-switching group MTX induced reduction in proinflammatory (IL-6, -17, TNF-α), anti-inflammatory (IL-4, -5, -9, -13) cytokines, chemokines (IP-10) and growth factors (FGF) at week 12; IL-6, IL-9, IP-10, PDGF-bb at week 24 (p&lt;0,05). The serum levels of IL-10, IFN-γ increased at week 24 (p&lt;0,05). In switching group MTX induced reduction in IL-6, IL-1Pa, IP-10 at week 12 (p&lt;0,05). ADA induced significant reduction in proinflammatory (IL-12), anti-inflammatory (IL-9) cytokines, chemokines (IP-10, MCP-1, MIP-1β) and growth factors (VEGF), and increased in IL-10 and IFN-γ (week 12 of treatment) (Fig. 1) <h3>Conclusions</h3> Clinical efficacy of SC MTX therapy is associated with reduced of proinflammatory cytokines, chemokines and growth factors at weeks 12-24 of therapy. ADA therapy is characterized by a decrease in disease activity and reduction chemokine type cytokines in pts with early RA <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2698
Defining the endoscopic appearances of tylosis using conventional and narrow-band imaging: a case series
Authors: H. Smart, R. Kia, S. Subramanian, S. Khalid, F. Campbell, A. Ellis
Journal: Endoscopy (2011)

Tylosis is an autosomal dominant skin disorder strongly associated with esophageal squamous cell cancer. We present a single-operator experience of utilizing conventional endoscopy and narrow-band imaging with magnification to characterize esophageal appearances in tylosis. Nineteen consecutive patients with tylosis attending for surveillance endoscopy were studied. White-light imaging (WLI) and narrow-band imaging (NBI) were undertaken, with magnification being performed as necessary. On WLI, we classified 12 patients as having mild change, 5 moderate change, and 2 severe change. WLI can define changes to the esophageal mucosa of variable hyperkeratosis and identify more significant focal abnormalities. NBI enhances these mucosal changes, and NBI with magnification can demonstrate intrapapillary capillary loop changes compatible with dysplasia, prompting consideration of surgery. This report is the first to characterize the endoscopic appearances in tylosis.
Guide to Postgraduate Medical Education, by Brian Keighley, Stuart Murray
Authors: J. Thistlethwaite
Journal: BMJ (1997)

Brian Keighley, Stuart Murray BMJ Publishing Group, £17.95, pp 160 ISBN 0 7279 1072 8

General practitioners must continue to update their knowledge and skills. They need to discuss topics pertinent to their professional practice including ethical issues, health economics, and business management. And clearly there is a desire among general practitioners to do this: many spend more time in educational activities than is necessary to earn the postgraduate education allowance. What they need to help them is a comprehensive review of the types of education on offer, the resources available, and how to make the best use of their time in a learning environment. The aim of this …
Airflow obstruction is associated with increased smooth muscle extracellular matrix
Authors: Robyn L. Jones, Peter B. Noble, John G. Elliot, Howard W. Mitchell, Peter K. McFawn, James C. Hogg, Alan L. James
Journal: European Respiratory Journal (2016)

Increased thickness of the airway smooth muscle (ASM) layer is a characteristic feature of airway remodelling in both asthma and chronic obstructive pulmonary disease (COPD) [1, 2]. The composition of the ASM layer has been well studied in asthma where the increased thickness of the ASM layer is due to hypertrophy and/or hyperplasia [3–5] of ASM cells. These changes are associated with a concomitant increase in absolute volumes of both ASM and extracellular matrix (ECM), without changes in their relative volume fractions [5]. Although ASM cell hypertrophy has been reported in the large airways of patients with COPD [6], these findings did not exclude the effect of an increase in the volume fraction of ECM on the estimated average volume of the ASM cells [7]. Remodelling of the layer of airway smooth muscle in COPD is characterised by an increase in the extracellular matrix <http://ow.ly/YZqhz> Funding provided by the National Health and Medical Research Council (NHMRC) of Australia (513842 and 1063068) and Sir Charles Gairdner and Osborne Park Health Care Group Research Advisory Committee and Charlies Foundation for Research (APP1045674). Peter B. Noble's salary was provided by a Career Development Fellowship from the NHMRC of Australia (1045824).
PWE-052 Why Colonoscopy does not Prevent Right Sided Colorectal Cancer?
Authors: L Krupa, R Tighe, G Phillips
Journal: Gut (2013)

<h3>Introduction</h3> Colonoscopy is widely used for colorectal cancer screening and prevention. There is good evidence that it is associated with lower CRC mortality due to fewer deaths from left-sided cancers. Unfortunately it seems to be less effective in preventing right-sided colorectal cancers (1.2). There are several plausible causes for this finding. One of the reasons could be that right sided lesions are more difficult to detect due to different morphological characteristics. <h3>Methods</h3> The adenoma detection rates (ADR) across the East of England within the Bowel cancer screening programme are monitored as part of the QA process. 30 colonoscopists across 8 screening centres acheived ADRs for 2012 varying from 60.1% to 32.7% with 26/30 above the QA standard of 35%ADR. We looked in detail at the ADRs of two colonoscopists in Norwich, who acheived ADRs of 60.1% (endoscopist A) and 35.3% (endoscopist B), over a 2 year timespan. <h3>Results</h3> Endoscopist A performed 441 colonoscopies and endoscopist B 544. Endoscopist A detected 815 adenomas and endoscopist B 545 (p &lt; 0.0001), with endoscopist A recorded no adenoma or cancer in 125/441 patients vs endoscopist B 251/544 (p &lt; 0.0001). Each endoscopist detected similar numbers of pedunculated adenomas (112/441 vs 130/544) (p = 0.5866) but endoscopist A identified significantly more sessile adenomas 700/441 vs 409/544 (p &lt; 0.0001). Adenomatous polyps were graded by size : &gt; 10 mm A 113/441 vs B 95/544 (p = 0.0018); 6–10 mm A 165/441 vs B 132/544 (p &lt; 0.0001); and &lt; 6 mm A537/441 vs B 318/544 (p &lt; 0.0001). Endoscopist A detected more adenomas proximal to the splenic flexure 425/441 vs B 205/544 (p &lt; 0.0001), whereas the ADRs distal to the splenic flexure were similar A330/441 vs B 340/544 (p &lt; 0.0001). Endoscopist A had a higher completion rate of 99.7% compared with 94.67% for endoscopist B (p &lt; 0.0001). Withdrawal times were similar (for procedures in which no polyps were found) A 10.59 min vs B 9.28 min. <h3>Conclusion</h3> Sessile polyps in the right colon are commonly overlooked even by expert bcss accredited colonoscopists. Over half the patients discharged from the programme by endoscopist B with a “normal” colon have had a small right sided adenoma overlooked and it seems likely this is the reason that colonoscopy fails to prevent the development of right sided colonic cancer. The current QA standard for ADR in bcss is too low at 35%. The current JAG QA standard for ADR among the wider colonoscopy community is 10% and it is likely that this problem is widespread. <h3>Disclosure of Interest</h3> None Declared. <h3>References</h3> Baxter NN, Goldwasser MA, Paszat LF,<i> et al. Association of colonoscopy and death from colorectal cancer: a population-based, casecontrol study. Ann Intern Med 2009;</i><b> 150</b><i>:1–8.</i> Brenner H, Hoffmeister M, Arndt V, <i>et al. Protection from right- and left-sided colorectal neoplasms after colonoscopy: population-based study. J Natl Cancer Inst 2010; 102:89–95.</i>
A Short-Term Trial of Butyrate to Stimulate Fetal-Globin-Gene Expression in the β-Globin Disorders
Authors: Susan P. Perrine, Gordon D. Ginder, Douglas V. Faller, George H. Dover, Tohru Ikuta, H. Ewa Witkowska, Shi-ping Cai, Elliott P. Vichinsky, Nancy F. Olivieri
Journal: New England Journal of Medicine (1993)

Fetal-globin (γ-globin) chains inhibit the polymerization of hemoglobin S (sickle hemoglobin) and can functionally substitute for the β-globin chains that are defective or absent in patients with the β-thalassemias. Identifying safe mechanisms to stimulate fetal-hemoglobin production is therefore of great interest. Previous studies have shown that administering butyrate selectively stimulates the promoter of the human fetal-globin gene and leads to increases in γ-globin-gene expression in the developing fetus, cultured cells, and animal models.
Abstract 88: Stabilizing but not activating β-catenin by E-cad/CTF2
Authors: Sheng-Chieh Hsu
Journal: Cancer Research (2012)

Abstract E-cadherin is an important mediator of cell-cell adhesion and plays a vital role to modulate intracellular signaling pathways. E-cadherin binds p120catenin (p120) and β-catenin at cadherin homology 2 (CH2) domain and CH3 domain, respectively. Recent studies show E-cadherin could be cleaved by γ-secretase and released the intracellular C-terminal fragment 2 (E-cad/CTF2) to regulate the p120-kaiso mediated signaling pathway in the nucleus. However, the functional effect of E-cad/CTF2 on its binding partners, β-catenin and p120, remains elusive. Here, we show E-cad/CTF2, like full-length E-cadherin, can interact and increase the expression of β-catenin. Using reverse transcription-quantitative PCR (RT-qPCR), the transcription of β-catenin mRNA is not affected by the expression of E-cad/CTF2 or E-cadherin. Interestingly, while the nuclear expression of β-catenin is enhanced by E-cad/CTF2 or NLS-tagged E-cad/CTF2, the transcriptional activity of β-catenin does not increase. It indicates the interaction between E-cad/CTF2 and β-catenin is much stronger then TCF4/β-catenin complex. This study provides the evidence that the transcriptional activity of β-catenin is not activated by E-cad/CTF2 although the stability of β-catenin is greatly enhanced by E-cad/CTF2. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 88. doi:1538-7445.AM2012-88
The Risk of Birth Defects among Children of Persian Gulf War Veterans
Authors: David N. Cowan, Robert F. DeFraites, Gregory C. Gray, Mary B. Goldenbaum, Samuel M. Wishik
Journal: New England Journal of Medicine (1997)

There has been suspicion that service in the Persian Gulf War affected the health of veterans adversely, and there have been claims of an increased rate of birth defects among the children of those veterans.
Safety and Efficacy of Recombinant Human α-Galactosidase A Replacement Therapy in Fabry's Disease
Authors: Christine M. Eng, Nathalie Guffon, William R. Wilcox, Dominique P. Germain, Philip Lee, Steve Waldek, Louis Caplan, Gabor E. Linthorst, Robert J. Desnick
Journal: New England Journal of Medicine (2001)

Fabry's disease, lysosomal alpha-galactosidase A deficiency, results from the progressive accumulation of globotriaosylceramide and related glycosphingolipids. Affected patients have microvascular disease of the kidneys, heart, and brain.We evaluated the safety and effectiveness of recombinant alpha-galactosidase A in a multicenter, randomized, placebo-controlled, double-blind study of 58 patients who were treated every 2 weeks for 20 weeks. Thereafter, all patients received recombinant alpha-galactosidase A in an open-label extension study. The primary efficacy end point was the percentage of patients in whom renal microvascular endothelial deposits of globotriaosylceramide were cleared (reduced to normal or near-normal levels). We also evaluated the histologic clearance of microvascular endothelial deposits of globotriaosylceramide in the endomyocardium and skin, as well as changes in the level of pain and the quality of life.In the double-blind study, 20 of the 29 patients in the recombinant alpha-galactosidase A group (69 percent) had no microvascular endothelial deposits of globotriaosylceramide after 20 weeks, as compared with none of the 29 patients in the placebo group (P<0.001). Patients in the recombinant alpha-galactosidase A group also had decreased microvascular endothelial deposits of globotriaosylceramide in the skin (P<0.001) and heart (P<0.001). Plasma levels of globotriaosylceramide were directly correlated with clearance of the microvascular deposits. After six months of open-label therapy, all patients in the former placebo group and 98 percent of patients in the former recombinant alpha-galactosidase A group who had biopsies had clearance of microvascular endothelial deposits of globotriaosylceramide. The incidence of most treatment-related adverse events was similar in the two groups, with the exception of mild-to-moderate infusion reactions (i.e., rigors and fever), which were more common in the recombinant alpha-galactosidase A group. IgG seroconversion occurred in 88 percent of patients who received recombinant alpha-galactosidase A.Recombinant alpha-galactosidase A replacement therapy cleared microvascular endothelial deposits of globotriaosylceramide from the kidneys, heart, and skin in patients with Fabry's disease, reversing the pathogenesis of the chief clinical manifestations of this disease.
OP22 * SOCIAL DEPRIVATION SHORTENS SURVIVAL IN PATIENTS WITH HIGH GRADE GLIOMA
Authors: D. Ngoga, F. Evison, D. Tennant, G. Cruickshank
Journal: Neuro-Oncology (2014)

INTRODUCTION: Low socioeconomic status is associated with increased frequency of chronic conditions, a higher frequency of mental health illness, greater use of primary care and hospital services and a lower relative cancer survival for some of the commonest cancers. The impact of social deprivation on the survival of patents with glial tumours however is poorly understood. We examine the role of social deprivation on the survival of patients with glial tumours METHOD: We performed a retrospective analysis of clinical records of patients with histologically confirmed glial tumours treated at our institution between 2009 and February 2013. The overall survival (from time of tissue diagnosis) and index of multiple deprivation (IMD - 2010) were obtained. Potential confounding factors incorporated into a multivariable Cox regression model included age, gender, ethnicity, tumour location, neurosurgical procedure, antiepileptic drug taken and past medical history. RESULTS: 485 patients with WHO Grade II, III and IV glioma were identified with all five quintiles of deprivation classes represented. 96 patients fell into the most deprived class (1), while 49 patients were found to be within the least deprived class (5). Patients in the lowest socioeconomic class had a significantly worse survival compared with those in the least deprived class. (p = 0.03) The significance of this finding persisted even after incorporation into a cox multivariable regression model to take account for other factors likely to affect survival. CONCLUSION:This study highlights the importance of addressing social deprivation and its effects in the effort to improve patient outcomes for patients with high grade glioma.
Predictive values of egg‐specific IgE by two commonly used assay systems for the diagnosis of egg allergy in young children: a prospective multicenter study
Authors: K. Furuya, M. Nagao, Y. Sato, S. Ito, T. Fujisawa
Journal: Allergy (2016)

Abstract Background Specific IgE ( sIgE ) is often used to predict oral food challenge ( OFC ) outcomes in food allergy, but interpretation of the results may vary depending on the assay method employed and the patient population tested. The aim of this study was to use two commercial assay systems to determine egg‐ sIgE values predictive of allergy within the most common populations treated at pediatric clinics. Methods In a multicenter prospective study, 433 children with suspected or confirmed egg allergy underwent oral challenge ( OFC ) using cooked egg ( CE ) and raw egg ( RE ) powders to diagnose either true allergy in 1‐year‐old (group A, n = 220) or tolerance in 2‐ to 6‐year‐old (group B, n = 213). Egg white ( EW )‐ and ovomucoid ( OM )‐ sIgE values were measured using the Immuno CAP ® sIgE (Immuno CAP ) and the IMMULITE ® 2000 3 gAllergy ™ (3gAllergy) systems. Children were recruited from six primary care clinics and 18 hospitals in Japan. Results Receiver‐operating characteristic ( ROC ) curve analysis yielded similar areas under the curve ( AUC ) for the two assays (0.7–0.8). The optimal cutoff values and the probability curves ( PC s) of the sIgE by the two assays to predict CE and RE OFC outcomes were determined for both groups. Values for 3gAllergy were higher than for Immuno CAP ; however, correlation of sIgE and predicted probability calculated by PC s were strong between the two methods. Conclusions Cutoff values and PC s for egg‐ sIgE established using both Immuno CAP and 3gAllergy may be useful for predicting egg allergy in early childhood patient populations.
Relation between Mutations of the Cystic Fibrosis Gene and Idiopathic Pancreatitis
Authors: Jonathan A. Cohn, Kenneth J. Friedman, Peadar G. Noone, Michael R. Knowles, Lawrence M. Silverman, Paul S. Jowell
Journal: New England Journal of Medicine (1998)

It is unknown whether genetic factors predispose patients to idiopathic pancreatitis. In patients with cystic fibrosis, mutations of the cystic fibrosis transmembrane conductance regulator (CFTR ) gene typically cause pulmonary and pancreatic insufficiency while rarely causing pancreatitis. We examined whether idiopathic pancreatitis is associated with CFTR mutations in persons who do not have lung disease of cystic fibrosis.