tbuckley/cabot-search huggingface dataset:
Inflammatory responses to the occupational inhalation of metal fume
Authors: K. T. Palmer
Journal: European Respiratory Journal (2006)

Occupational exposure to metal fume promotes a reversible increase in the risk of pneumonia, but by mechanisms which are unclear. To investigate, the current authors measured various markers of host defence function in welders and nonwelders. Induced sputum and venous blood samples were collected from 27 welders with regular long-term exposure to ferrous metal fume and 31 unexposed matched controls. In sputum, the present authors measured cell counts, the soluble and cellular iron concentration, and levels of interleukin-8, tumour necrosis factor-α, myeloperoxidase, matrix metalloproteinase-9, immunoglobulin (Ig)A, α<sub>2</sub>-macroglobulin and unsaturated iron-binding capacity. Blood samples were assayed for evidence of neutrophil activation and pneumococcal IgG antibodies. Welders had significantly higher iron levels and a substantially lower unsaturated iron-binding capacity in their sputum, but, despite a high iron challenge, there was a noteworthy absence of an inflammatory response. Only blood counts of eosinophils and basophils were significantly related to the extent of welding. Weak nonsignificant trends were observed for several other measures, consistent with low-grade priming of neutrophils. In conclusion, these data suggest that chronic exposure to metal fume blunts responsiveness to inhaled particulate matter. However, the mechanism behind the lack of detectable local inflammatory response requires further investigation.
PTH-126 Assessment Of Cardiovascular Risk Of Patients On Home Parenteral Nutrition
Authors: DS Chilkunda, J Scantlebury, J Wood, I Reid, H Lynch, G Sayell, G Ani, D Burke, C Donnellan
Journal: Gut (2014)

<h3>Introduction</h3> Prognostic factors in patients on home parenteral nutrition (HPN) are primarily thought to be related to the underlying disease. <b><sup>1</sup></b> To the best of our knowledge, there is no data so far pertaining to long-term cardiovascular disease (CVD) risk in these patients. We aimed to review our cohort of HPN patients to assess their 10-year CVD risk using the validated QRisk2 score<b><sup>2</sup></b>and to explore possible associations between HPN and CVD. <h3>Methods</h3> We conducted a <i>retrospective observational study</i> of patients on HPN using the Leeds HPN database. We included all patients on parenteral nutrition (PN) and parenteral fluids (PF). Further relevant data such as smoking history, blood pressure, etc. were collected at outpatient clinics and their respective general practitioners. Data were entered into an online calculator to obtain QRisk2 scores and analysed using MicroSoft<sup>TM</sup> Excel. We also reviewed the indication for HPN and assessed their association with CVD risk. <h3>Results</h3> A total of 73 patients were included in this study. Their mean age was 53.12 years (range 19 to 83 years) with male: female ratio of 40:60. 78.08% patients were on PN and 21.91% on PF. Indications for HPN are summarised in the pie chart below. QRisk2 score of ≥20% (classed as ‘high risk’ for CVD) was noted in 15.06% patients. Of the patients with high CVD risk, ischaemic bowel was the underlying indication for HPN in 36.36%, Crohn’s disease in 18.18%, GI malignancy in 9.09% and miscellaneous indications in 36.36% (including dumping syndrome, enterocutaneous fistula, refractory coeliac disease and diverticular perforation). <h3>Conclusion</h3> No study has so far assessed the possibility of a link between HPN and CVD risk. From our pilot retrospective study, 15% patients on HPN were found to have a high 10-year CVD risk. This could potentially have an impact on the overall outcome of this subgroup of chronically ill patients, which needs to be evaluated further. More than a third of patients with high QRisk2 had had ischaemic bowel. Limitations of our study are its retrospective nature and smaller numbers. It is not clear whether the type and volume of HPN could have any impact on their long-term CVD risk. Future research should perhaps focus on further exploring the possible link between CVD and HPN, in the form of a large prospective trial of patients on HPN. <h3>References</h3> Staun <i>et al</i>. – ESPEN guidelines on Parenteral Nutrition: Home Parenteral Nutrition in adult patients.<i> Clin Nutr</i> 2009 Aug; 28(4):467–79 Predicting cardiovascular risk in England and Wales: prospective derivation and validation of QRisk2.<i> BMJ</i> 2008:336:1475–82 <h3>Disclosure of Interest</h3> None Declared.
Physical activity. A guide for community action.: US Department of Health and Human Services. (Pp 386; soft cover pound26.50.) Leeds: Human Kinetics, 1999. ISBN 0-7360-0152-2.
Authors: A Langton
Journal: British Journal of Sports Medicine (2000)

As a general practitioner working in sports medicine and on a PCG board, I found this an interesting and stimulating book. Its main drawback is that is written for an American audience, but it is a welcome resource and it would be good to have in a library or …
Reiter's syndrome versus seronegative rheumatoid arthritis.
Authors: A T Masi, S L Feigenbaum
Journal: Annals of the Rheumatic Diseases (1979)

Because of our longitudinal studies of early rheumatoid arthritis (RA) in young adults'06'210211 we have been asked to compare the findings in males with Reiter's syndrome (RS) with those in patients with seronegative RA or arthritis of unknown diagnosis.*See paper by T. Bitter at page 84.tA lower degree of B27 association than usually reported, illustrating the difficulty of early clinical diagnosis among seronegative arthritides and the need for clinical classi- fication criteria-Editor.
Diagnostic Utility of Candidate Definitions for Demonstrating Axial Spondyloarthritis on Magnetic Resonance Imaging of the Spine
Authors: Ulrich Weber, Zheng Zhao, Kaspar Rufibach, Veronika Zubler, Robert G. W. Lambert, Stanley M. Chan, Mikkel Østergaard, Susanne J. Pedersen, Walter P. Maksymowych
Journal: Arthritis & Rheumatology (2014)

A recent consensus statement has suggested ≥3 corner inflammatory lesions (CILs) or several corner fatty lesions (CFLs) as candidate criteria indicative of axial spondyloarthritis (SpA) on magnetic resonance imaging (MRI) of the spine. The aim of this study was to evaluate the diagnostic utility of these cutoffs in nonradiographic axial SpA and ankylosing spondylitis (AS).One hundred thirty consecutive patients with back pain who were ≤50 years of age and newly referred to 2 university clinics (cohorts A and B) were classified according to rheumatologist expert opinion based on results of clinical examination and pelvic radiography as having nonradiographic axial SpA (n = 50), AS (n = 33), or nonspecific back pain (n = 47). Cohort A also included 20 age-matched healthy controls. Four blinded readers assessed MRIs of the spine using the standardized Canada-Denmark module. Readers recorded CILs and CFLs in 23 discovertebral units. We tested the diagnostic utility (mean sensitivity and specificity over 4 readers) of the cutoff for the number of lesions on spinal MRI as proposed in the literature (≥2 or ≥3 CILs and ≥6 CFLs), and we tested for possible thresholds (from ≥1 CIL or CFL to ≥10 CILs or CFLs) for nonradiographic axial SpA and AS patients in both cohorts.None of the spinal thresholds (≥2 or ≥3 CILs and ≥6 CFLs) showed clinically relevant diagnostic utility (positive likelihood ratio [LR] range 1.38-2.36) when comparing patients with nonradiographic axial SpA to patients with nonspecific back pain. A threshold of ≥6 CILs had moderate to substantial diagnostic utility (positive LR 13.26 and 6.74 in cohorts A and B, respectively) in nonradiographic axial SpA, while ≥4 CILs showed small diagnostic utility (positive LR 3.83 and 2.72 in cohorts A and B, respectively) but specificities of >0.90.None of the previously proposed candidate criteria for a positive spinal MRI finding of axial SpA showed clinically relevant diagnostic utility in nonradiographic axial SpA. These results question the value of proposed definitions for a positive finding of SpA based on MRI of the spine alone.
Davunetide in patients with progressive supranuclear palsy: a randomised, double-blind, placebo-controlled phase 2/3 trial
Authors: Adam L Boxer, Anthony E Lang, Murray Grossman, David S Knopman, Bruce L Miller, Lon S Schneider, Rachelle S Doody, Andrew Lees, Lawrence I Golbe, David R Williams, Jean-Cristophe Corvol, Albert Ludolph, David Burn, Stefan Lorenzl, Irene Litvan, Erik D Roberson, Günter U Höglinger, Mary Koestler, Clifford R Jack, Viviana Van Deerlin, Christopher Randolph, Iryna V Lobach, Hilary W Heuer, Illana Gozes, Lesley Parker, Steve Whitaker, Joe Hirman, Alistair J Stewart, Michael Gold, Bruce H Morimoto
Journal: The Lancet Neurology (2014)
Human Papillomavirus as an Independent Predictor in Oral Squamous Cell Cancer
Authors: Dan Zhao, Qin‐gan Xu, Xin‐ming Chen, Ming‐wen Fan
Journal: International Journal of Oral Science (2009)

There is an increasing evidence for the role of high risk human papillomavirus (HPV) in the pathogenesis of oral squamous cell carcinoma (OSCC). The purpose of this study is to evaluate the relevance of HPV infection to the survival and prognosis of OSCC. Fifty‐two patients with OSCC were followed from 4 to 88 months with a median of 50.7 months. HPV DNA was identified in formalin‐fixed, paraffin‐embedded tumor specimens by nested PCR with MY09/MY11 and GP5+/GP6+ primer pairs and the HPV genotype was determined by direct DNA sequencing. Association between the HPV status and risk factors for cancer as well as tumor‐host characteristics were analyzed. Survival curves were calculated by the Kaplan‐Meier method and analyzed using the log‐rank test. HPV was found in 40.4% of the tumors with HPV16 accounting for 63.5%, HPV18 for 30.8%, HPV6 for 3.9% and HPV11 for 1.8%. No infection with more than one HPV genotype was detected. HPV infection was significantly associated with poor histological grade, TNM stage I–II, alcohol usage and no smoking status. Multi‐variate analysis showed that HPV had an independent prognostic effect on the overall survival after adjusting other confounding factors such as histological grade, TNM stage and tobacco usage. The presence of HPV was significantly correlated with a better survival in patients with OSCC. HPV infection can act as an independent predictor for the survival and prognosis of OSCC.
Nephrologists' experience with and attitudes towards decisions to forego dialysis. The End-Stage Renal Disease Network of New England.
Authors: P A Singer
Journal: Journal of the American Society of Nephrology (1992)

Ethicists and lawyers agree that competent adult patients or their surrogate decision-makers have the right to forego life-sustaining treatment, but the views of practicing physicians have not been well-studied. To examine nephrologists' experience with and attitudes towards decisions to forego dialysis, a questionnaire was sent to all 161 nephrologists performing chronic dialysis in six New England states; 118 (73%) responded. The proportion of nephrologists who reported withholding (not starting) dialysis from the cited numbers of patients during the previous year was 11%, 0; 58%, 1 to 5; 20%, 6 to 10; 8%, 11 to 15; and 3%, greater than or equal to 16. For withdrawing (stopping), the proportions were 19%, 0; 73%, 1 to 5; 9%, 6 to 10; and 0%, greater than or equal to 11. The nephrologists withheld dialysis more times than they withdrew it (chi 2 = 26; P = 0.004). If requested to do so by a competent patient, 88% of nephrologists would stop dialysis. If requested by the family of an incompetent patient, 90% would stop if the patient had clear prior wishes, but only 63% would stop if prior wishes were unclear. With competent patients, the issue of withdrawal of dialysis was usually raised by the patient (56%). With incompetent patients, the issue was raised by the family (42%) or nephrologist (30%). It was concluded that decisions to withhold dialysis are more frequent than decisions to withdraw it. Moreover, nephrologists agree about the management of requests to withdraw dialysis in competent patients or incompetent patients with clear prior wishes; they disagree about the management of incompetent patients with unclear prior wishes.(ABSTRACT TRUNCATED AT 250 WORDS)
Improving Safety of Diabetes Mellitus Management
Authors: Kasia J. Lipska
Journal: JAMA Internal Medicine (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Unregulated prescribing of anti-tumour necrosis factor agents does not mean inappropriate prescribing: Table 1
Authors: C T Ng, B J Radovits, W Kievit, J Fransen, P L C M van Riel, O FitzGerald, D J Veale, B Bresnihan
Journal: Annals of the Rheumatic Diseases (2009)

Treatment with anti-tumour necrosis factor (anti-TNF) agents has consistently improved the clinical features of rheumatoid arthritis (RA).1 They reduce the rate of articular damage and loss of physical function and enable continuance at work.2 There is evidence to suggest that, despite their high price, anti-TNF agents may be cost-effective3 4 and data from large national registries have highlighted long-term safety.5

In many countries the availability of anti-TNF agents is strictly regulated and there is a variability in the framework for its initiation across Europe.6 Between 1999 and 2008, rheumatologists in the Republic of Ireland could freely prescribe anti-TNF agents under a …
Random-Effects Meta-analysis of Inconsistent Effects: A Time for Change
Authors: John E. Cornell, Cynthia D. Mulrow, Russell Localio, Catharine B. Stack, Anne R. Meibohm, Eliseo Guallar, Steven N. Goodman
Journal: Annals of Internal Medicine (2014)

A primary goal of meta-analysis is to improve the estimation of treatment effects by pooling results of similar studies. This article explains how the most widely used method for pooling heterogeneous studies--the Der Simonian-Laird (DL) estimator--can produce biased estimates with falsely high precision. A classic example is presented to show that use of the DL estimator can lead to erroneous conclusions. Particular problems with the DL estimator are discussed, and several alternative methods for summarizing heterogeneous evidence are presented. The authors support replacing universal use of the DL estimator with analyses based on a critical synthesis that recognizes the uncertainty in the evidence,focuses on describing and explaining the probable sources of variation in the evidence, and uses random-effects estimates that provide more accurate confidence limits than the DL estimator.
Stresses and displacements for normal human knee menisci and for sectioned menisci using finite element method
Authors: Tarnita Daniela, D N Tarnita, D Grecu, D Popa, F I Rusu
Journal: British Journal of Sports Medicine (2011)

Introduction The paper has the following objectives: The obtaining of virtual 3D parameterised models of the menisci; the determination of the stresses, deformations and displacements of menisci for different cases and for different mechanical solicitations, using finite element method. Methods To obtain the bones cross sections we used a Aura Philips tomograph. – The obtained images were redrawn in AutoCad over the real tomographies and the drawings were imported in SolidWorks (a parametrical Computer Aided Design software), section by section, in parallel planes. The virtual models of the internal menisci and external menisci were obtained. – The initial parameters and kinematical and kinetostatical functions of the virtual biomechanical system of the knee joint were established. – This system was imported in VisualNastran software. – The virtual models of the internal menisci, external menisci were discretised and analysed using the finite element method. Results We obtained the finite elements structure of both human knee menisci. Maps for the von Misses stresses, for the displacements, for the deformations and for the deformation energy in normal menisci. In the cases of 1/3 from the volume of the medial menisci is cut and 1/3 from the volume of the lateral menisci is cut, we simulated a virtual meniscetomy. The stresses and the displacements diagrams were also obtained. Conclusions For an indemn anatomical knee, the stress in menisci is un-uniform distributed, the zone of menisci body being the most loaded in both cases: extension and flexion. The deformations in menisci are unequal distributed, the maximum being obtained at the level of the menisci body. In the knee extension, the deformations are almost twice bigger than the deformations in the case of knee flexion. The increasing twice of the loading force in the knee joint determines an increasing of stresses with only 20% because of the amortiser role of the menisci.
Genomic Medicine Frontier in Human Solid Tumors: Prospects and Challenges
Authors: Rodrigo Dienstmann, Jordi Rodon, Jordi Barretina, Josep Tabernero
Journal: Journal of Clinical Oncology (2013)

Recent discoveries of genomic alterations that underlie and promote the malignant phenotype, together with an expanded repertoire of targeted agents, have provided many opportunities to conduct hypothesis-driven clinical trials. The ability to profile each unique cancer for actionable aberrations by using high-throughput technologies in a cost-effective way provides unprecedented opportunities for using matched therapies in a selected patient population. The major challenges are to integrate and make biologic sense of the substantial genomic data derived from multiple platforms. We define two different approaches for the analysis, interpretation, and clinical applicability of genomic data: (1) the genomically stratified model originates from the "one test-one drug" paradigm and is currently being expanded with an upfront multicategorical approach following recent advances in multiplexed genotyping platforms; and (2) the comprehensive assessment model is based on whole-genome, -exome, and -transcriptome data and allows identification of novel drivers and subsequent therapies in the experimental setting. Tumor heterogeneity and evolution of the diverse populations of cancer cells during cancer progression, influenced by the effects of systemic treatments, will need to be addressed in the new scenario of early drug development. Logistical issues related to prescreening strategies and trial allocation, in addition to concerns in the economic and ethical domains, must be taken into consideration. Here we present a historical view of how increased understanding of cancer genomics has been translated to the clinic and discuss the prospects and challenges for further implementation of a personalized treatment strategy for human solid tumors.
Differential Clinical Significance of Individual NKG2D Ligands in Melanoma: Soluble ULBP2 as an Indicator of Poor Prognosis Superior to S100B
Authors: Annette Paschen, Antje Sucker, Bettina Hill, Iris Moll, Marc Zapatka, Xuan Duc Nguyen, Geok Choo Sim, Isabelle Gutmann, Jessica Hassel, Jürgen C. Becker, Alexander Steinle, Dirk Schadendorf, Selma Ugurel
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Cytotoxic lymphocytes interact with human tumor cells via the activating immunoreceptor NKG2D, recognizing a variety of stress-associated MIC and ULBP surface molecules. However, tumors can escape from this immunosurveillance by shedding NKG2D ligands (NKG2DL), rendering the soluble products detectable in patients' sera. Experimental Design: To elucidate the clinical significance of NKG2DL diversity, we studied their expression on melanoma tissues and their presence as soluble molecules in sera from &amp;gt;200 melanoma patients and compared the latter with the well-established serum marker S100B. Results: Immunohistochemistry revealed a heterogeneous expression of MIC and ULBP2 molecules between and within melanoma metastases. Compared with MIC, ULBP2 was less frequently expressed. Accordingly, elevated levels of soluble ULBP2 (sULBP2) were detected in sera of melanoma patients less frequently than elevated levels of soluble MICA (sMICA), although both soluble NKG2DL (sNKG2DL) were significantly increased compared with sera of healthy controls (P &amp;lt; 0.0001). Strikingly, elevated concentrations of sULBP2, but not of sMICA, were strongly associated with disease progression (P &amp;lt; 0.0001) and tumor load (P = 0.0003). Elevated serum levels of either sNKG2DL correlated with reduced overall survival, albeit considerably stronger for sULBP2 (P &amp;lt; 0.0001) than for sMICA (P = 0.011). In early-stage (I-III) melanoma patients, only sULBP2 (P &amp;lt; 0.0001) but neither sMICA nor S100B revealed prognostic significance. Multivariate analysis identified sULBP2 (P = 0.0015) and S100B (P = 0.013) but not sMICA as independent predictors of prognosis. Conclusion: Our data reveal marked differences in the clinical significance of individual sNKG2DL. Only sULBP2 is an independent predictor of prognosis, the significance of which is superior to the well-established and widely used melanoma serum marker S100B. (Clin Cancer Res 2009;15(16):5208–15)
Identification of the <i>NF-κB</i> activating protein-like locus as a risk locus for rheumatoid arthritis
Authors: Gang Xie, Yue Lu, Ye Sun, Steven Shiyang Zhang, Edward Clark Keystone, Peter K Gregersen, Robert M Plenge, Christopher I Amos, Katherine A Siminovitch
Journal: Annals of the Rheumatic Diseases (2012)

Objective To fine-map the NF-κB activating protein-like ( NKAPL ) locus identified in a prior genome-wide study as a possible rheumatoid arthritis (RA) risk locus and thereby delineate additional variants with stronger and/or independent disease association. Methods Genotypes for 101 SNPs across the NKAPL locus on chromosome 6p22.1 were obtained on 1368 Canadian RA cases and 1471 controls. Single marker associations were examined using logistic regression and the most strongly associated NKAPL locus SNPs then typed in another Canadian and a US-based RA case/control cohort. Results Fine-mapping analyses identified six NKAPL locus variants in a single haplotype block showing association with p≤5.6×10 −8 in the combined Canadian cohort. Among these SNPs, rs35656932 in the zinc finger 193 gene and rs13208096 in the NKAPL gene remained significant after conditional logistic regression, contributed independently to risk for disease, and were replicated in the US cohort (P comb =4.24×10 −10 and 2.44×10 −9 , respectively). These associations remained significant after conditioning on SNPs tagging the HLA-shared epitope (SE) DRB1*0401 allele and were significantly stronger in the HLA-SE negative versus positive subgroup, with a significant negative interaction apparent between HLA-DRB1 SE and NKAPL risk alleles. Conclusions By illuminating additional NKAPL variants with highly significant effects on risk that are distinct from, but interactive with those arising from the HLA-DRB1 locus, our data conclusively identify NKAPL as an RA susceptibility locus.