tbuckley/cabot-search huggingface dataset:
Influence of replacing tuberculin skin test with ex vivo interferon γ release assays on decision to administer prophylactic antituberculosis antibiotics before anti-TNF therapy
Authors: Xavier Mariette, Gabriel Baron, Florence Tubach, Frédéric Lioté, Bernard Combe, Corinne Miceli-Richard, René-Marc Flipo, Philippe Goupille, Matthieu Allez, Dominique Salmon, Dominique Emilie, Guislaine Carcelain, Philippe Ravaud
Journal: Annals of the Rheumatic Diseases (2012)

The recommendations for detecting latent tuberculosis infection (LTBI) before antitumour necrosis factor (anti-TNF) therapy are based on the tuberculin skin test (TST), which lacks both specificity and sensitivity and can lead to unnecessary treatment with antibiotics. A study was undertaken to investigate the effect of replacing TST with interferon γ (IFNγ) release assays (IGRA) in screening for LTBI and deciding to begin prophylactic antituberculosis (TB) antibiotics before anti-TNF therapy in immune-mediated inflammatory diseases.In 15 tertiary care hospitals, consecutive patients with rheumatoid arthritis, spondylarthropathies or Crohn's disease were screened for LTBI before anti-TNF therapy with TST, QuantiFERON TB Gold in tube (QTF-Gold IT) and T-SPOT.TB at the same time. The potential diagnosis of LTBI and the effect on the decision to begin antibiotic prophylaxis were assessed.Among 429 patients, 392 had results for the three tests. The results for TST, T-SPOT.TB and QTF Gold IT were positive for 35.2%, 15.1% and 9.9% of patients, respectively (p<0.0001). Antibiotics were required for 177 patients (45.2%) if positive TST results were included in the LTBI definition, 107 patients (27.3%) if TST results were replaced with results from one of the IGRA tests and 84 patients (21.4%) if TST results were replaced with QTF-Gold IT results (p<0.0001). The decision on the use of antibiotic prophylaxis was changed for 113 patients (28.8%, 95% CI 24.4% to 33.6%) if TST results were replaced with QTF-Gold IT results.Replacing TST with IGRA for determining LTBI allowed the proportion of patients with immune-mediated inflammatory diseases needing prophylactic anti-TB antibiotics before beginning anti-TNF agents to be reduced by half.
Deletion of the WNT Target and Cancer Stem Cell Marker CD44 in Apc(Min/+) Mice Attenuates Intestinal Tumorigenesis
Authors: Jurrit Zeilstra, Sander P.J. Joosten, Maarten Dokter, Eugène Verwiel, Marcel Spaargaren, Steven T. Pals
Journal: Cancer Research (2008)

Abstract Mutation of the genes encoding the WNT signaling components adenomatous polyposis coli or β-catenin plays a critical role in the initiation of colorectal cancer. These mutations cause constitutively active β-catenin/TCF–mediated transcription, driving the transformation of intestinal crypts to colorectal cancer precursor lesions, called dysplastic aberrant crypt foci. CD44 is a prominent WNT signaling target in the intestine and is selectively expressed on the renewing epithelial cells lining the crypts. The expression of CD44 is dramatically increased in aberrant crypt foci in both humans and tumor-susceptible ApcMin/+ mice, suggesting a role for CD44 in intestinal tumorigenesis. To study this role, we crossed C57BL/6J-Cd44−/− mice with C57BL/6J-ApcMin/+ mice. Compared with C57BL/6J-Cd44+/+/ApcMin/+ mice, C57BL/6J-Cd44−/−/ApcMin/+ mice showed an almost 50% reduction in the number of intestinal adenomas. This reduction was primarily caused by a decrease in the formation of aberrant crypts, implying the involvement of CD44 in tumor initiation. The absence of CD44 in the normal (nonneoplastic) crypts of Cd44−/−/ApcMin/+ mice did not alter the proliferative capacity and size of the intestinal stem cell and transit-amplifying compartments. However, compared with Cd44+/+/ApcMin/+ mice, Cd44−/−/ApcMin/+ showed an increase in the number of apoptotic epithelial cells at the base of the crypt which correlated with an increased expression of the proapoptotic genes Bok and Dr6. Our results show an important role for CD44 in intestinal tumorigenesis and suggest that CD44 does not affect proliferation but is involved in the control of the balance between survival and apoptosis in the intestinal crypt. [Cancer Res 2008;68(10):3655–61]
Different airway inflammatory responses in asthmatic and healthy humans exposed to diesel
Authors: N. Stenfors, C. Nordenhäll, S.S. Salvi, I. Mudway, M. Söderberg, A. Blomberg, R. Helleday, J-O. Levin, S.T. Holgate, F.J. Kelly, A.J. Frew, T. Sandström
Journal: European Respiratory Journal (2003)

Particulate matter (PM) pollution adversely affects the airways, with asthmatic subjects thought to be especially sensitive. The authors hypothesised that exposure to diesel exhaust (DE), a major source of PM, would induce airway neutrophilia in healthy subjects, and that either these responses would be exaggerated in subjects with mild allergic asthma, or DE would exacerbate pre-existent allergic airways. Healthy and mild asthmatic subjects were exposed for 2 h to ambient levels of DE (particles with a 50% cut-off aerodynamic diameter of 10 µm (PM 10 ) 108 µg·m −3 ) and lung function and airway inflammation were assessed. Both groups showed an increase in airway resistance of similar magnitude after DE exposure. Healthy subjects developed airway inflammation 6 h after DE exposure, with airways neutrophilia and lymphocytosis together with an increase in interleukin‐8 (IL‐8) protein in lavage fluid, increased IL‐8 messenger ribonucleic acid expression in the bronchial mucosa and upregulation of the endothelial adhesion molecules. In asthmatic subjects, DE exposure did not induce a neutrophilic response or exacerbate their pre-existing eosinophilic airway inflammation. Epithelial staining for the cytokine IL‐10 was increased after DE in the asthmatic group. Differential effects on the airways of healthy subjects and asthmatics of particles with a 50% cut-off aerodynamic diameter of 10 µm at concentrations below current World Health Organisation air quality standards have been observed in this study. Further work is required to elucidate the significance of these differential responses.
Protective effect of sensory denervation in inflammatory arthritis (evidence of regulatory neuroimmune pathways in the arthritic joint)
Authors: D Kane
Journal: Annals of the Rheumatic Diseases (2004)

To investigate the direct effect of joint innervation on immune mediated joint inflammation in a patient with psoriatic arthritis (PsA).The patient developed arthritis mutilans in all digits of both hands with the exception of the left 4th finger, which had prior sensory denervation following traumatic nerve dissection. Plain radiography, ultrasonography and nerve conduction studies of the hands confirmed the absence of articular disease and sensory innervation in the left 4th digit.This relationship between joint innervation and joint inflammation was investigated experimentally by prior surgical sensory denervation of the medial aspect of the knee in six Wistar rats in which carrageenan induced arthritis was subsequently induced. Prior sensory denervation--with preservation of muscle function--prevented the development of inflammatory arthritis in the denervated knee.Observations in human and animal inflammatory arthritis suggest that regulatory neuroimmune pathways in the joint are an important mechanism that modulates the clinical expression of inflammatory arthritis.
A Novel Role for Carcinoembryonic Antigen-Related Cell Adhesion Molecule 6 as a Determinant of Gemcitabine Chemoresistance in Pancreatic Adenocarcinoma Cells
Authors: Mark S. Duxbury, Hiromichi Ito, Eric Benoit, Talat Waseem, Stanley W. Ashley, Edward E. Whang
Journal: Cancer Research (2004)

Abstract Most patients with pancreatic adenocarcinoma present with surgically incurable disease. Gemcitabine, the principal agent used to treat such patients, has little impact on outcome. Overexpression of carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 6, a feature of this malignancy, is associated with resistance to anoikis and increased metastasis. The purpose of this study was to determine the role of CEACAM6 in cellular chemoresistance to gemcitabine. CEACAM6 was stably overexpressed in Capan2 cells, which inherently express very low levels of the protein. Suppression of CEACAM6 expression was achieved in BxPC3 cells, which inherently overexpress CEACAM6, by stable transfection of a CEACAM6 small interfering RNA-generating vector. The effects of modulating CEACAM6 expression on gemcitabine-induced cytotoxicity were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cytotoxicity assay, flow cytometric apoptosis quantification, caspase profiling, and Western analysis of cytoplasmic cytochrome c release. The roles of Akt and c-Src kinases as downstream targets of CEACAM6 signaling were examined. Stable overexpression of CEACAM6 in Capan2 increased gemcitabine chemoresistance, whereas CEACAM6 gene silencing in BxPC3 markedly increased the sensitivity of these cells to gemcitabine. Differential expression of CEACAM6 modulates Akt activity in a c-Src-dependent manner, and CEACAM6 overexpression appears to protect cells from cytochrome c-induced caspase 3 activation and apoptosis.
0.03% tacrolimus ointment applied once or twice daily is more efficacious than 1% hydrocortisone acetate in children with moderate to severe atopic dermatitis: results of a randomized double-blind controlled trial
Authors: S. Reitamo, J. Harper, J.D. Bos, F. Cambazard, C. Bruijnzeel-Koomen, P. Valk, C. Smith, C. Moss, A. Dobozy, R. Palatsi
Journal: British Journal of Dermatology (2004)

Background Topical corticosteroids are the usual treatment for atopic dermatitis (AD) in children but can have side-effects. Objectives This study compared the efficacy and safety of 0·03% tacrolimus ointment applied once or twice daily over a 3-week period with the twice daily application of 1% hydrocortisone acetate (HA) ointment in children with moderate to severe AD. Patients and methods Patients applied ointment daily to all affected body surface areas. The primary study endpoint was the percentage change in the modified Eczema Area and Severity Index (mEASI) between baseline and treatment end. Results Six hundred and twenty-four patients, aged 2–15 years, applied 0·03% tacrolimus ointment once daily (n = 207), twice daily (n = 210) or 1% HA twice daily (n = 207). By the end of treatment, application of 0·03% tacrolimus ointment both once or twice daily resulted in significantly greater median percentage decreases in mEASI (66·7% and 76·7%, respectively) compared with 1% HA (47·6%; P < 0·001). Furthermore, the median percentage decrease in mEASI was significantly greater for patients applying 0·03% tacrolimus twice daily compared with once daily (P = 0·007). Patients with severe AD benefited especially from twice daily application of 0·03% tacrolimus ointment compared with once daily application (P = 0·001). Transient mild to moderate skin burning occurred significantly more often in the 0·03% tacrolimus groups (P = 0·028) but resolved in most cases within 3–4 days. Laboratory parameters showed no clinically relevant changes. Conclusions 0·03% tacrolimus ointment applied once or twice daily is significantly more efficacious than 1% HA in treating moderate–severe AD in children. Twice daily application of 0·03% tacrolimus ointment results in the greatest improvement in mEASI, and is especially effective in patients with severe baseline disease.
Effectiveness of Different Modalities of Psychotherapeutic Treatment for Patients with Cluster C Personality Disorders: Results of a Large Prospective Multicentre Study
Authors: Anna Bartak, Marieke D. Spreeuwenberg, Helene Andrea, Lot Holleman, Piet Rijnierse, Bert V. Rossum, Elisabeth F.M. Hamers, Anke M.M.A. Meerman, Janneke Aerts, Jan J.V. Busschbach, Roel Verheul, Theo Stijnen, Paul M.G. Emmelkamp
Journal: Psychotherapy and Psychosomatics (2009)

&lt;i&gt;Background:&lt;/i&gt; No previous studies have compared the effectiveness of different modalities of psychotherapeutic treatment, as defined by different settings and durations, for patients with cluster C personality disorders. The aim of this multicentre study was to compare the effectiveness of 5 treatment modalities for patients with cluster C personality disorders in terms of psychiatric symptoms, psychosocial functioning, and quality of life. The following treatment modalities were compared: long-term outpatient (more than 6 months), short-term day hospital (up to 6 months), long-term day hospital, short-term inpatient, and long-term inpatient psychotherapy. &lt;i&gt;Methods:&lt;/i&gt; The study was conducted between March 2003 and June 2008 in 6 mental health care centres in the Netherlands, with a sample of 371 patients with a DSM-IV-TR axis-II cluster C diagnosis. Patients were assigned to 5 different modalities of psychotherapeutic treatment, and effectiveness was assessed at 12 months after baseline. An intention-to-treat analysis was conducted for psychiatric symptoms (Brief Symptom Inventory), psychosocial functioning (Outcome Questionnaire-45), and quality of life (EQ-5D), using multilevel statistical modelling. As the study was non-randomised, the propensity score method was used to control for initial differences. &lt;i&gt;Results:&lt;/i&gt; Patients in all treatment groups had improved on all outcomes 12 months after baseline. Patients receiving short-term inpatient treatment showed more improvement than patients receiving other treatment modalities. &lt;i&gt;Conclusions:&lt;/i&gt; Psychotherapeutic treatment, especially in the short-term inpatient modality, is an effective treatment for patients with cluster C personality disorders.
Safety of Capecitabine in Treatment of Patients with Metastatic Colorectal Cancer – Interim Analysis From “Axiom” Trial
Authors: Vladimir Kovcin, Svetislav Vrbic, Dusan Jovanovic, Tamara Ursulovic, Nebojsa Manojlovic, Zoran Andric, Sanja Kostic, Milan Markovic, Ivan Nikolic, Jelena Spasic, Zoran Petrovic, Slobodan Milicevic
Journal: Annals of Oncology (2013)
Review of ICT-based services for identified unmet needs in people with dementia
Authors: S. Lauriks, A. Reinersmann, H.G. Van der Roest, F.J.M. Meiland, R.J. Davies, F. Moelaert, M.D. Mulvenna, C.D. Nugent, R.M. Dröes
Journal: Ageing Research Reviews (2007)
The Varieties of Phthisis
Authors: R. D. Powell
Journal: BMJ (1873)

him their professional services for one year ; the physician to take with him three mounted archers or men-at-arms in his suite ; and the sur- geon, twelve men of his owxn profession and three men-at-arms likewise.The scale of pay of the arnmy w!as fixed- £ s.d.s. (1.
cDNA cloning and expression of a novel family of enzymes with calcium-independent phospholipase A2 and lysophospholipase activities.
Authors: D Portilla, M D Crew, D Grant, G Serrero, L M Bates, G Dai, M Sasner, J Cheng, A Buonanno
Journal: Journal of the American Society of Nephrology (1998)

Previous studies have suggested that activation of calcium-independent PLA2 (CaIPLA2) is an early event in cell death after hypoxic injury in proximal tubule cells. An approximately 28-kD CaIPLA2 with preferential activity toward plasmalogen phospholipids has been recently purified from rabbit kidney cortex (D. Portilla and G. Dai, J Biol Chem 271, 15,451-15,457, 1996). Their report describes the cloning of a full-length rat cDNA encoding CaIPLA2, using sequences derived from the purified rabbit kidney cortex enzyme. In addition, cDNA from rabbit kidney that encode the rabbit homologue of the enzyme and a closely related isoform were isolated. The rat cDNA is predicted to encode an approximately 24-kD protein, and each cDNA contains the sequence G-F-S-Q-G, which fits the active site consensus sequence G-X-S-X-G of carboxylesterases. Several lines of evidence (DNA sequence comparison, Southern blot analysis, and examination of the expressed sequence tag database) show that CaIPLA2 enzymes are encoded by a multigene family in rats, mice, rabbits, and humans. Northern analysis of various tissues from the rat indicated that the CaIPLA2 gene is ubiquitously expressed, with highest mRNA abundance observed in the kidney and small intestine. The rat CaIPLA2 cDNA, when expressed in a baculovirus expression system, and the purified rabbit kidney cortex protein exhibit both CaIPLA2 and lysophospholipase activities. The cloned CaIPLA2 cDNA are expected to aid in understanding the role of CaIPLA2 in cell death after hypoxic/ischemic cell injury.
Half a million people using food banks in UK as food poverty grows
Authors: A. O'Dowd
Journal: BMJ (2013)

Around half a million people are facing poor health as a result of food poverty and are seeking help from food banks around the United Kingdom, a report claims.

The report from charities Oxfam and Church Action Poverty, published on 30 May, claims that the numbers of people thought to be in need of food aid to help them eat—in the form of food parcels and food banks—have …
Effect of immunostimulating and anti-inflammatory agents on the biosynthesis of prostaglandins E2, F2α, prostacyclin (PGI2) and thromboxane A2 (TXA2) by mouse embryo fibroblasts in tissue culture
Authors: P. WEINLING, FRANÇOISE HOMO-DELARCHE
Journal: British Journal of Dermatology (2006)

Experiments performed in cultures of mouse embryo fibroblasts have shown that dexamethasone (10(-6) M) significantly inhibits the production of PGE2 and PGI2 but only moderately inhibits that of PGF2 alpha. Conversely, lipopolysacharide treatment (5 micrograms/ml) markedly stimulated the secretion of PGE2 and PGI2 and only slightly that of PGF2 alpha. In these cultures, the secretion of TXA2 remained unaffected either in the presence of dexamethasone or LPS.
ON SPRAYS AND SPRAYING IN THE TREATMENT OF CERTAIN SURFACE AFFECTIONS OF THE SKIN
Authors: W. ALLAN JAMIESON
Journal: British Journal of Dermatology (1916)

British Journal of DermatologyVolume 28, Issue 4-6 p. 104-105 ON SPRAYS AND SPRAYING IN THE TREATMENT OF CERTAIN SURFACE AFFECTIONS OF THE SKIN W. ALLAN JAMIESON M.D., LL.D., F.R.C.P.E., W. ALLAN JAMIESON M.D., LL.D., F.R.C.P.E. Knight of Grace of the Order of St. John of Jerusalem This paper was received shortly before Dr. Jamieson's death, and is probably his last contribution to DermatologySearch for more papers by this author W. ALLAN JAMIESON M.D., LL.D., F.R.C.P.E., W. ALLAN JAMIESON M.D., LL.D., F.R.C.P.E. Knight of Grace of the Order of St. John of Jerusalem This paper was received shortly before Dr. Jamieson's death, and is probably his last contribution to DermatologySearch for more papers by this author First published: April‐June 1916 https://doi.org/10.1111/j.1365-2133.1916.tb16764.x AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume28, Issue4-6April‐June 1916Pages 104-105 RelatedInformation
Efficacy and Safety of the Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Added to Ongoing Metformin Therapy in Patients With Type 2 Diabetes Inadequately Controlled With Metformin Alone
Authors: Bernard Charbonnel, Avraham Karasik, Ji Liu, Mei Wu, Gary Meininger
Journal: Diabetes Care (2006)

The efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, added to ongoing metformin therapy, were assessed in patients with type 2 diabetes who had inadequate glycemic control (HbA(1c) [A1C] >or=7 and <or=10%) with metformin alone.After a screening diet/exercise run-in period, a metformin dose titration/stabilization period, and a 2-week, single-blind, placebo run-in period, 701 patients, aged 19-78 years, with mild to moderate hyperglycemia (mean A1C 8.0%) receiving ongoing metformin (>or=1,500 mg/day) were randomly assigned to receive the addition of placebo or sitagliptin 100 mg once-daily in a 1:2 ratio for 24 weeks. Patients exceeding specific glycemic limits were provided rescue therapy (pioglitazone) until the end of the study. The efficacy analyses were based on an all-patients-treated population using an ANCOVA and excluded data obtained after glycemic rescue.At week 24, sitagliptin treatment led to significant reductions compared with placebo in A1C (-0.65%), fasting plasma glucose, and 2-h postmeal glucose. Fasting insulin, fasting C-peptide, fasting proinsulin-to-insulin ratio, postmeal insulin and C-peptide areas under the curve (AUCs), postmeal insulin AUC-to-glucose AUC ratio, homeostasis model assessment of beta-cell function, and quantitative insulin sensitivity check index were significantly improved with sitagliptin relative to placebo. A significantly greater proportion of patients achieved an A1C <7% with sitagliptin (47.0%) than with placebo (18.3%). There was no increased risk of hypoglycemia or gastrointestinal adverse experiences with sitagliptin compared with placebo. Body weight decreased similarly with sitagliptin and placebo.Sitagliptin 100 mg once-daily added to ongoing metformin therapy was efficacious and well tolerated in patients with type 2 diabetes who had inadequate glycemic control with metformin alone.
Bedaquiline: finding the pores on the pot
Authors: Max Salfinger, Giovanni Battista Migliori
Journal: European Respiratory Journal (2015)

We read with interest the correspondence by Prasanta Raghab Mohapatra commenting on our editorial [1], which was aimed at discussing the absence of adequate drug susceptibility protocol for the new drug bedaquiline. How to ensure best use of bedaquiline <http://ow.ly/MTW09>
Phase II study of sorafenib in children with recurrent or progressive low-grade astrocytomas
Authors: M. A. Karajannis, G. Legault, M. J. Fisher, S. S. Milla, K. J. Cohen, J. H. Wisoff, D. H. Harter, J. D. Goldberg, T. Hochman, A. Merkelson, M. C. Bloom, A. J. Sievert, A. C. Resnick, G. Dhall, D. T. W. Jones, A. Korshunov, S. M. Pfister, C. G. Eberhart, D. Zagzag, J. C. Allen
Journal: Neuro-Oncology (2014)

Activation of the RAS-RAF-MEK-ERK signaling pathway is thought to be the key driver of pediatric low-grade astrocytoma (PLGA) growth. Sorafenib is a multikinase inhibitor targeting BRAF, VEGFR, PDGFR, and c-kit. This multicenter phase II study was conducted to determine the response rate to sorafenib in patients with recurrent or progressive PLGA. Key eligibility criteria included age ≥2 years, progressive PLGA evaluable on MRI, and at least one prior chemotherapy treatment. Sorafenib was administered twice daily at 200 mg/m2/dose (maximum of 400 mg/dose) in continuous 28-day cycles. MRI, including 3-dimensional volumetric tumor analysis, was performed every 12 weeks. BRAF molecular testing was performed on tumor tissue when available. Eleven patients, including 3 with neurofibromatosis type 1 (NF1), were evaluable for response; 5 tested positive for BRAF duplication. Nine patients (82%) came off trial due to radiological tumor progression after 2 or 3 cycles, including 3 patients with confirmed BRAF duplication. Median time to progression was 2.8 months (95% CI, 2.1–31.0 months). Enrollment was terminated early due to this rapid and unexpectedly high progression rate. Tumor tissue obtained from 4 patients after termination of the study showed viable pilocytic or pilomyxoid astrocytoma. Sorafenib produced unexpected and unprecedented acceleration of tumor growth in children with PLGA, irrespective of NF1 or tumor BRAF status. In vitro studies with sorafenib indicate that this effect is likely related to paradoxical ERK activation. Close monitoring for early tumor progression should be included in trials of novel agents that modulate signal transduction.