tbuckley/cabot-search huggingface dataset:
SERUM TREATMENT OF INFLUENZAL MENINGITIS
Authors: Martha Wollstein
Journal: The Journal of Experimental Medicine (1911)

The injection of virulent cultures of Bacillus influenzae into the subdural space of several species of lower monkeys is followed by the development of an acute inflammation of the meninges, corresponding in clinical, bacteriological, and pathological effects with influenzal cerebrospinal meningitis in human beings. Experimental influenzal meningitis in the monkey is a lethal disease which terminates fatally in from thirty-six hours to four days after the inoculation. The injected influenza bacilli produce their effects through multiplication in the course of which they penetrate from the subdural space into the general blood current, from which they may be recovered during life and at autopsy, as is also true of the spontaneous form of influenzal meningitis in man. By repeated injection, over a period of many months, of living virulent cultures of Bacillus influenzae into the goat, an immune serum possessing moderate agglutinating and high opsonic power may be produced, which is capable, when injected into the subdural space, of arresting the progress of an experimental influenzal meningitis, and of bringing about recovery in monkeys thus affected. As a result of the serum injections, the influenza bacilli in the meninges are more freely englobed by phagocytes, their number is reduced, their capacity of growth diminished, and the eruption into the blood arrested. Along with these effects go, hand in hand, cessation of the local inflammatory process and progressive amelioration of the symptoms of illness, to be followed usually by rapid restoration of health. In view of the highly fatal character of influenzal meningitis in human beings, the employment of an immune serum by subdural injection is recommended. Undoubtedly it will be necessary to apply the serum early and by repeated injections, by means of lumbar puncture, to secure beneficial results. The early application will, in turn, be dependent upon prompt bacteriological diagnosis, which can be made, as a rule, by the immediate microscopical examination of the cerebrospinal fluid without the employment of cultural methods. When possible, the microscopical diagnosis should be confirmed by cultural tests.
Differential effects of class I isoform histone deacetylase depletion and enzymatic inhibition by belinostat or valproic acid in HeLa cells
Authors: Marielle Dejligbjerg, Morten Grauslund, Thomas Litman, Laura Collins, Xiaozhong Qian, Michael Jeffers, Henri Lichenstein, Peter Jensen, Maxwell Sehested
Journal: Molecular Cancer (2008)

Histone acetylation is an epigenetic modification involved in the regulation of gene expression, balanced by histone acetyl transferases and histone deacetylase (HDAC) enzymes. HDAC inhibitors (HDACi) induce growth arrest and cell death in transformed cells, and are currently in many clinical cancer trials. The transcriptional response to HDACi is complex, as is the response to HDAC isoform knockdown (KD). Here, we describe for the first time in a human cancer cell line, a transcriptional comparison of treatment by two structurally unrelated HDACi; belinostat and valproic acid with the KD of HDAC1, 2 and 3 isoforms. HDAC KD showed anti-proliferative effects, although to a lesser extent than HDACi treatment. Moreover, we found a 2-fold increased resistance of HDAC1 knockdown cells to belinostat, suggesting this isoenzyme as a selective target. While both HDACi treatment and individual class I HDAC KD produce significant transcriptional effects, three-times higher for HDACi, the gene-expression profiles of class I HDAC KD compared with that obtained by HDACi treatment exhibited less than 4% of altered genes in common between the two modes of inhibition. Further, cell-specific effects of HDAC KD are evident by comparison with a recent study in a different cell line. The increased resistance to belinostat in response to HDAC1 depletion indicates the possibility of using this isoform as a predictive biomarker of response to HDACi treatment. Further, the transcriptional response to chemical inhibition of HDACs is very different from that of KD of individual class I HDAC isoforms. These data suggest that the anti-tumor effect of HDACi is indeed linked to class I inhibition, but may be more complex than simply targeting individual HDAC enzymes.
Respiratory disability in coal miners
Authors: D. L. Ramussen
Journal: JAMA (1980)

To the Editor.—  My experience with blood gas analysis in evaluating respiratory disability among coal miners differs substantially from that of Morgan et al. The exercise protocol used by my laboratory, which is more suitable for the often sedentary subjects studied, is less abrupt than that of Morgan et al. After a light warm-up, two to five graded levels of tread-mill exercise are given, to a measured oxygen uptake of up to 20 to 25 cc/kg/min, if possible. Increments are based on each patient's tolerance and the examiner's clinical judgment, with 30 to 40 minutes' rest between levels. Determination of arterial blood level is obtained after 5 1/2 minutes of a six-minute exercise and is immediately analyzed simultaneously in three analyzers (Po 2 and Pco 2 electrodes, one model 113 and two model 813 analyzers).  Most of the miners referred here by the Department of Labor (DOL) are from southern
Salvage Surgery After Chemoradiotherapy in the Management of Esophageal Cancer: Is It a Viable Therapeutic Option?
Authors: Sheraz Markar, Caroline Gronnier, Alain Duhamel, Arnaud Pasquer, Jérémie Théreaux, Mael Chalret du Rieu, Jérémie H. Lefevre, Kathleen Turner, Guillaume Luc, Christophe Mariette
Journal: Journal of Clinical Oncology (2015)

The aim of this large multicenter study was to assess the impact of salvage esophagectomy after definitive chemoradiotherapy (SALV) on clinical outcome.Data from consecutive adult patients undergoing resection for esophageal cancer in 30 European centers from 2000 to 2010 were collected. First, groups undergoing SALV (n = 308) and neoadjuvant chemoradiotherapy followed by planned esophagectomy (NCRS; n = 540) were compared. Second, patients who benefited from SALV for persistent (n = 234) versus recurrent disease (n = 74) were compared. Propensity score matching and multivariable analyses were used to compensate for differences in some baseline characteristics.SALV versus NCRS groups: In-hospital mortality was similar in both groups (8.4% v 9.3%). The only significant differences in complications were seen for anastomotic leak (17.2% v 10.7%; P = .007) and surgical site infection, which were both more frequent in the SALV group. At 3 years, groups had similar overall (43.3% v 40.1%; P = .542) and disease-free survival (39.2% v 32.8%; P = .232) after matching, along with a similar recurrence pattern. Persistent versus recurrent disease groups: There were no significant differences between groups in incidence of in-hospital mortality or major complications. At 3 years, overall (40.9% v 56.2%; P = .046) and disease-free survival (36.6% v 51.6%; P = .095) were lower in the persistent disease group.The results of this large multicenter study from the modern era suggest that SALV can offer acceptable short- and long-term outcomes in selected patients at experienced centers. Persistent cancer after definitive chemoradiotherapy seems to be more biologically aggressive, with poorer survival compared with recurrent cancer.
Increased ratio of helper to suppressor T cells in alopecia areata
Authors: B. B. J. MAJEWSKI, M. S. KOH, D. R. TAYLOR, B. WATSON, E. L. RHODES
Journal: British Journal of Dermatology (1984)

Journal Article Increased ratio of helper to suppressor T cells in alopecia areata Get access B. B. J. MAJEWSKI, B. B. J. MAJEWSKI Department of Dermatology, St. Helier Hospital, Carshalton, Surrey Search for other works by this author on: Oxford Academic Google Scholar M. S. KOH, M. S. KOH Department of Dermatology, St. Helier Hospital, Carshalton, Surrey Search for other works by this author on: Oxford Academic Google Scholar D. R. TAYLOR, D. R. TAYLOR Department of Dermatology, St. Helier Hospital, Carshalton, Surrey Search for other works by this author on: Oxford Academic Google Scholar B. WATSON, B. WATSON Department of Immunology, St. Helier Hospital, Carshalton, Surrey Search for other works by this author on: Oxford Academic Google Scholar E. L. RHODES E. L. RHODES Department of Dermatology, St. Helier Hospital, Carshalton, Surrey Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 110, Issue 2, 1 February 1984, Pages 171–175, https://doi.org/10.1111/j.1365-2133.1984.tb07463.x Published: 01 February 1984 Article history Accepted: 15 August 1983 Published: 01 February 1984
Emerging Epigenetic Targets and Therapies in Cancer Medicine
Authors: Relja Popovic, Jonathan D. Licht
Journal: Cancer Discovery (2012)

Abnormalities in the epigenetic regulation of chromatin structure and function can lead to aberrant gene expression and cancer development. Consequently, epigenetic therapies aim to restore normal chromatin modification patterns through the inhibition of various components of the epigenetic machinery. Histone deacetylase and DNA methyltransferase inhibitors represent the first putative epigenetic therapies; however, these agents have pleiotropic effects and it remains unclear how they lead to therapeutic responses. More recently, drugs that inhibit histone methyltransferases were developed, perhaps representing more specific agents. We review emerging epigenetic targets in cancer and present recent models of promising epigenetic therapies.The use of DNA methyltransferase and histone deacetylase inhibitors in patients has validated the use of drugs targeted to epigenetic enzymes and strengthened the need for development of additional therapies. In this review, we summarize recently discovered epigenetic abnormalities, their implications for cancer, and the approaches taken for discovering small-molecule inhibitors targeting various properties of the epigenetic machinery.
Intranasal steroids decrease eosinophils but not mucin expression in nasal polyps
Authors: P-R. Burgel, L.O. Cardell, I.F. Ueki, J.A. Nadel
Journal: European Respiratory Journal (2004)

Increased mucin expression is a feature of nasal polyposis. Corticosteroids reduce polyp size and symptoms, but their effect on mucin production remains unknown. In this study, the effects of intranasal corticosteroids on MUC5AC mucin expression, nasal resistance, eosinophil and neutrophil infiltration, epidermal growth factor receptor (EGFR), interleukin (IL)-8, and tumour necrosis factor (TNF)-α expression was assessed in nasal polyps. In nine subjects, one nasal polyp was removed surgically before treatment and another was removed after 8 weeks of intranasal fluticasone (400 µg·day −1 ). Tissues were processed for in situ hybridisation and immunohistochemical staining. Described effects of fluticasone on nasal polyps (reduction in nasal resistance and in eosinophil infiltration) were evaluated. Morphometric analysis was performed to assess the effect of fluticasone on epithelial-, MUC5AC-, EGFR- and IL-8-stained areas, TNF-α-stained cells, and neutrophil numbers. Treatment with fluticasone decreased nasal resistance and intra-epithelial eosinophils. The MUC5AC-stained area in the epithelium was unchanged by treatment; MUC5AC mRNA expression was unaffected by treatment. EGFR-stained area, intra-epithelial neutrophil numbers, IL-8 and TNF-α expression were also unchanged by therapy. Intranasal fluticasone was effective in decreasing nasal airflow resistance and intra-epithelial eosinophils but had no effect on mucin or epidermal growth factor receptor expression or on neutrophil recruitment.
Injury and illness definitions and data collection procedures for use in epidemiological studies in Athletics (track and field): Consensus statement
Authors: Toomas Timpka, Juan-Manuel Alonso, Jenny Jacobsson, Astrid Junge, Pedro Branco, Ben Clarsen, Jan Kowalski, Margo Mountjoy, Sverker Nilsson, Babette Pluim, Per Renström, Ola Rønsen, Kathrin Steffen, Pascal Edouard
Journal: British Journal of Sports Medicine (2014)

Movement towards sport safety in Athletics through the introduction of preventive strategies requires consensus on definitions and methods for reporting epidemiological data in the various populations of athletes.To define health-related incidents (injuries and illnesses) that should be recorded in epidemiological studies in Athletics, and the criteria for recording their nature, cause and severity, as well as standards for data collection and analysis procedures.A 1-day meeting of 14 experts from eight countries representing a range of Athletics stakeholders and sport science researchers was facilitated. Definitions of injuries and illnesses, study design and data collection for epidemiological studies in Athletics were discussed during the meeting. Two members of the group produced a draft statement after this meeting, and distributed to the group members for their input. A revision was prepared, and the procedure was repeated to finalise the consensus statement.Definitions of injuries and illnesses and categories for recording of their nature, cause and severity were provided. Essential baseline information was listed. Guidelines on the recording of exposure data during competition and training and the calculation of prevalence and incidences were given. Finally, methodological guidance for consistent recording and reporting on injury and illness in athletics was described.This consensus statement provides definitions and methodological guidance for epidemiological studies in Athletics. Consistent use of the definitions and methodological guidance would lead to more reliable and comparable evidence.
Clinical Significance of Dysadherin Expression in Gastric Cancer Patients
Authors: Yutaka Shimada, Seiji Yamasaki, Yosuke Hashimoto, Tetsuo Ito, Jun-ichiro Kawamura, Toshiya Soma, Yoshinori Ino, Yukihiro Nakanishi, Michiie Sakamoto, Setsuo Hirohashi, Masayuki Imamura
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Dysadherin, a cancer-associated cell membrane glycoprotein, has been reported to down-regulate E-cadherin expression and promote metastasis. To evaluate the role of dysadherin in gastric cancer, we examined dysadherin and E-cadherin expression in gastric cancer patients. Experimental Design: Dysadherin and E-cadherin expression were evaluated in 276 gastric cancer patients by immunohistochemistry, and the results were compared with the clinicopathological findings of the subjects. Results: Dysadherin was not expressed in normal gastric epithelium. Both dysadherin and E-cadherin were localized to the cell membrane. Dysadherin expression was sometimes largely localized to infiltrating tumor cells or cells dissociating. Ninety gastric cancer patients (32.6%) were positive for dysadherin, and 151 patients (54.7%) showed preservation of E-cadherin expression. Expression of dysadherin was associated with moderately differentiated carcinoma and hematogenous metastasis, whereas reduced expression of E-cadherin showed an association with poorly differentiated carcinoma and peritoneal dissemination. As a result, dysadherin positivity and reduced E-cadherin expression were associated with a poor prognosis. In addition, patients with both dysadherin positivity and reduced E-cadherin had the worst prognosis. Multivariate analysis revealed that reduced E-cadherin expression was an independent prognostic factor, but dysadherin expression was not. Conclusion: Combined analysis of dysadherin and E-cadherin expression may help to predict the prognosis and the mode of metastasis in gastric cancer patients. Patients with dysadherin positivity have a higher risk of hematogenous metastasis, whereas patients with reduced E-cadherin expression have an increased risk of peritoneal dissemination.
Genome-wide association study identifies eight loci associated with blood pressure
Authors: Christopher Newton-Cheh, Toby Johnson, Vesela Gateva, Martin D Tobin, Murielle Bochud, Lachlan Coin, Samer S Najjar, Jing Hua Zhao, Simon C Heath, Susana Eyheramendy, Konstantinos Papadakis, Benjamin F Voight, Laura J Scott, Feng Zhang, Martin Farrall, Toshiko Tanaka, Chris Wallace, John C Chambers, Kay-Tee Khaw, Peter Nilsson, Pim van der Harst, Silvia Polidoro, Diederick E Grobbee, N Charlotte Onland-Moret, Michiel L Bots, Louise V Wain, Katherine S Elliott, Alexander Teumer, Jian'an Luan, Gavin Lucas, Johanna Kuusisto, Paul R Burton, David Hadley, Wendy L McArdle, Morris Brown, Anna Dominiczak, Stephen J Newhouse, Nilesh J Samani, John Webster, Eleftheria Zeggini, Jacques S Beckmann, Sven Bergmann, Noha Lim, Kijoung Song, Peter Vollenweider, Gerard Waeber, Dawn M Waterworth, Xin Yuan, Leif Groop, Marju Orho-Melander, Alessandra Allione, Alessandra Di Gregorio, Simonetta Guarrera, Salvatore Panico, Fulvio Ricceri, Valeria Romanazzi, Carlotta Sacerdote, Paolo Vineis, Inês Barroso, Manjinder S Sandhu, Robert N Luben, Gabriel J Crawford, Pekka Jousilahti, Markus Perola, Michael Boehnke, Lori L Bonnycastle, Francis S Collins, Anne U Jackson, Karen L Mohlke, Heather M Stringham, Timo T Valle, Cristen J Willer, Richard N Bergman, Mario A Morken, Angela Döring, Christian Gieger, Thomas Illig, Thomas Meitinger, Elin Org, Arne Pfeufer, H Erich Wichmann, Sekar Kathiresan, Jaume Marrugat, Christopher J O'Donnell, Stephen M Schwartz, David S Siscovick, Isaac Subirana, Nelson B Freimer, Anna-Liisa Hartikainen, Mark I McCarthy, Paul F O'Reilly, Leena Peltonen, Anneli Pouta, Paul E de Jong, Harold Snieder, Wiek H van Gilst, Robert Clarke, Anuj Goel, Anders Hamsten, John F Peden, Udo Seedorf, Ann-Christine Syvänen, Giovanni Tognoni, Edward G Lakatta, Serena Sanna, Paul Scheet, David Schlessinger, Angelo Scuteri, Marcus Dörr, Florian Ernst, Stephan B Felix, Georg Homuth, Roberto Lorbeer, Thorsten Reffelmann, Rainer Rettig, Uwe Völker, Pilar Galan, Ivo G Gut, Serge Hercberg, G Mark Lathrop, Diana Zelenika, Panos Deloukas, Nicole Soranzo, Frances M Williams, Guangju Zhai, Veikko Salomaa, Markku Laakso, Roberto Elosua, Nita G Forouhi, Henry Völzke, Cuno S Uiterwaal, Yvonne T van der Schouw, Mattijs E Numans, Giuseppe Matullo, Gerjan Navis, Göran Berglund, Sheila A Bingham, Jaspal S Kooner, John M Connell, Stefania Bandinelli, Luigi Ferrucci, Hugh Watkins, Tim D Spector, Jaakko Tuomilehto, David Altshuler, David P Strachan, Maris Laan, Pierre Meneton, Nicholas J Wareham, Manuela Uda, Marjo-Riitta Jarvelin, Vincent Mooser, Olle Melander, Ruth JF Loos, Paul Elliott, Gonçalo R Abecasis, Mark Caulfield, Patricia B Munroe
Journal: Nature Genetics (2009)
TCT-719 Clinical Outcomes after Transcatheter Aortic Valve Implantation Under Local Analgesia
Authors: Esther M. Wiegerinck, Susanne Eberl, Kirsten Boerlage-van Dijk, Karel T. Koch, Ze Yie Yong, Marije M. Vis, Bas A.J.M. De Mol, Jan Piek, Jan G. Tijssen, Jan Baan
Journal: Journal of the American College of Cardiology (2013)
Paediatric specialist registrars’ views of educational supervision and how it can be improved: A questionnaire study
Authors: B W Lloyd, D Becker
Journal: Journal of the Royal Society of Medicine (2007)

To determine what paediatric specialist registrars think of the educational supervision they have received and what advice they would give to a consultant who wanted to be a more effective educational supervisor. A questionnaire study. The North Thames Deanery, UK. 129 year 3, 4 or 5 paediatric specialist registrars in the North Thames Deanery. Reported value of educational supervision on a Likert scale; what elements of educational supervision were reported to be most useful; what elements of educational supervision were reported to be done poorly; what advice would specialist registrars give to a consultant who wanted to be a more effective educational supervisor. 86/129 specialist registrars responded (67%). The mean score on the Likert scale (0-a complete waste of time; 100-excellent) was 57 with 37% of respondents giving a score of less than 50. The most valued aspects of educational supervision were: feedback on performance--cited by 50 respondents (56% of respondents); career advice--cited by 43 (48%); objective setting--cited by 36 (40%); pastoral support--cited by 25 (28%). Aspects of educational supervision that were reported to be often not done well were: commitment to educational supervision--cited by 44 respondents (49% of respondents); ensuring sessions are bleep-free-cited by 43 (48%); listening rather than talking--cited by 23 (26%); being encouraging--cited by 18 (20%). Advice to consultants about how to improve educational supervision included: listen rather than talk; be encouraging; treat the trainee as an individual with individual needs. We can find no other study of trainees' views about how educational supervision can be improved. Although some trainees found educational supervision very valuable, many did not. Educational supervision should only be carried out by consultants who are committed to the task. An educational supervisor should listen carefully in order to understand the trainee's individual ambitions and needs, should provide specific feedback on performance and should be encouraging.
Phase III Trial of Cetuximab With Continuous or Intermittent Fluorouracil, Leucovorin, and Oxaliplatin (Nordic FLOX) Versus FLOX Alone in First-Line Treatment of Metastatic Colorectal Cancer: The NORDIC-VII Study
Authors: Kjell Magne Tveit, Tormod Guren, Bengt Glimelius, Per Pfeiffer, Halfdan Sorbye, Seppo Pyrhonen, Fridbjorn Sigurdsson, Elin Kure, Tone Ikdahl, Eva Skovlund, Tone Fokstuen, Flemming Hansen, Eva Hofsli, Elke Birkemeyer, Anders Johnsson, Hans Starkhammar, Mette Karen Yilmaz, Nina Keldsen, Anne Berit Erdal, Olav Dajani, Olav Dahl, Thoralf Christoffersen
Journal: Journal of Clinical Oncology (2012)

The NORDIC-VII multicenter phase III trial investigated the efficacy of cetuximab when added to bolus fluorouracil/folinic acid and oxaliplatin (Nordic FLOX), administered continuously or intermittently, in previously untreated metastatic colorectal cancer (mCRC). The influence of KRAS mutation status on treatment outcome was also investigated.Patients were randomly assigned to receive either standard Nordic FLOX (arm A), cetuximab and FLOX (arm B), or cetuximab combined with intermittent FLOX (arm C). Primary end point was progression-free survival (PFS). Overall survival (OS), response rate, R0 resection rate, and safety were secondary end points.Of the 571 patients randomly assigned, 566 were evaluable in intention-to-treat (ITT) analyses. KRAS and BRAF mutation analyses were obtained in 498 (88%) and 457 patients (81%), respectively. KRAS mutations were present in 39% of the tumors; 12% of tumors had BRAF mutations. The presence of BRAF mutations was a strong negative prognostic factor. In the ITT population, median PFS was 7.9, 8.3, and 7.3 months for the three arms, respectively (not significantly different). OS was almost identical for the three groups (20.4, 19.7, 20.3 months, respectively), and confirmed response rates were 41%, 49%, and 47%, respectively. In patients with KRAS wild-type tumors, cetuximab did not provide any additional benefit compared with FLOX alone. In patients with KRAS mutations, no significant difference was detected, although a trend toward improved PFS was observed in arm B. The regimens were well tolerated.Cetuximab did not add significant benefit to the Nordic FLOX regimen in first-line treatment of mCRC.