tbuckley/cabot-search huggingface dataset:
End-Results of Artificial Pneumothorax
Authors: S. V. Pearson
Journal: BMJ (1926)

ARTIFICIArL PNEUMOTHORAXL. (THE BIJIIEaS .~~~~~~~~~~be subjected to deep kneading, with the object of softening and stretching the scar tissue and, if possible, getting rid of it altogether.The patient must be warned that this process will be painful, but at the same time encouraged to expect the benefit which results from successful treatmiient.
ESRD and Death after Heart Failure in CKD
Authors: Maneesh Sud, Navdeep Tangri, Melania Pintilie, Andrew S. Levey, David M.J. Naimark
Journal: Journal of the American Society of Nephrology (2014)

CKD is a risk factor for heart failure, but there is no data on the risk of ESRD and death after recurrent hospitalizations for heart failure. We sought to determine how interim heart failure hospitalizations modify the subsequent risk of ESRD or death before ESRD in patients with CKD. We retrospectively identified 2887 patients with a GFR between 15 and 60 ml/min per 1.73 m2 referred between January of 2001 and December of 2008 to a nephrology clinic in Toronto, Canada. We ascertained interim first, second, and third heart failure hospitalizations as well as ESRD and death before ESRD outcomes from administrative data. Over a median follow-up time of 3.01 (interquartile range=1.56–4.99) years, interim heart failure hospitalizations occurred in 359 (12%) patients, whereas 234 (8%) patients developed ESRD, and 499 (17%) patients died before ESRD. Compared with no heart failure hospitalizations, one, two, or three or more heart failure hospitalizations increased the adjusted hazard ratio of ESRD from 4.89 (95% confidence interval [95% CI], 3.21 to 7.44) to 10.27 (95% CI, 5.54 to 19.04) to 14.16 (95% CI, 8.07 to 24.83), respectively, and the adjusted hazard ratio death before ESRD from 3.30 (95% CI, 2.55 to 4.27) to 4.20 (95% CI, 2.82 to 6.25) to 6.87 (95% CI, 4.96 to 9.51), respectively. We conclude that recurrent interim heart failure is associated with a stepwise increase in the risk of ESRD and death before ESRD in patients with CKD.
FRI0289 Three phenotype profiles are revealed by cluster analysis in early inflammatory back pain suggestive of spondyloarthritis (SPA). Results from the devenir des spondyloarthropathies indifferenciΈes rΈcentes (DESIR) cohort:
Authors: M.-A. D’Agostino, P. Aegerter, M. Dougados, M. Breban
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Spondylarthritis (SPA) spectrum refers to a variety of skeletal and extra-articular inflammatory manifestations that may combine differently among patients. <h3>Objectives</h3> To examine whether SPA disease manifestations at baseline would combine according to an ordered or random pattern in patients with early inflammatory low back pain (IBP) and suggestive of SPA. <h3>Methods</h3> Baseline clinical and demographic characteristics, as well as imaging (i.e. pelvic X-rays, pelvic MRI and peripheral entheses ultrasound) and biological data (including HLA-B27) of patients included in the French multicenter DESIR cohort of early (&lt;3 yrs duration) IBP suggestive of SPA were analysed by multiple correspondence analysis in order to graphically assess the association between the studied manifestations. Several methods of cluster analysis using those variables were then performed to identify subgroups of patients with similar characteristics. <h3>Results</h3> Seven hundred and eight patients were included into the Cohort. Among the 700 analysed patients cluster analysis allowed us to classify 688 patients in 3 major groups (table 1). Cluster A contained a majority of men, with predominant isolated axial manifestations, and higher frequency of uveitis and positivity of HLA-B27. Cluster B predominantly consisted of women, with higher frequency of peripheral signs (including vascularisation at entheses by power Doppler ultrasound (PDUS)), psoriasis and younger onset of disease symptoms. Cluster C was composed by patients with predominant axial symptoms, equal distribution of sex, highest presence of pelvic X-rays and MRI positivity, and higher prevalence of HLA-B27 positivity. <h3>Conclusions</h3> Cluster analysis of SPA manifestations among patients with early IBP allowed us to clearly identify at baseline 3 different groups of clinical phenotypes. Ongoing follow up will allow to determine whether these clusters may correspond to different severity patterns. <h3>Funding</h3> The DESIR cohort is supported by an unrestricted grant from PFIZER France <h3>Disclosure of Interest</h3> None Declared
EGFR Protein Expression in Non–Small Cell Lung Cancer Predicts Response to an EGFR Tyrosine Kinase Inhibitor—A Novel Antibody for Immunohistochemistry or AQUA Technology
Authors: Celine Mascaux, Murry W. Wynes, Yasufumi Kato, Cindy Tran, Bernadette Reyna Asuncion, Jason M. Zhao, Mark Gustavson, Jim Ranger-Moore, Fabien Gaire, Jun Matsubayashi, Toshitaka Nagao, Koichi Yoshida, Tatuso Ohira, Norihiko Ikeda, Fred R. Hirsch
Journal: Clinical Cancer Research (2011)

Epidermal growth factor receptor (EGFR) protein expression in non-small cell lung cancer (NSCLC) is not recommended for predicting response to EGFR tyrosine kinase inhibitors (TKI) due to conflicting results, all using antibodies detecting EGFR external domain (ED). We tested the predictive value of EGFR protein expression for response to an EGFR TKI with an antibody that detects the intracellular domain (ID) and compared fluorescence-based Automated QUantitative Analysis (AQUA) technology to immunohistochemistry (IHC).Specimens from 98 gefitinib-treated NSCLC Japanese patients were evaluated by IHC (n = 98 of 98) and AQUA technology (n = 70 of 98). EGFR ID (5B7)- and ED-specific antibodies (3C6 and 31G7) were compared.EGFR expression evaluated with 5B7 was significantly higher in responders versus nonresponders to gefitinib both with IHC and with AQUA. ED-specific antibodies did not significantly predict response. Using AQUA and ID-specific antibody resulted in the best prediction performance with a positive and negative predictive value (PPV/NPV) for responders of 50% and 87%, respectively. EGFR expression with ID-specific antibody and AQUA also predicted responders in EGFR-mutated patients. Increased EGFR expression with the ID antibody is associated with increased median progression free survival (PFS; 11.7 months vs. 5.0, log rank, P = 0.034) and overall survival (OS; 38.6 vs. 14.9, P = 0.040) from gefitinib therapy.EGFR protein expression using an ID-specific antibody specifically predicts response to gefitinib in NSCLC patients, including in EGFR-mutated patients, and increased PFS/OS from gefitinib. These data suggest that the choice of diagnostic antibody and methodology matters to predict response and outcome to specific therapies. The potential clinical application needs further validation. Clin Cancer Res; 17(24); 7796-807. ©2011 AACR.
Randomized, Placebo-Controlled, Phase III Study of First-Line Oxaliplatin-Based Chemotherapy Plus PTK787/ZK 222584, an Oral Vascular Endothelial Growth Factor Receptor Inhibitor, in Patients With Metastatic Colorectal Adenocarcinoma
Authors: J. Randolph Hecht, Tanja Trarbach, John D. Hainsworth, Pierre Major, Elke Jäger, Robert A. Wolff, Katherine Lloyd-Salvant, György Bodoky, Kelly Pendergrass, William Berg, Bee-Lian Chen, Tarja Jalava, Gerold Meinhardt, Dirk Laurent, David Lebwohl, David Kerr
Journal: Journal of Clinical Oncology (2011)

PTK787/ZK 222584 (PTK/ZK; vatalanib), an orally active, multitargeted angiogenesis inhibitor, has shown tolerability and promising activity in early-phase studies, which led to a phase III trial in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4).Patients (N = 1,168) with previously untreated metastatic colorectal cancer were randomly assigned 1:1 to receive FOLFOX4 plus PTK/ZK or placebo (ClinicalTrials.gov identifier: NCT00056459). Stratification factors included WHO performance status (0 v 1 or 2) and serum lactate dehydrogenase (LDH; ≤ v > 1.5× the upper limit of normal). The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS) and overall response rate (ORR).PFS, OS, and ORR were not statistically improved with PTK/ZK (P > .05). Median PFS by central review was 7.7 months with PTK/ZK versus 7.6 months with placebo (hazard ratio [HR], 0.88; 95% CI, 0.74 to 1.03; P = .118); median OS was 21.4 months with PTK/ZK versus 20.5 months with placebo (HR, 1.08; 95% CI, 0.94 to 1.24; P = .260). In an exploratory post hoc analysis of PFS in patients (n = 158 per arm) with high serum LDH, a potential marker of hypoxia, PFS was longer with PTK/ZK versus placebo (7.7 v 5.8 months, respectively; HR, 0.67; 95% CI, 0.49 to 0.91; P = .009).Although the efficacy objectives of this study were not met, a subgroup of patients who may potentially benefit from small-molecule vascular endothelial growth factor receptor inhibitor therapy has been identified and further research is warranted.
Health outcomes assessment and economic evaluation in COPD: challenges and opportunities
Authors: S.D. Sullivan, A.S. Buist, K. Weiss
Journal: European Respiratory Journal (2003)

As a leading and growing cause of mortality and morbidity worldwide, chronic obstructive pulmonary disease (COPD) is now widely recognised as a major global public health problem with substantial medical and economic burdens. A decade ago, the annual per capita expenditure for COPD treatment in the USA was $8,482, more than twice that for people without COPD 1. With an increasingly older population in most countries, the prevalence of COPD and its associated healthcare costs will grow. In a disturbing report, the Global Burden of Disease Study concluded that from 1990–2020, COPD would increase worldwide from the sixth- to the third-leading cause of death and from the twelfth- to the fifth-leading cause of disability-adjusted life years lost 2.

To develop a coordinated international strategy for diagnosing and managing COPD, the National Heart, Lung and Blood Institute in conjunction with the World Health Organization, organised the Global Obstructive Lung Disease Initiative. This programme's objectives were to enhance awareness among public health officials, the medical community and the public, concerning the mounting health problems associated with COPD, to promote studies investigating the causes for increasing COPD prevalence and to implement programmes for COPD prevention 3.

Partly because of the emerging public health concern, there is now an acute interest in COPD and in defining treatments and treatment strategies that make a difference in the outcomes of patients. Unfortunately, there is some disagreement concerning optimal outcomes of care in this population. Regulatory authorities require lung function measurements for licensing of new products, whereas clinicians and patients are more interested in symptoms, functioning and health status. Payers and reimbursement authorities want to know whether new treatments will provide better outcomes at a reasonable price. In spite of this, little attention has been given to the issues and challenges that face health …
Changes in knee joint biomechanics following balance and technique training and a season of Australian football
Authors: Cyril J Donnelly, Bruce C Elliott, Tim L A Doyle, Caroline F Finch, Alasdair R Dempsey, David G Lloyd
Journal: British Journal of Sports Medicine (2012)

Determine if balance and technique training (BTT) implemented adjunct to normal Australian football (AF) training reduces external knee loading during sidestepping. Additionally, the authors determined if an athlete's knee joint kinematics and kinetics change over a season of AF.Eight amateur-level AF clubs (n=1,001 males) volunteered to participate in either 28 weeks of BTT or a 'sham' training (ST) adjunct to their normal preseason and regular training. A subset of 34 athletes (BTT, n=20; ST, n=14) were recruited for biomechanical testing in weeks 1-7 and 18-25 of the 28-week training intervention. During biomechanical testing, participants completed a series running, preplanned (PpSS) and unplanned sidestepping (UnSS) tasks. A linear mixed model (α=0.05) was used to determine if knee kinematics and peak moments during PpSS and UnSS were influenced by BTT and/or a season of AF.Both training groups significantly (p=0.025) decreased their peak internal-rotation knee moments during PpSS, and significantly (p=0.022) increased their peak valgus knee moments during UnSS following their respective training interventions.BTT was not effective in changing an athlete's knee joint biomechanics during sidestepping when conducted in 'real-world' training environments. Following normal AF training, the players had different changes to their knee joint biomechanics during both preplanned and unplanned sidestepping. When performing an unplanned sidestepping task in the latter half of a playing season, athletes are at an increased risk of ACL injury. The authors therefore recommend both sidestepping tasks are performed during biomechanical testing when assessing the effectiveness of prophylactic training protocols.
Role of Dok-1 and Dok-2 in Myeloid Homeostasis and Suppression of Leukemia
Authors: Tomoharu Yasuda, Masaki Shirakata, Atsushi Iwama, Asuka Ishii, Yasuhiro Ebihara, Mitsujiro Osawa, Kazuho Honda, Hisaaki Shinohara, Katsuko Sudo, Kohichiro Tsuji, Hiromitsu Nakauchi, Yoichiro Iwakura, Hisamaru Hirai, Hideaki Oda, Tadashi Yamamoto, Yuji Yamanashi
Journal: The Journal of Experimental Medicine (2004)

Dok-1 and Dok-2 are closely related rasGAP-associated docking proteins expressed preferentially in hematopoietic cells. Although they are phosphorylated upon activation of many protein tyrosine kinases (PTKs), including those coupled with cytokine receptors and oncogenic PTKs like Bcr-Abl, their physiological roles are largely unidentified. Here, we generated mice lacking Dok-1 and/or Dok-2, which included the double-deficient mice succumbed to myeloproliferative disease resembling human chronic myelogenous leukemia (CML) and chronic myelomonocytic leukemia. The double-deficient mice displayed medullary and extramedullary hyperplasia of granulocyte/macrophage progenitors with leukemic potential, and their myeloid cells showed hyperproliferation and hypo-apoptosis upon treatment and deprivation of cytokines, respectively. Consistently, the mutant myeloid cells showed enhanced Erk and Akt activation upon cytokine stimulation. Moreover, loss of Dok-1 and/or Dok-2 induced blastic transformation of chronic phase CML-like disease in mice carrying the bcr-abl gene, a cause of CML. These findings demonstrate that Dok-1 and Dok-2 are key negative regulators of cytokine responses and are essential for myeloid homeostasis and suppression of leukemia.
Role of tumour molecular and pathology features to estimate colorectal cancer risk for first-degree relatives
Authors: Aung Ko Win, Daniel D Buchanan, Christophe Rosty, Robert J MacInnis, James G Dowty, Gillian S Dite, Graham G Giles, Melissa C Southey, Joanne P Young, Mark Clendenning, Michael D Walsh, Rhiannon J Walters, Alex Boussioutas, Thomas C Smyrk, Stephen N Thibodeau, John A Baron, John D Potter, Polly A Newcomb, Loïc Le Marchand, Robert W Haile, Steven Gallinger, Noralane M Lindor, John L Hopper, Dennis J Ahnen, Mark A Jenkins
Journal: Gut (2014)

<h3>Objective</h3> To estimate risk of colorectal cancer (CRC) for first-degree relatives of CRC cases based on CRC molecular subtypes and tumour pathology features. <h3>Design</h3> We studied a cohort of 33 496 first-degree relatives of 4853 incident invasive CRC cases (probands) who were recruited to the Colon Cancer Family Registry through population cancer registries in the USA, Canada and Australia. We categorised the first-degree relatives into four groups: 28 156 of 4095 mismatch repair (MMR)-proficient probands, 2302 of 301 MMR-deficient non-Lynch syndrome probands, 1799 of 271 suspected Lynch syndrome probands and 1239 of 186 Lynch syndrome probands. We compared CRC risk for first-degree relatives stratified by the absence or presence of specific tumour molecular pathology features in probands across each of these four groups and for all groups combined. <h3>Results</h3> Compared with first-degree relatives of MMR-proficient CRC cases, a higher risk of CRC was estimated for first-degree relatives of CRC cases with suspected Lynch syndrome (HR 2.06, 95% CI 1.59 to 2.67) and with Lynch syndrome (HR 5.37, 95% CI 4.16 to 6.94), but not with MMR-deficient non-Lynch syndrome (HR 1.04, 95% CI 0.82 to 1.31). A greater risk of CRC was estimated for first-degree relatives if CRC cases were diagnosed before age 50 years, had proximal colon cancer or if their tumours had any of the following: expanding tumour margin, peritumoral lymphocytes, tumour-infiltrating lymphocytes or synchronous CRC. <h3>Conclusions</h3> Molecular pathology features are potentially useful to refine screening recommendations for first-degree relatives of CRC cases and to identify which cases are more likely to be caused by genetic or other familial factors.
Gabapentin Extended Release for the Treatment of Painful Diabetic Peripheral Neuropathy
Authors: David Sandercock, Marilou Cramer, Jacqueline Wu, Yu-Kun Chiang, Victor Biton, Michelle Heritier
Journal: Diabetes Care (2009)

A randomized, double-blind, placebo-controlled study was conducted in 147 patients to determine the efficacy and safety of gabapentin extended release (g-ER) in treating pain associated with diabetic peripheral neuropathy (DPN). Gabapentin, an immediate-release formulation, has demonstrated clinical efficacy in DPN patients but also a relatively high incidence of somnolence and dizziness at the doses required for effective treatment of DPN pain (1,2). Using the polymer-based AcuForm technology, g-ER tablets have been formulated to handle the saturable transport mechanism responsible for the lack of dose proportionality seen with gabapentin. When administered with a meal, g-ER tablets gradually expand and release the drug to the upper gastrointestinal …
Loss of proliferative capacity in immunohemopoietic stem cells caused by serial transplantation rather than aging.
Authors: D E Harrison, C M Astle, J A Delaittre
Journal: The Journal of Experimental Medicine (1978)

Marrow stem cell lines from old donors and those from young controls gave equally rapid rates of colony growth on spleens of irradiated mice. Old and young stem cell lines competed equally well with chromosomally marked marrow stem cells from a young donor in producing cell types that are stimulated by bleeding; old cells competed 70% as well as young in producing cell types stimulated by phytohemagglutinin (PHA) in vitro. After a single serial transplantation, the rates of colony growth declined 1.5- to 2.5-fold, and the ability to compete declined 2- to 4-fold for bleeding-stimulated and 4- to 10-fold for PHA-stimulated cells. Thus, immediate stem cell proliferative capacities decline much more after one serial transplantation than after a lifetime of normal function.
ATM Regulates 3-Methylpurine-DNA Glycosylase and Promotes Therapeutic Resistance to Alkylating Agents
Authors: Sameer Agnihotri, Kelly Burrell, Pawel Buczkowicz, Marc Remke, Brian Golbourn, Yevgen Chornenkyy, Aaron Gajadhar, Nestor A. Fernandez, Ian D. Clarke, Mark S. Barszczyk, Sanja Pajovic, Christian Ternamian, Renee Head, Nesrin Sabha, Robert W. Sobol, Michael D. Taylor, James T. Rutka, Chris Jones, Peter B. Dirks, Gelareh Zadeh, Cynthia Hawkins
Journal: Cancer Discovery (2014)

Alkylating agents are a first-line therapy for the treatment of several aggressive cancers, including pediatric glioblastoma, a lethal tumor in children. Unfortunately, many tumors are resistant to this therapy. We sought to identify ways of sensitizing tumor cells to alkylating agents while leaving normal cells unharmed, increasing therapeutic response while minimizing toxicity. Using an siRNA screen targeting over 240 DNA damage response genes, we identified novel sensitizers to alkylating agents. In particular, the base excision repair (BER) pathway, including 3-methylpurine-DNA glycosylase (MPG), as well as ataxia telangiectasia mutated (ATM), were identified in our screen. Interestingly, we identified MPG as a direct novel substrate of ATM. ATM-mediated phosphorylation of MPG was required for enhanced MPG function. Importantly, combined inhibition or loss of MPG and ATM resulted in increased alkylating agent-induced cytotoxicity in vitro and prolonged survival in vivo. The discovery of the ATM-MPG axis will lead to improved treatment of alkylating agent-resistant tumors.Inhibition of ATM and MPG-mediated BER cooperate to sensitize tumor cells to alkylating agents, impairing tumor growth in vitro and in vivo with no toxicity to normal cells, providing an ideal therapeutic window.
Relationship of Plasma Peptides to the Myocardial Depressant Factor in Hemorrhagic Shock in Cats
Authors: ALLAN M. LEFER, JULIAN MARTIN
Journal: Circulation Research (1970)

The pathophysiological relationships of a myocardial depressant factor (MDF) present in the plasma of cats in hemorrhagic shock were studied. Aprotinin (Trasylol), an inhibitor of a variety of proteases including kallikrein and trypsin, prolonged survival of cats in postoligemic shock as well as prevented the appearance of MDF in the plasma. Trasylol did not alter the arterial blood pressure, venous pressure, or heart rate of these cats in shock, nor did it protect by exerting a positive inotropic effect. Trasylol was ineffective in preventing or reversing the negative inotropic effects of MDF in isolated cat papillary muscles. Column chromatography of plasma from control cats, from untreated shocked cats and from cats treated with Trasylol before shock showed six peptide peaks, designated A, B, C, D, E, and F in decreasing order of molecular weights. Peptides corresponding to peaks A, B, E, and F exhibited insignificant myocardial depressant activity. The peptide corresponding to peak C was present in control plasma and accounted for some of the small negative inotropic effect of control plasma. The peptide corresponding to peak D had a marked myocardial depressant effect which could account for all the activity of shock plasma. The molecular weight of this peptide was estimated to be 800 to 1000. This peptide is not bradykinin, but appears to be produced by a protease present in shock.
MKS1, encoding a component of the flagellar apparatus basal body proteome, is mutated in Meckel syndrome
Authors: Mira Kyttälä, Jonna Tallila, Riitta Salonen, Outi Kopra, Nicolai Kohlschmidt, Paulina Paavola-Sakki, Leena Peltonen, Marjo Kestilä
Journal: Nature Genetics (2006)
Transient Neurological Attack
Authors: S. Claiborne Johnston
Journal: JAMA (2007)

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