tbuckley/cabot-search huggingface dataset:
Treatment Outcome and Prognostic Factors for Infants With Acute Lymphoblastic Leukemia Treated on Two Consecutive Trials of the Children's Cancer Group
Authors: Gregory H. Reaman, Richard Sposto, Martha G. Sensel, Beverly J. Lange, James H. Feusner, Nyla A. Heerema, Marcia Leonard, Emiko J. Holmes, Harland N. Sather, Thomas W. Pendergrass, Helen S. Johnstone, Richard T. O'Brien, Peter G. Steinherz, Paul M. Zeltzer, Paul S. Gaynon, Michael E. Trigg, Fatih M. Uckun
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Infants represent a very poor risk group for acute lymphoblastic leukemia (ALL). We report treatment outcome for such patients treated with intensive therapy on consecutive Children's Cancer Group (CCG) protocols. PATIENTS AND METHODS: Between 1984 and 1993, infants with newly diagnosed ALL were enrolled onto CCG-107 (n = 99) and CCG-1883 (n = 135) protocols. Postconsolidation therapy was more intensive on CCG-1883. On both studies, prophylactic treatment of the CNS included both high-dose systemic chemotherapy and intrathecal therapy, in contrast to whole-brain radiotherapy, which was used in earlier studies. RESULTS: Most patients (&gt; 95%) achieved remission with induction therapy. The most frequent event was a marrow relapse (46 patients on CCG-107 and 66 patients on CCG-1883). Four-year event-free survival was 33% (SE = 4.7%) on CCG-107 and 39% (SE = 4.2%) on CCG-1883. Both studies represent an improvement compared with a 22% (SE = 5.1%) event-free survival for historical controls. Four-year cumulative probabilities of any marrow relapse or an isolated CNS relapse were, respectively, 49% (SE = 5%) and 9% (SE = 3%) on CCG-107 and 50% (SE = 5%) and 3% (SE = 2%) on CCG-1883, compared with 63% (SE = 6%) and 5% (SE = 3%) for the historical controls. Independent adverse prognostic factors were age less than 3 months, WBC count of more than 50,000/μL, CD10 negativity, slow response to induction therapy, and presence of the translocation t(4;11). CONCLUSION: Outcome for infants on CCG-107 and CCG-1883 improved, compared with historical controls. Marrow relapse remains the primary mode of failure. Isolated CNS relapse rates are low, indicating that intrathecal chemotherapy combined with very-high-dose systemic therapy provides adequate protection of the CNS. The overall unsatisfactory outcome observed for the infant ALL population warrants the future use of novel alternative therapies.
Unusual Sites of Involvement in Non-Hodgkin's Lymphoma
Authors: C. Sucker, K.-M. Klima, G. Doelken, C.-D. Heidecke, G. Lorenz, M. Stockschlaeder
Journal: Journal of Clinical Oncology (2002)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.21.4397 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12409341 Unusual Sites of Involvement in Non-Hodgkin's Lymphoma Case 3. Intussusception as a Rare Complication of Mantle-Cell Lymphoma C. SuckerxC. SuckerSearch for articles by this author , K.-M. KlimaxK.-M. KlimaSearch for articles by this author , G. DoelkenxG. DoelkenSearch for articles by this author , C.-D. HeideckexC.-D. HeideckeSearch for articles by this author , G. LorenzxG. LorenzSearch for articles by this author , M. StockschlaederxM. StockschlaederSearch for articles by this author Show More Ernst-Moritz-Arndt University, Greifswald, Germany https://doi.org/10.1200/JCO.2002.20.21.4397 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
Arthroscopy in Children
Authors: P G Hope
Journal: Journal of the Royal Society of Medicine (1991)

Arthroscopy was performed on the knees of 67 children aged 2-16 years with an overall clinical diagnostic accuracy of 45%. The most common clinical diagnoses were meniscal tear and patello-femoral pain and the accuracy of these diagnoses was 33% and 59% respectively. Diagnostic accuracy seemed unrelated to age. Arthroscopy led to definitive treatment which relieved symptoms in 21 (31%) of cases, revealed a diagnosis only in 43 (64%), and was non-contributory in 3 (4.5%). The procedure did not significantly help patients with patello-femoral pain.
It may be harder than we thought, but political diversity will (still) improve social psychological science
Authors: Jarret T. Crawford, José L. Duarte, Jonathan Haidt, Lee Jussim, Charlotta Stern, Philip E. Tetlock
Journal: Behavioral and Brain Sciences (2015)

Abstract In our target article, we made four claims: (1) Social psychology is now politically homogeneous; (2) this homogeneity sometimes harms the science; (3) increasing political diversity would reduce this damage; and (4) some portion of the homogeneity is due to a hostile climate and outright discrimination against non-liberals. In this response, we review these claims in light of the arguments made by a diverse group of commentators. We were surprised to find near-universal agreement with our first two claims, and we note that few challenged our fourth claim. Most of the disagreements came in response to our claim that increasing political diversity would be beneficial. We agree with our critics that increasing political diversity may be harder than we had thought, but we explain why we still believe that it is possible and desirable to do so. We conclude with a revised list of 12 recommendations for improving political diversity in social psychology, as well as in other areas of the academy.
Immunoglobulin D multiple myeloma: presenting features, response to therapy, and survival in a series of 53 cases.
Authors: J Bladé, J A Lust, R A Kyle
Journal: Journal of Clinical Oncology (1994)

PURPOSE To analyze the clinical and laboratory characteristics, response to therapy, and survival in 53 patients with immunoglobulin D (IgD) multiple myeloma (MM) from a single institution. PATIENTS AND METHODS Records of all Mayo Clinic patients with IgD MM seen between January 1, 1965 and December 31, 1992 were reviewed. Survival curves were plotted according to the Kaplan-Meier method and statistically compared using the log-rank test. RESULTS The main presenting features were bone pain (72%), fatigue (36%), weight loss (32%), extramedullary plasmacytomas (19%), and associated amyloidosis (19%). Renal function impairment and hypercalcemia were present in 33% and 22% of patients, respectively. The serum electrophoretic pattern showed an M-spike in only 60% of the patients, the remaining having either hypogammaglobulinemia or a normal-appearing pattern. Bence Jones proteinuria was identified in 96%. The type of light chain was lambda in 60% of the patients, kappa in 38%, and indeterminate in 2%. Among 45 patients assessable for response, the objective response rate was 58%. The median duration of survival in the whole series was 21 months. There was a trend for longer survival in patients given combination chemotherapy (median, 20 v 64 months; P = .09). The proportions of patients alive at 3 and 5 years were 36% and 21%, respectively. CONCLUSION Patients with IgD myeloma usually present with a small or no visible monoclonal spike on serum electrophoresis and light-chain proteinuria, thus resembling Bence Jones myeloma. Response to therapy is similar to that observed in other myeloma types. Although the median duration of survival is shorter than that currently achieved in patients with myeloma, one third and one fifth survive for more than 3 and 5 years, respectively.
Abstract 11633: Phosphodiesterase-5 (PDE-5) Inhibitor, Tadalafil, Activates NO/Sirt1/PGC-1 Signaling And Attenuates Mitochondrial Dysfunction In Type 2 Diabetic Hearts
Authors: Saisudha Koka, Hema S Aluri, Edward J Lesnefsky, Rakesh C Kukreja
Journal: Circulation (2012)

Background: Enhanced nitric oxide (NO) production is known to activate Sirt1, which is a histone deacetylase that regulates peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) ...
The impact of age on bronchoalveolar lavage (BAL) cytoimmunological pattern in interstitial lung diseases (ILD) and in healthy controls
Authors: Piotr Kopinski, Andrzej Dyczek, Barbara Balicka-Slusarczyk, Grzegorz Przybylski, Ewelina Wedrowska, Joanna Golinska, Joanna Chorostowska-Wynimko
Journal: European Respiratory Journal (2014)

BACKGROUND. BAL cytoimmunological pattern, e.g. value of CD4/CD8 ratio, depends on individual patient age. We present our experience in ILD patients and healthy controls.  METHODS: BAL was performed in ILD, incl. sarcoidosis (PS), hypersensitivity pneumonitis (HP), asbestosis, silicosis, systemic sclerosis, idiopathic pulmonary fibrosis (IPF), nonspecific interstitial pneumonitis and in controls; n=198, 21, 23, 88, 12, 33,19, and 62, resp. We examined BAL routine cytology, BAL lymphocyte typing and apoptosis. Data were analyzed separately for nonsmokers (NS) and smokers.  RESULTS: The age of NS healthy individuals was negatively correlated with total BAL cell number, AL number and BAL eosinophilia. Positive correlation with CD4/CD8 ratio (+0.42, p  CONCLUSIONS: In ILD diagnostics, BAL cytoimmunological pattern should be considered in the context of patient age. Age-related changes seem to be more expressed in controls than in ILD.
NF-κB and the Immunoglobulin <b> <i>κ</i> </b> Gene Enhancer
Authors: Ranjan Sen
Journal: The Journal of Experimental Medicine (2004)

Enhancers regulate lineage choice and the developmental timing of antigen receptor gene rearrangements. The transcription factor NF-kappaB has been implicated as a key component of the recombination and transcription activation potential of the immunoglobulin kappa chain gene intronic enhancer. Here, I discuss the implications of the new observation that an NF-kappaB binding site-mutated enhancer in the correct biological context does not appear to affect kappa gene expression.
From DNA Damage to Nucleic Acid Sensing: A Strategy to Enhance Radiation Therapy
Authors: Liufu Deng, Hua Liang, Sherry Fu, Ralph R. Weichselbaum, Yang-Xin Fu
Journal: Clinical Cancer Research (2015)

Local irradiation (IR) is widely used in the treatment of primary and metastatic tumors. However, the impact of IR on the immune response is currently being defined. Local and distant relapse after radiotherapy often occurs. The current rationale for the use of IR is based on direct cytotoxicity to cancer cells; however, recent studies have shown that reduction of tumor burden following ablative (large-dose) IR largely depends on type I IFN signaling and CD8(+) T-cell response. Here, we review recent findings indicating that antitumor effects of radiation are contributed by both innate and adaptive immune responses. We focus on immune mechanisms, including cytosolic DNA sensing pathways that bridge the traditional view of IR-mediated DNA damage to DNA-sensing immune pathways. Also, we discuss how the efficacy of radiotherapy might be enhanced by targeting nucleic acid-sensing pathways. These findings highlight the mechanisms governing tumor escape from the immune response and the therapeutic potential of synergistic strategies to improve the efficacy of radiotherapy via immunotherapeutic intervention.
A phase 2 study of ponatinib in patients (pts) with advanced gastrointestinal stromal tumors (GIST) after failure of tyrosine kinase inhibitor (TKI) therapy: Initial report.
Authors: Michael C. Heinrich, Margaret vonMehren, George D. Demetri, Jonathan A. Fletcher, Jichao Sun, J. Graeme Hodgson, Victor M. Rivera, Christopher D. Turner, Suzanne George
Journal: Journal of Clinical Oncology (2014)

10506 Background: Ponatinib is an oral TKI that has potent preclinical activity against several mutant isoforms of KIT, including secondary exon 17 resistance mutants, and PDGFRA. Its preclinical activity against a broad spectrum of clinically-relevant resistance mutations suggests it may provide clinical benefit in pts with GIST resistant to standard approved TKI therapies. Methods: This phase 2 single arm trial evaluates efficacy and safety of ponatinib at 45 mg QD in advanced GIST pts after TKI failure. Cohorts are enrolled based on the presence (A) or absence (B) of primary mutations in KIT exon 11. Primary end point: clinical benefit rate (CBR=CR+PR+SD ≥16 wks) by modified RECIST 1.1 in Cohort A. Secondary end points include CBR in Cohort B, ORR, safety/tolerability. Enrollment of new pts is on hold due to safety observations in other ponatinib trials; enrollment criteria are being revised to include only pts with failure of all 3 TKIs approved for GIST. NCT01874665. Results: From June to Oct 2013, 35 of a planned 45 pts have been enrolled (24 in Cohort A). Baseline characteristics: median age 58 yrs; 46% 2 prior approved TKIs, 46% 3 prior approved TKIs. 74% of pts had ≥4 prior cancer regimens. The median time since diagnosis was 6 yrs. 17 pts discontinued (8 PD, 5 AE, 4 other). As of 6 Jan 2014, median follow-up: Cohort A 4 mos, Cohort B 3 mos. Cohort A CBR at ≥16 wks: 55% (11/20 pts) 1 PR and 10 SD. Cohort A ORR: 8% (2/24). All 5 Cohort A pts with matched PET scans (BL v. C1) had decreased FDG uptake in active lesions and remain on study with SD or better. Cohort B CBR: 22% (2/9); Cohort B ORR: 0%. Most common (≥30%) treatment-emergent AEs of any grade are: rash (54%), fatigue (46%), myalgia (46%), dry skin (40%), headache (40%), abdominal pain (34%), constipation (34%). Treatment-emergent serious AEs (SAEs) occurring in ≥2 pts are: abdominal pain (11%), nausea (6%), vomiting (6%), fatigue (6%). One pt had myocardial ischemia. There was 1 death (pneumonia) possibly ponatinib-related. Conclusions: Initial analysis of this ongoing trial suggests that ponatinib has activity in pts with advanced GIST after failure of prior TKI therapy. Clinical trial information: NCT01874665.
Intrinsic and environmental factors contribute to ciliary dysfunction of human airway epithelial cells in asthma
Authors: Wing Yan Heidi Wan, Lucy B. Woodman, Robert A. Hirst, Edith Gomez, Andrew J. Wardlaw, Christopher O'Callaghan, Christopher E. Brightling
Journal: European Respiratory Journal (2012)

Dysfunctional epithelial ciliary function plays a major role in chronic respiratory diseases such as asthma. However the underlying mechanism is not yet clear. We hypothesized that ciliary dysfunction of distal epithelial cells is due to intrinsic and/or environmental factors.  Primary human basal epithelial cell cultures were differentiated  in vitro  (ALI). Following pre-incubation ±antibiotics and exposure to fresh asthmatic sputum for 24h cell strips were collected. Videos of ciliary epithelial side profiles were recorded using a high-speed camera. Ciliary beat frequency (CBF) and beat patterns were assessed. Microbiology was assessed by routine culture & qPCR, reactive oxygen species (ROS) generation by DCFDA assays.  Asthmatic and healthy ALI showed a similar baseline ciliary function. The effect of asthmatic sputum, without antibiotics, on ciliary function in asthmatic ALI is shown below:  Bacterial load increased overtime but was not different between groups. ROS generation was increased in asthmatic vs healthy basal cells (LogEC 50  -0.5±0.2 vs -1.3±0.2, p=0.05).  Our data suggests that both extrinsic factors i.e. bacterial load and intrinsic abnormalities e.g. ROS handling may contribute to the asthmatic ciliary dysfunction.
Home-Monitoring of Peak Expiratory Flow Rate using Mini-Wright Peak Flow Meter in Diagnosis of Asthma<sup>1</sup>
Authors: John G Prior, G M Cochrane
Journal: Journal of the Royal Society of Medicine (1980)

Home-monitoring of peak expiratory flow rate using the mini-Wright peak flow meter is a useful technique for determining whether or not unexplained respiratory symptoms are caused by asthma. It is of particular value when airflow obstruction cannot be demonstrated at the time of consultation.
Polymyositis and Dermatomyositis
Authors: Anthony Bohan, James B. Peter
Journal: New England Journal of Medicine (1975)

Laboratory FeaturesElevation of sarcoplasmic enzymes in serum (creatine phosphokinase, aldolase, transaminases and lactic dehydrogenase) is valuable both for diagnosis and for following the clinical activity and response to treatment. Although some state that the transaminases are the most reliable,31,33,35 most authorities favor the creatine phosphokinase.2These serum enzymes are not infallible guidelines, for occasionally they remain entirely within the normal range despite active myositis1,51; likewise, when muscle atrophy is extensive in long standing disease, the enzymes may be normal despite active myositis. Motor-neuron diseases, Duchenne muscular dystrophy and other dystrophies, metabolic disorders, endocrinopathies, toxins . . .
Role of pulmonary bio-markers in systemic inflammation in chronic obstructive pulmonary disease: A one year follow up study
Authors: Mradul Daga, Naushad Khan, S. Krishna Prakash, Govind Mawari, S. Akhter Husain, Naresh Kumar
Journal: European Respiratory Journal (2012)

Background & Aim: Elevated circulating levels of inflammatory biomarkers have been found to play an important role in Patients of COPD. We measured TNF alpha, IL6, and CRP levels in COPD patients and assessed their relationship with smoking status, inflammation and disease.  Methods: we assessed three blood biomarkers in 202 COPD patients, 50 current smokers with normal lung function and 30 non smokers. Subjects were evaluated with medical history, Spirometry, 6-minute walk test, BODE index. Biomarkers repeatability was assessed using baseline and 1- year follow up samples.  Results: Serum TNF Alpha Level was higher in COPD patients than smokers controls and Non smokers controls at the base line and at 1 year interval (p value- 0.001]. CRP and IL6 were also significantly higher in COPD patients compared to smoker and non smoker controls. TNF Alpha showed moderate repeatability and was found to be least variable bio-marker over 1- year period with a high degree of statistical significance and multiple regression analysis for CRP, IL-6 confirmed only their association with disease and not smoking status.  Conclusions: Smoking is associated with higher levels of TNF- alpha mediated systemic inflammation with or without COPD.
Nontuberculous mycobacteria lung infection in bronchiectasis: Prevalence and clinical characteristics
Authors: Jin-Fu Xu, Xiao-bin Ji, Li-chao Fan, He-ping Xiao, Hai-Wen Lu
Journal: European Respiratory Journal (2014)

The prevalence, risk factors and clinical features of bronchiectasis with NTM lung infection in China remain unclear. Retrospective analysis of patients diagnosed as bronchiectasis or bronchiectasis with NTM lung infection(NTMLI) from January 2009 to December 2012 in a tertiary hospital. The demographic data, risk factors and clinical characteristics data were concluded and comparatively analyzed. Systematic analysis was performed in 192 cases who diagnosed as bronchiectasis with NTMLI. The number of patients with bronchiectasis was 3,857 cases. Patients with ultimate diagnosis of bronchiectasis with NTMLI were 192 cases, accounting for 4.98%. The sex ratio of bronchiectasis with NTMLI group was 1:2.1. The percentages of past history of pulmonary tuberculosis in bronchiectasis patients with or without NTMLI were significantly different (16.7% vs. 28.8%). The proportion of history of long-term use of immunosuppressive agents in bronchiectasis with NTMLI patients (11.5%) was significantly higher than that in bronchiectasis patients (5%). There are no differences on age, smoking history and history of diabetes between two groups. 24.3% of the bronchiectasis with NTMLI patients showed CD4 + T/CD8 + T cell ratio decreased. The positive rates of blood interferon gamma release assay (IGRA/T-SPOT) test in bronchiectasis with NTMLI patients were low. The separation rate of other bacteria in bronchiectasis with NTM lung infection (14.1%) was lower than that in bronchiectasis patients (24.5%). Women, long-term use of immunosuppressive agents in bronchiectasis patients were prone to accompany NTM lung infection. For susceptible patients, doctors should take the initiative to screen NTMLI.
Abstract 3693: Early Growth Response Gene-1 Deficiency In Bone-marrow-derived Cells Reduces Macrophage Accumulation And Atherosclerotic Lesion Formation In A Hyperlipidemic Mouse Model
Authors: Michael R Preusch, Claudia Albrecht, Gotz Hofmann, Erwin Blessing, Hugo A Katus, Florian Bea
Journal: Circulation (2008)

Early growth response gene-1 (Egr-1), a prototype of a family of zinc-finger transcription factors, is a master regulator of many genes which play important roles in cardiovascular diseases. Within atherosclerotic lesions Egr-1 is expressed in several cell types, such as smooth muscle cells, endothelial cells and monocytes/macrophages. Since macrophages play a pivotal role in atherosclerotic lesion development, this study investigated the effects of Egr-1-deficiency within bone-marrow derived cells on the development of atherosclerosis in a hyperlipidemic mouse model. Therefore we transplanted bone-marrow from Egr-1 deficient mice and wild type controls into lethally irradiated low-density lipoprotein receptor deficient mice. After 20 weeks on a western diet atherosclerotic lesions within the aortic sinus and gene expression of inflammatory genes in the aortas of the recipients were evaluated. Mice receiving Egr-1 deficient bone-marrow had less atherosclerotic lesion development compared with mice receiving wild type bone-marrow (318 736 ± 98 910μm 2 vs. 404 539 ± 92 408μm 2 , p&lt;0.05). The size of the necrotic core within the lesions was also reduced. Immunohistochemistry revealed that mice receiving Egr-1 deficient bone-marrow had less macrophages in comparison to controls. Gene expression analysis in the aortas of the mice demonstrated reduced expression of Vascular Cell Adhesion Molecule (VCAM-1), an important adhesion molecule during the development of atherosclerosis. These results were validated with in vitro studies where Egr-1-deficient peritoneal macrophages revealed less VCAM-1 mRNA expression after stimulation with lipopolysaccharide in comparison to wildtype macrophages. This study demonstrates that bone-marrow derived Egr-1 promotes macrophage accumulation and atherosclerotic lesion development possible over an increased expression of VCAM-1.
Abnormal heart rate recovery and chronotropic incompetence on submaximal exercise in COPD
Authors: Mansi Gupta, Vishal Bansal, Sunil Chhabra
Journal: European Respiratory Journal (2011)

Background: A delayed heart rate recovery (HRR) after graded and an attenuated heart rate response (chronotropic incompetence, CI) are markers of cardiac autonomic dysfunction and predict cardiovascular mortality. The latter also characterize COPD. Therefore we hypothesized that decreased HRR and CI should coexist in COPD.

Methods: After lung function evaluation, 39 stable COPD patients and 11 healthy controls underwent submaximal cycle ergometry. Heart rate was measured at peak exercise and at 1-min recovery. Abnormal HRR was defined as a recovery of ≤12 beats in the first minute post-exercise. Chronotropic incompetence was evaluated by measuring the Chronotropic Response Index (CRI = \[(peak heart rate - resting heart rate)/\] \[(220 - age) – (resting heart rate)\].

Results: The HRR was 13±9.1 beats and 23.9±5.9 beats in patients and controls (p<0.001) while CRI was 44.59±13.9 and 61.2±5.1 (p<0.01) in these groups, respectively. An abnormal HRR was observed in 29 (74.4%) of the patients. The HRR and CRI were significantly correlated. Both HRR and CRI showed a decreasing trend with increasing GOLD severity and BODE index. On univariate analysis, HRR was negatively associated with age, pack-years of smoking and diffusion capacity/alveolar volume (DLCO/VA). On multiple logistic regression, after adjusting for other variables, a reduced DLCO/VA was the only significant, though weak, determinant of reduced HRR.

Conclusions: Patients with COPD have a decreased HRR and CI on exercise indicating autonomic dysfunction. These well-established markers of cardiovascular morbidity and mortality should be clinically useful tools for risk stratification and prognostication in patients with COPD.