tbuckley/cabot-search huggingface dataset:
Impact of positron emission tomography (PET) in stage III non-small cell lung cancer (NSCLC): A prospective randomized trial (PET START)
Authors: Y. Ung, A. Sun, R. MacRae, C. Gu, J. Wright, E. Yu, G. Darling, N. Leighl, W. Evans, M. Levine
Journal: Journal of Clinical Oncology (2009)

7548 Background: Patients with stage III NSCLC are potentially curable using combined modality therapy (CMT) with chemotherapy and radical radiation (RT). The use of PET-CT rather than conventional imaging (CI) may better identify patients for CMT by enhanced tumor staging and improved definition of RT treatment volumes. Methods: Patients with stage III NSCLC (based on histology/cytology, brain CT/MRI, CT thorax, CT/US abdomen, and bone scan) who were considered candidates for CMT were randomized to either PET-CT or CT for RT treatment planning. The primary outcome was the proportion of patients who did not receive CMT because their tumor was upstaged to Stage 4 or their intrathoracic tumor was too extensive for radical RT. Overall survival (OS) and alteration of RT treatment planning volume were secondary outcomes. Target sample size was 400 patients based on a hazard rate reduction of 30% in OS at 2 years in favor of PET-CT with 2-sided alpha = 0.05 and 80% power. We also postulated that 200 patients would be required to detect a 20% difference between arms for the primary endpoint. 5 centers in Ontario participated. Results: The trial commenced in August 2004. In November 2008 after a planned interim analysis for the primary outcome, the Data Safety Monitoring Board recommended stopping recruitment because of superior efficacy with PET-CT. 304 patients were randomized and 289 had analyzable data. 25 patients were unsuitable for CMT: 21 in the PET-CT arm (16 upstaged to Stage 4 and 5 unsuitable for radical RT) and 4 in the CT arm (unsuitable for radical RT). Thus, 21 of 140 (15%) patients in the PET-CT arm achieved the primary outcome compared with 4 of 149 (2.7%) in the CT arm, P= 0.0002. Conclusions: This is the first randomized trial in stage III NSCLC showing that PET-CT is superior to CT planning alone in selecting appropriate patients for CMT. Longer patient follow-up will determine potential impact on OS. No significant financial relationships to disclose.
Experience with pulmonary selective vasodilator treatment in COPD with severe pulmonary hypertension
Authors: Silvia Ulrich, Gonca Suna, Lars Huber, Ursula Treder, Rudolf Speich
Journal: European Respiratory Journal (2011)

Background: Pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD) is frequent and usually mild. However, some COPD patients present with severe dyspnea and marked PH. Whether pulmonary specific vasodilator therapy would be beneficial in this COPD subgroup is not known.  Methods: We analysed all patients with COPD ≥ GOLD II which were treated with either inhaled Iloprost (Ih), Bosentan (B) or Sildenafil (S) in our PH clinic.  Results: From 2000 to 2007 we identified 14 patients (age 65±9 years, 5 females, 13 ex-smokers, BMI 26±5 kg/m2, mPAP 36±7 mmHg, SaO2 90±4%, FEV1 53±18%pred, TLCO 45±28%) treated with Ih (4), B (4), S (6). All patients were treated with inhaled beta-stimulators, anticholinergics and steroids according to their pulmonologists, all were orally anticoagulated and 10 were under supplemental oxygen. After 3 month, 5 patients improved their WHO/NYHA class (1 B, 4 S) and 10 their 6 minute walk distance (6MWD, 3 B, 2 Ih, 5 S, mean 67±54 m), the mean resting SaO2 remained stable (91±5%). After 6 month, WHO/NYHA class maintained improved in 5 patients (1 B, 1 Ih, 3 S) and 6MWD in 8 patients (3 B, 3 Ih, 2 S, mean 77±46m) with a preserved SaO2 91±5%. 9 patients are still alive 49±39 month after initiation of therapy.  Conclusions: In a highly selective COPD population with severe dyspnea and PH at rest, specific vasodilator therapy may be beneficial and well tolerated. Further studies in this field are highly warranted.
Effects of Developmental Activation of the Aryl Hydrocarbon Receptor by 2,3,7,8-Tetrachlorodibenzo- <i>p</i> -dioxin on Long-term Self-renewal of Murine Hematopoietic Stem Cells
Authors: Michael D. Laiosa, Everett R. Tate, Lori S. Ahrenhoerster, Yuhong Chen, Demin Wang
Journal: Environmental Health Perspectives (2015)

Background:Human epidemiological and animal studies suggest that developmental exposure to contaminants that activate the aryl hydrocarbon receptor (AHR) lead to suppression of immune system function throughout life. The persistence of immune deficiency throughout life suggests that the cellular target of AHR activation is a fetal hematopoietic progenitor or stem cell.Objectives:The aim of this study was to identify the effects of transplacental exposure to an AHR agonist on long-term self-renewal of fetal hematopoietic stem cells.Methods:Pregnant C57BL/6 or AHR+/– mice were exposed to the AHR agonist, 2,3,7,8-tetra-​chlorodibenzo-p-dioxin (TCDD). On day 14 of gestation, hematopoietic progenitors from wild-type or AHR-deficient fetuses were placed into in vitro T-lymphocyte differentiation cultures to identify the effects of transplacental TCDD on AHR activation in the fetus. We next analyzed the fetal hematopoietic progenitor cells for changes in reactive oxygen species (ROS). Finally, hematopoietic progenitors from fetuses exposed transplacentally to TCDD were mixed 1:1 with cells from congenic controls and used to reconstitute lethally irradiated recipients for analysis of long-term self-renewal potential.Results:Our findings suggested that the effects of TCDD on the developing hematopoietic system were mediated by direct AHR activation in the fetus. Furthermore, developmental AHR activation by TCDD increased ROS in the fetal hematopoietic stem cells, and the elevated ROS was associated with a reduced capacity of the TCDD-exposed fetal cells to compete with control cells in a mixed competitive irradiation/reconstitution assay.Conclusions:Our findings indicate that AHR activation by TCDD in the fetus during pregnancy leads to impairment of long-term self-renewal of hematopoietic stem cells.Citation:Laiosa MD, Tate ER, Ahrenhoerster LS, Chen Y, Wang D. 2016. Effects of developmental activation of the aryl hydrocarbon receptor by 2,3,7,8-tetrachlorodibenzo-p-dioxin on long-term self-renewal of murine hematopoietic stem cells. Environ Health Perspect 124:957–965; http://dx.doi.org/10.1289/ehp.1509820
The myofibroblast in pulmonary fibrosis displays distinct functional characteristics, depending on its source of origin
Authors: Sinead M. Walsh, Denise A. Boylan, Julie C. Worrell, Robert V. Lumsden, Rosemary Kane, Michael P. Keane
Journal: European Respiratory Journal (2014)

Introduction  Idiopathic pulmonary fibrosis (IPF) is the most common form of idiopathic interstitial pneumonia, with an extremely poor prognosis. The key effector cell is the myofibroblast, characterised by alpha smooth muscle actin (α-SMA) expression. Recruitment of myofibroblasts is from three potential sources: resident fibroblasts, fibrocytes and epithelial cells. However, the relative contribution of each of these sources remains unclear.  Methods  Primary human normal pulmonary fibroblasts, IPF fibroblasts, fibrocytes and small airway epithelial cells were transitioned to myofibroblasts using transforming growth factor-beta (TGF-β) and tumour necrosis factor alpha (TNF-α). Real time PCR, western blotting and immunofluorescence confirmed the myofibroblast transition. A soluble collagen assay (sircol®) and proliferation assay (bromodeoxyuridine/BrdU) was then performed to assess functional characteristics of the myofibroblast populations.  Results  In terms of soluble collagen production, myofibroblasts derived from IPF fibroblasts are most responsive to TGF-β and TNF-α (mean soluble collagen pre treatment 5.2μg/ml, post treatment 10.5μg/ml), followed in turn by fibrocytes, epithelial cells and normal fibroblasts. However, it is the myofibroblast derived from the fibrocyte that produces the highest amount of soluble collagen (17.7μg/ml). In terms of proliferation, it is the normal fibroblasts that are most proliferative, followed by epithelial cells, IPF fibroblasts and fibrocytes.  Conclusion  The myofibroblast in pulmonary fibrosis differs in terms of soluble collagen production and proliferation, depending on its source of origin.
Mass gathering and globalization of respiratory pathogens during the 2013 Hajj
Authors: Z.A. Memish, A. Assiri, A. Turkestani, S. Yezli, M. al Masri, R. Charrel, T. Drali, J. Gaudart, S. Edouard, P. Parola, P. Gautret
Journal: Clinical Microbiology and Infection (2015)
Abstract MP20: Vitamin D Supplementation Increases Global DNA Methylation in Overweight and Obese African Americans with Vitamin D Deficiency
Authors: Haidong Zhu, Ying Huang, Jigar Bhagatwala, Samip Parikh, Robyn Havens, Ishita Kotak, Yanbin Dong
Journal: Circulation (2014)

Introduction: Vitamin D deficiency is associated with cardiovascular disease, diabetes and cancer. Individuals with obesity or darker skin are at risk for vitamin D deficiency. Our genome-wide methylation study has shown that African Americans with vitamin D deficiency have reduced levels of methylation compared with controls. Global decrease in DNA methylation, a common feature of cancer, is associated with genomic and chromosomal instability. Therefore, we aimed to test our hypothesis that vitamin D supplementation will increase global DNA methylation level in overweight and obese African Americans with vitamin D deficiency. Methods: We recently conducted a 16 weeks randomized, placebo controlled clinical trial of vitamin D3 supplementation (NCT01583621). A total of 65 young overweight and obese African Americans (13-45 years, 83% females) with vitamin D deficiency (25-hydroxyvitamin D3 [25(OH)D] &lt; 20 ng/ml) were randomly assigned to receive a supervised monthly oral vitamin D3 dose of placebo (n=16), 18,000 IU (~600 IU/day, the current RDA; n=15), 60,000 IU (~2,000 IU/day; n=17), or 120,000 IU (~4,000 IU/day, the deemed tolerable upper intake level; n=17). Global DNA methylation level (percentage of 5-methylcytosine, %5-mC) was quantified using leukocyte DNA with the MethylFlash Methylated DNA Quantification kit (Epigentek) in a total of 58 participants. Results: At baseline, serum 25(OH)D levels were positively correlated with %5-mC (r=0.26, p=0.04) in the entire cohort. A significant increase was observed in the changes of serum 25(OH)D from baseline to 16 weeks (0.9 ± 2.0, placebo; 8.6 ± 2.1, 600 IU/day; 20.1 ± 2.0, 2,000 IU/day; and 21.2 ± 2.0 ng/ml, 4,000 IU/day; p&lt;0.01). In addition, a significant dose-responsive increase was observed in the changes of %5-mC from baseline to 16 weeks (0.00 ± 0.18, placebo; 0.02 ± 0.20, 600 IU/day; 0.29 ± 0.17, 2,000 IU/day; and 0.66 ± 0.18%, 4,000 IU/day group; p&lt;0.01). This response remained significant even after adjusting for age, sex and BMI. Moreover, the changes in %5-mC were significantly correlated with the changes in serum 25(OH)D (r=0.60, p=0.02) in the 4,000 IU group. Conclusions: Vitamin D supplementation increases global DNA methylation level in a dose-responsive manner. Increased global DNA methylation, subsequently increased genomic and chromosomal stability may be one of the underlying mechanisms by which vitamin D exerts its beneficial effects on cardiovascular disease, diabetes and cancer. Large scale vitamin D supplementation clinical trial is warranted to verify our findings.
Suppression of Established Friend Virus Leukemia by Statolon. III. Development of FV-Leukemogenic and FV-Immunogenic Activities in Bloods, Spleens, and Lymph Nodes&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: E. Frederick Wheelock, Nancy L. Caroline, Richard D. Moore
Journal: JNCI Journal of the National Cancer Institute (1971)

Statolon, a mycophage from Penicillium stoloniferum, cleared Friend virus (FV) from the blood of infected mice within 3 days after administration and suppressed all leukemogenic activity in the spleens of 40–90% of the DBA/2 mice by the 38th day after inoculation. At that time, the spleen contained many cells capable of inducing resistance to FV in normal mice. As these FV resistance-inducing cells decreased in number over the subsequent 200 days, leukemogenic cells reappeared and characteristic FV leukemia emerged. Statolon-protected mice developed numerous normal-appearing plasma cells in their spleens and lymph nodes, whereas leukemic mice not protected by statolon developed only a few plasma cells, many of which were abnormal. It is postulated that statolon may produce long-lasting suppression of FV leukemia by promoting an effective immunologic response to FV-leukemic cells.
Safety and practices during stress cardiac magnetic resonance in COPD: A 3-year experience from a tertiary referral centre
Authors: Ian S. Stone, Thivya Thirukumar, Mohammed Kanji, Neil C. Barnes, Steffen E. Petersen
Journal: European Respiratory Journal (2013)

Introduction Significant cardiovascular mortality exists in COPD which may prompt increased referrals to exclude coronary disease. Reservations persist about cardiovascular magnetic resonance (CMR) adenosine perfusion imaging (PI) in COPD. Aims To look at patterns of referral, safety and practices of PI in COPD. Methods 54 consecutive COPD patients (mean age 66.2±9, 41 Male, 13 females) who underwent CMR between 2008-2011 were identified from the hospital imaging registry and a retrospective record review performed. Results There were increased COPD referrals for CMR year on year. Reasons included PI (44), anatomy (3), cardiomyopathy (2), pre-operative (2) and routine function (2) assessment. Tolerability of CMR was good. Difficulties included claustrophobia (2) and poor image quality due to dyspnea (4) and arrhythmia (1). 32/44 underwent PI and all but 2 were successfully completed, with no reported chest pain, palpitations, wheeze, nausea or heart block and only one case of dysnpnoea. Reasons for not proceeding with PI were COPD (6), “airways disease” (4), claustrophobia (2) and asthma (1), which appears to have been based on physician’s judgment rather than objective measures, with only 8/44 pulmonary function test (PFT) records being available at the tertiary centre at the time of the scan. Review of 31/44 PFTs showed no difference in age (p=0.53), FEV1% predicted (p=0.37) or Airflow obstruction (AO) (p=0.78) between those that did and did not proceed to PI with 9.7% misdiagnosed as having AO. Conclusion The use of PI in COPD is increasing. Concerns over safety persists but appear unfounded and may result in suboptimal management of this high-risk group.
Eu-estrogenemia, KNDy Neurons, and Vasomotor Symptoms
Authors: Irwin J. Kerber, Ralph J. Turner
Journal: JAMA Internal Medicine (2015)

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ChlVPP/PABlOE and radiotherapy in advanced Hodgkin's disease. The Central Lymphoma Group.
Authors: M H Cullen, N S Stuart, C Woodroffe, A Murphy, J Fletcher, G R Blackledge, J A Child, R J Grieve, E L Jones
Journal: Journal of Clinical Oncology (1994)

PURPOSE The United Kingdom Central Lymphoma Group (CLG) has modified mechlorethamine, vincristine, procarbazine, and prednisone/doxorubicin, bleomycin, vinblastine, and dacarbazine (MOPP/ABVD) by substituting mechlorethamine with chlorambucil and dacarbazine with etoposide in the treatment of patients with advanced Hodgkin's disease (HD). Prednisolone is included in the bleomycin-containing combination, and the vinca alkaloids have been switched to balance the myelotoxicity of the two component regimens. PATIENTS AND METHODS The resulting ChlVPP/PABlOE regimen is as follows: on days 1 to 14, chlorambucil 6 mg/m2 orally, procarbazine 100 mg/m2 orally, and prednisolone 30 mg/m2 orally; on days 1 and 8, vinblastine 6 mg/m2 intravenously (i.v.); on day 29, doxorubicin 40 mg/m2 i.v.; on days 29 and 36, vincristine 1.4 mg/m2 (maximum, 2 mg) i.v., and bleomycin 10 mg/m2 i.v.; on days 30, 31, and 32, etoposide 200 mg/m2/d orally; on days 29 to 43, inclusive, prednisolone, 30 mg/m2 orally. The second full cycle restarts on day 50. Treatment continues to maximum response plus two full cycles, but with a minimum of three full cycles. Radiotherapy is administered, after chemotherapy, to sites of previously bulky disease. Since 1983, 216 patients with previously untreated, advanced Hodgkin's disease (HD) have entered this study. RESULTS The complete remission (CR) rate after chemotherapy was 73% (95% confidence interval [CI], 67% to 79%), and after additional radiotherapy was 85% (95% CI, 80% to 90%). The failure-free survival (FFS) rate at 5 years was 68% (95% CI, 61% to 74%), and the overall actuarial survival at 5 years was 78% (95% CI, 72% to 84%). The CR rate in patients in the poorer prognostic categories was high: 81% in patients with albumin levels less than 37 g/L, 79% in patients older than 40 years of age, 84% in stages IIIB plus i.v. disease, and 79% in patients presenting with B symptoms. As expected, nausea and vomiting were not major problems, although infection, often in the context of myelosuppression, complicated almost half the cases, and 29% of patients required admission at some stage for treatment of infection. CONCLUSION In this multicenter study, ChlVPP/PABlOE produced results comparable to those reported for MOPP/ABVD, but with less nausea and vomiting. Treatment duration was shorter than in the original MOPP/ABVD regimen, and than that used in the Cancer and Leukemia Group B (CALGB) trial. It will now be compared with PABlOE alone.
Identification of bacterial pulmonary infection by a PCR based rapid molecular diagnostic assay in bronchoalveolar lavage
Authors: Kathleen Jahn, Michael Tamm, Minna Maki, Marko Kuisma, Daina Stolz
Journal: European Respiratory Journal (2012)

Rapid PCR based diagnostic tools have been developed to diagnose early bacterial sepsis. If there is a suspicion of pneumonia patients are usually empirically treated. Bronchoscopy with BAL is advocated in patients with nonresolving pneumonia. Bacterial PCR might allow to find bacterial pathogens in patients with nonresolving pneumonia under current treatment. In a pilot-study we analysed the diagnostic yield of a new PCR- and microarray-based rapid molecular diagnostic assay (Prove-it) with 35 samples auf BAL-fluid including patients with non-resolving pneumonia.  Most of the patients are already pretreated before a sampling with BAL could be done. We included 22 patients (group A) undergoing bronchoscopy with BAL with a strong clinical suggestion of bacterial infection (purulent bronchial secretions) and 13 patients (group B) with no evidence of bacterial infection and no inflammatory signs in the peripheral blood (low CRP). 73% of group A were under antibiotic treatment as compared to 15% in group B. Conventional microbiological cultures showed no growth in group B. In group A there were bacteria grown from 10 samples (45%). The Prove it assay identified additional bacteria in 7 BALs of group A with negative culture results (mainly haemophilus influenzae). 3 cases were cultural positive (pseudomonas aeruginosa, klebsiella oxytoca, enterobacter) without detection in Prove it assay. On the other hand bacteria were identified by Prove it in 6 cases of group B.   Conclusion : Bacterial Multiplex PCR (Prove it) might be an interesting tool to diagnose bacterial infection in the BAL of patients with nonresolving pneumonia under current treatment with antibiotics.
Role of systemic inflammation mediated by IL-6 and TNF-alpha cytokines in chronic obstructive pulmonary disease and its progression: A three year follow up study
Authors: Naushad Khan, Mradul Daga, Govind Mawari, Syed Akhter Husain
Journal: European Respiratory Journal (2013)

Background: Many of the systemic manifestations of COPD are mediated through increased levels of inflammatory proteins. Past studies have shown that mean value of Interleukin-6 (IL-6) and TNF Alpha do not change significantly in COPD patients over a one-year period. However, longer period follow-up studies are still lacking. We assessed the long term repeatability of IL-6 and TNF-alpha in COPD patients to test the association between these inflammatory mediators, smoking status and disease progression.  Methods: A cross sectional analysis comparing 250 COPD patients, 50 current smokers and 30 never smoker controls was performed. Assessments included medical history, BMI, spirometry, 6MWT, BODE index at baseline and after three years. Serum & plasma concentrations of IL-6 and plasma TNF Alpha was measured by high sensitivity ELISA.  Results: Serum TNF Alpha and IL-6 were higher in COPD patients (4.2; 0.9 pg/ml) and in current smokers (3.8;0.3pg/ml) compared to non smoker controls (2.9; 0.27 pg/ml) at the baseline. TNF alpha showed moderate repeatability and increase over 3 year period and multiple regression analysis with or without adjustments models showed that TNF alpha levels were associated with smoking status (p  Conclusions: Systemic inflammatory process mediated by IL-6 seems to be persistent, progressive and associated with worse physical performance in COPD Patients and smoking may influence TNF- Alpha mediated systemic inflammation.
The significance of Alfred Adler for the concept of narcissism
Authors: H L Ansbacher
Journal: American Journal of Psychiatry (1985)

Alfred Adler's significance for the concept of narcissism is presented with reference to four aspects: 1) Adler's theory of masculine protest was evidently a factor influencing Freud to turn toward the phenomenon of narcissism. 2) Present-day understanding of narcissism shows remarkable similarity to Adler's views on psychodynamics and neurotic egocentricity. 3) Some contemporary criticisms of Freud's theory of narcissism are very similar to Adler's criticism. 4) Adler's theory of social interest permits subsumption of narcissism under lack of social interest rather than acceptance of it as an expression of innate socially negative tendencies.