tbuckley/cabot-search huggingface dataset:
Long-Acting Coronary Vasodilator Drugs:Metamine, Paveril, Nitroglyn and Peritrate
Authors: HENRY I. RUSSEK, BURTON L. ZOHMAN, ALICE E. DRUMM, WILLIAM WEINGARTEN, VIRGIL J. DORSET
Journal: Circulation (1955)

Recognition of the value of glyceryl trinitrate (nitroglycerine) in the treatment and prevention of anginal attacks has confirmed the belief that coronary blood flow may be influenced favorably by drug therapy and has led to a search for vasodilators capable of more prolonged action. The most popular of the newer agents which are alleged to have this desirable effect are Metamine, Paveril, Nitroglyn and Peritrate. In order to evaluate these drugs, the modifying action of each agent on the electrocardiographic response to standard exercise (Master two-step test) was recorded and compared in 21 carefully selected patients with coronary disease. Analysis of the results obtained with varying dosage administered from one to six hours prior to exercise disclosed that Peritrate was vastly superior to the other three drugs and that it alone was worthy of the designation "long-acting coronary vasodilator."
Randomised trial of interferon α-2a as adjuvant therapy in resected primary melanoma thicker than 1·5 mm without clinically detectable node metastases
Authors: Jean Jacques Grob, Brigitte Dreno, Pauline de la Salmoniere, Michele Delaunay, Didier Cupissol, Bernard Guillot, Pierre Souteyrand, Bruno Sassolas, Jean-Pierre Cesarini, Sylvie Lionnet, Catherine Lok, Claude Chastang, Jean Jacques Bonerandi
Journal: The Lancet (1998)
Ventricular vulnerability during sympathetic stimulation: role of heart rate and blood pressure
Authors: R. L. VERRIER, P. L. THOMPSON, B. LOWN
Journal: Cardiovascular Research (1974)

Sequential pulsing of the normal ventricle of intact dogs with twice threshold stimuli during stellate ganglion stimulation resulted in a 60% incidence of ventricular fibrillation (VF). The occurrence of VF was independent of accompanying changes in heart rate and arterial blood pressure. Reserpine pretreatment prevented the development of VF.
Effectiveness of rugby headgear in preventing soft tissue injuries to the head: a case-control and video cohort study: Table 1
Authors: S J Jones, R A Lyons, R Evans, R G Newcombe, P Nash, M McCabe, S R Palmer
Journal: British Journal of Sports Medicine (2004)

Objective: To determine if headgear use by rugby players was associated with a reduced risk of head or facial laceration, abrasion, or fracture. Methods: An emergency department based case-control study in South Wales, UK, with cases being rugby players treated for superficial head and facial injuries and controls being their matched opponents during the game. A review of videos of the 41 games in the 1999 Rugby World Cup was also carried out to compare with the case-control study. Odds ratios (OR) and 95% confidence intervals (95% CI) were used to measure association between exposure (headgear wearing) and outcome (head and facial injuries). Results: In the case-control study, 164 pairs were analysed, with headgear worn by 12.8% of cases and 21.3% of controls. Headgear use was associated with substantial but non-significant reductions in superficial head (OR = 0.43, 95% CI 0.13 to 1.19) and facial (OR = 0.57, 95% CI 0.21 to 1.46) injuries. The video study followed 547 players over 41 games, during which there were 47 bleeding injuries to the head. Headgear use significantly reduced the risk of bleeding head injury in forwards (OR = 0.14, 95% CI 0.01 to 0.99, p = 0.02), but not in backs. There was also a higher risk of facial injury among forwards, but this was not significant. Conclusions: The combined results suggest that headgear can prevent certain types of superficial head injuries in players at all levels of the game, but the evidence is strongest for superficial head injury in elite forwards. A randomised controlled trial would be the best way to study this further.
Application of conditional probability analysis to the clinical diagnosis of coronary artery disease.
Authors: G A Diamond, J S Forrester, M Hirsch, H M Staniloff, R Vas, D S Berman, H J Swan
Journal: Journal of Clinical Investigation (1980)

Analysis of multiple noninvasive tests offers the promise of more accurate diagnosis of coronary artery disease, but discordant test responses can occur frequently and, when observed, result in diagnostic uncertainty. Accordingly, 43 patients undergoing diagnostic coronary angiography were evaluated by noninvasive testing and the results subjected to analysis using Bayes' theorem of conditional probability. The procedures used included electrocardiographic stress testing for detection of exercise-induced ST segment depression, cardiokymographic stress testing for detection of exercise-induced precordial dyskinesis, myocardial perfusion scintigraphy for detection of exercise-induced relative regional hypoperfusion, and cardiac fluoroscopy for detection of coronary artery calcification. The probability for coronary artery disease was estimated by Bayes' theorem from each patient's age, sex, and symptom classification, and from the observed test responses. This analysis revealed a significant linear correlation between the predicted probability for coronary artery disease and the observed prevalence of angiographic disease over the entire range of probability from 0 to 100% (P less than 0.001 by linear regression). The 12 patients without angiographic disease had a mean posttest likelihood of only 7.0 +/- 2.6% despite the fact that 13 of the 60 historical and test responses were falsely "positive." In contrast, the mean posttest likelihood was 94.1 +/- 2.8% in the 31 patients with angiographic coronary artery disease, although 45 of the 155 historical and test responses were falsely "negative." In 8 of the 12 normal patients, the final posttest likelihood was under 10% and in 26 of the 31 coronary artery disease patients, it was over 90%. These estimates also correlated well with the pooled clinical judgment of five experienced cardiologists (P less than 0.001 by linear regression). The observed change in probability for disease for each of the 15 different test combinations correlated with their information content predicted according to Shannon's theorem (P less than 0.001 by linear regression). These results support the use of probability analysis in the clinical diagnosis of coronary artery disease and provide a formal basis for comparing the relative diagnostic effectiveness and cost-effectiveness of different test combinations.
Granzyme B–Mediated Cytochrome C Release Is Regulated by the Bcl-2 Family Members Bid and Bax
Authors: Jeffrey A. Heibein, Ing Swie Goping, Michele Barry, Michael J. Pinkoski, Gordon C. Shore, Douglas R. Green, R. Chris Bleackley
Journal: The Journal of Experimental Medicine (2000)

Cytotoxic T lymphocytes (CTLs) destroy target cells through a mechanism involving the exocytosis of cytolytic granule components including granzyme B (grB) and perforin, which have been shown to induce apoptosis through caspase activation. However, grB has also been linked with caspase-independent disruption of mitochondrial function. We show here that cytochrome c release requires the direct proteolytic cleavage of Bid by grB to generate a 14-kD grB-truncated product (gtBid) that translocates to mitochondria. In turn, gtBid recruits Bax to mitochondria through a caspase-independent mechanism where it becomes integrated into the membrane and induces cytochrome c release. Our results provide evidence for a new pathway by which CTLs inflict damage and explain the caspase-independent mechanism of mitochondrial dysfunction.
Combined disc methods for the detection of KPC- and/or VIM-positive Klebsiella pneumoniae: improving reliability for the double carbapenemase producers
Authors: V. Miriagou, E. Tzelepi, S.D. Kotsakis, G.L. Daikos, J. Bou Casals, L.S. Tzouvelekis
Journal: Clinical Microbiology and Infection (2013)
Contributions to Drug Resistance in Glioblastoma Derived from Malignant Cells in the Sub-Ependymal Zone
Authors: Sara G.M. Piccirillo, Inmaculada Spiteri, Andrea Sottoriva, Anestis Touloumis, Suzan Ber, Stephen J. Price, Richard Heywood, Nicola-Jane Francis, Karen D. Howarth, Vincent P. Collins, Ashok R. Venkitaraman, Christina Curtis, John C. Marioni, Simon Tavaré, Colin Watts
Journal: Cancer Research (2014)

Abstract Glioblastoma, the most common and aggressive adult brain tumor, is characterized by extreme phenotypic diversity and treatment failure. Through fluorescence-guided resection, we identified fluorescent tissue in the sub-ependymal zone (SEZ) of patients with glioblastoma. Histologic analysis and genomic characterization revealed that the SEZ harbors malignant cells with tumor-initiating capacity, analogous to cells isolated from the fluorescent tumor mass (T). We observed resistance to supramaximal chemotherapy doses along with differential patterns of drug response between T and SEZ in the same tumor. Our results reveal novel insights into glioblastoma growth dynamics, with implications for understanding and limiting treatment resistance. Cancer Res; 75(1); 194–202. ©2014 AACR.
Maternal vitamin D and E intakes during pregnancy are associated with asthma in children
Authors: Keith M. Allan, Nanda Prabhu, Leone C.A. Craig, Geraldine McNeill, Bradley Kirby, James McLay, Peter J. Helms, Jon G. Ayres, Anthony Seaton, Stephen W. Turner, Graham Devereux
Journal: European Respiratory Journal (2014)

Are maternal vitamin D and E intakes during pregnancy associated with asthma in 10-year-old children? In a longitudinal study of 1924 children born to women recruited during pregnancy, maternal vitamin D intake during pregnancy was assessed by the Food Frequency Questionnaire (FFQ) and vitamin E by FFQ and plasma α-tocopherol; respiratory questionnaires were completed for the 10-year-old children. Their treatment for asthma was also ascertained using administrative data. Longitudinal analyses included data collected at 1, 2, 5 and 10 years. Symptom data were available for 934 (49%) children and use of asthma medication for 1748 (91%). In the children maternal vitamin D intake during pregnancy was negatively associated with doctor-diagnosed asthma at 10 years of age (OR per intake quintile 0.86, 95% CI 0.74-0.99) and over the first 10 years (hazard ratio 0.90, 95% CI 0.81-1.00). Maternal plasma α-tocopherol at 11 weeks gestation was negatively associated with children receiving asthma treatment (OR per standard deviation increase 0.52, 95% CI 0.31-0.87). Maternal vitamin E intake was negatively associated with doctor-diagnosed asthma (OR 0.89, 95% CI 0.81-0.99) in the first 10 years. Low maternal vitamin D and E intakes during pregnancy are associated with increased risk of children developing asthma in the first 10 years of life. These associations may have significant public health implications.
Register shifting of an insulin peptide–MHC complex allows diabetogenic T cells to escape thymic deletion
Authors: James F. Mohan, Shirley J. Petzold, Emil R. Unanue
Journal: The Journal of Experimental Medicine (2011)

In nonobese diabetic (NOD) mice, two sets of autoreactive CD4+ T cells recognize the B:9–23 segment of the insulin B chain. One set, type A, recognizes insulin presented by antigen-presenting cells (APCs). These T cells are highly deleted in the thymus. The second set, type B, does not recognize insulin protein but reacts with soluble B chain peptide. This set is not deleted in the thymus but is activated in the islets of Langerhans. In this study, we examine the specificity of these two types of T cells. The protein-reactive set recognizes the stretch of residues 13–21 of the insulin B chain. The set reactive to peptide only recognizes the stretch from residues 12–20. A single amino acid shift of the B chain peptide bound to I-Ag7 determines whether T cells recognize peptides generated by the processing of insulin, and consequently their escape from thymic purging. Biochemical experiments indicate that peptides bound in the 13–21 register interact more favorably with I-Ag7 than peptides that bind in the 12–20 register. Thus, self-reactive T cells can become pathogenic in the target organ where high concentrations of antigen and/or differences in intracellular processing present peptides in registers distinct from those found in the thymus.
The impact of azithromycin therapy on the airway microbiota in asthma
Authors: Mariel Slater, Damian W Rivett, Lisa Williams, Matthew Martin, Tim Harrison, Ian Sayers, Kenneth D Bruce, Dominick Shaw
Journal: Thorax (2013)

There is interest in the use of macrolide antibiotics in asthma. Macrolides have been shown to improve airway hyper-responsiveness (AHR) and measures of airway inflammation.1 The degree of AHR may relate to the microbiota present in the airways,2 with a recent study reporting that patients with asthma with a significant improvement in AHR following treatment with clarithromycin had a higher bacterial diversity prior to treatment.3 To our knowledge, the impact on the asthmatic airway microbiota of an antibiotic has not been reported and we therefore set out to establish if macrolide therapy was associated with a change in airway microbiota in asthma.
Cancer Cells Regulate Lymphocyte Recruitment and Leukocyte-Endothelium Interactions in the Tumor-Draining Lymph Node
Authors: Virginie Carrière, Renaud Colisson, Carine Jiguet-Jiglaire, Elisabeth Bellard, Gérard Bouche, Talal Al Saati, François Amalric, Jean-Philippe Girard, Christine M'Rini
Journal: Cancer Research (2005)

The physiologic function of the secondary lymphoid organs to recruit large numbers of naïve lymphocytes increases the probability that antigens encounter their rare, sometimes unique, specific T lymphocytes and initiate a specific immune response. In peripheral lymph nodes (LNs), this recruitment is a multistep process, initiated predominantly within the high endothelial venules (HEVs), beginning with rolling and chemokine-dependent firm adhesion of the lymphocytes on the venular endothelium surface. We report here that, in C57BL/6 mice, the recruitment of naïve lymphocytes is impaired in LNs draining a B16 melanoma tumor. Intravital microscopy analysis of the tumor-draining LNs revealed that this effect is associated with an important defect in lymphocyte adhesion in the HEVs and a progressive decrease in the expression of the LN chemokine CCL21. In parallel with these effects, the tumor up-regulated, essentially through a P-selectin-dependent mechanism, the rolling and sticking of circulating polymorphonuclear cells within the LN low-order venules where few rolling and sticking events are usually observed. These effects of the tumor were independent of the presence of metastasis into the LN and occurred as long as the tumor developed. Together, these results indicate that the tumor proximity disturbs the LN physiology by modifying the molecular, spatial, and cellular rules that usually control leukocyte-endothelium interactions into the peripheral LNs. In addition, they emphasize a new role for the low-order venules of the peripheral LNs, which compared with the HEVs, seem to be the preferential port of entry for cells linked to inflammatory processes.
Valproic Acid–Induced Gene Expression through Production of Reactive Oxygen Species
Authors: Yumiko Kawai, Ifeanyi J. Arinze
Journal: Cancer Research (2006)

Abstract Valproic acid (VPA) is a widely used anticonvulsive agent that has profound antiproliferative effects in many cell types, as well as inductive effects on a number of genes. The mechanism of its gene-inducing effect has been reported to involve transcription factors, Sp1 and activator protein-1. Using two well-characterized antioxidant response element (ARE)–driven gene promoters, i.e., mouse heme oxygenase-1 and human NAD(P)H:quinone oxidoreductase 1 genes as tools to monitor the transcriptional response to VPA, we show here that VPA-induced gene transcription was abrogated by antioxidants. With the human Gαi2 gene promoter, which was previously used to establish the involvement of Sp1 in the transcriptional action of VPA, we found that VPA-induced gene transcription was also blocked by antioxidants. Mutation of the ARE (5′-TGACtggGC-3′) in this promoter abrogated the transcriptional response to VPA. With such mutants, the NADPH oxidase inhibitor, diphenyleneiodonium, had no effect on VPA-induced transcription. In gel mobility shift assays, VPA-induced binding of nuclear proteins to a DNA probe containing the relevant ARE sequence in the Gαi2 gene promoter was decreased in nuclear extracts from cells pretreated with antioxidants. Chromatin immunoprecipitation assays showed that the prototype redox-sensitive transcription factors, Nrf2, small Maf protein(s), and c-Fos, were recruited to this promoter in VPA-treated cells. Overall, this study reveals that the mechanism of the transcriptional response to VPA includes VPA-induced production of reactive oxygen species which induce the activation of redox-sensitive transcription factors that interact with the ARE. (Cancer Res 2006; 66(13): 6563-9)
Impact of Positron Emission Tomography/Computed Tomography and Positron Emission Tomography (PET) Alone on Expected Management of Patients With Cancer: Initial Results From the National Oncologic PET Registry
Authors: Bruce E. Hillner, Barry A. Siegel, Dawei Liu, Anthony F. Shields, Ilana F. Gareen, Lucy Hanna, Sharon Hartson Stine, R. Edward Coleman
Journal: Journal of Clinical Oncology (2008)

Purpose Under Medicare's Coverage with Evidence Development policy, positron emission tomography (PET)/computed tomography (CT) and PET became covered services for previously noncovered cancer indications if prospective registry data were collected. The National Oncologic PET Registry (NOPR) was developed to meet these coverage requirements and to assess how PET affects care decisions. Methods The NOPR collected questionnaire data from referring physicians on intended patient management before and after PET. After 1 year, the cohort included data from 22,975 studies (83.7% PET/CT) from 1,178 centers. The numbers of scans performed for diagnosis of suspected cancer (or unknown primary cancer), initial cancer staging, restaging, and suspected cancer recurrence were approximately equal. Prostatic, pancreatic and ovarian cancers represented approximately 30% of cases. Results If PET data were not available, the most common pre-PET plan would have been other imaging. In these patients, the post-PET strategies changed to watching in 37% and treatment in 48%. In patients with planned biopsy before PET, biopsy was avoided in approximately 70%. If the pre-PET strategy was treatment, the post-PET strategy involved a major change in type in 8.7% and goal in 5.6%. When intended management was classified as either treatment or nontreatment, the post-PET plan was three-fold more likely to lead to treatment than nontreatment (28.3% v 8.2%; odds ratio = 3.4; 95% CI, 3.2 to 3.6). Overall, physicians changed their intended management in 36.5% (95% CI, 35.9 to 37.2) of cases after PET. Conclusion This large, prospective, nationally representative registry of elderly cancer patients found that physicians often change their intended management on the basis of PET scan results across the full spectrum of its potential uses.
Quality of Life Differences between Children with and without Atopic Dermatitis
Authors: L.E.P. Salazar, V.P. Rajamanickam, E.L. Anderson, C.J. Tisler, R.E. Gangnon, D.J. Jackson, J.E. Gern, R.F. Lemanske Jr.
Journal: Journal of Allergy and Clinical Immunology (2011)
Vatalanib in Advanced Colorectal Cancer: Two Studies With Identical Results
Authors: Alberto F. Sobrero, Paolo Bruzzi
Journal: Journal of Clinical Oncology (2011)

Thus, the articles by Schanz et al 5 and by Ja ¨dersten et al 8 present findings that highlight cytogenetic and molecular insights into mechanisms underlying the heterogeneity of MDS and the propensity MDS has to progress to a more aggressive stage.Use of more comprehensive and sensitive methods for molecular profiling and inclusion of genetic features associated with disease prognosis in MDS classification systems will likely further define critical biologic lesions that are fundamental to this spectrum of diseases.
Membership in a Diabetes Care Network Improves General Practitioners’ Practices for HbA1c and Microalbuminuria Monitoring: A Cohort Study Among Patients With Type 2 Diabetes
Authors: Ludovic Casanova, Aurélie Bocquier, Sébastien Cortaredona, Stève Nauleau, Laurent Sauze, Vincent Sciortino, Patrick Villani, Pierre Verger
Journal: Diabetes Care (2014)

ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Development of Extensively Drug-resistant Tuberculosis during Multidrug-resistant Tuberculosis Treatment
Authors: Sonya S. Shin, Salmaan Keshavjee, Irina Y. Gelmanova, Sidney Atwood, Molly F. Franke, Sergey P. Mishustin, Aivar K. Strelis, Yevgeny G. Andreev, Alexander D. Pasechnikov, Alexander Barnashov, Tamara P. Tonkel, Ted Cohen
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Extensively drug-resistant (XDR) tuberculosis (TB) may arise in individuals on treatment for multidrug-resistant (MDR) TB. Preventing this amplification of resistance will likely improve clinical outcomes and delay the secondary spread of XDR-TB.To measure the proportion of individuals that develops XDR-TB during the course of MDR-TB treatment, and to identify those factors associated with the development of XDR.We performed a retrospective analysis of 608 consecutive patients with documented MDR-TB who were started on MDR-TB treatment between September 10, 2000 and November 1, 2004 in the Tomsk Oblast TB Treatment Services in Western Siberia, Russian Federation.A total of 6% of patients were observed to develop XDR-TB while on MDR-TB treatment. These patients were significantly less likely to be cured or to complete treatment. Using Cox proportional hazard models, we found that the presence of bilateral and cavitary lesions was associated with a greater than threefold increase in hazard (adjusted hazard ratio [HR], 3.47; 95% confidence interval [CI], 1.32-9.14). Prior exposure to a second-line injectable antibiotic was associated with a greater than threefold increase in hazard (adjusted HR, 3.65; 95% CI, 1.81-7.37), and each additional month in which a patient failed to take at least 80% of their prescribed drugs was associated with nearly an additional 20% hazard of developing XDR-TB (adjusted HR, 1.17; 95% CI, 1.01-1.35).Early and rapid diagnosis, timely initiation of appropriate therapy, and programmatic efforts to optimize treatment adherence during MDR-TB therapy are crucial to avoiding the generation of excess XDR-TB in MDR-TB treatment programs.