tbuckley/cabot-search huggingface dataset:
Does Granulocyte Colony-Stimulating Factor Worsen Anemia in Early Breast Cancer Patients Treated With Epirubicin and Cyclophosphamide?
Authors: Paola Papaldo, Gianluigi Ferretti, Serena Di Cosimo, Diana Giannarelli, Paolo Marolla, Massimo Lopez, Enrico Cortesi, Mauro Antimi, Edmondo Terzoli, Paolo Carlini, Patrizia Vici, Claudio Botti, Luigi Di Lauro, Giuseppe Naso, Cecilia Nisticò, Marcella Mottolese, Franco Di Filippo, Enzo Maria Ruggeri, Anna Ceribelli, Francesco Cognetti
Journal: Journal of Clinical Oncology (2006)

We report on the effects of granulocyte colony-stimulating factor (G-CSF) on hemoglobin (Hb) value in early breast cancer patients receiving high-dose epirubicin and cyclophosphamide (EC) adjuvant treatment.Five hundred and six stage I or stage II female breast cancer patients were treated with E 120 mg/m2 and C 600 mg/m2 with or without G-CSF and randomly assigned to receive in a factorial 2 x 2 design: EC; EC + lonidamine; EC + G-CSF; EC + lonidamine + G-CSF. Five consecutive G-CSF schedules tested 100 randomly assigned patients each: (1) 480 microg subcutaneously on days 8 to 14; (2) 480 microg on days 8, 10, 12, 14; (3) 300 microg on days 8 to 14; (4) 300 microg on days 8, 10, 12, and 14; and (5) 300 microg on days 8 and 12. The mean Hb level of 246 patients receiving EC plus G-CSF was compared with that of 240 patients receiving EC alone. The data presented are derived from an exploratory hypothesis-generating analysis.The EC dose intensity did not statistically differ between the G-CSF and the control arm. From the third cycle onward, the mean Hb value resulted significantly lower in G-CSF arm compared with control at each time point of each cycle (P < .0001). No statistically significant difference in the mean Hb level was observed between schedule 5 and control. Of interest, from the second course onward, the mean Hb level tended to be lower in patients receiving seven or four G-CSF injections compared with those patients who received only two injections.Our data suggest that a G-CSF dose-related effect may play a role in worsening anemia in patients receiving adjuvant EC.
Cell specific markers for eosinophils and neutrophils in sputum and bronchoalveolar lavage fluid of patients with respiratory conditions and healthy subjects
Authors: T Metso
Journal: Thorax (2002)

Background: Highly specific protein markers for eosinophils and neutrophils could be a valuable diagnostic aid in various respiratory disorders. The cell specificity of monoclonal antibodies against eosinophil peroxidase (EPO), eosinophil cationic protein (ECP), human neutrophil lipocalin (HNL), and myeloperoxidase (MPO) was investigated using immunocytochemical techniques. Methods: Induced sputum and bronchoalveolar lavage fluid samples from 14 patients with respiratory conditions and four healthy individuals were studied. Antigens were detected at their intracellular sites in cells with well preserved structures using optimal techniques for fixation, permeabilisation, and immunolabelling. Results: Anti-EPO antibodies reacted only with eosinophils, and anti-HNL antibodies only with neutrophils. Anti-ECP antibodies reacted with both eosinophils and neutrophils and anti-MPO antibodies with neutrophils and monocytes. Cells not stained by monoclonal anti-EPO and anti-HNL antibodies included lymphocytes, monocytes, macrophages, squamous epithelial cells, and ciliated epithelial cells. Conclusions: EPO, a unique component of eosinophils, and HNL, a unique component of neutrophils, are useful markers for the identification of eosinophils and neutrophils, respectively, in sputum and bronchoalveolar lavage fluid.
Standardization of antituberculosis drug resistance surveillance in EuropeRecommendations of a World Health Organization (WHO) and International Union Against Tuberculosis and Lung Disease (IUATLD) Working Group
Authors: V. Schwobel, C.S.B. Lambregts-van Weezenbeek, M-L. Moro, F Drobniewski, S.E Hoffner, M.C Raviglione, H.L Rieder
Journal: European Respiratory Journal (2000)

Surveillance of antituberculosis drug resistance is an essential tool for evaluating the quality of tuberculosis control programmes. Consensus-based recommendations on uniform reporting of antituberculosis drug resistance surveillance data in Europe have been developed by a Working Group of the World Health Organization (WHO) and the International Union Against Tuberculosis and Lung Disease (IUATLD). Laboratories should use standardized methods for testing drug susceptibility with a quality assurance programme including national and international proficiency testing. The proportion of drug resistance, particularly resistance to isoniazid, rifampicin or both (multidrug resistance) among all definite, i.e. culture-positive, tuberculosis cases at the start of treatment is the major indicator of interest. It should be calculated separately among patients treated previously and among those who have never been treated with &gt; or = 1 month of combined antituberculosis drugs. The Working Group recommends that, in countries in which resources allow, laboratories report drug susceptibility test results on all isolates of the Mycobacterium tuberculosis complex. Test results of the specimen at the start of treatment and clinical data from the notification should be linked using a suitable identifier. Results should be presented by calendar year and analysed by age, sex, place of birth, site of disease and sputum smear results. In countries in which a routine system cannot be organized, representative surveys or sentinel systems are possible alternatives. In some countries, the annual prevalence of multidrug-resistant tuberculosis may be estimated through a national laboratory reporting system.
Impaired Regulatory T-Cell Response and Enhanced Atherosclerosis in the Absence of Inducible Costimulatory Molecule
Authors: Israel Gotsman, Nir Grabie, Rajat Gupta, Rosa Dacosta, Malcolm MacConmara, James Lederer, Galina Sukhova, Joseph L. Witztum, Arlene H. Sharpe, Andrew H. Lichtman
Journal: Circulation (2006)

Background— T-cell–mediated immunity contributes to the pathogenesis of atherosclerosis, but little is known about how these responses are regulated. We explored the influence of the inducible costimulatory molecule (ICOS) on atherosclerosis and associated immune responses. Methods and Results— Bone morrow chimeras were generated by transplanting ICOS-deficient or wild-type bone marrow into irradiated atherosclerosis-prone, LDR receptor–deficient mice, and the chimeric mice were fed a high-cholesterol diet for 8 weeks. Compared with controls, mice transplanted with ICOS-deficient marrow had a 43% increase in the atherosclerotic burden, and importantly, their lesions had a 3-fold increase in CD4 + T cells, as well as increased macrophage, smooth muscle cell, and collagen content. CD4 + T cells from ICOS-deficient chimeras proliferated more and secreted more interferon-γ and tumor necrosis factor-α than T cells from control mice, which suggests a lack of regulation. FoxP3 + regulatory T cells (Treg) were found to constitutively express high ICOS levels, which suggests a role for ICOS in Treg function. ICOS-deficient mice had decreased numbers of FoxP3 + Treg and impaired in vitro Treg suppressive function compared with control mice. Conclusions— ICOS has a key role in regulation of atherosclerosis, through its effect on regulatory T-cell responses.
Muscle stiffness determined from canine left ventricular pressure-volume curves.
Authors: S A Glantz, R S Kernoff
Journal: Circulation Research (1975)

We measured pressure-volume curves in nine excised dog ventricles and stress-strain curves in two to five muscle specimens from each ventricle to verify a derived formula that relates muscle stiffness to the ventricular pressure-volume curve. The assumptions underlying this formula are: (1) the ventricle is a uniform spherical shell, (2) all muscle fibers carry average stress and deform as if they were at the midwall, (3) static equilibrium exists, (4) internal pressure induces the only load, and (5) the muscles exhibit an exponential stress-strain curve given by the equation sigma(epsilon) = alpha(ebeta epsilon - 1), where sigma = stress, epsilon = strain, and alpha and beta are constants. There was no significant difference between the stiffness constant, beta, inferred from the left ventricle pressure-volume curves (14+/-4.3[SD]) and that measured directly from the muscle stress-strain curves (16+/-2.8).
Biomarker changes associated with the development of resistance to aromatase inhibitors (AIs) in estrogen receptor-positive breast cancer
Authors: M. Arnedos, S. Drury, M. Afentakis, R. A'Hern, M. Hills, J. Salter, I.E. Smith, J.S. Reis-Filho, M. Dowsett
Journal: Annals of Oncology (2014)
Risk factors and treatment outcome of ertapenem non-susceptible enterobacteriaceae bacteraemia
Authors: Kalisvar Marimuthu, Tat Ming Ng, Christine Teng, Tse Peng Lim, Tse Hsien Koh, Thean Yen Tan, Prabha Unny Krishnan, David Lye
Journal: Journal of Infection (2012)
Primary angioplasty reduces the risk of left ventricular free wall rupture compared with thrombolysis in patients with acute myocardial infarction
Authors: Raúl Moreno, José López-Sendón, Eulogio García, Leopoldo Pérez de Isla, Esteban López de Sá, Ana Ortega, Mar Moreno, Rafael Rubio, Javier Soriano, Manuel Abeytua, Miguel-Angel García-Fernández
Journal: Journal of the American College of Cardiology (2002)
Tailored Chemotherapy Information Faxed to General Practitioners Improves Confidence in Managing Adverse Effects and Satisfaction With Shared Care: Results From a Randomized Controlled Trial
Authors: Michael Jefford, Carl Baravelli, Paul Dudgeon, Adrian Dabscheck, Melanie Evans, Michael Moloney, Penelope Schofield
Journal: Journal of Clinical Oncology (2008)

Purpose General practitioners (GPs) play a critical role in the treatment of patients with cancer; yet often lack information for optimal care. We developed standardized information for GPs about chemotherapy (CT). In a randomized controlled trial we assessed the impact of sending, by fax, information tailored to the particular patient's CT regimen. Primary end points were: confidence treating patients who were receiving CT (confidence), knowledge of adverse effects and reasons to refer the patient to the treatment center (knowledge), and satisfaction with information and shared care of patients (satisfaction). Methods Focus group work informed the development of the CT information which focused on potential adverse effects and recommended management strategies. GPs of patients due to commence CT were randomly assigned to receive usual correspondence with or without the faxed patient/regimen-specific information. Telephone questionnaire at baseline and 1 week postintervention assessed knowledge, confidence, and satisfaction. Results Ninety-seven GPs managed 97 patients receiving 23 types of CT. Eighty-one (83.5%) completed the follow-up questionnaire. GPs in the intervention group demonstrated a significantly greater increase in confidence (mean difference, 0.28; 95% CI, 0.10 to 0.47) and satisfaction (mean difference, 0.57; 95% CI, 0.27 to 0.88) compared with usual care, reflecting a 7.1% and 10.5% difference in score, respectively. No differences were detected for knowledge. GPs receiving the CT sheet found correspondence significantly more useful (P &lt; .001) and instructive (P &lt; .001) than GPs who received standard correspondence alone. Conclusion Information about CT faxed to GPs is a simple, inexpensive intervention that increases confidence managing CT adverse effects and satisfaction with shared care. This intervention could have widespread application.
Comment on “Progesterone/RANKL Is a Major Regulatory Axis in the Human Breast”
Authors: Jun Wang, Akash Gupta, Hong Hu, Robert T. Chatterton, Charles V. Clevenger, Seema A. Khan
Journal: Science Translational Medicine (2013)

In vivo menstrual cycle data support the findings by Tanos et al . that progesterone regulates RANKL in an ex vivo microstructure model of the human breast, but dispute the suppression of estradiol on progesterone-stimulated RANKL expression. RANKL responds to progesterone in a three-dimensional organoid culture model under conditions mimicking luteal-phase hormone concentration, suggesting that the microstructure may not be crucial to demonstrate progesterone responsiveness.
Therapeutic Intervention and Targets for Sepsis
Authors: Todd W. Rice, Gordon R. Bernard
Journal: Annual Review of Medicine (2004)

Sepsis syndrome, a systemic response to infection, can beget devastating outcomes even in previously normal individuals. Recent research in septic patients has led to the discovery that early goal-directed resuscitation guided by continuous monitoring of mixed venous hemoglobin saturation, along with moderate doses of corticosteroids, can reduce mortality. An improved understanding of the complex interaction between the inflammatory and coagulant systems in sepsis pathophysiology has resulted in novel treatments, such as recombinant human activated protein C, which improves survival in patients with severe sepsis and a high risk of death. However, despite an increased understanding of the complex pathophysiology of this syndrome and the discovery of new, effective treatments, severe sepsis still results in significant morbidity and mortality. Consequently, investigations continue into additional therapeutic agents directed against novel targets. Following a review of recent advances in sepsis treatment, we briefly discuss a few of the new, promising therapeutic strategies currently being investigated.
Relationship between adenine nucleotide metabolism and irreversible ischemic tissue damage in isolated perfused rat heart.
Authors: T C Vary, E T Angelakos, S W Schaffer
Journal: Circulation Research (1979)

The relationship between energy metabolism and the extent of irreversible ischemic damage was examined in an isolated perfused working rat heart. The amount of cardiac work recovered after reperfusion of hearts exposed to severe global ischemia was dependent upon both the duration of ischemia and the type of substrate provided (either 5 mM glucose or 5 mM glucose + acetate). There appear to be two distinct phases in the ability to recover mechanical function in the reperfused ischemic heart. The second phase corresponds to the onset of severe irreversible tissue damage. Irreversible mitochondrial damage was not found to correspond with the onset of heart failure since the ATP/ADP ratio remained constant in the reperfused myocardium. Furthermore, there does not appear to be a direct correlation between the total ATP content and the extent of irreversible damage, either during ischemia or following reperfusion. However, the total adenine nucleotide content during ischemia showed dramatic changes which correspond temporally with the initiation of the second phase of damage. The observation that the adenine nucleotide pool becomes further depleted during reperfusion suggests that alterations in the salvage pathway for adenine nucleotide synthesis have occurred. Loss of adenine nucleotides appears to be an excellent marker for irreversible heart failure. Acetate provides some protection the the ischemic myocardium. The mechanism by which acetate mediates this protective effect is discussed.
Fertility and ileal pouch-anal anastomosis * Authors' response
Authors: T. W Eglinton, A. K Waljee, J. F Waljee, A. M Morris, P. D R Higgins
Journal: Gut (2007)

I read with interest the meta-analysis of infertility post ileal pouch-anal anastomosis (IPAA) published by Waljee and colleagues in the November issue.1 The article consolidates the increasing evidence that this procedure is associated with a significant decrease in female fertility.

Having recently reviewed the studies in their analysis, however, I was surprised the authors had included data from the following two trials; the first by Wikland et al 2 assessed 41 patients treated exclusively with conventional proctocolectomy with ileostomy rather than IPAA; the other, by Hudson et al ,3 included 20 patients treated with surgery of which only two had IPAA, while the remainder were treated with …
Disturbance of respiratory muscle control in a patient with early-stage multiple sclerosis
Authors: Maha R. Farhat, Stephen H. Loring, Peter Riskind, Gerald Weinhouse
Journal: European Respiratory Journal (2013)

To the Editor: 

Respiratory dysfunction from multiple sclerosis (MS) is most commonly of insidious onset and related to progressive respiratory muscle weakness [1]. Disorders of respiratory muscle coordination are poorly recognised and challenging to diagnose. We present a case of a patient with MS and no clear muscle weakness whose dyspnoea was associated with a disorder of respiratory muscle control. The potential utility of oesophageal manometry for diagnosis of unexplained dyspnoea is highlighted.

A 54-year-old female with relapsing-remitting MS presented with 2 weeks of dyspnoea and orthopnoea. She was ambulatory with a low extended disability score of 1.5.

6 months earlier she started cyclophosphamide for disease progression recognised by magnetic resonance imaging (MRI). A week after her last infusion she developed severe dyspnoea and orthopnoea. She had no other symptoms. Her vital signs were normal. Her laboratory tests and arterial blood gas were unremarkable. Chest computed tomography showed no pulmonary parenchymal disease. Echocardiography was unremarkable. Pulmonary function testing (PFTs) demonstrated severe restriction, with a 14% lower vital capacity in the supine position.

Her dyspnoea and PFTs improved over the following 1–2 months, but she did not return to her baseline level of pulmonary function. Electromyography (EMG) with phrenic nerve conduction studies demonstrated no abnormalities. MRI was prohibited by her orthopnoea. Previously, MRI demonstrated extensive demyelination in the brain and brainstem that was asymptomatic.

Oesophageal manometry was performed to exclude the possibility of bilateral diaphragmatic dysfunction and to elucidate her unexplained dyspnoea. A balloon-catheter was inserted via the nose to position the balloon in the distal oesophagus to estimate pleural pressure. Repeated attempts to perform a forced vital capacity manoeuvre consistently demonstrated fluctuating exhalations, as evidenced by the saw tooth pattern of the flow volume curve (fig. …
Human Papillomavirus–Based Cervical Cancer Prevention: Long-term Results of a Randomized Screening Trial
Authors: Lynette Denny, Louise Kuhn, Chih-Chi Hu, Wei-Yann Tsai, Thomas C. Wright
Journal: JNCI Journal of the National Cancer Institute (2010)

BackgroundScreen-and-treat approaches to cervical cancer prevention are an attractive option for low-resource settings, but data on their long-term efficacy are lacking. We evaluated the efficacy of two screen-and-treat approaches through 36 months of follow-up in a randomized trial.
Succinate Dehydrogenase Mutation Underlies Global Epigenomic Divergence in Gastrointestinal Stromal Tumor
Authors: J. Keith Killian, Su Young Kim, Markku Miettinen, Carly Smith, Maria Merino, Maria Tsokos, Martha Quezado, William I. Smith, Mona S. Jahromi, Paraskevi Xekouki, Eva Szarek, Robert L. Walker, Jerzy Lasota, Mark Raffeld, Brandy Klotzle, Zengfeng Wang, Laura Jones, Yuelin Zhu, Yonghong Wang, Joshua J. Waterfall, Maureen J. O'Sullivan, Marina Bibikova, Karel Pacak, Constantine Stratakis, Katherine A. Janeway, Joshua D. Schiffman, Jian-Bing Fan, Lee Helman, Paul S. Meltzer
Journal: Cancer Discovery (2013)

Gastrointestinal stromal tumors (GIST) harbor driver mutations of signal transduction kinases such as KIT, or, alternatively, manifest loss-of-function defects in the mitochondrial succinate dehydrogenase (SDH) complex, a component of the Krebs cycle and electron transport chain. We have uncovered a striking divergence between the DNA methylation profiles of SDH-deficient GIST (n = 24) versus KIT tyrosine kinase pathway-mutated GIST (n = 39). Infinium 450K methylation array analysis of formalin-fixed paraffin-embedded tissues disclosed an order of magnitude greater genomic hypermethylation relative to SDH-deficient GIST versus the KIT-mutant group (84.9 K vs. 8.4 K targets). Epigenomic divergence was further found among SDH-mutant paraganglioma/pheochromocytoma (n = 29), a developmentally distinct SDH-deficient tumor system. Comparison of SDH-mutant GIST with isocitrate dehydrogenase-mutant glioma, another Krebs cycle-defective tumor type, revealed comparable measures of global hypo- and hypermethylation. These data expose a vital connection between succinate metabolism and genomic DNA methylation during tumorigenesis, and generally implicate the mitochondrial Krebs cycle in nuclear epigenomic maintenance.
Effects of aerobic training on perivascular inflammation and on vascular activation in a model of asthma
Authors: Adilson Santos Andrade de Sousa, Nicole Rigonato-Oliveira, Flavia Regina Greiffo, Ana Roberta Almeida-Oliveira, Guilherme Cristianini Baldivia, Jefferson Comin Jonco Aquino-Junior, Manoel Carneiro Oliveira-Junior, Ricardo Wesley Alberca Custodio, Paulo Rogério Pereira, Ana Paula Ligeiro Oliveira, Rodolfo Paula Vieira
Journal: European Respiratory Journal (2014)

The airways are the main inflammatory site in asthma, histopathological studies also shows an involvement of pulmonary vessels.Since that aerobic training (AT) inhibits airways inflammation in asthma, this study investigated the possible effects of AT on the activation/deactivation of the perivascular leukocytes and also of the vascular cells. Asthmatic response was induced by ovalbumin (ip injections on days 0, 14, 28 and 42 and aerosol challenge since day 21 (3x/week) until day 53. Low intensity treadmill AT was performed since day 23 until day 52. The quantitative analysis of the expression of the markers described bellow, was performed through histomorphometric technique in the perivascular leukocytes and also the total expression in the vascular wall. The results demonstrated that AT reduced ovalbumin-induced perivascular leukocytes expression of NF-kB (pl0.01), 3-nitrotyrosine (pl0.05), GP91phox (pl0.001), MMP-9 (pl0.05), MMP-12 (pl0.001), TIMP-1 (pl0.01) when compared with OVA group. On the other side, AT increased the expression of SOD-1(pl0.001) and SOD-2(pl0.05). However, no effects of AT was observed on TIMP-1, TIMP-2 and on GPX. Concerning the expression of these markers by the vessels wall, AT only reduced the expression of 8-isoprostane (pl0.05) and 3-nitrotyrosine (pl0.05), suggesting a small participation of the cells of the pulmonary vasculature in this response. We conclude that AT reduces the activation of perivascular leukocytes and also the vascular nitrosative stress in a model of asthma.