tbuckley/cabot-search huggingface dataset:
Safety Of Splenectomy In Hematological Diseases
Authors: Maria Cristina Moragues Martinez, Kati Hurst, Maria Eva Mingot Castellano, Jose Coin Ruiz, Maria Elisa Prieto Sanchez, Isabel Vidales Mancha, Macarena Ortiz Pareja, Manuel Espeso de Haro, Maria Dolores Bautista Ojeda, Ana Isabel Heiniger Mazo
Journal: Blood (2013)
Relation between hostility and coronary heart disease
Authors: M. Petticrew, S. Gilbody, T. A Sheldon, H. Hemingway, M. Marmot
Journal: BMJ (1999)

Editor—The summary points of Hemingway and Marmot’s review of psychosocial risk factors for coronary heart disease may be misleading.1 The first of these states that “prospective cohort studies show a possible aetiological role for type A/hostility.” However, of the four prospective studies of hostility, only two show any significant association between hostility and coronary heart disease (one for women only). Six of the nine aetiological studies of type A behaviour also show no association with coronary heart disease. The other three studies give no information on completeness of follow up or whether outcomes such as angina were assessed in a blinded manner. One of these studies had minimal adjustment for confounding. No study showed any prognostic role for type A behaviour or hostility. Taken together, these studies do not represent robust evidence that these psychological variables have an important role in the development or prognosis of coronary heart disease. 

The authors also rightly suggest that the role of publication bias should be considered. We recently investigated this by re-examining a meta-analysis, also cited by Hemingway and Marmot, which pooled several prospective and retrospective studies of hostility and coronary heart disease and concluded that hostility was an independent risk factor.2 A funnel plot of these studies suggests publication and related biases (figure (top)), indicating underpublication of negative results. However, the apparent publication bias is more likely to be a result of poor methodological quality—in particular, inadequate adjustment for confounding in the primary studies. When we took this into account (using regression to adjust the effect sizes according to the number of variables used as adjusters in the primary study) the relation between hostility and coronary heart disease disappeared and the funnel plot became symmetrical (figure (bottom)). This supports the view that publication bias among these studies should be considered only when other sources of bias, such as the internal validity of the included studies, are taken into account, as suggested by Egger et al.3

Claims about the toxicity of type A behaviour and hostility have led to the development of behavioural “treatments” for these putative risk factors. A recent editorial also went as far as to suggest that, as hostility appeared to be a “toxic component,” we should all be nice to each other.4 Perhaps in the light of Hemingway and Marmot’s review, and the above comments, this advice should be reconsidered.
Signs and symptoms of peripheral neuropathy in adult survivors of childhood acute lymphoblastic leukemia (ALL): Associations with physical performance and chemotherapy doses.
Authors: K. K. Ness, M. M. Hudson, C. Pui, D. M. Green, R. Karlage, L. L. Robison, E. B. Morris
Journal: Journal of Clinical Oncology (2010)

9030 Background: Treatment regimens for childhood ALL continue to contain neurotoxic agents that may interfere with neuromuscular health and physical function. The purpose of this analysis was to examine associations between persistent signs and symptoms of peripheral neuropathy and physical function, and to determine dose response relationships between vincristine, methotrexate, and neuromuscular impairments among survivors of childhood ALL. Methods: Medical records were abstracted and neuromuscular function and physical performance evaluated in adults surviving 10+ years after ALL diagnosis. Associations were examined in regression models. Results: Among 302 survivors (median age 35 years; range 20-57), 36.8% had absent Achilles tendon reflexes, 35.4% < 5 degrees dorsiflexion range of motion (ROM), and 26.2% limited plantarflexion strength. Balance, mobility and six minute walk (6MW) distances were 2.5 or more standard deviations below age and gender expected values in 14.9%, 43.4% and 17.9% of participants, respectively. In age and sex adjusted models, impaired ankle ROM and strength were associated with limited balance, mobility and 6MW distances (p-values < 0.01). In adjusted models (including cranial radiation), survivors treated with intrathecal methotrexate cumulative doses 1-132 mg/m2 were 3.2 (95% CI 2.2-9.7) and those with doses 133+ mg/m2 were 4.7 (95% CI 1.3-15.7) times more likely than patients who received no intrathecal methotrexate to have limited ROM. Those who received vincristine cumulative doses 33+ mg/m2 were 2.1 (95% CI 1.2-3.6) times more likely than those who received lower doses to have limited ROM. Higher vincristine dose was also associated with a 2.1 fold (95% CI 1.1-4.0) increase in the likelihood of reduced ankle strength. Conclusions: Signs and symptoms of peripheral neuropathy in childhood ALL survivors persist and eventually interfere with physical performance. Higher cumulative doses of vincristine and/or intrathecal methotrexate administration are associated with persistent neuromuscular impairments, which have implications on future physical performance as this population ages. No significant financial relationships to disclose.
Abstract 12616: Walking Beyond the Grace Model in the Risk Stratification of Patients With Acute Coronary Syndrome: What Does the Arg, Ncdr and the Euroheart Scores Provide?
Authors: Sergio Raposeiras Roubin, Emad Abu Assi, Pilar Cabanas, Rosa Agra, Eva Pereira, Santiago Gestal, Ruben Fandino, Marta Rodriguez Cordero, Irene Mateo, Amparo Martinez Monzonis, Alberto Garcia Castelo, Jose Maria Garcia Acuna, Carlos Pena Gil, Jose Ramon Gonzalez-Juanatey
Journal: Circulation (2011)

INTRODUCTION. Risk stratification plays a pivotal role in the optimal management of acute coronary syndrome (ACS). The most validated risk score (RS) is the GRACE RS, described in 2003. In 2009 an ...
Abstract 2112: Impact of Sleep-Disordered Breathing on Life-Threatening Ventricular Arrhythmia in Patients with Dilated Cardiomyopathy
Authors: Naoki Serizawa, Dai Yumino, Katsuya Kajimoto, Keiko Gomita, Yoshimi Tagawa, Masayuki Mizuno, Yoichi Ajiro, Atsushi Takagi, Morio Shoda, Yukio Tsurumi, Nobuhisa Hagiwara, Hiroshi Kasanuki
Journal: Circulation (2006)
Clinicopathologic Features and Outcome of Chinese Patients with Myelofibrosis
Authors: Harinder Gill, Yu Yan Hwang, Thomas Sau Yan Chan, Chi Chung Chan, Candia Hay Nun Chan, Herman S.Y. Liu, Vivien Mak, Shek Ying Lin, Chi Kuen Lau, Anskar Y.H. Leung, Albert Kwok Wai Lie, Yok Lam Kwong
Journal: Blood (2014)
Abstract 8978: NADPH Oxidase Inhibition Improves Cardiac Dysfunction Through Cardiac Mast Cell Stabilization and Suppression of the Renin-Angiotensin System
Authors: Takehiro Matsumoto, Atsuyuki Wada, Masato Ohnishi, Masanori Fujii, Takashi Yamamoto, Tomohiro Dohke, Tomoyuki Takayama, Takayoshi Tsutamoto, Minoru Horie
Journal: Circulation (2011)

Reactive oxygen species (ROS) participate in the pathogenesis of cardiac inflammation and the activation of the renin-angiotensin (RA) system in the progression of heart failure (HF). NADPH oxidase is one of the major sources of the ROS production. Mast cells migrated into the failing heart mainly recruited by the locally produced chemokine, stem cell factor, and are involved in the inflammatory process since they generate various substances such as not only chymase which is an ACE independent angiotensin-II formation enzyme but also tumor necrotic factor (TNF)-alpha and transforming growth factor (TGF)-beta in HF. However, It has not been well documented whether NADPH oxidase inhibition affects cardiac inflammatory changes via mast cells and the RA system in HF. Thus, we evaluated the long-term effects of a specific NADPH oxidase inhibitor; apocynin (15mg/kg/day; n=6) on changes in cardiac function and the expression of several inflammatory related genes in dogs with tachycardia induced HF. Cardiac contractile function markedly deteriorated and left ventricular (LV) end-diastolic pressure (EDP) was increased after the induction of HF. However, apocynin significantly improved the ejection fraction and decreased the elevated LVEDP. The inhibitor significantly decreased the enhanced superoxide production (vehicle 78 vs. apocynin 40RLU/min/mg, p&lt;0.05) and NADPH oxidase activity (vehicle 3300 vs. apocynin 1400RLU/min/mg, p&lt;0.05) in the LV assessed by lucigenin-enhanced chemiluminescence compared with the vehicle. Cardiac ACE and NADPH oxidase subunits, gp91phox and p47phox, gene expressions significantly upregurated in HF, however, apocynine attenuated those gene activation. Moreover, apocynine decreased the number of the infiltrated mast cells and suppressed the mRNA of stem cell factor, chymase, TGF-beta, TNF-alpha in the failing heart. In conclusion, specific NADPH oxidase inhibition may become an important strategy in the treatment of cardiac dysfunction via mast cell stabilization and the suppression of RA system.
Abstract 4842: Diagnostic Contribute of Left Ventricular Endomyocardial Biopsy in Patients with Clinical Phenotype of Hypertrophic Cardiomyopathy
Authors: Cristina Chimenti, Angelo Cioppa, Marina Rossi, Romina Verardo, Marco Agrusta, Matteo A Russo, Paolo Rubino, Andrea Frustaci
Journal: Circulation (2008)
Abstract 12820: Predictors of Resuscitation in a Swine Model of Vf Cardiac Arrest: Amplitude Spectral Area (amsa) and Slope Predict a Return of Spontaneous Circulation Independent of the Presence of a Prior Non-Acute Myocardial Infarction
Authors: Julia Indik, Daniel Allen, Michael Gura, Christian Dameff, Ronald W Hilwig, Karl B Kern
Journal: Circulation (2010)
Abstract 238: Oxygen Regulates the Flux of Nitric Oxide Diffusion across the Vascular Wall
Authors: Xiaoping Liu, Parthasarathy Srinivasan, Eric Collard, Paula Grajdeanu, Jay L Zweier, Avner Friedman
Journal: Circulation (2007)

Endothelium-derived nitric oxide (NO) plays an important role in maintaining vascular tone. It is known that NO may be consumed by heme proteins, superoxide and oxygen during diffusion from the endothelium to smooth muscle cells in the vascular wall. Due to the limitation of available techniques, it is unclear to what extent these consumptions can affect the diffusion distance of NO, and if the vascular NO consumption could serve as a “sensor” of oxygen concentrations in the blood vessels. In this study, rat aortas were used as an experimental model for studying NO diffusion process in the vascular system. A Clark-type NO electrode was used to directly measure the flux of NO diffusion across the vascular wall at 37 °C. A segment of aorta was isolated from a 12-week old WKY rat. After the aorta was cleaned and surrounding tissue was removed, it was longitudinally opened. A specifically-designed aorta holder was attached on the tip of the Clark-type NO electrode. The aorta holder surface and the electrode tip surface were aligned in the same plane so that the opened aorta segment could be placed flat on the electrode tip surface and pinned to the aorta holder. Using this technique, we measured the flux of NO diffusion across the aortic wall at different oxygen concentration. It was observed that the NO flux increased 6 to 10 fold when oxygen concentrations dropped from 200 μM to zero. A mathematical model describing the steady-state diffusion-reaction was used in analyzing the experimental data. It was found that the rate of NO decay is first order with respect to [O 2 ] and first order with respect to [NO], and hence of the form k[O 2 ][NO]. The rate constant k was determined as (3.8±0.4)x10 −3 μM −1 s −1 (n=6). With this rate constant, the half-life of NO in the aortic wall in the presence of 200 μM O 2 (equilibrium with room air) will be 0.9 seconds. Our results show that the flux and diffusion distance of NO in the aortic wall is largely regulated by oxygen concentration. When oxygen concentrations drop, NO diffusion distance will significantly increase. As a result, the blood vessel will dilate to a larger extent to allow more blood to be delivered to the hypoxic tissues. Therefore this vascular NO consumption appears to play the role of an oxygen sensor in the regulation of blood flow in the body.
Mutation-based detection of molecular tumor margins in colorectal liver metastasis.
Authors: K. Schmidt, M. Holdhoff, F. Diehl, P. Angenendt, N. Agrawal, K. Judge, K. W. Kinzler, B. Vogelstein, M. A. Choti, L. A. Diaz
Journal: Journal of Clinical Oncology (2010)

3610 Background: Defining adequate resection margins of liver metastasis especially after preoperative chemotherapy is based on empirically determined recommendations and random screening of macroscopic and microscopic tissue sections surrounding the liver metastasis. Mutations are highly specific for tumors and therefore can be used as a marker to accurately determine molecular tumor margins. Methods: In our study we evaluated 12 patients with metastatic colon cancer who underwent partial hepatectomy of 1-6 liver metastasis. Samples were obtained by 2-4 punch biopsies in different directions of surrounding liver tissue at 4, 8, 12 and 16 mm distance to the macroscopic tumor border. A total of 88 samples were analyzed. Tumor specific mutations including KRAS, PIK3CA, APC and TP53 were determined by sequencing tumor tissue. DNA was isolated from biopsies of surrounding liver tissue and analyzed by BEAMing, a highly sensitive PCR based method of mutation detection. Molecular results were correlated with microscopic tissue analysis and clinical data. Results: We were able to detect tumor DNA in surrounding liver tissue in 3 out of 12 patients with 4 samples positive at 4 mm and all samples negative at 8, 12 and 16 mm distance to the macroscopic tumor border with negative control samples. In average 1,047 mutant single stranded DNA fragments were found in 150,000 analyzed DNA fragments. 3 out of 10 patients with previous chemotherapy had positive molecular margins, whereas the 2 patients with naive liver tissue were tested negative for tumor DNA in their marginal zones. Conclusions: The measurement of tumor DNA in tissue is a highly sensitive molecular marker of tumor margins identifying consistently negative margins at > 0.4 cm distance to the macroscopic tumor border in all samples. Tumor DNA as a marker of molecular tumor margins could be helpful in determining accurate biological resection guidelines of liver metastasis and can help to understand the process of tumor reduction after preoperative chemotherapy. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Inostics Inostics Inostics
Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening
Journal: New England Journal of Medicine (2011)

The aggressive and heterogeneous nature of lung cancer has thwarted efforts to reduce mortality from this cancer through the use of screening. The advent of low-dose helical computed tomography (CT) altered the landscape of lung-cancer screening, with studies indicating that low-dose CT detects many tumors at early stages. The National Lung Screening Trial (NLST) was conducted to determine whether screening with low-dose CT could reduce mortality from lung cancer.
Abstract 2227: Results of Primary Percutaneous Coronary Intervention in ST-Elevation Myocardial Infarction Patients Following Cardiac Arrest
Authors: Timothy D Henry, Sue Duval, Michael R Mooney, Katie M Menssen, Christopher E Kapsner, David I Page, William Parham, Barbara T Unger, M N Burke, Ivan J Chavez, Jay H Traverse, David M Larson
Journal: Circulation (2007)

Background: Patients with cardiac arrest associated with STEMI are routinely excluded from clinical trials and therefore, almost no data exist regarding their outcomes with primary PCI. Patients with out of hospital cardiac arrest (OOHCA) are a particularly high-risk cohort and the appropriate reperfusion strategy for these patients is controversial. Methods/Results: We determined the outcomes of patients who sustained a cardiac arrest prior to primary PCI in 1,500 consecutive patients with STEMI admitted to or transferred to a regional PCI center. Overall 159(10.6%) STEMI patients sustained a cardiac arrest prior to PCI, including 47 (3.1%) with OOHCA. The in-hospital, 30-day and 1-year mortality for patients without cardiac arrest, cardiac arrest excluding OOHCA and patients with OOHCA are included in table . 53.3% of the deaths in OOHCA were related to anoxic brain injury compared to 9.1% of the deaths in patients with in-hospital cardiac arrest (p&lt;0.003). Thirty-six percent of patients with OOHCA underwent a cooling protocol (return of spontaneous circulation and persistent neurologic impairment) with a 41% in-hospital mortality. Conclusions: Cardiac arrest prior to PCI (including both OOHCA and in-hospital) in patients with STEMI is a major predictor for in-hospital mortality. Patients with cardiac arrest who survive to discharge subsequently do well. OOHCA has a higher mortality than in-hospital cardiac arrest and the majority of deaths are due to anoxic brain injury. Still, nearly 70% of OOHCA survived to discharge without neurological impairment.
Serological Diagnosis of Tuberculosis
Authors: G H Bothamley
Journal: BMJ (1964)

The past decade has seen dramatic developments in serological tests for tuberculosis. The long history of serological tests for tuberculosis is a testimony to the need for a sensitive diagnostic test, especially when the sputum smear is unhelpful. New reagents, both purified antigens and monoclonal antibodies, provide the means to obtain a sensitivity and specificity to rival the tuberculin skin test and equal other commonly used diagnostic blood tests. Evaluation with sera from patients with smear-positive pulmonary tuberculosis has identified one antigen (antigen 5, the 38 kDa antigen) as a potential screening reagent for infectious tuberculosis and another (16 kDa antigen) for monitoring compliance. A monoclonal antibody competition assay anti-38 kDa antibody is the most sensitive serological test for smear-negative tuberculosis so far. Tests for tuberculous meningitis need clinical evaluation. Serological tests for human immunodeficiency virus (HIV)-related tuberculosis are disappointing. In general, antibody levels in primary tuberculosis are low and appear directed towards cytoplasmic antigens, whilst in post-primary disease antibody levels are higher and appear to bind to secreted antigens. No single reagent gives a 100% sensitivity; future research should identify the best combination of antigens for the serodiagnosis of tuberculosis.
Abstract 297: Nkx2–5 Transcriptionally Activates C-kit-ligand And Regulates Cardiac Progenitor Cell Populations
Authors: Rebecca L Scotland, Xiaozhong Shi, Anwarul Ferdous, Michael Kyba, Daniel J Garry
Journal: Circulation (2008)

C-kit-ligand, also known as stem cell factor, is expressed broadly and has a functional role during hematopoesis, gametogenesis, melanogenesis, mast cell growth and differentiation. Although the receptor for c-kit-ligand, c-kit, has been utilized as a marker to identify cardiac stem cell and progenitor cell populations, the transcriptional regulation and biological function of c-kit-ligand during cardiogenesis has not been defined. Here we demonstrate that c-kit-ligand is a novel downstream target of Nkx2–5. The homeodomain transcription factor, Nkx2–5, is one of the earliest markers of the cardiac lineage and mice lacking this transcription factor are nonviable. To identify potential Nkx2–5 downstream target genes, we utilized ES/EBs that were engineered to overexpress Nkx2–5 and undertook transcriptome analysis of embyroid bodies with and without Nkx2–5 induction. We observed a significant increase in c-kit-ligand expression following Nkx2–5 induction suggesting a role for Nkx2–5 in the activation of c-kit-ligand. Furthermore, analysis of the c-kit-ligand promoter revealed three evolutionarily conserved Nkx2–5 response elements, supporting the notion that Nkx2–5 is a transcriptional regulator of gene expression. We undertook transcriptional assays and transfected the c-kit-ligand promoter-luciferase reporter in the absence and presence of increasing amounts of Nkx2–5. We observed that Nkx2–5, in a dose dependent fashion, was a potent transcriptional activator of c-kit-ligand. These studies enhance our understanding of Nkx2–5 mediated transcriptional networks and further emphasize that Nkx2–5 is an important transcriptional regulator of cardiac progenitor cell populations.
Oncogene-Induced DNA Repair Defects Promote PARP1-Mediated “Dual Synthetic Lethality” To Eradicate Quiescent and Proliferating Leukemia Stem and Progenitor Cells
Authors: Margaret Nieborowska-Skorska, Artur Slupianek, Grazyna Hoser, Elisabeth Bolton-Gillespie, Alexei Tulin, Sabine Cerny-Reiterer, Peter Valent, Markus Muschen, Stephen M. Sykes, Tomasz Skorski
Journal: Blood (2013)
Granulocyte Colony-Stimulating Factor Upregulates the Vacuolar Proton ATPase in Human Neutrophils
Authors: Hans Niessen, Grant W. Meisenholder, Hai-Ling Li, Stephen L. Gluck, Beth S. Lee, Barry Bowman, Robert L. Engler, Bernard M. Babior, Roberta A. Gottlieb
Journal: Blood (1997)
Cholinergic Stimulation of Norepinephrine Release in Man
Authors: Steven A. Leveston, Suresh D. Shah, Philip E. Cryer
Journal: Journal of Clinical Investigation (1979)

Amplification of endogenous cholinergic activity—produced by the intravenous injection of edrophonium, an acetylcholinesterase inhibitor which does not enter the central nervous system, into normal subjects—resulted in significant and briefly sustained increments in the plasma concentrations of norepinephrine (153±15−234±29 pg/ml, P < 0.01) and epinephrine (16±3−34±5 pg/ml, P < 0.01) measured with a single-isotope derivative method. These increments were not attributable to reflex responses to hemodynamic changes and similar increments in plasma norepinephrine occurred in adrenalectomized (epinephrine deficient) patients. Thus, cholinergic activation results in direct stimulation of sympathetic postganglionic neurons, with augmented norepinephrine release, and of the adrenal medullae, with augmented epinephrine release, in man. Four diabetic patients with hypoadrenergic postural hypotension exhibited blunted sympathetic postganglionic neural responses, and normal adrenomedullary responses, to cholinergic stimulation (and to standing) indicative of the presence of a sympathetic postganglionic axonal lesion in diabetic adrenergic neuropathy. Nondiabetic patients with hypoadrenergic postural hypotension due to documented or probable central nervous system lesions exhibited normal responses to cholinergic stimulation produced in this fashion demonstrating the presence of intact sympathetic postganglionic neurons and adrenal medullae in these patients and providing further support for the conceptual soundness of this approach to the study of human adrenergic physiology and pathophysiology.