tbuckley/cabot-search huggingface dataset:
Cost of Care for Elderly Cancer Patients in the United States
Authors: K. Robin Yabroff, Elizabeth B. Lamont, Angela Mariotto, Joan L. Warren, Marie Topor, Angela Meekins, Martin L. Brown
Journal: JNCI Journal of the National Cancer Institute (2008)

Timely estimates of the costs of care for cancer patients are an important element in the formulation of national cancer programs and policies. We estimated net costs of care for elderly cancer patients in the United States for the 18 most prevalent cancers and for all other tumor sites combined.We used Surveillance, Epidemiology, and End Results-Medicare files to identify 718,907 cancer patients and 1,623,651 noncancer control subjects. Within each tumor site, noncancer control subjects were matched to patients by sex, age group, geographic location, and phase of care (ie, initial, continuing, and last year of life). Costs of care were estimated for each phase by use of Medicare claims data from January 1, 1999, through December 31, 2003. Per-patient net costs of care were applied to the 5-year survival of cancer patients by phase of care to estimate 5-year costs of care and extrapolated to the elderly US Medicare population diagnosed with cancer in 2004.Across tumor sites, mean net costs of care were highest in the initial and last year of life phases of care and lowest in the continuing phase. Mean 5-year net costs varied widely, from less than $20,000 for patients with breast cancer or melanoma of the skin to more than $40,000 for patients with brain or other nervous system, esophageal, gastric, or ovarian cancers or lymphoma. For elderly cancer patients diagnosed in 2004, aggregate 5-year net costs of care to Medicare were estimated to be approximately $21.1 billion. Costs to Medicare were highest for lung, colorectal, and prostate cancers, reflecting underlying incidence, stage distribution at diagnosis, survival, and phase-specific costs for these tumor sites.The costs of cancer care to Medicare are substantial and vary by tumor site, phase of care, stage at diagnosis, and survival.
Transcriptional Regulation of Innate and Adaptive Lymphocyte Lineages
Authors: Maria Elena De Obaldia, Avinash Bhandoola
Journal: Annual Review of Immunology (2015)

The lymphocyte family has expanded significantly in recent years to include not only the adaptive lymphocytes (T cells, B cells) and NK cells, but also several additional innate lymphoid cell (ILC) types. ILCs lack clonally distributed antigen receptors characteristic of adaptive lymphocytes and instead respond exclusively to signaling via germline-encoded receptors. ILCs resemble T cells more closely than any other leukocyte lineage at the transcriptome level and express many elements of the core T cell transcriptional program, including Notch, Gata3, Tcf7, and Bcl11b. We present our current understanding of the shared and distinct transcriptional regulatory mechanisms involved in the development of adaptive T lymphocytes and closely related ILCs. We discuss the possibility that a core set of transcriptional regulators common to ILCs and T cells establish enhancers that enable implementation of closely aligned effector pathways. Studies of the transcriptional regulation of lymphopoiesis will support the development of novel therapeutic approaches to correct early lymphoid developmental defects and aberrant lymphocyte function.
Divergent metabolic outcomes arising from targeted manipulation of the gut microbiota in diet-induced obesity
Authors: Eileen F Murphy, Paul D Cotter, Aileen Hogan, Orla O'Sullivan, Andy Joyce, Fiona Fouhy, Siobhan F Clarke, Tatiana M Marques, Paul W O'Toole, Catherine Stanton, Eamonn M M Quigley, Charlie Daly, Paul R Ross, Robert M O'Doherty, Fergus Shanahan
Journal: Gut (2012)

<h3>Objective</h3> The gut microbiota is an environmental regulator of fat storage and adiposity. Whether the microbiota represents a realistic therapeutic target for improving metabolic health is unclear. This study explored two antimicrobial strategies for their impact on metabolic abnormalities in murine diet-induced obesity: oral vancomycin and a bacteriocin-producing probiotic (<i>Lactobacillus salivarius</i> UCC118 Bac<sup>+</sup>). <h3>Design</h3> Male (7-week-old) C57BL/J6 mice (9–10/group) were fed a low-fat (lean) or a high-fat diet for 20 weeks with/without vancomycin by gavage at 2 mg/day, or with <i>L salivarius</i> UCC118Bac<sup>+</sup> or the bacteriocin-negative derivative <i>L salivarius</i> UCC118Bac<sup>−</sup> (each at a dose of 1×10<sup>9</sup> cfu/day by gavage). Compositional analysis of the microbiota was by 16S rDNA amplicon pyrosequencing. <h3>Results</h3> Analysis of the gut microbiota showed that vancomycin treatment led to significant reductions in the proportions of <i>Firmicutes</i> and <i>Bacteroidetes</i> and a dramatic increase in <i>Proteobacteria</i>, with no change in <i>Actinobacteria.</i> Vancomycin-treated high-fat-fed mice gained less weight over the intervention period despite similar caloric intake, and had lower fasting blood glucose, plasma TNFα and triglyceride levels compared with diet-induced obese controls. The bacteriocin-producing probiotic had no significant impact on the proportions of <i>Firmicutes</i> but resulted in a relative increase in <i>Bacteroidetes</i> and <i>Proteobacteria</i> and a decrease in <i>Actinobacteria</i> compared with the non-bacteriocin-producing control. No improvement in metabolic profiles was observed in probiotic-fed diet-induced obese mice. <h3>Conclusion</h3> Both vancomycin and the bacteriocin-producing probiotic altered the gut microbiota in diet-induced obese mice, but in distinct ways. Only vancomycin treatment resulted in an improvement in the metabolic abnormalities associated with obesity thereby establishing that while the gut microbiota is a realistic therapeutic target, the specificity of the antimicrobial agent employed is critical.
Nonspecific Interstitial Pneumonitis without Evidence of Pneumocystis carinii in Asymptomatic Patients Infected with Human Immunodeficiency Virus (HIV)
Authors: F P Ognibene, H Masur, P Rogers, W D Travis, A F Suffredini, I Feuerstein, V J Gill, B F Baird, J A Carrasquillo, J E Parrillo
Journal: Annals of Internal Medicine (1988)

To assess how often Pneumocystis carinii organisms, P. carinii pneumonia, or other pulmonary pathologic processes were present in persons infected with human immunodeficiency virus (HIV) without pulmonary symptoms or previous history of P. carinii, and with a normal chest roentgenogram.Serial, prospective assessment of eligible HIV-seropositive patients over 21 months.Twenty-four HIV-seropositive patients with either a nonpulmonary manifestation of the acquired immunodeficiency syndrome (AIDS) (n = 12) or an absolute CD4 lymphocyte count of 0.200 X 10(9) cells/L or less (n = 12), no pulmonary symptoms, a normal chest roentgenogram, no history of P. carinii pneumonia, and no history of treatment with antipneumocystis prophylaxis.Pulmonary assessment with arterial blood gases, pulmonary function tests, gallium-67 citrate scans, and bronchoscopy with bronchoalveolar lavage and transbronchial biopsies.Mean alveolar-arterial gradient was 11.1 mm Hg +/- 8.5 and mean diffusion capacity was 73.0% +/- 20.0% of predicted. None of the 24 patients showed P. carinii or other pathogens on stains of bronchoalveolar lavage fluid. No patient had histologic evidence of P. carinii pneumonia. Transbronchial biopsy specimens showed chronic, nonspecific interstitial pneumonitis (11 of 23) and no pathologic abnormality (12 of 23). Six patients have developed P. carinii pneumonia during 2 to 18 months of follow-up.HIV-infected patients without pulmonary symptoms did not have detectable Pneumocystis organisms in bronchoalveolar lavage fluid or transbronchial biopsy specimens; but 11 of 23 had evidence of chronic, nonspecific interstitial pneumonitis. Pneumocystis organisms in a pulmonary specimen from a symptomatic patient probably indicate the cause of the pulmonary dysfunction even if only a few are detected.
Detecting Circulating Tumor Cells: Current Challenges and New Trends
Authors: Bin Hong, Youli Zu
Journal: Theranostics (2013)

Circulating tumor cells (CTCs) in the blood stream play a critical role in establishing metastases.The clinical value of CTCs as a biomarker for early cancer detection, diagnosis, prognosis, prediction, stratification, and pharmacodynamics have been widely explored in recent years.However, the clinical utility of current CTC tests is limited mainly due to methodological constraints.In this review, the pros and cons of the reported CTC assays are comprehensively discussed.In addition, the potential of tumor cell-derived materials as new targets for CTC detection, including circulating tumor microemboli, cell fragments, and circulating DNA, is evaluated.Finally, emerging approaches for CTC detection, including telomerase-based or aptamer-based assays and cell functional analysis, are also assessed.Expectantly, a thorough review of the current knowledge and technology of CTC detection will assist the scientific community in the development of more efficient CTC assay systems.
Role of resistance and exchange vessels in local microvascular control of skeletal muscle oxygenation in the dog.
Authors: H J Granger, A H Goodman, D N Granger
Journal: Circulation Research (1976)

The effects of reduction in perfusion pressure, arterial hypoxia, muscle contraction, and adrenergic stimulation on the hindlimb muscle circulation were studied. Under normal conditions (venous PO2 greater than or equal to 40 mm Hg), oxygen delivery to the muscle was maintained mainly by large increases in the capillary exchange capacity and the oxygen extraction ratio in accord with tissue demand following the application of the above stresses. The participation of the resistance vessels under these conditions was minimal. The prevailing venous oxygen tension then was reduced by several means and the response of vascular resistance and capillary exchange capacity to the same stresses was reexamined. At the lower prevailing venous PO2, the sensitivity of the resistance vessels to metabolic and hemodynamic disturbances was greatly increased. Consequently, blood flow autoregulation, functional hyperemia, and hypoxic hyperemia were more intense when venous oxygen tension was low. In contrast, the contribution of exchange capacity was diminished, probably owing to the fact that most of the capillaries already are open at low venous PO2. These data suggest that the locus of local microvascular control of muscle oxygenation shifts from the normally more sensitive precapillary sphincters to the proximal flow-controlling arterioles as the prevailing venous oxygen tension falls. Yet, although the relative contribution of the resistance and exchange vessels to intrinsic regulation of tissue oxygenation is related to the prevailing venous oxygen tension, the two compensatory mechanisms operating in concert maintain tissue PO2 above the critical level over a wide range of stresses.
Effects of calcium channel blockade on histamine induced bronchoconstriction in mild asthma.
Authors: E H Walters, J Banks, A Fennerty, B H Davies
Journal: Thorax (1984)

Inhalation histamine dose-response curves were constructed 15 minutes after inhalation of saline placebo or verapamil (4 mg) for eight patients with mild atopic asthma in a double blind, random manner. No significant change in baseline specific airways conductance occurred after inhalation of verapamil, though there was a significant decrease in sensitivity to histamine (increase in threshold of response) (p less than 0.01). There was, however, an associated significant increase (p less than 0.01) in the slopes of the subsequent histamine dose-response curves.
Adverse reactions in patients with rheumatic diseases. Retrospective analysis of causes of admission and out-patient attendance in a specialist centre.
Authors: P Lee, S McCusker, A Allison, G Nuki
Journal: Annals of the Rheumatic Diseases (1973)

It is now widely understood that the use of any therapeutic agent is inevitably associated with some risk of adverse effect.A rapidly expanding literature dealing with the manifestations of drug-induced disease testifies to an increasing awareness and con- cern about the wide spectrum of adverse effects that can accompany drug therapy, especially with newer and more potent pharmacological agents (Moser, 1969; Goodman and Gilman, 1970; Meyler and Herxheimer, 1968; D'Arcy and Griffin, 1972).By comparison there are relatively few published reports dealing with the prevalence or incidence of drug- induced iatrogenic disease.Such epidemiological studies as have been undertaken have established that adverse reactions to drugs are important causes of admission to general hospital medical wards and also of morbidity and mortality in patients admitted to hospital (Barr,
Impact of introducing the 10-valent pneumococcal conjugate vaccine on childhood hospitalizations for bacterial pneumonia in Brazil
Authors: Leonardo Pinto, Tiago Veras, Marcelo Scotta, Virginia Tronco, Paula Klein, Arthur Daudt, Paulo Pitrez, Marcus Jones, Renato Stein
Journal: European Respiratory Journal (2013)

Pneumococcal disease is a major public health problem all over the world. In 2010 the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) was introduced to the childhood national immunization programme. The aim of this study was to report national time-trends in hospital admissions for childhood bacterial pneumonia in Brazil before and after the introduction of this new pneumococcal conjugate vaccination. A time-trend analysis of hospitalization data of children aged 0-4 years admitted by the Brazilian public health system with a diagnosis of bacterial pneumonia from 2007 to 2012 was performed. Hospital admission rates for bacterial pneumonia were obtained from DATASUS, a Brazilian Government, and open-access public health database. Pneumonia hospitalization rates were compared to bronchitis/bronchiolitis hospital admissions. Admission rates for bacterial pneumonia increased from 2007 to 2009, and then declined to 2012. Bacterial pneumonia hospitalizations decreased to 97 per month per million in 2012, compared to 137 per month per million in 2009. Childhood bacterial pneumonia hospitalization rates were increasing prior to 2010 and decreased by 29% between 2009 and 2012, following the introduction of PHiD-CV programme. On the other hand, respiratory infections predominantly caused by viruses have shown a different trend after 2010. This data is an important evidence of the effectiveness and the health public impact of this new pneumococcal vaccine.
Sustained atrial tachycardia in adult patients. Electrophysiological characteristics, pharmacological response, possible mechanisms, and effects of radiofrequency ablation.
Authors: S A Chen, C E Chiang, C J Yang, C C Cheng, T J Wu, S P Wang, B N Chiang, M S Chang
Journal: Circulation (1994)

BACKGROUND Mechanisms and electropharmacological characteristics in adult patients with atrial tachycardia (AT) are not well described. We proposed that a combination of electropharmacological characteristics, recording of monophasic action potential, and effects of radiofrequency ablation could further determine the mechanisms and achieve a new classification in adults with various types of AT because they were important in regard to the correlation between mechanisms and pathophysiology, clinical syndrome, and responses to specific pharmacological or nonpharmacological therapies. METHODS AND RESULTS Thirty-six patients (11 female, 25 male; mean age, 57 +/- 13 years) with AT were referred for electropharmacological studies and radiofrequency ablation. Resetting response pattern, entrainment phenomenon, recording of monophasic action potential, serial drug test, response to Valsalva maneuver, endocardial mapping technique, and radiofrequency ablation were performed. Seven patients had automatic AT provocable with isoproterenol; neither initiation nor termination was related to programmed electrical stimulation. The other 29 patients had AT initiated or terminated by electrical stimulation and mechanisms related to triggered activity or reentry; nine of them needed isoproterenol to facilitate initiation of AT, associated with delayed afterdepolarization in monophasic action potential. All responded to adenosine (15 to 60 micrograms/kg) and Valsalva maneuver. Dipyridamole terminated AT and decreased the slope of afterdepolarization. Afterdepolarization was not found in the patients with automatic or reentrant AT. In 40 of 41 (98%), AT was ablated successfully, with late recurrence in 2 of 40 (5%) (follow-up, 18 +/- 4 months). CONCLUSIONS This study demonstrates the diverse mechanisms and electropharmacological characteristics of AT in adults. Furthermore, radiofrequency ablation of various types of AT could achieve high success and low recurrence rates.
Health service accessibility and deaths from asthma in 401 local authority districts in England and Wales, 1988-92
Authors: A. P. Jones, G. Bentham
Journal: Thorax (1997)

The possible contribution of health service accessibility to asthma mortality has not previously been studied in the UK.Using regression analysis, the relationship between geographical isolation from large acute hospital services and mortality from asthma for 401 local authority districts in England and Wales was examined for the period 1988-92.Asthma mortality was found to be strongly associated with the proportion of district households where the head was of social class 4 or 5 (adjusted relative risk 1.61, 95% confidence interval (CI) 1.12 to 2.33), and the proportion of households without access to a car (adjusted relative risk 1.59, 95% CI 0.97 to 2.62). After controlling for these factors, there was a tendency for mortality to rise with increasing distance from hospital, with a relative risk of 1.01 for an increase in distance of one kilometre (95% CI 1.00 to 1.02).The findings suggest that problems of accessibility of care may mean that the control of asthma amongst sufferers living in districts most remote from major health service units might be less than optimal, and this could result in a number of potentially avoidable deaths.
Early Electrocardiographic Findings and MR Imaging-Verified Microvascular Injury and Myocardial Infarct Size
Authors: Robin Nijveldt, Pieter A. van der Vleuten, Alexander Hirsch, Aernout M. Beek, René A. Tio, Jan G.P. Tijssen, Jan J. Piek, Albert C. van Rossum, Felix Zijlstra
Journal: JACC. Cardiovascular imaging (2009)
Role of the pro-apoptotic pyrin-interacting protein Siva in the pathogenesis of familial Mediterranean fever
Authors: D Vassou, E Petraki, E Eliopoulos, D Iliopoulos, I Aksentijevich, P Sidiropoulos, D Kardassis, D T Boumpas, G N Goulielmos
Journal: Annals of the Rheumatic Diseases (2010)

Background Familial Mediterranean fever (FMF) is an autosomal recessive disease attributed to mutations in the MEFV gene encoding pyrin, which is characterised by recurrent, acute and self-limiting attacks of fever.Most disease-associated mutations in the MEFV gene reside on the C-terminal PRYSPRY (B30.2) domain of pyrin, an area found to interact with the pro-apoptotic protein Siva.Aim (1) To defi ne the topology of the (full-length) Siva-1 with respect to its interaction with pyrin and other interacting proteins; (2) to investigate the ability of mutant forms of pyrin to interact with Siva-1; and (3) to explore the potential increase of GITR/Siva-induced apoptosis in the presence of the mutant forms of pyrin.Materials and Methods A three-dimensional model of Siva-1 was created with MODELLER and a Swiss model automated protein structure homology-modelling server.HEK293 (human embryonic kidney) and THP-1 (human monocytic leukaemia) cell lines were used for transfection experiments using Lipofectamine 2000 or the Amaxa nucleofection technology, respectively.Apoptosis was measured by FACS-Annexin-PE staining using the Annexin-V kit (Pharmingen). ResultsThe authors constructed a three-dimensional model of Siva-1 and three distinct domains were defi ned, an N-terminal domain containing amphipathic helices with potential to interact with the PRYSPRY domain of pyrin, a B-box-like domain and a zinc fi nger-like C-terminal domain that the authors assume to bind the cytoplasmic tail domain of GITR protein.In immunoprecipitation experiments on transfected HEK293 cells, Siva bound both to wild-type pyrin and its mutant forms, but no differences were observed in the rates of apoptosis in THP-1 upon transfection with either wild-type pyrin or mutant forms of pyrin.Patients with FMF did not display any mutations in the Siva gene. ConclusionsThe three-dimensional model of Siva-1 constructed showed that GITR and pyrin do not antagonise for the same binding site(s).The data obtained by using various mutants of pyrin and Siva-1 for cotransfecting HEK293 cells suggest that the positions of the PRYSPRY domain, found mutated in FMF patients, are not required for binding to Siva-1.The authors were not able to demonstrate an increase in GITR/Siva-induced apoptosis in the presence of the mutant on July 22,
Fractional flow reserve versus angiography for guidance of PCI in patients with multivessel coronary artery disease (FAME): 5-year follow-up of a randomised controlled trial
Authors: Lokien X van Nunen, Frederik M Zimmermann, Pim A L Tonino, Emanuele Barbato, Andreas Baumbach, Thomas Engstrøm, Volker Klauss, Philip A MacCarthy, Ganesh Manoharan, Keith G Oldroyd, Peter N Ver Lee, Marcel van't Veer, William F Fearon, Bernard De Bruyne, Nico H J Pijls
Journal: The Lancet (2015)
Insulin Receptor Substrate Is a Mediator of Phosphoinositide 3-Kinase Activation in Quiescent Pancreatic Cancer Cells
Authors: Takayuki Asano, Yixin Yao, Sonyo Shin, James McCubrey, James L. Abbruzzese, Shrikanth A.G. Reddy
Journal: Cancer Research (2005)

Phosphoinositide 3-kinase (PI3K) is activated in pancreatic cancer cells and plays a central role in their proliferation, survival, and drug resistance. Although the mechanism is unclear, PI3K activation in these cells could be due to physical interaction between its regulatory subunit (p85) and specific tyrosine kinases or their mediators. Consistent with this possibility, PI3K was precipitated with anti-phosphotyrosine antibodies and Akt phosphorylation was blocked by the tyrosine kinase inhibitors SU6656 and PD158780 in quiescent pancreatic cancer cells. Pull-down assays with a fusion protein (GST-p85NC-SH2), and coimmunoprecipitation studies, indicated that the insulin receptor substrate (IRS), and not the epidermal growth factor and insulin-like growth factor receptors or the Src tyrosine kinase, was physically associated with PI3K in these cells. Our data also indicated that SU6656 and PD158780 inhibited Akt activation in pancreatic cancer cells by interfering with the ability of IRS-1 to recruit PI3K. Furthermore, IRS-1 was phosphorylated on a p85-binding site (Y(612)), and IRS-specific small interfering RNA potently inhibited activation of PI3K and Akt in transfected cells. Taken together, these observations indicate that IRS is a mediator of PI3K activation in quiescent pancreatic cancer cells.