tbuckley/cabot-search huggingface dataset:
Inhibition of Coronary Vasodilating Action of Dipyridamole and Adenosine by Aminophylline in the Dog
Authors: SKODA AFONSO
Journal: Circulation Research (1970)

Experiments were performed to determine (1) whether intravenously administered aminophylline inhibits the coronary vasodilating effects of intravenous or intracoronary administration of dipyridamole or adenosine and (2) whether aminophylline locally administered in the coronary artery inhibits the vasodilating action of adenosine given intravenously or injected into the coronary artery. Coronary vasodilator responses to dipyridamole or adenosine were determined before and after administration of aminophylline. Intravenous aminophylline was found to inhibit coronary vasodilatation induced by intravenous or intracoronary dipyridamole or adenosine. After intravenous aminophylline, adenosine administered intravenously or into the coronary artery was 2.5 to 4 times less effective in inducing coronary vasodilatation. Aminophylline injected locally into the coronary artery was also effective in inhibiting coronary vasodilatation induced by intravenous and intracoronary adenosine. The mechanism of this inhibitory phenomenon has not been elucidated.
Serum Levels of the Antiinflammatory Cytokine Interleukin-10 Are Decreased in Patients With Unstable Angina
Authors: David A. Smith, Sandra D. Irving, Joanna Sheldon, Della Cole, Juan Carlos Kaski
Journal: Circulation (2001)

Background Proinflammatory cytokines play a role in acute coronary events. However, the potential role of antiinflammatory cytokines in the modulation of the atherosclerotic process remains unknown. Interleukin (IL)-10, which is expressed in human atherosclerotic plaques, has potent deactivating properties in macrophages and T cells. The aim of this study was to assess whether serum concentrations of IL-10 differed between patients with unstable and stable angina pectoris. Methods and Results A total of 95 patients with angina pectoris and angiographically documented coronary artery disease were studied. Of these, 50 patients had chronic stable angina (with stable symptoms over 3 months), and 45 patients had Braunwald class IIIB unstable angina with ST-segment changes. Serum IL-10 and IL-6 concentrations were measured on admission using commercially available immunoassays. Serum IL-10 concentrations were lower in unstable angina patients compared with those who had chronic stable angina (28.4 versus 14.0 pg/mL; 95% CI, 9.8 to 19.0; P &lt;0.0001), even after adjustment for variables that were significantly different on univariate analysis. IL-6 concentrations were higher in the unstable angina group (20.9 versus 11.4 pg/mL; 95% CI, 1.0 to 12.6; P =0.04). Conclusions Patients with unstable angina had significantly lower serum IL-10 concentrations than did patients with chronic stable angina. This important finding is in keeping with previous data from animal model studies that suggest that IL-10 has a protective role in atherosclerosis.
Unflued gas heaters and respiratory symptoms in older people with asthma
Authors: P J Franklin, J Loveday, A Cook
Journal: Thorax (2012)

<h3>Background</h3> Unflued gas heaters (UFGHs) and cookers are a major contributor to air pollution in homes. Gas appliances have been associated with adverse respiratory outcomes in children and, less consistently, adults. There have been very few studies on the effects of gas appliances on the respiratory health of older people. <h3>Objectives</h3> This study investigated the daily lung function and respiratory symptoms of older people (&gt;55 years of age) who did and did not use an UFGH as a primary source of heating. <h3>Methods</h3> 71 patients with asthma were recruited for the study. Each patient participated for one 12-week winter period. All patients recorded daytime and night-time symptoms in a diary and completed morning and evening peak flow and forced expiratory volume in 1 s for the study period. General estimating equations were used to measure the associations between symptoms and lung function outcomes and same and previous day (lag 1) UFGH exposure. <h3>Results</h3> Same and previous day (lag 1) UFGH exposure was associated with significantly increased ORs for wheeze and dyspnoea compared with days on which no heating was used. Furthermore, there were significant increases in the average odds of reported wheeze and dyspnoea per hour of UFGH heater use. Small but significant reductions in morning to evening peak flow and forced expiratory volume in 1 s were observed on the days an UFGH was used compared with days when other heating was used or there was no heating. <h3>Conclusion</h3> Exposure to UFGHs may have a detrimental effect on symptoms and lung function in older people with mild to moderate asthma.
Smooth Pursuit Eye-Tracking Impairment in Childhood-Onset Psychotic Disorders
Authors: Sanjiv Kumra, Alexandra Sporn, Daniel W. Hommer, Robert Nicolson, Gunvant Thaker, Elizabeth Israel, Marge Lenane, Jeffrey Bedwell, Leslie K. Jacobsen, Peter Gochman, Judith L. Rapoport
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: Although childhood-onset schizophrenia is relatively rare, a sizable group of children with severe emotional disturbances have transient psychotic symptoms that fall outside of current syndrome boundaries. The relationship of this group of children to those with childhood-onset schizophrenia and other childhood psychiatric disorders is unclear. In this study, the authors compared smooth pursuit eye tracking, a biological trait marker associated with schizophrenia, of children and adolescents with psychotic disorder not otherwise specified to that of children with childhood-onset schizophrenia and healthy comparison subjects. METHOD: By means of infrared oculography, smooth pursuit eye movements during a 17°/second visual pursuit task were quantitatively and qualitatively compared in 55 young adolescents (29 with childhood-onset schizophrenia and 26 with psychotic disorder not otherwise specified) and their respective independent healthy comparison groups (a total of 38 healthy subjects). RESULTS: Subjects with childhood-onset schizophrenia had qualitatively poorer eye tracking, higher root mean square error, lower gain, and a greater frequency of catch-up saccades than healthy children. Subjects with psychotic disorder not otherwise specified also had qualitatively poorer eye tracking, higher root mean square error, and lower gain than healthy children, but saccade frequency did not differ significantly. CONCLUSIONS: Children with childhood-onset schizophrenia exhibit a pattern of eye-tracking dysfunction similar to that reported for adult patients. Similar abnormalities were seen in the subjects with psychotic disorder not otherwise specified except that they did not exhibit a greater frequency of catch-up saccades. Prospective longitudinal neurobiological and clinical follow-up studies of both groups are currently underway to further validate the distinction between these two disorders. Also, family studies are planned to establish whether eye-tracking dysfunction represents a trait- or state-related phenomenon in subjects with psychotic disorder not otherwise specified.
Indirect genomic effects on survival from gene expression data
Authors: Egil Ferkingstad, Arnoldo Frigessi, Heidi Lyng
Journal: Genome biology (2008)

In cancer, genes may have indirect effects on patient survival, mediated through interactions with other genes. Methods to study the indirect effects that contribute significantly to survival are not available. We propose a novel methodology to detect and quantify indirect effects from gene expression data. We discover indirect effects through several target genes of transcription factors in cancer microarray data, pointing to genetic interactions that play a significant role in tumor progression.
Five System Barriers to Achieving Ultrasafe Health Care
Authors: René Amalberti, Yves Auroy, Don Berwick, Paul Barach
Journal: Annals of Internal Medicine (2005)

Although debate continues over estimates of the amount of preventable medical harm that occurs in health care, there seems to be a consensus that health care is not as safe and reliable as it might be. It is often assumed that copying and adapting the success stories of nonmedical industries, such as civil aviation and nuclear power, will make medicine as safe as these industries. However, the solution is not that simple. This article explains why a benchmarking approach to safety in high-risk industries is needed to help translate lessons so that they are usable and long lasting in health care. The most important difference among industries lies not so much in the pertinent safety toolkit, which is similar for most industries, but in an industry's willingness to abandon historical and cultural precedents and beliefs that are linked to performance and autonomy, in a constant drive toward a culture of safety. Five successive systemic barriers currently prevent health care from becoming an ultrasafe industrial system: the need to limit the discretion of workers, the need to reduce worker autonomy, the need to make the transition from a craftsmanship mindset to that of equivalent actors, the need for system-level (senior leadership) arbitration to optimize safety strategies, and the need for simplification. Finally, health care must overcome 3 unique problems: a wide range of risk among medical specialties, difficulty in defining medical error, and various structural constraints (such as public demand, teaching role, and chronic shortage of staff). Without such a framework to guide development, ongoing efforts to improve safety by adopting the safety strategies of other industries may yield reduced dividends. Rapid progress is possible only if the health care industry is willing to address these structural constraints needed to overcome the 5 barriers to ultrasafe performance.
Enhanced Pressor Responsiveness to Norepinephrine in Type II Diabetes: Effect of ACE inhibition
Authors: Adolfo Ciavarella, Anna Mustacchio, Chistina Ricci, Maurizio Capelli, Pietro Vannini
Journal: Diabetes Care (1994)

OBJECTIVE To evaluate the effect of angiotensin-converting enzyme (ACE) inhibition on the pressor responsiveness to norepinephrine in type II diabetes. RESEARCH DESIGN AND METHODS Eight normotensive subjects, eight mild-to-moderate hypertensive type II diabetic patients, and eight nondiabetic patients with essential hypertension were studied before and after 4 weeks of being administered enalapril. The pressor response to norepinephrine was assessed by infusing the hormone in an antecubital vein at incremental doses of 30 ng·kg−1 · min−1 for periods of 5 min until reaching an increase of 20 ± 2 mmHg in mean arterial pressure (MAP) measured by an automatic device at 1-min intervals. An effective dosage of norepinephrine that increased MAP by 20 mmHg (EDNE 20) was thereafter calculated. Before and during the last minute of norepinephrine infusion at maximum dosage, a venous blood sample was drawn to determine plasma renin activity (PRA), aldosterone, and norepinephrine levels. RESULTS In the three groups of patients, blood pressure and aldosterone were reduced while PRA was raised following ACE inhibition. Basal and maximum postinfusion levels of norepinephrine were not modified by enalapril. The EDNE 20 was basally lower in diabetic patients and remained unchanged after ACE inhibition, contrary to that observed in nondiabetic patients with essential hypertension. CONCLUSIONS Both normotensive and hypertensive type II diabetic patients have an increased pressor responsiveness to norepinephrine that is not modified by therapeutic doses of enalapril, contrary to what is observed in nondiabetic patients with essential hypertension.
Effect of 3 years of SAFE (surgery, antibiotics, facial cleanliness, and environmental change) strategy for trachoma control in southern Sudan: a cross-sectional study
Authors: Jeremiah Ngondi, Alice Onsarigo, Fiona Matthews, Mark Reacher, Carol Brayne, Samson Baba, Anthony W Solomon, James Zingeser, Paul M Emerson
Journal: The Lancet (2006)
Mast cell control: likely modus operandi of panhaematin in experimental pancreatitis
Authors: Joan M Braganza
Journal: Gut (2011)

In the May 2011 issue of Gut , Habtezion and colleagues report that panhaematin treatment ameliorates experimental acute pancreatitis (AP) by reducing neutrophil infiltration, and they propose that the drug may resolve the therapeutic impasse in clinical AP.1 I see the study results as further evidence of mast cell pathology. The limited number of citations permitted in ‘letters’ precludes a full bibliography, which can be provided on request.

Haem preparations induce haem oxygenase-1 (HO-1), which then degrades haem to generate bilirubin (via biliverdin) and carbon monoxide: the enzyme—which is transported in blood plasma from liver, spleen and other sites—and both end-products are antioxidants/anti-inflammatory agents. HO-1 is up-regulated by a …
Quality of life and cost-effectiveness of levonorgestrel-releasing intrauterine system versus hysterectomy for treatment of menorrhagia: a randomised trial
Authors: Ritva Hurskainen, Juha Teperi, Pekka Rissanen, Anna-Mari Aalto, Seija Grenman, Aarre Kivelä, Erkki Kujansuu, Sirkku Vuorma, Merja Yliskoski, Jorma Paavonen
Journal: The Lancet (2001)
Targeting cathepsins: a new glimmer of hope for pancreatic cancer therapy?
Authors: Patrick Michl
Journal: Gut (2012)

Recent whole-genome sequencing efforts have facilitated the detailed characterisation of the human degradome consisting of almost 600 proteases and homologues, which can be grouped into various classes including metalloproteinases, serine proteases and cysteine cathepsins.1 Whereas most proteases such as metalloproteinases and serine proteases are secreted and act extracellularly by modifying extracellular matrix or cell surface proteins, cathepsins are prototypical lysosomal cysteine proteases, which are predominantly located intracellularly in endolysosomal vesicles. In various types of malignancies, cathepsins have been associated with tumour progression and metastasis.2

Cathepsin B is strongly expressed in pancreatic cancer, and high levels of this protease have been linked to reduced survival in patients after curative resection.3 The molecular basis for the elevated expression levels of cathepsin B in pancreatic cancer remains to be elucidated. In other cancers, however, genomic amplification, alternative splicing, as well as transcriptional and posttranscriptional upregulation have been reported.2 Interestingly, cathepsin B can be detected in both tumour cells and surrounding stromal cells such as tumour-associated macrophages and fibroblasts, indicating distinct roles of this protease during tumour progression in both the tumour microenvironment and the tumour cells themselves.2 Moreover, cathepsin B and several other cathepsins have been shown to function intracellularly as well as extracellularly, which puts them in a unique position and contrasts them with most other proteases such as metalloproteases or serine proteases.

Extracellularly, cathepsins are secreted both as active enzymes and as inactive proforms, which are subsequently activated by interaction with extracellular matrix components and cell-surface proteins. Interestingly, cathepsin …
Implementation of an Interleukin-2 National Registry: an opportunity to improve cancer outcomes
Authors: Michael K Wong, Howard L Kaufman, Gregory A Daniels, David F McDermott, Sandra Aung, James N Lowder, Michael A Morse
Journal: Journal for ImmunoTherapy of Cancer (2014)

Cancer registries have proven valuable with respect to validating therapeutic safety and drug efficacy, uncovering real-world implementation practices, and their evolution over time. Modern cancer therapeutics are approved as single agents oftentimes compared to the least active approved standard agent in randomized trials. However, the burgeoning diversity and number of drugs introduces a complexity that quickly outstrips the knowledge provided by these pivotal trials. This gap in information is particularly relevant when survival is the primary therapeutic endpoint. In addition, the inherent complexity of the immune response will make registries a particularly important tool in expeditiously understanding solid tumor immunotherapy and patient outcomes.
Relaxin: New Pathophysiological Aspects and Pharmacological Perspectives for an Old Protein
Authors: Valeria Cernaro, Antonio Lacquaniti, Rosaria Lupica, Antoine Buemi, Domenico Trimboli, Grazia Giorgianni, Davide Bolignano, Michele Buemi
Journal: Medicinal Research Reviews (2013)

Abstract Human relaxin‐2 (hereafter simply defined as “relaxin”) is a 6‐kDa peptidic hormone best known for the physiological role played during pregnancy in the growth and differentiation of the reproductive tract and in the renal and systemic hemodynamic changes. This factor can also be involved in the pathophysiology of arterial hypertension and heart failure, in the molecular pathways of fibrosis and cancer, and in angiogenesis and bone remodeling. It belongs to the relaxin peptide family, whose members comprehensively exert numerous effects through interaction with different types of receptors, classified as relaxin family peptide (RXFP) receptors (RXFP1, RXFP2, RXFP3, RXFP4). Research looks toward the in‐depth examination and complete understanding of relaxin in its various pleiotropic actions. The intent is to evaluate the likelihood of employing this substance for therapeutic purposes, for instance in diseases where a deficit could be part of the underlying pathophysiological mechanisms, also avoiding any adverse effect. Relaxin is already being considered as a promising drug, especially in acute heart failure. A careful study of the different RXFPs and their receptors and the comprehension of all biological activities of these hormones will probably provide new drugs with a potential wide range of therapeutic applications in the near future.
A systematic video analysis of National Hockey League (NHL) concussions, part II: how concussions occur in the NHL
Authors: Michael G Hutchison, Paul Comper, Willem H Meeuwisse, Ruben J Echemendia
Journal: British Journal of Sports Medicine (2013)

Background Concussions in sports are a growing cause of concern, as these injuries can have debilitating short-term effects and little is known about the potential long-term consequences. This work aims to describe how concussions occur in the National Hockey League. Methods Case series of medically diagnosed concussions for regular season games over a 3.5-year period during the 2006–2010 seasons. Digital video records were coded and analysed using a standardised protocol. Results 88% (n=174/197) of concussions involved player-to-opponent contact. 16 diagnosed concussions were a result of fighting. Of the 158 concussions that involved player-to-opponent body contact, the most common mechanisms were direct contact to the head initiated by the shoulder 42% of the time (n=66/158), by the elbow 15% (n=24/158) and by gloves in 5% of cases (n=8/158). When the results of anatomical location are combined with initial contact, almost half of these events (n=74/158) were classified as direct contact to the lateral aspect of the head. Conclusions The predominant mechanism of concussion was consistently characterised by player-to-opponent contact, typically directed to the head by the shoulder, elbow or gloves. Also, several important characteristics were apparent: (1) contact was often to the lateral aspect of the head; (2) the player who suffered a concussion was often not in possession of the puck and (3) no penalty was called on the play.
Metabotropic glutamate receptor-4 modulates adaptive immunity and restrains neuroinflammation
Authors: Francesca Fallarino, Claudia Volpi, Francesco Fazio, Serena Notartomaso, Carmine Vacca, Carla Busceti, Silvio Bicciato, Giuseppe Battaglia, Valeria Bruno, Paolo Puccetti, Maria C Fioretti, Ferdinando Nicoletti, Ursula Grohmann, Roberto Di Marco
Journal: Nature Medicine (2010)
Prevalence of Rheumatic Heart Disease Detected by Echocardiographic Screening
Authors: Eloi Marijon, Phalla Ou, David S. Celermajer, Beatriz Ferreira, Ana Olga Mocumbi, Dinesh Jani, Christophe Paquet, Sophie Jacob, Daniel Sidi, Xavier Jouven
Journal: New England Journal of Medicine (2007)

Epidemiologic studies of the prevalence of rheumatic heart disease have used clinical screening with echocardiographic confirmation of suspected cases. We hypothesized that echocardiographic screening of all surveyed children would show a significantly higher prevalence of rheumatic heart disease.Randomly selected schoolchildren from 6 through 17 years of age in Cambodia and Mozambique were screened for rheumatic heart disease according to standard clinical and echocardiographic criteria.Clinical examination detected rheumatic heart disease that was confirmed by echocardiography in 8 of 3677 children in Cambodia and 5 of 2170 children in Mozambique; the corresponding prevalence rates and 95% confidence intervals (CIs) were 2.2 cases per 1000 (95% CI, 0.7 to 3.7) for Cambodia and 2.3 cases per 1000 (95% CI, 0.3 to 4.3) for Mozambique. In contrast, echocardiographic screening detected 79 cases of rheumatic heart disease in Cambodia and 66 cases in Mozambique, corresponding to prevalence rates of 21.5 cases per 1000 (95% CI, 16.8 to 26.2) and 30.4 cases per 1000 (95% CI, 23.2 to 37.6), respectively. The mitral valve was involved in the great majority of cases (87.3% in Cambodia and 98.4% in Mozambique).Systematic screening with echocardiography, as compared with clinical screening, reveals a much higher prevalence of rheumatic heart disease (approximately 10 times as great). Since rheumatic heart disease frequently has devastating clinical consequences and secondary prevention may be effective after accurate identification of early cases, these results have important public health implications.
Identification of Dialysis Patients with Panel-Reactive Memory T Cells before Kidney Transplantation Using an Allogeneic Cell Bank
Authors: Holger Andree, Peter Nickel, Christin Nasiadko, Markus H. Hammer, Constanze Schönemann, Axel Pruss, Hans-Dieter Volk, Petra Reinke
Journal: Journal of the American Society of Nephrology (2006)

Donor-reactive cellular sensitization does not routinely suggest humoral sensitization and vice versa, but both predict poor kidney transplant outcome. Irrespective of donor reactivity, panel-reactive antibody (PRA) screening identifies patients who are at enhanced risk. Therefore, it was hypothesized that panel-reactive memory T cell reactivity (PRT) might be an additional risk assessment factor of dialysis patients who are on the transplant waiting list. IFN-gamma-enzyme-linked immunosorbent spot memory T cell frequencies were determined in 10 healthy volunteers and 41 hemodialysis patients using for stimulation an allogeneic cell bank (ACB) from 17 healthy individuals who represented the most frequent white HLA antigens. Positive responses to ACB were analogous to PRA defined as percentage of positive assays of the ACB sets. Hemodialysis patients expressed higher PRT levels compared with healthy volunteers. Five of 10 PRT++ patients were PRA negative, and only four of 10 PRA++ patients exhibited PRT reactivity, suggesting independence of humoral and cellular sensitization. Pretransplantation PRT testing of recipients might improve individual risk assessment to make individualized therapy decisions.
Atherosclerosis Regression, Plaque Disruption, and Cardiovascular Events: A Rationale for Lipid Lowering in Coronary Artery Disease
Authors: B G Brown, X Q Zhao, D E Sacco, J J Albers
Journal: Annual Review of Medicine (1993)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More