tbuckley/cabot-search huggingface dataset:
Attained Educational Level and Incident Atherothrombotic Events in Low- and Middle-Income Compared With High-Income Countries
Authors: Abhinav Goyal, Deepak L. Bhatt, P. Gabriel Steg, Bernard J. Gersh, Mark J. Alberts, E. Magnus Ohman, Ramón Corbalán, Kim A. Eagle, Efrain Gaxiola, Runlin Gao, Shinya Goto, Ralph B. D'Agostino, Robert M. Califf, Sidney C. Smith, Peter W.F. Wilson
Journal: Circulation (2010)

Background— Studies report a protective effect of higher attained educational level (AEL) on cardiovascular outcomes. However, most of these studies have been conducted in high-income countries (HICs) and lack representation from low- and middle-income countries (LMICs), which bear &gt;80% of the global burden of cardiovascular disease. Methods and Results— The Reduction of Atherothrombosis for Continued Health (REACH) Registry is a prospective study of 67 888 subjects with either established atherothrombotic (coronary, cerebrovascular, and/or peripheral arterial) disease or multiple atherothrombotic risk factors enrolled from 5587 physician practices in 44 countries. At baseline, AEL (0 to 8 years, 9 to 12 years, trade or technical school, and university) was self-reported for 61 332 subjects. Outcomes included the baseline prevalence of atherothrombotic risk factors and the rate of incident cardiovascular events (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) through 23 months across AEL groups, stratified by sex and world region (LMICs or HICs). Educational attainment was inversely associated with age and diabetes mellitus and directly associated with hypercholesterolemia in all subjects. However, for other risk factors such as obesity, smoking, hypertension, and baseline burden of vascular disease, AEL was protective (inversely associated) in HICs but not protective in LMICs. The protective effect of greater AEL on incident cardiovascular events was strongest in men from HICs ( P &lt;0.0001), more modest in women from HICs ( P =0.0026) and in men from LMICs ( P =0.082), and essentially absent in women from LMICs ( P =0.32). Conclusion— In contrast to HICs, higher AEL may not be protective against cardiovascular events in LMICs, particularly in women.
Randomised, placebo controlled trial of nebulised furosemide for breathlessness in patients with cancer
Authors: A Wilcock, A Walton, C Manderson, L Feathers, B E. Khoury, M Lewis, A Chauhan, P Howard, S Bell, J Frisby, A Tattersfield
Journal: Thorax (2008)

Breathlessness is a common and difficult symptom to treat in patients with cancer. Case reports suggest that nebulised furosemide can relieve breathlessness in such patients but few data are available.Patients with primary or secondary lung cancer and a Dyspnoea Exertion Scale score of >or=3 were recruited. Following familiarisation, patients received either nebulised furosemide 40 mg or nebulised 0.9% saline under double blind conditions or no treatment, in random order on 3 consecutive days. Patients undertook number reading and arm exercise tests to assess breathlessness and its impact, and were asked to report subjective benefit and any preference between nebulised treatments.15 patients took part. There were no differences between furosemide, saline and no treatment in the outcomes of the number reading test (eg, mean number read per breath was 6.7, 6.4 and 6.7, respectively) or arm exercise test (eg, mean Borg score at maximum equivalent workload was 2.3, 2.5 and 2.7, respectively). No adverse effects were reported, although there was a small fall in forced expiratory volume in 1 s and forced vital capacity following saline. Six patients considered that their breathlessness improved with nebulised treatment, three preferring saline, one furosemide and two reporting they were of equal benefit.Our findings do not support a beneficial effect from nebulised furosemide in patients with cancer related breathlessness. Listed on the National Research Register (N0170118249) and the UK Clinical Research Network Portfolio Database (1428).
Sarcoplasmic reticulum calcium release function and FK binding proteins in heart failure: another piece of a complex jigsaw
Authors: C Terracciano
Journal: Cardiovascular Research (2000)

See article by Ono et al. [1] (pages 323–331) in this issue. 

Dysfunction is a complex phenomenon in heart failure. Most cardiac structures are altered and functional relationships are disrupted. A global picture of the pathophysiology of heart failure is not yet available. However, many studies showing modifications of different aspects of cardiac physiology have been carried out and more pieces of this complex jigsaw are revealed. Amongst these, the paper by Ono et al., published in the present issue of Cardiovascular Research [1], focuses on the role of FK binding proteins (FKBPs) in heart failure.

FKBPs are immunophilin proteins associated with the SR Ca release channel (ryanodine receptor (RYR)), which have attracted attention because of their possible involvement in the pathophysiology of cardiac muscle. It has been suggested that, in muscle, FKBP stabilizes RYR function and this could be involved in the gating of the RYR [2,3]. Disruption of this binding leads to modifications of the channel properties that manifest as appearances of sub-conductance states and/or increased open probability ( P o) [3]. The paper by Ono et al. [1] is the last of a trilogy from the same research group, which has focused on the importance of the RYR–FKBP relationship in heart failure. The first paper [4] showed that, in heart failure, polylysine-induced Ca release from SR vesicles was decreased, suggesting an impaired gating function of the RYR. The authors subsequently observed that the ratio between FKBP12.6 (the cardiac isoform of FKBP) and RYR in heart failure was reduced compared with normal hearts and that this was associated with an abnormal Ca leak through the RYR [5]. In the present study the authors have combined the previous observations in the hypothesis that the altered gating function of RYR is caused by a defect in FKBP. … 

* Tel.: +44-20-7352-8121, ext. 3322; fax: +44-20-7351-8145 c.terracciano{at}ic.ac.uk
44 INDUCTION OF AN EARLY PATHOGEN RECOGNITION RECEPTOR EXPRESSION AND ANTIVIRAL CYTOKINE RESPONSE IN HUMAN HEPATOCYTES AFTER HEPATITIS B VIRUS INFECTION
Authors: S. Luangsay, M. Ait-Goughoulte, M. Gruffaz, N. Isorce, S. Fletcher, M. Tommasino, D. Durantel, F. Zoulim
Journal: Journal of Hepatology (2012)
Cell-Derived Microparticles Generated in Patients During Cardiopulmonary Bypass Are Highly Procoagulant
Authors: Rienk Nieuwland, René J. Berckmans, Reni C. Rotteveel-Eijkman, Kyra N. Maquelin, Klaas J. Roozendaal, Piet G. M. Jansen, Klaas ten Have, León Eijsman, C. Erik Hack, Augueste Sturk
Journal: Circulation (1997)

Microparticles from platelets and other cells have been extensively studied and characterized in vitro. Although the level of platelet-derived microparticles is elevated in a variety of diseases, including cardiac surgery, virtually nothing is known about their functions in vivo. The aim of the present study was to investigate the procoagulant properties of microparticles generated in vivo.In 6 patients at the end of cardiopulmonary bypass, 14.8 x 10(9)/L (median; range, 9.7 to 27.4 x 10(9)/L) platelet-derived microparticles were present in pericardial blood, whereas blood obtained from the systemic circulation contained 1.6 x 10(9)/L (median; range, 0.4 to 8.9 x 10(9)/L) of such microparticles, as determined by flow cytometry. Microparticles stained positively for phosphatidylserine as determined with labeled annexin V. In contrast to systemic blood, pericardial blood contained not only microparticles of platelet origin but also microparticles that originated from erythrocytes, monocytes, or granulocytes, and other hitherto unknown cellular sources. Plasma prepared from pericardial blood and to a lesser extent plasma from systemic blood obtained at the same time, stimulated formation of thrombin in vitro. This activity of pericardial plasma was lost after removal of its microparticles by high-speed centrifugation, whereas the corresponding microparticle pellet was strongly procoagulant. The generation of thrombin in vitro involved a tissue factor/factor VII-dependent and factor XII-independent pathway.This study is the first to demonstrate that microparticles generated in vivo can stimulate coagulation.
Activation phenotype, rather than central– or effector–memory phenotype, predicts the recall efficacy of memory CD8+ T cells
Authors: Hirokazu Hikono, Jacob E. Kohlmeier, Shiki Takamura, Susan T. Wittmer, Alan D. Roberts, David L. Woodland
Journal: The Journal of Experimental Medicine (2007)

The contributions of different subsets of memory CD8+ T cells to recall responses at mucosal sites of infection are poorly understood. Here, we analyzed the CD8+ T cell recall responses to respiratory virus infection in mice and demonstrate that activation markers, such as CD27 and CD43, define three distinct subpopulations of memory CD8+ T cells that differ in their capacities to mount recall responses. These subpopulations are distinct from effector– and central–memory subsets, coordinately express other markers associated with activation status, including CXCR3, CD127, and killer cell lectin-like receptor G1, and are superior to CD62L in predicting the capacity of memory T cells to mediate recall responses. Furthermore, the capacity of vaccines to elicit these memory T cell subpopulations predicted the efficacy of the recall response. These findings extend our understanding of how recall responses are generated and suggest that activation and migration markers define distinct, and unrelated, characteristics of memory T cells.
Prevalence and Prognostic Significance of Preprocedural Cardiac Troponin Elevation Among Patients With Stable Coronary Artery Disease Undergoing Percutaneous Coronary Intervention
Authors: Allen Jeremias, Neal S. Kleiman, Deborah Nassif, Wen-Hua Hsieh, Michael Pencina, Kelly Maresh, Manish Parikh, Donald E. Cutlip, Ron Waksman, Steven Goldberg, Peter B. Berger, David J. Cohen
Journal: Circulation (2008)

Although cardiac troponin (cTn) elevation is associated with periprocedural complications during percutaneous coronary intervention (PCI) in the setting of acute coronary syndromes, the prevalence and prognostic significance of preprocedural cTn elevation among patients with stable coronary artery disease undergoing PCI are unknown.Between July 2004 and September 2006, 7592 consecutive patients who underwent attempted stent placement at 47 hospitals throughout the United States were enrolled in a prospective multicenter registry. We analyzed the frequency of an elevated cTn immediately before PCI and its relationship to in-hospital and 1-year outcomes among patients who underwent PCI for either stable angina or a positive stress test. Among the stable coronary artery disease population (n=2382, 31.4%), 142 (6.0%) had a cTn level above the upper limit of normal before the procedure. Compared with patients who had normal baseline cTn, patients with elevated cTn had a higher rate of in-hospital death or myocardial infarction (13.4% versus 5.6%; P<0.001) and a trend toward higher rates of urgent repeat PCI (1.4% versus 0.2%; P=0.06). In multivariable analyses adjusted for demographic, clinical, angiographic, and procedural factors, baseline cTn elevation remained independently associated with the composite of death or myocardial infarction at hospital discharge (odds ratio, 2.1; 95% confidence interval, 1.2 to 3.8; P=0.01) and at the 1-year follow-up (odds ratio, 2.0; 95% confidence interval, 1.2 to 3.3; P=0.005).Baseline elevation of cTn is relatively common among patients with stable coronary artery disease undergoing PCI and is an independent prognostic indicator of ischemic complications. If these data are confirmed in future studies, consideration should be given to routine testing of cTn before performance of PCI in this patient population.
Upregulation of mouse CD14 expression in Kupffer cells by lipopolysaccharide.
Authors: K Matsuura, T Ishida, M Setoguchi, Y Higuchi, S Akizuki, S Yamamoto
Journal: The Journal of Experimental Medicine (1994)

Western blot analysis showed that a monoclonal antibody against recombinant mouse CD14 (mCD14), designated rmC5-3, specifically reacted with mouse macrophage cell line J774, but not myeloma cell line NS1. Fluorographic and immunocytochemical analysis demonstrated specific binding of rmC5-3 with mouse resident macrophages, inflammatory monocytes and neutrophils, and macrophage cell lines. Immunohistochemical staining using rmC5-3 showed that CD14-positive Kupffer cells (KC) were small in number in the liver in nonstimulated mice. The number of stained KC, which were rich in the midzonal and periportal regions, gradually increased with time after intraperitoneal injection of lipopolysaccharide (LPS), peaked 6 h after injection, and returned to normal by 20 h after injection. Staining intensity over time was proportional to the number of KC. A slight increase in mCD14 expression was observed in peritoneal macrophages 2 h after LPS administration in vivo using flow cytometric analysis. mCD14 mRNA became detectable at 1 h after the intraperitoneal injection of LPS (20 micrograms/mice), and the level dramatically increased with time, peaking at 3 h, and sharply dropped at 6 h. The resident peritoneal macrophages demonstrated a constitutively high mCD14 mRNA expression, which slightly increased 2 h after LPS (100 ng/ml) stimulation in vitro. The level of mCD14 expression in macrophages did not increase after intraperitoneal injection of LPS (20 micrograms/mice).
Time Spent in Hospital in the Last Six Months of Life in Patients Who Died of Cancer in Ontario
Authors: J. Huang
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To describe hospital bed utilization in the final 6 months of life in patients dying of cancer in Ontario, Canada. PATIENTS AND METHODS: Hospital separation records were linked to a population-based cancer registry to identify factors associated with hospitalization in the 203,713 patients who died of cancer in Ontario between 1986 and 1998. RESULTS: Between 1986 and 1998, 5.3% of all acute care beds in Ontario were devoted to the care of cancer patients in the last 6 months of life. The mean time spent in hospital in the last 6 months of life decreased from 34.3 days in 1986 to 22.7 days in 1998. Hospitalization rates increased exponentially during the last month of life. Patients younger than 50 years of age, women, and residents of poorer communities spent significantly longer in hospital than others. Hospitalization rates differed very little among the common solid tumors, but patients with CNS malignancies, the lymphomas, and the leukemias spent significantly longer in hospital than the other groups. There was significant interregional variations in hospitalization that were not explained by differences in case mix. There was a statistically significant inverse correlation between the rate of use of palliative radiotherapy and the hospital bed use in the county in which the patient resided. CONCLUSION: The total time spent in hospital in the last 6 months of life has decreased over the last decade, but acute care hospitals continue to play a large role in the care of patients who are dying of cancer.
Breast Cancer Incidence, 1980 2006: Combined Roles of Menopausal Hormone Therapy, Screening Mammography, and Estrogen Receptor Status
Authors: Andrew G Glass, James V Lacey, J Daniel Carreon, Robert N Hoover
Journal: JNCI Journal of the National Cancer Institute (2007)

Breast cancer incidence has been rising since at least 1935-1939, but recent US data reveal a statistically significant decline in breast cancer incidence in 2003 that persisted through 2004. Identifying the specific contributions of the potential causes of this long-term increase and the recent decrease in incidence has been challenging. Marked changes in rates of mammography screening and use of menopausal hormone therapy since 1980 have added further complexity. We examined the potential association between menopausal hormone therapy use and recent changes in breast cancer incidence.Using tumor registry, clinical, pathology, and pharmacy data from Kaiser Permanente Northwest, a large prepaid US health plan, we compared age-specific and age-adjusted breast cancer incidence rates (2-year moving averages) with use of screening mammography and dispensed menopausal hormone therapy prescriptions between 1980 and 2006. Temporal changes in incidence rates were assessed via joinpoint regression.A total of 7386 incident invasive breast cancers were diagnosed in plan members from 1980 through 2006. Overall age-adjusted breast cancer incidence rates per 100,000 women rose 25% from the early 1980s (105.6) to 1992-1993 (131.7) and an additional 15% through 2000-2001 (151.3), then dropped by 18% to 2003-2004 (123.6) and edged up slightly in 2005-2006 (126.2). These patterns were largely restricted to women aged 45 years or older and to estrogen receptor-positive (ER+) breast cancers. Incidence rates of ER-negative tumors experienced neither of the rises seen for ER+ tumors but also fell precipitously from 2003 through 2006. Rates of mammography screening sharply increased from 1980 to 1993 but then leveled off, and 75%-79% of women aged 45 years or older received a mammogram at least once every 2 years from 1993 through 2006. Menopausal hormone therapy dispensings, particularly of estrogen-plus-progestin formulations, increased from 1988 to 2002 but then dropped by approximately 75% after 2002.From 1980 through 2006, quantitative and qualitative trends in breast cancer incidence rates, particularly for ER+ tumors, parallel major changes in patterns of mammography screening and use of menopausal hormone therapy.
Long-Term Renal Effects of Low-Dose Cyclosporine in Uveitis-Treated Patients
Authors: Corinne Isnard Bagnis, Sophie Tezenas du Montcel, He[Combining Acute Accent]le[Combining Grave Accent]ne Beaufils, Chantal Jouanneau, Marie Chantal Jaudon, Philippe Maksud, Alain Mallet, Phuc LeHoang, Gilbert Deray
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Cyclosporine (CsA), a widely used immunosuppressive drug, is an effective treatment of sight-threatening posterior idiopathic uveitis. CsA's main side effect is nephrotoxicity. The aim of this single-center prospective cohort study (conducted in a tertiary care teaching hospital in Paris, France) was to assess the long-term renal tolerance of a low-dose CsA treatment in patients with previously healthy kidneys on clinical, biologic, and pathologic criteria. Forty-one patients treated with 4.3 ± 1.6 mg/kg body wt per day CsA for 44.9 ± 3.6 mo were included. Mean follow-up was 55.4 ± 0.2 mo. BP, CsA trough level, and renal function were prospectively monitored together with blood urea, creatinine clearance, GFR, and effective renal plasma flow. Eleven patients underwent serial kidney biopsies before and after 2 yr of a 4 ± 0.9 mg/kg daily CsA treatment. Sustained low-dose CsA treatment induced a significant increase in plasma creatinine (P < 0.0001), a significant decrease in creatinine clearance (P < 0.0001), and isotopic GFR (P < 0.0001) over time. The highest dose induced more severe alterations in any of the renal parameters than the lowest dose. Prevalence of hypertension was particularly high. Histopathologic data showed significant interstitial fibrosis (P < 0.003) and tubular atrophy (P < 0.003) after 2 yr. Low-dose long-term CsA treatment induces significant renal impairment and a high incidence of hypertension. Our study suggests that lowering daily dosage may prevent CsA-induced nephrotoxicity if a daily dose of ≤3 mg/kg is used. Whether once established it is reversible is still prospective, although the occurrence of interstitial fibrosis in the kidney would argue against reversibility. Email [email protected]
A young girl with apparent treatment-resistant asthma treated at Bambino Gesù children's hospital
Authors: Francesca Petreschi, Nicola Ullmann, Sergio Bottero, Paolo Tomà, Alessandro Inserra, Paola Francalanci, Anna Maria Zicari, Renato Cutrera
Journal: Thorax (2013)

Francesca Petreschi (FP): A 9.8 year–old-girl was first admitted in our unit for a persistent bronchospasm, poorly responsive to salbutamol, and progressive onset of respiratory distress after spontaneous expectoration of a bronchial cast (figure 1A). Her clinical history was uneventful until she was 7 years old, when she suffered from two subsequent bouts of pneumonia, but no admission was required. In the following years, she presented few episodes of bronchospasm, clinically diagnosed, with good response to bronchodilator and no limitation on her daily activities. Her family history was positive for allergic disease. On physical examination at her arrival, she appeared quite unwell with persistent wet cough, bilateral respiratory wheeze but normal levels of saturation. The remaining examination was normal.



Figure 1 
(A) Bronchial cast. (B) Bronchial fistula secreting milky material under pressure. (C) CT scan of the thorax demonstrating left lower lobe opacity and pleural effusion. (D) Lung biopsy compatible with pulmonary lymphangiectasia. (E) CT scan showing chylopericardium.



Renato Cutrera (RC): We have a previously healthy young girl with positive family history for allergies and personal history of few lower respiratory infections and intermittent episodes of wheezing. Patient's history and the spontaneous expectoration of a bronchial cast during an acute episode of bronchospasm, together with her physical examination characterised by intense cough and diffuse wheeze are suggestive of a case of plastic bronchitis (PB), already described as possible complication of allergic asthma. The differential diagnosis, though, should always include more inflammatory diseases of the lung, such as cystic fibrosis, pulmonary infections and acute chest syndrome in sickle-cell anaemia.1

Nicola Ullmann (NU): Patient was afebrile; blood exams were normal, including: haemoglobin, c-reactive protein, immunoglobulins and lipid values. Allergy tests were positive to house dust mites and few pollen, but sweat tests and nasal brushing for ciliary dyskinesia were negative. Spirometry showed mainly …
Supermarket chains warn that minimum pricing of alcohol will not stop binge drinking
Authors: A. O'Dowd
Journal: BMJ (2009)

Any national policy that introduces minimum pricing of alcohol in the United Kingdom will not prevent binge drinking, supermarket giants told MPs on 15 October.

The concept of a minimum price for a unit of alcohol is not a “silver bullet” to solve the problem of excessive alcohol consumption, they told MPs on the parliamentary health select committee as part of its inquiry into alcohol.

MPs asked witnesses representing Asda, Sainsbury’s, and Waitrose their opinion of introducing a minimum price for alcohol, something that the MPs say could curb heavy drinking and so ease pressure on the NHS.

The idea of a minimum price for alcohol was examined in a study carried out …
5' nucleotidase activity in the human synovial lining in rheumatoid arthritis.
Authors: B Henderson, J J Johnstone, J Chayen
Journal: Annals of the Rheumatic Diseases (1980)

5'-Nucleotidase (EC 3.1.3.5), a plasma membrane-bound enzyme, has been assayed in unfixed tissue sections of human synovium, activity being measured by scanning and integrating microdensitometry. Activity was markedly increased in the lining cells of the rheumatoid synovial membranes.