tbuckley/cabot-search huggingface dataset:
EFFECTS OF RIBONUCLEIC ACID ON MEMORY DEFECT IN THE AGED
Authors: D. EWEN CAMERON, S. SVED, L. SOLYOM, B. WAINRIB, H. BARIK
Journal: American Journal of Psychiatry (1963)

1. We have shown again and with a larger group of patients the effects of RNA administered intravenously upon the memory performance of patients suffering from organic memory defect. 2. We have demonstrated that it is possible to make a beginning in the task of analyzing which mechanisms within the memorial process are particularly favorably affected by RNA. 3. Thus far the indications are: i) that RNA acts upon the mechanism for retention, ii) that there is possibly a hitherto unrecognized mechanism for the storage of data by classification, iii) that there are other as yet unidentified mechanisms within the memorial process apart from retention which are favourably affected by RNA.
Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study
Authors: W S Lim
Journal: Thorax (2003)

In the assessment of severity in community acquired pneumonia (CAP), the modified British Thoracic Society (mBTS) rule identifies patients with severe pneumonia but not patients who might be suitable for home management. A multicentre study was conducted to derive and validate a practical severity assessment model for stratifying adults hospitalised with CAP into different management groups.Data from three prospective studies of CAP conducted in the UK, New Zealand, and the Netherlands were combined. A derivation cohort comprising 80% of the data was used to develop the model. Prognostic variables were identified using multiple logistic regression with 30 day mortality as the outcome measure. The final model was tested against the validation cohort.1068 patients were studied (mean age 64 years, 51.5% male, 30 day mortality 9%). Age >/=65 years (OR 3.5, 95% CI 1.6 to 8.0) and albumin <30 g/dl (OR 4.7, 95% CI 2.5 to 8.7) were independently associated with mortality over and above the mBTS rule (OR 5.2, 95% CI 2.7 to 10). A six point score, one point for each of Confusion, Urea >7 mmol/l, Respiratory rate >/=30/min, low systolic(<90 mm Hg) or diastolic (</=60 mm Hg) Blood pressure), age >/=65 years (CURB-65 score) based on information available at initial hospital assessment, enabled patients to be stratified according to increasing risk of mortality: score 0, 0.7%; score 1, 3.2%; score 2, 3%; score 3, 17%; score 4, 41.5% and score 5, 57%. The validation cohort confirmed a similar pattern.A simple six point score based on confusion, urea, respiratory rate, blood pressure, and age can be used to stratify patients with CAP into different management groups.
Cisplatin and Etoposide Versus Carboplatin and Paclitaxel With Concurrent Radiotherapy for Stage III Non–Small-Cell Lung Cancer: An Analysis of Veterans Health Administration Data
Authors: Rafael Santana-Davila, Kiran Devisetty, Aniko Szabo, Rodney Sparapani, Carlos Arce-Lara, Elizabeth M. Gore, Amy Moran, Christina D. Williams, Michael J. Kelley, Jeffrey Whittle
Journal: Journal of Clinical Oncology (2014)

The optimal chemotherapy regimen to use with radiotherapy in stage III non-small-cell lung cancer is unknown. Here, we compare the outcome of patents treated within the Veterans Health Administration with either etoposide-cisplatin (EP) or carboplatin-paclitaxel (CP).We identified patients treated with EP and CP with concurrent radiotherapy from 2001 to 2010. Survival rates were compared using Cox proportional hazards regression models with adjustments for confounding provided by propensity score methods and an instrumental variables analysis. Comorbidities and treatment complications were identified through administrative data.A total of 1,842 patients were included; EP was used in 27% (n = 499). Treatment with EP was not associated with a survival advantage in a Cox proportional hazards model (hazard ratio [HR], 0.97; 95% CI, 0.85 to 1.10), a propensity score matched cohort (HR, 1.07; 95% CI, 0.91 to 1.24), or a propensity score adjusted model (HR, 0.97; 95% CI, 0.85 to 1.10). In an instrumental variables analysis, there was no survival advantage for patients treated in centers where EP was used more than 50% of the time as compared with centers where EP was used in less than 10% of the patients (HR, 1.07; 95% CI, 0.90 to 1.26). Patients treated with EP, compared with patients treated with CP, had more hospitalizations (2.4 v 1.7 hospitalizations, respectively; P < .001), outpatient visits (17.6 v 12.6 visits, respectively; P < .001), infectious complications (47.3% v 39.4%, respectively; P = .0022), acute kidney disease/dehydration (30.5% v 21.2%, respectively; P < .001), and mucositis/esophagitis (18.6% v 14.4%, respectively; P = .0246).After accounting for prognostic variables, patients treated with EP versus CP had similar overall survival, but EP was associated with increased morbidity.
Effect of a Multipayer Patient-Centered Medical Home on Health Care Utilization and Quality
Authors: Meredith B. Rosenthal, Mark W. Friedberg, Sara J. Singer, Diana Eastman, Zhonghe Li, Eric C. Schneider
Journal: JAMA Internal Medicine (2013)

The patient-centered medical home is advocated to reduce health care costs and improve the quality of care.To evaluate the effects of the pilot program of a multipayer patient-centered medical home on health care utilization and quality.An interrupted time series design with propensity score-matched comparison practices, including multipayer claims data from 2 years before (October 1, 2006-September 30, 2008) and 2 years after (October 1, 2008-September 30, 2010) the launch of the pilot program. Uptake of the intervention was measured with audit data from the National Committee for Quality Assurance patient-centered medical home recognition process. SETTING Five independent primary care practices and 3 private insurers in the Rhode Island Chronic Care Sustainability Initiative.Patients in 5 pilot and 34 comparison practices.Financial support, care managers, and technical assistance for quality improvement and practice transformation.Hospital admissions, emergency department visits, and 6 process measures of quality of care (3 for diabetes mellitus and 3 for colon, breast, and cervical cancer screening).The mean National Committee for Quality Assurance recognition scores of the pilot practices increased from 42 to 90 points of a possible 100 points. The pilot and comparison practices had statistically indistinguishable baseline patient characteristics and practice patterns, except for higher numbers of attributed member months per year in the pilot practices (31,130 per practice vs 14,779, P = .01) and lower rates of cervical cancer screening in the comparison practices. Although estimates of the emergency department visits and inpatient admissions of patients in the pilot practices trended toward lower utilization, the only significant difference was a lower rate of ambulatory care sensitive emergency department visits in the pilot practices. The Chronic Care Sustainability Initiative pilot program was associated with a reduction in ambulatory care-sensitive emergency department visits of approximately 0.8 per 1000 member months or approximately 11.6% compared with the baseline rate of 6.9 for emergency department visits per 1000 member months (P = .002). No significant improvements were found in any of the quality measures.After 2 years, a pilot program of a patient-centered medical home was associated with substantial improvements in medical home recognition scores and a significant reduction in ambulatory care sensitive emergency department visits. Although not achieving significance, there were downward trends in emergency department visits and inpatient admissions.
How Are Physical Activity, Fitness, and Sedentary Behavior Associated With Insulin Sensitivity in Children?
Authors: Mélanie Henderson, Katherine Gray-Donald, Marie-Eve Mathieu, Tracie A. Barnett, James A. Hanley, Jennifer O’Loughlin, Angelo Tremblay, Marie Lambert
Journal: Diabetes Care (2012)

To describe the associations among moderate-to-vigorous physical activity (MVPA), fitness, sedentary behavior (SB), and insulin sensitivity (IS).Data were drawn from the baseline assessment of the QUALITY cohort, which included 630 white youth (aged 8-10 years at recruitment), with at least one obese biological parent. IS was measured by two fasting indices (insulin, homeostasis model assessment of insulin resistance) and an oral glucose tolerance test (OGTT)-based index (Matsuda IS index [Matsuda-ISI]). Fitness was measured by Vo(2peak); percent fat mass (PFM) was measured by dual-energy X-ray absorptiometry; 7-day MVPA was measured with accelerometry. SB indicators included average hours daily of self-report screen time (SBst), and average minutes daily at <100 counts/min from accelerometry (SBacc). Multivariable linear regression models were adjusted for age, sex, season, and puberty.MVPA and SBacc were independently associated with IS, but this was no longer statistically significant after accounting for PFM. SBst was negatively associated with IS in girls only, even after controlling for physical activity (PA), fitness, and adiposity; for each additional hour of SBst daily, IS decreased by 4.6-5.6% across all IS indices. Fitness was positively associated with IS (measured by Matsuda-ISI) after accounting for PA, SB, and PFM; for every 1 unit increase in Vo(2peak), Matsuda-ISI increased by approximately 1.0% (P < 0.05).In children with an obese parent, PA and SBacc are associated with IS, but this association is mediated by adiposity. SBst is negatively associated with IS in girls, beyond its known impact on adiposity. Finally, fitness is independently associated with better IS measured by OGTT.
Renal Insufficiency and the Risk of Lower Extremity Peripheral Arterial Disease
Authors: Ann M. O’Hare, Eric Vittinghoff, Judith Hsia, Michael G. Shlipak
Journal: Journal of the American Society of Nephrology (2004)

Renal insufficiency is a risk factor for coronary heart disease and stroke, but whether it predicts lower extremity peripheral arterial disease (PAD) is unknown. The authors evaluated was the association of baseline renal insufficiency with future PAD events in the Heart and Estrogen/Progestin Replacement Study (HERS) and follow-up study (HERS II). A total of 2763 postmenopausal women with known coronary heart disease were enrolled in HERS and randomly assigned to receive hormone therapy with conjugated estrogens and medroxyprogesterone acetate or placebo and followed for up to 8 yr for clinical end points. The outcome was time from randomization to first occurrence of either a lower extremity amputation, revascularization (surgical or percutaneous), or lumbar sympathectomy during follow-up. Incident lower extremity PAD event rates among women with creatinine clearances > or =60, 30 to 59, and < 30 ml/min/1.73 m(2) were, respectively, 0.55%, 0.92%, and 2.73% per year. After multivariable proportional-hazard adjustment for potential confounders and other known risk factors for PAD, women with a creatinine clearance 30 to 59 ml/min/1.73 m(2) (hazard ratio [HR], 1.63; 95% confidence interval [CI], 1.04 to 2.54, P = 0.032) and <30 ml/min/1.73 m(2) (HR, 3.24; 95% CI, 1.20 to 8.78, P = 0.021) had a significantly increased risk of PAD compared with participants with a creatinine clearance > or =60 ml/min/1.73 m(2). Renal insufficiency was independently associated with future PAD events among postmenopausal women with coronary heart disease. Future studies should determine whether this association is present in other populations and investigate its potential mechanisms.
p8 inhibits the growth of human pancreatic cancer cells and its expression is induced through pathways involved in growth inhibition and repressed by factors promoting cell growth.
Authors: Cédric Malicet, Nathalie Lesavre, Sophie Vasseur, Juan L Iovanna
Journal: Molecular Cancer (2003)

p8 is a stress-induced protein with multiple functions and biochemically related to the architectural factor HMG-I/Y. We analyzed the expression and function of p8 in pancreatic cancer-derived cells. Expression of p8 was silenced in the human pancreatic cancer cell lines Panc-1 and BxPc-3 by infection with a retrovirus expressing p8 RNA in the antisense orientation. Cell growth was measured in control and p8-silenced cells. Influence on p8 expression of the induction of intracellular pathways promoting cellular growth or growth arrest was monitored. p8-silenced cells grew more rapidly than control cells transfected with the empty retrovirus. Activation of the Ras→Raf→MEK→ERK and JNK intracellular pathways down-regulated p8 expression. In addition, the MEK1/2 inhibitor U0126 and the JNK inhibitor SP600125 up-regulates expression of p8. Conversely, p38 or TGFβ-1 induced p8 expression whereas the specific p38 inhibitor SB203580 down-regulated p8 expression. Finally, TGFβ-1 induction was in part mediated through p38. p8 inhibits the growth of human pancreatic cancer cells. p8 expression is induced through pathways involved in growth inhibition and repressed by factors that promote cell growth. These results suggest that p8 belongs to a pathway regulating the growth of pancreatic cancer cells.
40-HOUR CONTRACT FOR JUNIOR HOSPITAL DOCTORS
Authors: Desmond Murphy, ColinM. Furnival, Duncan Macintyre, Allan Pack, I.Ross Mcdougall, D.M. Ward, J.F. Mackenzie, W.F. Kean, P. Stromberg, G.M. Mckendrick, D. Brown, G. Mcintyre, B.L. Devine, I.N. Scobie, D.C.C. Owens, A. Strong, A. Dougall, D.R.T. Gundry, C.E. Langan, M.M. Berry, D.E. Mitchell, M.H. Delaney, J. Reilly, W.G. Campbell, K.R. Patel, A. Shenkin, P.R. Beck, M. Smith, M. Mcenaney, A.D. Howie, A. Milne, A.K. Henderson, G. Boyd, I.D. Hay, C. Mckillop, J.H. Mckillop, J.A. Burton, P.M. Kyle, I. Mackenzie, K.A. McLay, B.F. O'Reilly, J. Carlin, D.L. Citrin, M.J. Smyth, J.M. Simms, H.J.G. Burns, D. Henry, W.F. Bremner, J.L.H.C. Third, R.G. Murray, J.V. Jones, G. Lowe, R. Sturrock, P.J. Rooney, A.L.C. McLay, B.F. Boyce, W.D. Thompson, W.A. Reid, J. Rodger, R.P. O'Hare, K.A. Fleming, K. O'Reilly, A.M. Mcnicol, W.S. Stockwell, N.M. Pettigrew, J.M. Bell, A. Harvie, D. Morgan, M.W. Walker, H.D. Punnyadasa, J.F. Winchester, I.M.R. Rogers
Journal: The Lancet (1975)
Effective Treatment of Acute Promyelocytic Leukemia With All-<i>Trans</i>-Retinoic Acid, Arsenic Trioxide, and Gemtuzumab Ozogamicin
Authors: Farhad Ravandi, Eli Estey, Dan Jones, Stefan Faderl, Susan O'Brien, Jackie Fiorentino, Sherry Pierce, Deborah Blamble, Zeev Estrov, William Wierda, Alessandra Ferrajoli, Srdan Verstovsek, Guillermo Garcia-Manero, Jorge Cortes, Hagop Kantarjian
Journal: Journal of Clinical Oncology (2008)

We examined the outcome of patients with newly diagnosed acute promyelocytic leukemia (APL) treated with all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) with or without gemtuzumab ozogamicin (GO) but without traditional cytotoxic chemotherapy.
Crucial role of the protein C pathway in governing microvascular inflammation in inflammatory bowel disease
Authors: Franco Scaldaferri, Miquel Sans, Stefania Vetrano, Cristina Graziani, Raimondo De Cristofaro, Bruce Gerlitz, Alessandro Repici, Vincenzo Arena, Alberto Malesci, Julian Panes, Brian W. Grinnell, Silvio Danese
Journal: Journal of Clinical Investigation (2007)

Endothelial protein C receptor (EPCR) and thrombomodulin (TM) are expressed at high levels in the resting microvasculature and convert protein C (PC) into its activated form, which is a potent anticoagulant and antiinflammatory molecule. Here we provide evidence that in Crohn disease (CD) and ulcerative colitis (UC), the 2 major forms of inflammatory bowel disease (IBD), there was loss of expression of endothelial EPCR and TM, which in turns caused impairment of PC activation by the inflamed mucosal microvasculature. In isolated human intestinal endothelial cells, administration of recombinant activated PC had a potent antiinflammatory effect, as demonstrated by downregulated cytokine-dependent cell adhesion molecule expression and chemokine production as well as inhibited leukocyte adhesion. In vivo, administration of activated PC was therapeutically effective in ameliorating experimental colitis as evidenced by reduced weight loss, disease activity index, and histological colitis scores as well as inhibited leukocyte adhesion to the inflamed intestinal vessels. The results suggest that the PC pathway represents a new system crucially involved in governing intestinal homeostasis mediated by the mucosal microvasculature. Restoring the PC pathway may represent a new therapeutic approach to suppress intestinal inflammation in IBD.
Lupus Atherosclerosis Prevention Study (LAPS)
Authors: M. A. Petri, A. N. Kiani, W. Post, L. Christopher-Stine, L. S. Magder
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Background</h3> Cardiovascular disease is one of the major causes of death in systemic lupus erythematosus (SLE). A study was undertaken to investigate whether treatment with statins would reduce subclinical measures of atherosclerosis over a 2-year period. <h3>Methods</h3> 200 patients with SLE without clinical cardiovascular disease were randomised to receive atorvastatin 40 mg daily or an identical placebo. At baseline and after 2 years of follow-up, helical CT scanning (for coronary artery calcium) and carotid duplex (for intima media thickness/plaque) were performed. Patients were seen for measures of disease activity at 1 month, 3 months and quarterly thereafter. The primary outcome variable was change in coronary artery calcium. <h3>Results</h3> At baseline, 43% had coronary artery calcium. At 2 years there was no significant difference between the groups in progression of coronary artery calcium, carotid intima media thickness or carotid plaque. There was no significant difference between the groups in disease activity, measures of inflammation or endothelial cell activation. <h3>Conclusion</h3> This study provides no evidence that atorvastatin reduces subclinical measures of atherosclerosis or disease activity over 2 years in patients with SLE. In fact, it does not appear to reduce biochemical measures of inflammation. The anti-inflammatory effects of statins observed in the general population were not replicated in this SLE clinical trial. <b>Clinicaltrials.gov (NCT 00120887).</b>
Frequent<i>EGFR</i>mutations in nonsmall cell lung cancer presenting with miliary intrapulmonary carcinomatosis
Authors: Shang-Gin Wu, Fu-Chang Hu, Yih-Leong Chang, Yung-Chie Lee, Chong-Jen Yu, Yeun-Chung Chang, Jenn-Yu Wu, Jin-Yuan Shih, Pan-Chyr Yang
Journal: European Respiratory Journal (2012)

Nonsmall cell lung cancer (NSCLC) presenting with miliary intrapulmonary carcinomatosis (MIPC) is rare. We investigated the clinical characteristics and epidermal growth factor receptor ( EGFR ) mutation rate of NSCLC patients with MIPC at initial diagnosis. From June 2004 to December 2008, we screened newly diagnosed NSCLC patients for MIPC using image-based criteria. We recorded clinical data and analysed EGFR mutation status. For comparison, we collected specimens from stage IV NSCLC patients without MIPC tested for EGFR mutations from April 2001 to November 2008. From 3,612 NSCLC patients, 85 patients with MIPC at initial diagnosis were identified; 81 had adenocarcinoma. Of the 85 patients, 60 had specimen sequencing to detect EGFR mutation; 42 (70%) were positive. Compared with 673 stage IV patients without MIPC, patients with MIPC had higher EGFR mutation rate (p=0.036); even male smokers had a high EGFR mutation rate (91%). Multivariate analysis of prognostic factors for overall survival of the 85 patients with MIPC revealed that adenocarcinoma, absence of extrapulmonary metastasis and having EGFR mutation were associated with longer overall survival. NSCLC patients with MIPC at initial diagnosis had higher rates of adenocarcinoma and EGFR mutation. EGFR tyrosine kinase inhibition may be the treatment of choice for NSCLC patients with MIPC at initial diagnosis among Asians.
Sca-1 Knockout Impairs Myocardial and Cardiac Progenitor Cell Function
Authors: Brandi Bailey, Jenna Fransioli, Natalie A. Gude, Roberto Alvarez, Xiaoxue Zhan, Åsa B. Gustafsson, Mark A. Sussman
Journal: Circulation Research (2012)

Cardiac progenitor cells are important for maintenance of myocardial structure and function, but molecular mechanisms governing these progenitor cells remain obscure and require elucidation to enhance regenerative therapeutic approaches.To understand consequences of stem cell antigen-1 (Sca-1) deletion on functional properties of c-kit+ cardiac progenitor cells and myocardial performance using a Sca-1 knock-out/green fluorescent protein knock-in reporter mouse (ScaKI).Genetic deletion of Sca-1 results in early-onset cardiac contractile deficiency as determined by echocardiography and hemodynamics as well as age-associated hypertrophy. Resident cardiac progenitor cells in ScaKI mice do not respond to pathological damage in vivo, consistent with observations of impaired growth and survival of ScaKI cardiac progenitor cells in vitro. The molecular basis of the defect in ScaKI cardiac progenitor cells is associated with increased canonical Wnt signaling pathway activation consistent with molecular characteristics of lineage commitment.Genetic deletion of Sca-1 causes primary cardiac defects in myocardial contractility and repair consistent with impairment of resident cardiac progenitor cell proliferative capacity associated with altered canonical Wnt signaling.
Administration of recombinant interleukin 2 in vivo induces a polyclonal IgM response.
Authors: C M Weyand, J Goronzy, M J Dallman, C G Fathman
Journal: The Journal of Experimental Medicine (1986)

We studied the potential immunoenhancing effects of high doses of rIL-2 on murine T and B cell functions in vivo. Injection of rIL-2 caused a threefold or more increase in the frequencies of antigen-specific proliferative T cells, suggesting that rIL-2 initiated a polyclonal T cell response. In primary and secondary humoral immune responses, administration of rIL-2 in vivo selectively enhanced the production of IgM antibodies, whereas the IgG response was unaffected. Coadministration of rIL-2 with antigen failed to induce an isotype switch from IgM to IgG in genetically low-responding mice. Interestingly, in mice treated with rIL-2 alone (in the absence of exogenous antigen), polyclonal IgM production was induced. Polyclonal IgM production of lesser magnitude was found when mice were immunized with specific antigen in the absence of exogenous rIL-2, suggesting that local IL-2 concentrations in a primary immune response might be sufficient to elicit a polyclonal IgM response.
Incidence of Choroidal Neovascularization in the Fellow Eye in the Comparison of Age-related Macular Degeneration Treatments Trials
Authors: Maureen G. Maguire, Ebenezer Daniel, Ankoor R. Shah, Juan E. Grunwald, Stephanie A. Hagstrom, Robert L. Avery, Jiayan Huang, Revell W. Martin, Daniel B. Roth, Alessandro A. Castellarin, Sophie J. Bakri, Stuart L. Fine, Daniel F. Martin
Journal: Ophthalmology (2013)