tbuckley/cabot-search huggingface dataset:
PSA screening rate and prostate cancer mortality reduction in the province of Quebec
Authors: B. Candas, F. Labrie
Journal: Journal of Clinical Oncology (2005)

1023 Background: The present study analyzes the rates of decrease in CaP mortality in each region of the Province of Quebec as a function of PSA testing. Methods: : Mortality data obtained from the provincial death registry were analyzed to identify the prostate cancer death rates in the whole Province between 1991 and 2002 as well as in each region and in the two largest metropolitan areas, namely Montreal and Quebec City. CaP specific death rates and PSA testing rates were age-standardized to the 1991 Canadian population aged 40 years and above and are expressed per 100,000 men and as percent of the studied population, respectively. The annual variation in CaP mortality was fitted to a region-specific mono-exponential model. The correlation between the decline in CaP mortality and PSA screening is analyzed using the rates of PSA screening reported in the 2001 Canadian Communities Health Survey. Results: In the whole Province, the CaP mortality rate dropped from 70.1 (cv=3.5%) to 47.5 (cv=3.6%) between 1991 and 2002,thus showing a statistically significant total decrease of 32% over 11 years that corresponds to a rate of 3.1%/year in the whole Province, ranging from 0.6 to 5.5%/year. The magnitude of the decrease ranged from 21% to 49% according to regions. The provincial age-adjusted rate of routine/screening PSA testing was 37.1% (SE=0.8%), ranging from 28.1% (SE=1.8%) to 39.5% (SE=2.9%) in the regions. PSA testing and CaP mortality reduction are positively correlated (p=0.005) so that a 10% increase in the rate of PSA testing translated into a 4% further decease in the annual rate of CaP mortality. Conclusions: There is a strongly positive and highly significant relationship between the rate of routine/screening PSA testing in each region and the rate of decrease in CaP mortality achieved in the corresponding regions. No significant financial relationships to disclose.
Abstract 18300: Myocardial Ischemia Induces Telomerase Activity in the Mouse Heart
Authors: Christian Werner, Christophe Arendt, Constantinos Bakogiannis, Stephan H Schirmer, Andreas Mueller, Michael Boehm, Ulrich Laufs
Journal: Circulation (2012)

Introduction: The incidence of cardiovascular disease rises with age. Ischemia and oxidative stress-induced DNA damage and telomere erosion may accelerate cardiac senescence. The enzyme telomerase has been shown to protect cardiovascular cells from mitochondrial oxidative stress independent of telomere elongation. We examined whether myocardial ischemia impacts on telomere biology and cellular aging in the infarcted mouse heart. Methods and results: C57Bl/6 mice (10 weeks old, n=6-8 per group) were subjected to anterior myocardial ischemia induced by proximal ligation of the left anterior descendant coronary artery or sham operation. Cardiac MRI was used to verify infarct localization and measure LV function, showing that ejection fraction was reduced in MI mice (47±5% vs. 68±3% in sham, p&lt;0.01). Sham and MI mice were compared 3 days, 7 days, or 4 weeks after LAD ligation and myocardial infarct zone (IZ) and remote zone (RZ) were analyzed. Telomerase activity as measured by TRAP assays was elevated in the infarct zone 3 days after LAD ligation (187±9% vs. sham mice, p&lt;0.01), but not in the remote zone (113±35%). Seven days after myocardial infarction, telomerase was up-regulated both, in the infarct zone (177±31%) and the remote zone (154±26%). This effect was even more pronounced 4 weeks after LAD ligation (IZ: 271±14%; RZ 223±28%). In concert with telomerase activation, telomere repeat binding factor (TRF) 2 protein expression was up-regulated in the infarct zone after three days (337±25%) and in both areas after 7 days (IZ: 431±48%; RZ: 380±31%) and less strongly after 4 weeks (IZ: 170±23%; RZ: 141±27%). In parallel to telomerase activity and TRF2 expression, the apoptosis and senescence markers p53 (189±11%), Chk2 (167±32%), bax/bcl2-ratio (278±27%) and p16 (518±42%) were up-regulated in the myocardium of MI mice after 4 weeks (all shown values p&lt;0.05 vs. myocardial tissue of sham-operated mice). Conclusion: Myocardial telomerase and telomere-associated factors are up-regulated in a time- and region-specific manner in the infarcted mouse heart in concert with apoptosis and cell-cycle regulators. This regulatory process may be of relevance for myocardial survival, inflammation, and remodelling after ischemia.
The Role of Surface Nanotopography and Chemistry on Primary Neutrophil and Macrophage Cellular Responses
Authors: Susan N. Christo, Akash Bachhuka, Kerrilyn R. Diener, Agnieszka Mierczynska, John D. Hayball, Krasimir Vasilev
Journal: Advanced Healthcare Materials (2016)

Synthetic materials employed for enhancing, replacing, or restoring biological functionality may be compromised by the host immune responses that they evoke. Surface modification has attracted substantial attention as a tool to modulate the host response to synthetic materials; however, how surface nanotopography combined with chemistry affects immune effector cell responses is still poorly understood. To address this open question, a unique set of model surfaces with controlled surface nanotopography in the range of 16, 38, and 68 nm has been generated. Tailored outermost surface chemistry that was amine, carboxyl, or methyl group rich has been provided. The combinations of these properties yield 12 surface types that are subject to functional assays assessing key immune effector cells, namely, primary neutrophil and macrophage responses in vitro. The data demonstrate that surface nanotopography leads to enhanced matrix metalloproteinase‐9 production from primary neutrophils, and a decrease in pro‐inflammatory cytokine secretion from primary macrophages. Together, these results are the first to directly compare the immunomodulatory effects of the cooperative interplay between surface nanotopography and chemistry.
Lysis of Tumor Cells by Antibody and Complement. I. Lack of Correlation Between Antigen Content and Lytic Susceptibility
Authors: Sarkis H. Ohanian, Tibor Borsos, Herbert J. Rapp
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Lysis of Tumor Cells by Antibody and Complement. I. Lack of Correlation Between Antigen Content and Lytic Susceptibility Get access Sarkis H. Ohanian, Sarkis H. Ohanian Biology Branch, National Cancer Institute,2Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar Tibor Borsos, Tibor Borsos Biology Branch, National Cancer Institute,2Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar Herbert J. Rapp Herbert J. Rapp Biology Branch, National Cancer Institute,2Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 50, Issue 5, May 1973, Pages 1313–1320, https://doi.org/10.1093/jnci/50.5.1313 Published: 01 May 1973 Article history Received: 22 September 1972 Accepted: 29 January 1973 Published: 01 May 1973
Potassium excretion
Authors: M L Halperin, S Cheema-Dhadli, L E Phillip
Journal: Journal of the American Society of Nephrology (1994)

The aim of this article is to consider how a large quantity of potassium (K+) can be excreted without the development of hyperkalemia. The hypothesis will focus on interactions between K+ and HCO3- primarily within the kidneys. It is speculated that the absorption of K+ from the gastrointestinal tract is accompanied by an initial addition of HCO3- to the body; this in turn could, via intrarenal events, promote the delivery of HCO3- to the cortical collecting duct (CCD), where interactions may permit the development of a very high rate of excretion of K+. To test one portion of this hypothesis, studies were performed in sheep because they normally consume approximately 10-fold more K+ per kilogram body weight than do humans. In the absence of a significant degree of anabolism, there is only a limited potential to shift K+ acutely into cells. Hence, an extremely large capacity to excrete K+ is required to avoid a severe degree of hyperkalemia. The excretion of K+ depends primarily on the ability to have a sustained rise in the (K) in each liter of luminal fluid exiting the CCD to very high levels and to have a large number of liters of fluid exit the terminal CCD while antidiuretic hormone is acting. A reasonable approximation of this CCD flow rate can be obtained by examining the osmole excretion rate when ADH acts. Because these sheep excreted 1,650 mosmol (2 L x 827 mosm/kg H2O) per day, a minimum estimate for volume delivery out of the CCD is 5 to 6 L/day.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract 13132: Heart Disease Mortality Trends During the 21st Century, United States, 2000-2010
Authors: Yuling Hong, Matthew Ritchey, Fleetwood Loustalot, Barbara A Bowman
Journal: Circulation (2013)

Background: Heart disease (HD) remains the leading cause of US deaths. However, knowledge of HD type’s role in these trends is lacking. Objective: To examine the relative impact HD types have had on overall HD mortality trends among US adults aged 35 years and older from 2000-2010. Methods: We used the CDC WONDER online database to determine HD mortality rates_based on underlying cause of death. We stratified the results by HD type, age standardized the rates and used SEER’s JoinPoint program to develop log-linear regression models to calculate the average annual percent change (AAPC) in rates. We determined the annual proportion of all HD deaths attributable to each HD type by dividing the number of deaths of each HD type by the number of all HD deaths. Results: During 2000-2010, 7,102,788 HD deaths were observed (645,708 average deaths per year). HD and coronary heart disease (CHD) mortality declined from 500.8 and 364.7 in 2000 to 347.3 and 221.6 per 100,000 in 2010, with AAPC of -3.8 and -5.1%, respec...
Abstract 10138: On-going Palliative Care Enhances Perceived Control and Patient Activation in Patients With Symptomatic Heart Failure
Authors: Lorraine Evangelista, Marjan Motie, Dawn Lombardo, Shaista Malik, Jennifer Ballard-Hernandez, Solomon Liao
Journal: Circulation (2013)

Introduction: Few studies have assessed the effectiveness of palliative care (PC) on perceived control (i.e. one’s perceived influence over outcomes or events in the environment) and activation (i....
Abstract 19113: Invasive Evaluation of Chest Pain in Patients With Angiographically Normal Coronary Arteries
Authors: Bong-Ki Lee, Andy C Yong, William F Fearon, Hong-Seok Lim, Patricia K Nguyen, Alan C Yeung, Jennifer A Tremmel
Journal: Circulation (2013)

Background: More than 20% of patients with angina have no angiographic evidence of coronary artery disease (CAD). Our aim was to investigate alternative etiologies for chest pain in these patients. Methods: In patients with angina who were referred for coronary angiography and had no angiographic CAD, endothelial function testing, intravascular ultrasound (IVUS), and physiology measurements were performed. Results: A total of 139 patients were enrolled. The average age was 54.0±11.4, with 107 women (77%). Seventy four patients (53.2%) had hypertension, 32 (23.2%) diabetes, 87 (62.6%) dyslipidemia, 10 (7.2%) tobacco use, and 45 (32.4%) a family history of CAD. Endothelial dysfunction (a decrease in luminal diameter of &gt;20% with intracoronary acetylcholine) was present in 61 patients (43.9%). Five patients (3.6%) had fractional flow reserve &lt;0.80. Microcirculatory impairment (an index of microcirculatory resistance ≥25) was present in 29 patients (20.9%). Myocardial bridging (an echolucent halo found on IVUS with systolic arterial compression &gt;10%) was present in 54 patients (43.9%). Thirty eight patients (27.3%) had no coronary explanation for their chest pain, with normal endothelial function and coronary physiologic assessment, and no myocardial bridging. There was no complication. Conclusion: Many patients with angina and no angiographic evidence of CAD have occult coronary circulatory abnormalities, while a minority has no coronary etiology to explain their symptoms. A complete invasive assessment of these patients at the time of coronary angiography provides important diagnostic information which may affect treatment.
Abstract 14612: Treatment of Ischemia/Reperfusion Injury Through Supplementation With Sodium Selenite: Modification of Oxidative Organ Damage and Inflammatory Response
Authors: Lena Wollschlager, Esra Bilgic, Melanie Engels, Antonio Pinto, Holger Steinbrenner, Payam Akhyari, Artur Lichtenberg, Udo Boeken
Journal: Circulation (2013)

Introduction:  Ischemia/reperfusion (I/R) injury leads to oxidative damage which contributes to the mortality of cardiopulmonary bypass (CPB). Supplementation of Sodium Selenite (Se) is known to induce selenoproteins and thus to counteract oxidative damage. The aim of this study was to investigate the impact of dietary selenium on markers of oxidative tissue damage and inflammation during CPB and deep hypothermic circulatory arrest (DHCA).   Methods:  Male rats (Wistar, 400-500g) were fed Se-supplemented chow for 5 weeks (1000μg Se/kg, n=7). Control group (n=7) were fed a Se-adequate diet with 300μg Se/kg. The rats were cannulated for CPB, connected to a heart-lung-machine and cooled down. At 17°C, CPB was interrupted for 45 minutes of DHCA. After rewarming and 60 minutes of reperfusion tissue samples were harvested. Immunoblot analysis was used to detect protein levels of the transcription factor STAT3, the heat shock protein 70 and MAP kinase ERK1/2. Requirement of catecholamine and vital parameters were documented continuously. Activity of the selenoenzyme glutathione peroxidase (GPX) and tissue selenium levels were measured. Serum markers of oxidative tissue damage and inflammation markers were analyzed.   Results:  Se-supplementation increased tissue selenium levels as well as GPX-activity and counter-acted I/R-induced ERK1/2 phosphorylation in the heart, while it increased STAT3 phosphorylation and HSP70 expression in the liver. Se-supplemented rats required less catecholaminesubstitution. In addition, Se-supplementation suppressed the I/R-induced increase in ALT, AST, LDH and troponin levels.   Conclusions:  According to our data Se-supplementation appears to be effective for prevention of acute I/R-induced tissue damage. The implications of its different actions with regard to oxidative stress markers on recovery after surgery require further investigation.
Reproducibility of non-invasive measures of arterial stiffness in mild to severe stable COPD using a new cuff-based operator independent device
Authors: Ian S. Stone, Steffen E. Petersen, Neil C. Barnes
Journal: European Respiratory Journal (2012)

Introduction  COPD is associated with significant cardiovascular morbidity and mortality. Recent evidence suggests that treating COPD may improve arterial stiffness, a key determinant of cardiac risk. Endpoints with high reproducibility are desirable when assessing the impact of an intervention. A new cuff-based operator-independent device (Vicorder) has been developed for measuring arterial stiffness.  Aims  To assess pulse wave velocity (PWV) and augmentation index (AI) reproducibility, using the Vicorder device, in clinically stable COPD patients.  Methods  Between 27/11/12-15/2/12 repeat measurements of PWV and AI were made on 23 consecutive mild to severe stable COPD patients (12 males, 11 Females; Mean age 66±8 years; Mean predicted FEV1 50±19%), recruited from an inner-city teaching hospital out-patients.  Results  PWV mean = 8.9±1.2 m/s, mean difference = 0.035 m/s, Co-efficient of variation (COV) = 4% and limits of agreement (LOA) = -0.68 - +0.76m/s.  AI mean = 17.8±6.7 mmHg, mean difference = -0.7 mmHg, COV = 27.9% and LOA = -10.4 - +9.02 mmHg. Based on the above data, a sample size of 30 pairs would detect a change in PWV of 0.27 m/s with a power of 80%.  Conclusion  Vicorder measurements of PWV, but not AI, in stable COPD patients are highly reproducible and ideal for use in screening programmes and COPD research due to its operator independent non-invasive nature.
Abstract 16467: Can a Model-Based Decision Support Tool Improve Anticoagulation Outcomes for Atrial Fibrillation? Results From a Large Database Cohort
Authors: Bradley C Martin, Julian P Casciano, W. J Kwong, Daniel E Singer
Journal: Circulation (2011)

Background We recently reported a novel decision model that integrates both stroke and bleeding risk scores to guide optimal use of anticoagulation (AC) for stroke prevention in atrial fibrillation...
Dacarbacine (DTIC) versus vaccination with autologous peptide-pulsed dendritic cells (DC) as first-line treatment of patients with metastatic melanoma: Results of a prospective-randomized phase III study
Authors: D. Schadendorf, F. O. Nestle, E.-B. Broecker, A. Enk, S. Grabbe, S. Ugurel, L. Edler, G. Schuler
Journal: Journal of Clinical Oncology (2004)

7508 Background: Progress in the treatment of patients with metastatic melanoma has been very limited over the last two decades. Vaccination with autologous DC was reported as being able to induce some clinical regression in early clinical phase I/II studies. Methods: Patients with advanced metastatic melanoma, HLA-A1, -A2, -A3, -A24 or -B44 positivity, no brain or bone metastases and any previous systemic chemotherapy were randomised to receive DTIC (850 mg/m2 d1, every 28 days with 4-week intervals (arm A) or intradermal vaccination with autologous peptide-pulsed dendritic cells in 2-week intervals for the first 5 vaccinations and every 4 weeks thereafter (arm B). DC were generated from peripheral blood after leukapheresis and culturing monocytes in-vitro in GM-CSF, IL-4 (d1-d5) and a maturing cytokine cocktail (IL-1β, IL-6, TNFα and PGE2) on day 6. Matured DC were pulsed subsequently with peptides derived from MAGE-1, MAGE-3, Melan-A, gp100, tyrosinase and influenza proteins as a control depending on the individual HLA-type (d6). Primary study endpoint was objective response to treatment (OR), secondary endpoints included safety, overall and progression-free survival. The planned accrual per arm was set at 119 patients under the basic assumption that the response rate would double from 15 % for treatment with DTIC to 30 % for DC-vaccination to reach significance at 0.05 with 80% power. Results: In the time period between 1/2001 and 6/2003 a total of 108 (intention-to-treat population, ITT; 55 DTIC, 53 DC) patients were randomized from 1 Swiss and 5 German centers with experience in DC generation and therapy. Accrual was halted prematurely by the data monitoring board because data indicated that the study goals could not be achieved. OR (CR+PR) were 5.5% in arm A and 3.8% in arm B, respectively (ITT). There was no statistically significant difference for response, toxicity, overall and progression-free survival between both study arms. Subset analysis indicated a trend for benefical effect of HLA-A2 and a disadvantage for HLA-B44. Conclusion: DC-based vaccination is as poorly active as standard DTIC chemotherapy in metastatic melanoma. Whether further selection of patients and improved DC generation protocols will lead to a statistical benefit remains topic of further studies. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merix
Programmed cell death ligand 1 alleviates psoriatic inflammation by suppressing IL-17A production from programmed cell death 1–high T cells
Authors: Jong Hoon Kim, Young Joon Choi, Byung Ha Lee, Mi-Young Song, Chae Yeon Ban, Jihye Kim, Junsik Park, Song-Ee Kim, Tae-Gyun Kim, Su-Hyung Park, Hyoung-Pyo Kim, Young-Chul Sung, Soo-Chan Kim, Eui-Cheol Shin
Journal: Journal of Allergy and Clinical Immunology (2016)
Randomized phase III trial of docetaxel and cisplatin combination chemotherapy versus mitomycin, vindesine, and cisplatin combination chemotherapy with concurrent thoracic radiation therapy for locally advanced non-small-cell lung cancer: OLCSG 0007
Authors: K. Kiura, N. Takigawa, Y. Segawa, H. Kamei, M. Takemoto, M. Tabata, H. Ueoka, S. Hiraki, K. Matsuo, M. Tanimoto
Journal: Journal of Clinical Oncology (2008)

7515 Background: Two groups in the US and Japan have demonstrated the superiority of cisplatin-based second-generation chemotherapy with concurrent thoracic radiation therapy (TRT) over sequential TRT in locally advanced non-small-cell lung cancer (LA-NSCLC). In our phase I/II trial, docetaxel and cisplatin (DP) chemotherapy with concurrent TRT gave a favorable response and survival (BJC 89, 2003). A phase III, randomized trial was conducted to assess the efficacy and safety of DP chemotherapy with concurrent TRT. Methods: Patients with LA-NSCLC were randomly assigned to two arms, according to stratification by performance status (PS, 0 versus 1), stage (IIIA versus IIIB), and institution. Chemotherapy consisted of docetaxel 40 mg/m2 and cisplatin 40 mg/m2 on days 1, 8, 29, and 36 in the DP arm, and mitomycin 8 mg/m2 and cisplatin 80 mg/m2 on days 1 and 29, and vindesine 3 mg/m2 on days 1, 8, 29, and 36 in the MVP arm. In both groups, TRT began on day 1 (2 Gy/5 fractions/week; total 60 Gy, no split). Results: Between July 2000 and July 2005, 200 patients entered the trial at 17 institutes in Japan. The table below summarizes patient characteristics and the results. At 2 years, the survival rate was significantly higher in the DP arm than in the MVP arm (stratified Wilcoxon test). Hematological toxicities and febrile neutropenia were significantly higher in the MVP arm than in the DP arm. No significant difference was observed in non-hematological toxicities. Treatment-related deaths occurred in the MVP arm (one pneumonia+pneumothorax) and in the DP arm (two radiation pneumonitis, one sepsis). Conclusions: The trial met the primary endpoint (2-year survival rate). In LA-NSCLC, DP chemotherapy was effective and had acceptable toxicity compared with cisplatin-based second-generation chemotherapy combined with concurrent TRT. Characteristics/Results MVP arm DP arm Number of randomized patients 101 99 Median age (range) 64 (34–75) 65 (40–75) Gender male/female 88/13 92/7 Performance status 0/1 50/51 46/53 Stage IIIA/IIIB 33/68 33/66 Overall response rate: CR+PR, % (95% CI) 70.3 (60.4–79.0) 78.8 (69.4–86.4) Median survival time, months (95% CI) 23.7 (15.9–33.2) 26.8 (23.6–33.4) 2-yr survival rate, % (95% CI) 48.1 (38.0–57.5)* 60.3 (49.9–69.2)* 5-yr survival rate, % (95% CI) 16.6 (8.0–28.0) 23.5 (13.8–34.7) * p = 0.0183 (crude 0.0251) by stratified Wilcoxon test; p = 0.0588 (crude 0.0419) by stratified log-rank test; CI, confidence interval. No significant financial relationships to disclose.