tbuckley/cabot-search huggingface dataset:
Abstract 17634: Increase in Epicardial Fat Volume is Associated with Greater Coronary Artery Calcification Progression in Subjects at Intermediate Risk by Coronary Calcium Score: A Serial Study Using Non-Contrast Cardiac CT
Authors: Rine Nakanishi, Ronak Rajani, Victor Y Cheng, Heidi Gransar, Ryo Nakazato, Haim Shmilovich, Yuka Otaki, Sean W Hayes, Louise E Thomson, John D Friedman, Piotr J Slomka, Daniel S Berman, Damini Dey
Journal: Circulation (2011)

Objective: Epicardial fat volume (EFV) is related to calcified coronary plaques. However, it is unknown whether baseline EFV or changes in EFV affect the progression of coronary artery calcification over time. Methods: We identified 375 consecutive asymptomatic subjects with an intermediate risk of developing coronary heart disease [1) a man ≥55 years or woman ≥65 years or 2) a man 45-54 years or woman 55-64 years with at least 1 traditional CAD risk factor and baseline coronary calcium score (CCS) 50-399] who underwent serial non-contrast CT at least 3-5 years apart. Subjects were divided into tertiles of CCS progression (% increase) between the 2 scans. Subjects from the upper tertile (High Progressors) were matched by age and gender to 81 subjects from the lower tertile (Low Progressors). All subjects underwent serial measurements of CCS and EFV. The relationship between EFV and CCS progression, and changes in plaque number were compared between the two groups. Results: At baseline, there was no difference in EFV, and EFV indexed to body surface area (EFVi) between the two groups. At follow-up, EFV, EFVi and percent increase in EFVi-change were higher in the High Progressors than the Low Progressors (EFV, 102 ± 38 cm 3 vs. 90 ± 35 cm 3 , p=0.03; EFVi, 50 ± 16 cm 3 /m 2 vs. 45 ± 15 cm 3 /m 2 , p=0.03; EFVi-change, 15 ± 22% vs. 7 ± 20%, p=0.02). Based on our previously determined inter-scanner and inter-observer variability, a ≥ 15 % increase from baseline EFVi was set as the criterion for significant EFVi increase. On multivariate analysis, after adjusting for conventional cardiovascular risk factors, EFVi increase ≥ 15% and scan interval time were predictive of being a High Progressor [EFVi increase ≥ 15%, p&lt;0.05, OR 2.3, 95% C.I 1.0-5.3, scan interval time p=0.003, OR 1.0, 95% CI 1.001-1.006]. By multivariable linear regression analysis, EFVi increase ≥ 15% (β= 3.0, 95% C.I. 0.4 - 5.6, p=0.02) and hypertension (β= 3.1, 95% C.I. 0.6 - 5.6, p=0.01) were independent predictors of the number of new calcified plaques on follow-up. Conclusion: Increase in EFV is associated with greater progression of coronary artery calcification in intermediate-risk subjects.
Abstract 2727: Mutation-linked Channel Disorder in Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is Caused by Abnormally Tight Domain-Domain Interaction in RyR2
Authors: Takeshi Suetomi, Masafumi Yano, Akihiro Hino, Makoto Ono, Xiaojuan Xu, Takehisa Susa, Hitoshi Uchinoumi, Tetsuro Oda, Masahiro Doi, Shinichi Okuda, Shigeki Kobayashi, Yasuhiro Ikeda, Takeshi Yamamoto, Masunori Matsuzaki
Journal: Circulation (2009)

CPVT is known to be caused by single point mutation in cardiac ryanodine receptor (RyR2). However, the underlying mechanism, by which a single mutation causes drastic effects on the channel functio...
Abstract 2168: The Endothelin Receptor Blocker Bosentan Inhibits Doxorubicin-Induced Cardiomyopathy
Authors: Sandra Bien, Alexander Riad, Christoph A Ritter, Florian Olshausen, Matthias Gratz, Markus Grube, Stephan B Felix, Ralf Ewert, Dirk Westermann, Carsten Tschope, Heyo K Kroemer
Journal: Circulation (2006)

Background: Doxorubicin is a frequently used anticancer drug. One major factor limiting its clinical application is doxorubicin induced cardiotoxicity characterized by left ventricular (LV) dysfunc...
Phase II study of combretastatin A4 phosphate (CA4P) in patients with advanced anaplastic thyroid carcinoma (ATC)
Authors: M. M. Cooney, P. Savvides, S. Agarwala, D. Wang, S. Flick, S. Bergant, S. Bhakta, P. Lavertu, J. Ortiz, S. Remick
Journal: Journal of Clinical Oncology (2006)

5580 Background: CA4P is the first tubulin-binding vascular disrupting agent tested in the clinic. Phase I studies were devoid of significant myelosuppression, DLT included cardiovascular side effects, and there was demonstrable activity in ATC (Cancer Res 2002; 62:3408; Clin Cancer Res 2004; 10:96). Methods: Patients with metastatic ATC, good performance status, normal ECG and cardiac function, and no prior therapy for disseminated disease were eligible for study. CA4P at a dose of 45 mg/m 2 was administered as 10-minute IV infusion on days 1, 8 and 15 every 28 days (1 cycle) until progression of disease. Results: A total of 18 patients (pts) (11M/7F), median age 62 (range 40–71 yrs), received a total of 55.67 cycles of treatment. Therapy was well tolerated with mild to moderate nausea, vomiting, headache, and tumor pain (3 pts with grade 3) all of which essentially resolved within first 24 hrs. There was no clinically meaningful myelosuppression or cardiac toxicity. No objective responses were seen; 6 pts with stable disease and 12 pts progressed. Median progression free survival (PFS) was 7.4 wks (range 2–84+ wks); with 28% of pts progression free &gt; 3.0 mos. (12.0+, 14.3, 15.3, 25.6 and 84.0+ wks). Pts without bulky disease tended to do better. Fourteen pts have died; 4 are alive; and 2 are alive and on-study at 12.0+ and 84.0+ wks. Median survival is on the order of approximately 20 wks. Conclusions: Approximately a quarter of patients treated with single-agent CA4P experience greater than 3 mos. freedom from progression. Combined modality strategies with CA4P and either chemotherapy and other targeted agents or with radiation are warranted. [Supported in part by a clinical grant from OXiGENE, Inc., Waltham, MA and NIH grant nos. M01 RR-00080]. No significant financial relationships to disclose.
Abstract 13818: The Prognostic Importance of Metabolic Syndrome in a Large Cardiac Rehabilitation Cohort
Authors: Billie-Jean Martin, Ross Arena, Trina Hauer, Leslie D Austford, Sandeep Aggarwal, James A Stone
Journal: Circulation (2011)

Background: The metabolic syndrome (MetSyn) is associated with an increased risk of diabetes and cardiovascular disease. The purpose of the present investigation was to assess the association betwe...
Airway Mucus Function and Dysfunction
Authors: Douglas C Johnson
Journal: New England Journal of Medicine (2011)

The lungs are remarkably resistant to environmental injury, despite continuous exposure to pathogens, particles, and toxic chemicals in inhaled air.Their resistance depends on a highly effective defense provided by airway mucus, 1-7 an extracellular gel in which water and mucins (heavily glycosylated proteins) are the most important components.Airway mucus traps inhaled toxins and transports them out of the lungs by means of ciliary beating and cough (Fig. 1).2][3][4] This review examines the normal formation and clearance of airway mucus, the formation of pathologic mucus, the failure of mucus clearance that results in symptoms and abnormal lung function, and the therapy of mucus dysfunction. STRUCTURE AND FUNCTION OF THE NORMAL AIRWAYEpithelial surfaces in contact with the outside environment are protected by mechanical barriers (e.g., keratinized skin) and chemical barriers (e.g., gastric acid).2][3][4][5][6][7] Mucus layers vary widely in composition and structure; for example, they are thick and adherent to the epithelium in the gut, but thin and mobile in the airway. SURFACE EPITHELIAL CELLSThe surface epithelium of intrapulmonary airways is composed of two principal cell types -ciliated and secretory (Fig. 2).These cells are present in similar numbers and form a mosaic.Secretory cells have been further divided into subtypes based on their microscopical appearance (e.g., Clara, goblet, and serous cells).1][12][13][14] Therefore, it is simplest to refer to them generically as "secretory cells."Besides mucins, secretory cells release a variety of antimicrobial molecules (e.g., defensins, lysozyme, and IgA), immunomodulatory molecules
Pertaining to Peptic Ulcer
Authors: Anthony Bassler
Journal: Annals of Internal Medicine (1931)

Article1 February 1931Pertaining to Peptic UlcerANTHONY BASSLER, M. D.ANTHONY BASSLER, M. D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-4-8-997 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptOne hundred years ago Cruveilhier showed that gastric ulcer was a clinical entity. Before him (in 1793) Matthhew Baillie wrote about it, and patients complaining of it were described in the 16th century. Thus for 300 years something was known about it, this knowledge for 100 years more fully employed, and in the last 25 years most intimately, and yet really nobody knows much of anything about. Someday, somewhere, somebody is going to tells us accurately what peptic ulcers are caused by, and then we are going to know something worth the while about it, and get somewhere with it.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York*Read by invitation before the Harlem Medical Association, Feb. 25th, 1930, and the Mount Vernon Medical Society, Apr. 10th, 1930. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 February 1931Volume 4, Issue 8Page: 997-1003KeywordsGastric ulcersPeptic ulcers Issue Published: 1 February 1931 PDF downloadLoading ...
Is recruitment more difficult with a placebo arm in RCTs?
Authors: L. Forbes, S. Chinn, J. Figueroa-Munoz, P. Seed, A J Welton, M R Vickers, J A Cooper, T W Meade, T M Marteau
Journal: BMJ (1999)

Editor—Welton et al found that the proportion of women who were willing to participate in a randomised controlled trial of hormone replacement therapy was higher if participation in a trial without a placebo arm was offered rather than participation in one with a placebo arm, although the difference was of borderline significance.1 Their conclusion was that inclusion of a placebo arm may reduce patients’ willingness to participate in a trial. We do not believe that this conclusion is justified.

Allocation of participants to either of the comparison groups was by the woman’s choice of appointment time: the nurses offered participation in trials with and without placebo groups in alternate weeks. This is not random allocation, in which only chance can influence which group a participant is allocated to.2 In this study the nurses could predict in which weeks they would be offering participation in trials with or without placebo groups and so could have influenced the choice of appointment time. This kind of bias would have been avoided by randomising the weekly blocks, the intervention for that week being revealed to the nurses only after all appointments for that week were made.

The nurses’ explanation of the reason for using a placebo could have influenced willingness to participate. We would have been reassured that nurses’ explanations were consistent and neutral by knowing that rates of willingness to participate across practices were similar. A lower rate of willingness to participate in some practices would imply differences between nurses in the way they described the reasons for inclusion of a placebo—that is, that it is not the placebo itself but the way in which it is explained that influences the decision to participate. This would make the study’s conclusion invalid.

The study shows only that the use of placebos may influence rates of willingness to participate, not actual participation rates, in a trial of hormone replacement therapy. We are concerned that this paper may be used to justify not including a placebo in randomised controlled trials. It is important to include a placebo when the only treatments available are of unknown efficacy or safety.3 The real challenge is to develop ways of effectively explaining the reasons for using a placebo to potential participants when a placebo is ethically justified.
Abstract 16290: Heart Failure Metabolomics by Nuclear Magnetic Resonance and the Effects of Ventricular Assist Devices
Authors: Lindsay Weitzel, Amrut Ambardekar, Andreas Brieke, Joseph Cleveland, Natalie Serkova, Paul Wischmeyer Wischmeyer, Brian D Lowes
Journal: Circulation (2011)

Background: Nuclear magnetic resonance (NMR) spectroscopy allows for the quantification of large numbers of metabolites in small tissue samples. Little is known about the effects of ventricular ass...
A PK-PD dose optimization strategy for the microtubule stabilizing agent ABJ879
Authors: Clifford Dilea, Markus Wartmann, Sauveur-Michel Maira, Josef Brueggen, Chiaki Tanaka, Kurt Sizer, Margaret Dugan
Journal: Cancer Research (2004)

5132  The purpose of the dose optimization strategy was to maximize efficacy and tolerability of a cytotoxic drug based on its pharmacokinetic (PK) and pharmacodynamic (PD) properties in a xenograft mouse model. If successful, the approach may be extended to clinical development. The objectives were to conduct a retrospective PK-PD analysis, formulate a drug response model and test it experimentally. ABJ879 is a semisynthetic epothilone B derivative with potent in vitro and in vivo antitumor activity in various tumor models. Dose dependent tumor regression and growth suppression were observed in mouse and rat subcutaneous xenograft models of human tumors. Dose limiting toxicity, body weight loss (mice) and diarrhea (rat), occurred at or below maximum antitumor response. A PK-PD analysis was performed on single dose data to formulate a drug response model followed by prospective testing of potentially effective multiple dose regimens predicted by the model. Intravenous (IV) single dose data, tumor volume (HT-29, NCI-H460), drug concentration (HT-29) in plasma (Cp) and tumor (Ctu), from mouse experiments were evaluated. A PK model of Cp and Ctu described by influx and efflux parameters and a PD model of Ctu dependent inhibition of exponential growth were constructed. Ctu at half maximum inhibition of tumor growth rate was approximately 650 ng/g. Simulation of drug response, characterized by the linked PK-PD model was used to identify potentially effective multiple dose regimens. Three prospective experiments were conducted in BALB/c nude mice bearing KB-8511 epidermoid xenografts to evaluate the efficacy and tolerability of various multiple dose regimens. Fixed dose (FD) regimens administered every week (qwk) and every 2 weeks (q2wk) and loading/maintenance (L/M) regimens administered qwk were studied. Tumor volume, body weight, Cp and Ctu were measured. Two FD regimens (1.5 mg/kg qwk and 2 mg/kg q2wk) were associated with intolerable body weight loss. Two FD (1.5 and 1.8 mg/kg q2wk) and three L/M (2.1/0.7, 1.5/0.7 and 1.5/0.5 mg/kg qwk) regimens were considered effective and tolerable. Tumor regression occurred with all regimens. The FD regimens administered q2wk suppressed tumor growth with 15% (1.8 mg/kg) and 9% (1.5 mg/kg) body weight loss at week 3. The L/M regimens suppressed tumor growth but re-growth was observed in some mice after 3-4 weeks of treatment. Body weight loss at week 3 was 12%, 16% and 3% for the 2.1/0.7, 1.5/0.7 and 1.5/0.5 mg/kg qwk regimens. In conclusion, ABJ879, as with other cytotoxic agents, has a narrow therapeutic index (ratio of antitumor activity to tolerability) in mice. Although not fully optimized, a FD regimen q2wk (4 tumor double times) and a L/M regimen qwk (2 tumor double times) were effective and tolerable in the mouse xenograft experiments. A PK-PD modelling strategy with experimental feedback can be used to optimize dosing.
Supportive care and chemotherapy (CT) versus supportive care alone in advanced non-small cell lung cancer (NSCLC): A meta-analysis using individual patient data (IPD) from randomised clinical trials (RCTs)
Authors: S. Burdett, L. A. Stewart, J. F. Tierney, C. Le Pechoux
Journal: Journal of Clinical Oncology (2007)

7582 Background: Building on a previous IPD meta-analysis of CT (BMJ 1995;311:899–909) which suggested that CT may have a role in the treatment of NSCLC, we have carried out a new, up-to-date IPD meta-analysis. This includes RCTs, regimens and outcomes that were not available in 1995. This new meta-analysis examines the role of CT in 7 treatment comparisons. Here we report the effectiveness of supportive care plus CT compared with supportive care alone. Methods: We conducted a systematic search for RCTs followed by the central collection, checking and re-analysis of updated IPD. Results from individual RCTs were combined using the stratified (by trial) log rank test to calculate individual and pooled hazard ratios (HRs). Previously included RCTs using long-term alkylating agents were excluded from this analysis due to their antiquity. Results: IPD were obtained on 2,666 patients from 15 RCTs. 11 RCTs used cisplatin-based CT regimens, 4 RCTs used single agent CT (etoposide, navelbine, gemcitabine, paclitaxel). This added 6 RCTs and 1,702 patients to the 1995 analyses. The results show a highly significant benefit of CT on survival (HR=0.78 95% Confidence Interval 0.71–0.84, p&lt;0.000001), with an absolute benefit of 8% (from 20% to 28%) at 12 months across all patients. There was no evidence of a difference in effect (p=0.69) between trials that used cisplatin-based regimens (11 RCTs, HR=0.76), etoposide alone (1 RCT, HR=0.87) or newer single agents (3 RCTs, HR=0.79) (Interaction p=0.69). There was no evidence that any patient subgroup defined by age, sex, stage or histology benefited more or less from CT. The absolute benefit of CT at 12 months did vary according to WHO/ECOG (or equivalent) performance status. PS 0=8% (from 26% to 34%), PS 1=8% (from 18% to 26%), PS 2=5% (from 6% to 11%) and PS 3=4% (from 5% to 9%). Conclusion: The results demonstrate a substantial and consistent relative benefit of CT in advanced NSCLC. The effectiveness of newer agents such as navelbine, paclitaxel and gemcitabine (used as single agents) appears to be similar to that of cisplatin combined with older agents such as vindesine and mitomycin C. The absolute effect of CT varied according to performance status. No significant financial relationships to disclose.
Abstract 23: Geriatric Experience Following Cardiac Arrest at 6 Interventional Cardiology Centers in the United States, 2007-2011
Authors: David B Seder, Michael Mooney, Nainesh Patel, John McPherson, Paul McMullen, Karl B Kern, Barb Unger, J Browning, S Nanda, Melkon Hacobian, M B Kelley, Niklas Nielsen
Journal: Circulation (2011)

Background: It is unknown if aggressive techniques such as therapeutic hypothermia (TH) and percutaneous coronary intervention (PCI) benefit cardiac arrest (CA) survivors over 75 years old. We evaluated the experiences of these patients at six regional PCI centers in the United States. Methods: Demographics, hospital course, adverse events, treatments, and outcomes of 542 cardiac arrest survivors aged 18-75 were compared to 122 similar patients aged &gt;76. These data were retrospectively and prospectively entered into a secure, web-based registry (INTCAR). Findings: Cardiac arrest survivors aged &gt;75 frequently underwent TH (98%), urgent coronary angiography (36.9%), and urgent PCI (24%) - rates similar to younger patients. Elderly patients had more comorbidities (3.0 +1.6 vs. 2.1+1.6, P&lt;0.001), worse presenting left ventricular ejection fraction, and shorter time to return of spontaneous circulation (20.4+13.1 vs. 24.2+16.9 minutes, P=0.029). Pneumonia occurred more often among the elderly (32.8% v 23.8%, P=0.04), who also trended toward more sustained hyperglycemia (73% vs 64.4%, P=0.07) and less post-cooling fever (24% vs 32.7%, P=0.06). There were no differences in bleeding, seizures, electrolyte disturbances, arrhythmias, or most other adverse events. Brain MRI was not performed in any patient &gt;75. Elderly patients were more likely to have DNR orders (66.4% vs 50.3%, P=0.001) and to undergo termination of life support (63.1% vs 49.4%, P=0.006). Good neurological outcome at 6-months (CPC 1-2) was seen in 27.9% elderly patients and 40.4% younger patients (P=0.01), and in 44% vs 55%, (P=0.13) of the subgroup presenting with VT/VF. Of 6-month survivors, 4% elderly patients remained severely disabled or vegetative, and 69% were classified as CPC 1. Conclusions: Patients over 75 years old were less likely to have a good neurological outcome at 6 months after cardiac arrest, but exclusion of elderly patients from standard post-resuscitation care is not warranted on the basis of age alone.
Effect of ozone, thunderstorms and other weather conditions on the respiratory function of asthmatics
Authors: Graham Bentham, Bdw Harrison, Ian H. Langford, K Zalavra, Ann Mcdonald, F Elender
Journal: Thorax (1996)

There is concern that exposure to the air pollutant ozone may adversely affect respiratory function. Ozone is formed photochemically by the action of sunlight on pre-cursor pollutants and peak concentrations usually occur during spells of hot sunny weather in summer. There is also evidence that summer thunderstorms may exacerbate asthma. In order to investigate the possible effects of ozone and summer weather conditions on asthma a panel of 29 patients was recruited from outpatients from a hospital asthma clinic in Norfolk. Daily morning peak-flow measurements (pre-medication) were analysed for June, July and August 1994. For each subject the daily measurements were expressed as the percentage of their best peak-flow and the average for the whole panel was then calculated. Daily ozone measurements from the national air pollution monitoring site at Sibton and data on weather conditions in Norwich were also collected. Multiple regression analysis was used to examine the association between daily peak flow, ozone and a number of weather variables, including the occurrence of thunderstorms, with lags of up to 5 days. A significant positive association (p<0.001) was found between peak flow and temperature over the previous 3 days. Peak flow was significantly negatively associated with the number of days with thunder in the previous 5 days (p=<0.001), the number of days with poor ozone (at or above 90 ppb) in the last 3 days (p<0.001) and the number of days with rain in the last 4 days (p<0.001). These 4 variables explained 48% of the variance in daily peak flow. The model estimate is that each day of poor ozone is associated with a change in peak flow (as % of best) of -1.07 (95% c.i. -1.52, -0.63) and each day with thunder -0.70 (95% c.i. -0.98, -0.43). During the summer period studied there was therefore evidence of small, but statistically significant adverse effects of ozone, thunderstorms and wet weather on the respiratory function of asthmatics in Norfolk.
Abstract 14830: Anti-inflammatory Effects of Nicotinic Acid: Mechanisms of Action in Human Monocytes
Authors: Janet E Digby, Fernando O Martinez, Andrew Jefferson, Neil Ruparelia, Malgorzata Wamil, David R Greaves, Robin P Choudhury
Journal: Circulation (2011)

Objectives: Nicotinic acid (NA) treatment is associated with benefits in atherosclerosis that are attributed to effects on plasma lipoproteins. The nicotinic acid receptor GPR109A is expressed in m...
Abstract 2022: Non Invasive Molecular Imaging of Inflammation/Apoptosis with 99mTc-Annexin A5 reveals Plaque Instability in Patients With Significant Carotid Artery Stenosis.
Authors: Sander Wolters, Steven Appleby, Jan Tordoir, Jaap Teule, Mat Daemen, Jagat Narula, Chris Reutelingsperger, Leo Hofstra
Journal: Circulation (2006)

Introduction Apoptosis and inflammation constitute important substrates of atherosclerotic plaques that are vulnerable to result in acute events such as Stroke, TIA or Myocardial Infarction and can...