tbuckley/cabot-search huggingface dataset:
Large-Scale Drug Screens Support Precision Medicine
Authors: Joe W. Gray, Gordon B. Mills
Journal: Cancer Discovery (2015)

Abstract Summary: The major challenge underlying the emerging precision medicine initiative is to make links between cancer subsets and drugs that can be used to guide treatment of individual patients, leading to improved outcomes and decreased toxicity. Seashore-Ludlow and colleagues support this effort by reporting measurements of responses of 664 adherent cancer cell lines to 70 FDA-approved drugs, 100 experimental compounds, and 311 small-molecule probes. They use a novel Annotated Cluster Multidimensional Enrichment algorithm to identify drug mechanisms of action, molecular markers of response, responsive cancer subtypes, and compounds that produce synergistic cell inhibition. Cancer Discov; 5(11); 1130–2. ©2015 AACR. See related article by Seashore-Ludlow et al., p. 1210.
Corticotropin-Releasing Hormone: Clinical Applications
Authors: L K Nieman, D L Loriaux
Journal: Annual Review of Medicine (1989)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Aspirin for Primary Prevention of Cardiovascular Events in People With Diabetes
Authors: Michael Pignone, Mark J. Alberts, John A. Colwell, Mary Cushman, Silvio E. Inzucchi, Debabrata Mukherjee, Robert S. Rosenson, Craig D. Williams, Peter W. Wilson, M. Sue Kirkman
Journal: Diabetes Care (2010)

The burden of cardiovascular disease (CVD) among patients with diabetes is substantial. Individuals with diabetes are at two- to fourfold increased risk of cardiovascular events compared with age- and sex-matched individuals without diabetes. In diabetic patients over the age of 65 years, 68% of deaths are from coronary heart disease (CHD) and 16% are from stroke (1). A number of mechanisms for the increased cardiovascular risk with diabetes have been proposed, including increased tendency toward intracoronary thrombus formation (2), increased platelet reactivity (3), and worsened endothelial dysfunction (4).

The increased risk for cardiovascular events and mortality in patients with diabetes has led to considerable interest in identifying effective means for cardiovascular risk reduction. Aspirin has been shown to be effective in reducing cardiovascular morbidity and mortality in high-risk patients with myocardial infarction (MI) or stroke (secondary prevention) (5). The Food and Drug Administration has not approved aspirin for use in primary prevention, and its net benefit among patients with no previous cardiovascular events is more controversial, for both patients with and without a history of diabetes (5). The U.S. Preventive Services Task Force recently updated its recommendation about aspirin use for primary prevention. The Task Force recommended encouraging aspirin use in men age 45–79 years and women age 55–79 years and not encouraging aspirin use in younger adults. They did not differentiate their recommendations based on the presence or absence of diabetes (6,7).

In 2007, the American Diabetes Association (ADA) and the American Heart Association (AHA) jointly recommended that aspirin therapy (75–162 mg/day) be used as a primary prevention strategy in those with diabetes at increased cardiovascular risk, including those who are over 40 years of age or who have additional risk factors (family history of CVD, hypertension, smoking, dyslipidemia, or albuminuria) (8). These recommendations were …
Phase II study of paclitaxel in patients with extensive-disease small-cell lung cancer: an Eastern Cooperative Oncology Group study.
Authors: D S Ettinger, D M Finkelstein, R P Sarma, D H Johnson
Journal: Journal of Clinical Oncology (1995)

PURPOSE To evaluate the efficacy and safety of paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ), a novel diterpene plant product in the treatment of previously untreated patients with extensive-disease small-cell lung cancer (SCLC). PATIENTS AND METHODS Patients with extensive-disease SCLC received paclitaxel 250 mg/m2 intravenously over 24 hours every 3 weeks. Nonresponders or partial responders, who received the maximum number of cycles (n = 4) of paclitaxel received salvage chemotherapy that consisted of etoposide (VP-16) 120 mg/m2 intravenously over 45 minutes on days 1, 2, and 3, and cisplatin 60 mg/m2 intravenously as a short infusion on day 1. Cycles were repeated every 3 weeks. RESULTS Of 36 patients entered onto the study, 34 and 32 patients were assessable for toxicity and response, respectively. No complete responses (CRs) were observed. Eleven patients (34%) had a partial response (PR) and six (19%) had stable disease (SD). In three of six patients categorized as having SD, there was greater than 50% tumor shrinkage. However, no 4-week follow-up measurements were made, so these could not be considered PRs, in part because patients received salvage chemotherapy by study design. In this trial, induction and salvage chemotherapy resulted in a response (two CRs and 15 PRs) (53%) in 17 patients. The estimated median survival duration was 43 weeks. Dose-limiting toxicity was leukopenia, with 19 patients (56%) having grade 4 leukopenia. The numbers of patients who experienced other grade 4 toxicities were as follows: pulmonary, three (9%); liver, two (6%); cardiac, one (3%); thrombocytopenia, one (3%); metabolic, one (3%); stomatitis, one (3%); and allergic reaction, one (3%). Four additional patients had grade 3 leukopenia and one patient (3%) died of sepsis (grade 5 toxicity). CONCLUSION Paclitaxel is an active new agent in the treatment of SCLC. Further investigation of this agent in combination with other active agents is appropriate.
Lack of serologic association of human herpesvirus-8 (KSHV) in patients with monoclonal gammopathy of undetermined significance with and without progression to multiple myeloma.
Authors: Dharam V. Ablashi, Louise Chatlynne, David Thomas, Dimitra Bourboulia, Matthew B. Rettig, Robert A. Vescio, Dimitri Viza, Parkash Gill, Robert A. Kyle, James R. Berenson, James E. Whitman
Journal: Blood (2000)
Access to psychiatrists should be improved
Authors: A. F Tarbuck
Journal: BMJ (1996)

EDITOR,—Inappropriate prescribing for elderly people remains a problem, and Alice McGrath and Graham Jackson have been successful in focusing media attention on the use of neuroleptic agents in nursing homes.1 The American legislation to which the authors refer has been criticised for penalising “incorrect” drug use while offering little guidance on alternative management.2 The American Geriatrics Society is concerned that the legislation may compromise the right to effective treatment for patients with serious mental disorders and dementia in …
Can venous-to-arterial carbon dioxide differences reflect microcirculatory alterations in patients with septic shock?
Authors: Gustavo A. Ospina-Tascón, Mauricio Umaña, William F. Bermúdez, Diego F. Bautista-Rincón, Juan D. Valencia, Humberto J. Madriñán, Glenn Hernandez, Alejandro Bruhn, César Arango-Dávila, Daniel De Backer
Journal: Intensive Care Medicine (2015)

Septic shock has been associated with microvascular alterations and these in turn with the development of organ dysfunction. Despite advances in video microscopic techniques, evaluation of microcirculation at the bedside is still limited. Venous-to-arterial carbon dioxide difference (Pv-aCO2) may be increased even when venous O2 saturation (SvO2) and cardiac output look normal, which could suggests microvascular derangements. We sought to evaluate whether Pv-aCO2 can reflect the adequacy of microvascular perfusion during the early stages of resuscitation of septic shock. Prospective observational study including 75 patients with septic shock in a 60-bed mixed ICU. Arterial and mixed-venous blood gases and hemodynamic variables were obtained at catheter insertion (T0) and 6 h after (T6). Using a sidestream dark-field device, we simultaneously acquired sublingual microcirculatory images for blinded semiquantitative analysis. Pv-aCO2 was defined as the difference between mixed-venous and arterial CO2 partial pressures. Progressively lower percentages of small perfused vessels (PPV), lower functional capillary density, and higher heterogeneity of microvascular blood flow were observed at higher Pv-aCO2 values at both T0 and T6. Pv-aCO2 was significantly correlated to PPV (T0: coefficient −5.35, 95 % CI −6.41 to −4.29, p < 0.001; T6: coefficient, −3.49, 95 % CI −4.43 to −2.55, p < 0.001) and changes in Pv-aCO2 between T0 and T6 were significantly related to changes in PPV (R 2 = 0.42, p < 0.001). Absolute values and changes in Pv-aCO2 were not related to global hemodynamic variables. Good agreement between venous-to-arterial CO2 and PPV was maintained even after corrections for the Haldane effect. During early phases of resuscitation of septic shock, Pv-aCO2 could reflect the adequacy of microvascular blood flow.
Meningococcal Disease Among Men Who Have Sex with Men — United States, January 2012–June 2015
Authors: Hajime Kamiya, Jessica MacNeil, Amy Blain, Manisha Patel, Stacey Martin, Don Weiss, Stephanie Ngai, Ifeoma Ezeoke, Laurene Mascola, Rachel Civen, Van Ngo, Stephanie Black, Sarah Kemble, Rashmi Chugh, Elizabeth Murphy, Colette Petit, Kathleen Harriman, Kathleen Winter, Andrew Beron, Whitney Clegg, Craig Conover, Lara Misegades
Journal: MMWR Morbidity and Mortality Weekly Report (2015)

Since 2012, three clusters of serogroup C meningococcal disease among men who have sex with men (MSM) have been reported in the United States. During 2012, 13 cases of meningococcal disease among MSM were reported by the New York City Department of Health and Mental Hygiene (1); over a 5-month period during 2012–2013, the Los Angeles County Department of Public Health reported four cases among MSM; and during May–June 2015, the Chicago Department of Public Health reported seven cases of meningococcal disease among MSM in the greater Chicago area. MSM have not previously been considered at increased risk for meningococcal disease. Determining outbreak thresholds* for special populations of unknown size (such as MSM) can be difficult. The New York City health department declared an outbreak based on an estimated increased risk for meningococcal infection in 2012 among MSM and human immunodeficiency virus (HIV)–infected MSM compared with city residents who were not MSM or for whom MSM status was unknown (1). The Chicago Department of Public Health also declared an outbreak based on an increase in case counts and thresholds calculated using population estimates of MSM and HIV-infected MSM. Local public health response included increasing awareness among MSM, conducting contact tracing and providing chemoprophylaxis to close contacts, and offering vaccination to the population at risk (1–3). To better understand the epidemiology and burden of meningococcal disease in MSM populations in the United States and to inform recommendations, CDC analyzed data from a retrospective review of reported cases from January 2012 through June 2015.
Structure/Function of Cytoplasmic Vitamin A-Binding Proteins
Authors: Ellen Li, Andrew W. Norris
Journal: Annual Review of Nutrition (1996)

Two cytoplasmic retinol-binding proteins, CRBP and CRBP II, and two cytoplasmic retinoic acid-binding proteins, CRABP-I and CRABP-II, have been well characterized. There has been significant progress in the structural analysis of these four proteins with X-ray crystallography, nuclear magnetic resonance, mutagenesis, and binding studies. In contrast, the cellular functions of these cytoplasmic vitamin A-binding proteins are less well understood. Since these proteins bind their respective ligands with high affinity, they are likely to influence retinoid signaling pathways. Analysis of retinoid metabolism in the presence or absence of these proteins provides support for the hypothesis that these proteins are involved in modulating intracellular retinoid metabolism. Molecular genetic approaches to alteration of the levels of these proteins in tissue culture cells and in whole animals have provided a powerful means toward defining the physiological roles of the cytoplasmic vitamin A-binding proteins in vivo.
An integrated assessment of morphology, size, and complement activation of the PEGylated liposomal doxorubicin products Doxil®, Caelyx®, DOXOrubicin, and SinaDoxosome
Authors: Peter P. Wibroe, Davoud Ahmadvand, Mohammad Ali Oghabian, Anan Yaghmur, S. Moein Moghimi
Journal: Journal of Controlled Release (2015)
A prospective randomized trial of maintenance versus nonmaintenance intravesical bacillus Calmette-Guérin therapy of superficial bladder cancer.
Authors: R A Badalament, H W Herr, G Y Wong, C Gnecco, C M Pinsky, W F Whitmore, W R Fair, H F Oettgen
Journal: Journal of Clinical Oncology (1987)

Between August 1981 and July 1984, 93 patients with polychronotopic superficial papillary carcinoma (Ta and/or T1), flat carcinoma in situ (Tis), or concomitant superficial papillary and in situ bladder carcinoma were entered into a prospective randomized trial of maintenance v nonmaintenance intravesical bacillus Calmette-Guérin (BCG) therapy. Forty-six patients who received BCG weekly for 6 weeks were compared with 47 patients receiving the six-weekly doses of BCG plus monthly BCG for 2 years. Both groups were evaluated every 3 months by cytology, cystoscopy, and biopsy. A significant reduction in the number of recurrent tumors per patient-month was demonstrated for both groups (P less than .0001); however, the difference in reduction of tumors between the two groups was not significant. Additionally, patients receiving maintenance and nonmaintenance therapy had similar tumor recurrence and progression rates. These results indicate that monthly maintenance BCG does not prevent, delay, or reduce tumor recurrence or progression observed with the 6-week regimen. Maintenance BCG was associated with increased local toxicity, primarily dysuria, frequency, and urgency. Dosage reduction was required in 22 of 47 patients (46.8%). When the data were subjected to multivariate analysis, the presence or absence of tumor following induction BCG and PPD skin test results were found to be significant variables. Controlling for either the presence or absence of tumor following induction BCG, tumor recurrence and progression rates were not significantly different for the two treatment groups. However, the absence of tumor after induction BCG was associated with a longer disease-free duration (P = .00001) and time to progression (P = .095). Patients with a reactive tuberculin skin test before and after induction BCG had significantly less tumor recurrences than patients with different PPD skin tests results (P = .02). Tumor progression was not related to tuberculin skin testing.
Molecular and Cellular Basis of Chemically Induced Immunotoxicity
Authors: M I Luster, J A Blank, J H Dean
Journal: The Annual Review of Pharmacology and Toxicology (1987)

Immunotoxicology is the study of adverse effects on the immune system resulting from occupational, inadvertent, or therapeutic exposure to drugs, environmental chemicals, and, in some instances, biological materials. For the purpose of this chapter, we refer to these substances collectively as xenobiotics. Immunotoxicity is subdivided into three main research areas: (a) studies of altered immunological events associated with exposure of humans and animals to xenobiotics, including altered host resistance to infectious disease; (b) studies of allergy and autoimmunity resulting from xenobiotic exposure; and (c) implementation of analytical immunological methods into toxicology research. This chapter focuses only on chemical­ induced immunomodulation and describes several classes of irnmunotoxic xenobiotics, emphasizing cellular and molecular targets. Laboratory studies, conducted primarily in rodents, have provided evi­ dence that the immune system is very sensitive to chemical injury (reviewed in 1-6). This sensitivity is probably due as much to the general properties of a xenobiotic (e.g. reactivity with macromolecules) as to the complex nature of the immune system, which encompasses antigen recognition and processing;
The rise in bacterial resistance
Authors: S G B Amyes
Journal: BMJ (2000)

Papers p 213 

Almost since the beginning of the antibiotic era bacterial resistance has been seen as the major obstacle to successful treatment. Hardly any group of antibiotics has been introduced into clinical practice to which some bacterium has not developed resistance. Quantifying the impact of this resistance has often proved difficult, and misconceptions have often resulted from incomplete surveillance. Now that our surveillance methods are much better, we know that levels of antibiotic resistance are rising inexorably—as illustrated by this week's paper on trends in England and Wales (p 213).1 Yet it has taken a long time to realise the extent of the problem, and there is still much that we need to learn about the mechanisms.

Resistance was often minimised as a problem simply because the problem was not known or recognised. At the end of the 1960s the surgeon general of the United States stated that “we could close the book on infectious diseases.” Although those words seem naive now, at the time they were said the emergence of …
Supported Lipid Bilayers for the Generation of Dynamic Cell–Material Interfaces
Authors: Jasper van Weerd, Marcel Karperien, Pascal Jonkheijm
Journal: Advanced Healthcare Materials (2015)

Supported lipid bilayers (SLB) offer unique possibilities for studying cellular membranes and have been used as a synthetic architecture to interact with cells. Here, the state-of-the-art in SLB-based technology is presented. The fabrication, analysis, characteristics and modification of SLBs are described in great detail. Numerous strategies to form SLBs on different substrates, and the means to patteren them, are described. The use of SLBs as model membranes for the study of membrane organization and membrane processes in vitro is highlighted. In addition, the use of SLBs as a substratum for cell analysis is presented, with discrimination between cell-cell and cell-extracellular matrix (ECM) mimicry. The study is concluded with a discussion of the potential for in vivo applications of SLBs.
Peroxo-citrate-vanadium(V) complex: protein tyrosine phosphatase inhibitory activity and anticancer potential
Authors: Keke Fan, Dan Lindner, Ernest Borden, Taolin Yi
Journal: Cancer Research (2005)

652  Simple vanadium salts are known to have inhibitory activity against protein tyrosine phosphatases (PTPases). However, they are unsuitable for pharmacological applications due to their lack of specificity. To investigate the potential of organic vanadium compounds as selective inhibitors of PTPases and anticancer agents, we synthesized peroxo-citrate-vanadium(V) complex (CaVO) and investigated its spectrum of inhibitory activity against a panel of PTPases in vitro and its growth inhibitory activity against cancer cell lines. CaVO was prepared through conjugation reaction of vanadium (V) oxytrichloride and citric acid. Consistent with its conjugated nature, CaVO migrated as a compound approximately 900 Da in molecular sieve chromatography, significantly larger than vanadium (V) oxytrichloride or citric acid. CaVO was a potent and selective inhibitor of recombinant PTPases in vitro. It induced 90% or more inhibition of SHP-1, PTP1B and PTPalpha at 0.1 microgram/ml. In contrast, it showed little effects on recombinant SHP-2, PRL-2 and MKP1 under comparable conditions. In cell growth inhibition assays, CaVO in a dose-dependent manner induced in vitro growth inhibition of cancer cell lines of different tissue origins, suggesting its potentially broad spectrum of anticancer activity. CaVO at 0.25 microgram/ml induced 100% of cell death in melanoma cell lines (WM9 and WM35) and 70%∼90% of cell death in leukemic (U937 and H9) or lung (A549) cancer cell lines. Interestingly, it induced only 36% of growth inhibition in a non-malignant melanocyte cell line (DMN-1) under comparable conditions, suggesting a selective action of the compound against cancer cells in vitro. Moreover, the use of 0.025 microgram/ml of CaVO in combination with 500 IU/ml of IFN-alpha induced 95% of cell death in WM9 cells while the agents individually killed only 60% of the cells, evidencing a synergistic action between CaVO and IFN-alpha in vitro. Indeed, CaVO in combination with IFN-alpha induced 50% growth inhibition of WM9 tumors in mice in a tolerated manner in comparison to 22% WM9 tumor growth inhibition induced by the two compounds used as single agents. These data together demonstrated for the first time that CaVO is a potent inhibitor of selective PTPases and has selective killing activity against cancer cells in vitro and in vivo that synergizes with IFN-alpha, suggesting the vanadium conjugated to differential organic moieties could be developed as specific PTPase inhibitors and novel anti-cancer agents.
Effect of Allowing Choice of Diet on Weight Loss
Authors: William S. Yancy, Megan A. McVay, Corrine I. Voils
Journal: Annals of Internal Medicine (2015)

Letters17 November 2015Effect of Allowing Choice of Diet on Weight LossWilliam S. Yancy Jr., MD, Megan A. McVay, PhD, and Corrine I. Voils, PhDWilliam S. Yancy Jr., MDFrom Durham Veterans Affairs Medical Center, Durham, North Carolina., Megan A. McVay, PhDFrom Durham Veterans Affairs Medical Center, Durham, North Carolina., and Corrine I. Voils, PhDFrom Durham Veterans Affairs Medical Center, Durham, North Carolina.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/L15-5159 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We agree with Drs. Pagoto and Appelhans that the effects of choice and the counseling procedures were conflated—indeed, this will always be the case if counseling is provided to a person faced with a choice. To clarify our study procedures, however, participants were not advised to select "the diet most consistent with their dietary preferences." Instead, we encouraged them to use all information provided and any additional information they obtained on their own when making their choice; in addition, although food preference information was provided, participants were explicitly informed that they could choose a diet consistent with or ...Reference1. McVay MA, Voils CI, Coffman CJ, Geiselman PJ, Kolotkin RL, Mayer SB, et al. Factors associated with choice of a low-fat or low-carbohydrate diet during a behavioral weight loss intervention. Appetite. 2014;83:117-24. [PMID: 25149197] doi:10.1016/j.appet.2014.08.023 CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Durham Veterans Affairs Medical Center, Durham, North Carolina.Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M14-2358. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDoes Giving Parents Their Choice of Interventions for Child Behavior Problems Improve Child Outcomes? 17 November 2015Volume 163, Issue 10Page: 805-806KeywordsDietDisclosureFactor analysisFoodNutrientsPerceptionWeight loss ePublished: 17 November 2015 Issue Published: 17 November 2015 Copyright & PermissionsCopyright © 2015 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...