tbuckley/cabot-search huggingface dataset:
Addressing End-of-Life Issues
Authors: David B Edwards
Journal: JAMA (2005)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 17185: Hemodynamic Variables and Vasopressor Support After Out-of-hospital Cardiac Arrest: Associations With 1-year Neurologic Outcome
Authors: Johanna Laurikkala, Erika Wilkman, Tero Varpula, Matti Reinikainen, Sanna Hoppu, Tero Ala-Kokko, Minna Tallgren, Esko Ruokonen, Marjaana Tiainen, Ville Pettilä, Jukka Vaahersalo, Markus Skrifvars
Journal: Circulation (2014)

Introduction: Optimal blood pressure target in resuscitated patients is unknown but current guidelines recommend maintaining mean arterial pressure (MAP) between 60 to 90 mmHg. Our aim was to determine associations between time-weighted MAP levels and vasopressor load (VL) during the first 48 hours after OHCA and 1-year neurologic outcome in a prospective observational cohort of OHCA patients treated in the ICU. Methods: We included 503 patients with out-of-hospital-cardiac arrest (OHCA) treated in 21 ICUs from the FINNRESUSCI study between 2010 and 2011. Hemodynamic data and vasopressor doses were collected prospectively in two, five or 15 minute intervals depending on the ICU. Totally 1.2 million blood pressure values were analysed. We identified optimal thresholds for time-weighted (TW) MAP and outcome with receiver operating characteristic curve analysis (ROC). Using multivariate regression including co-morbidities, factors at resuscitation, sequential organ failure scores, TW MAP and total VL, we tested associations with 1-year neurologic outcome, dichotomized to good (CPC 1-2) and poor (CPC 3-5), respectively. Results: Of 503 patients, 202 (40 %) patients had a good and 301 (60 %) patients had poor 1-year outcome. Receiver operating characteristic analysis regarding poor one year outcome was performed for different MAP areas: hypotension areas under 65 mmHg (AUC 0.607, 95% CI 0.558 - 0.656, P-value &lt; 0.001) and under 70 mmHg (AUC 0.605, 95% CI 0.555 - 0.654, P- value &lt; 0.001). The mean vasopressor load was higher in patients with good 1-year outcome than in those with poor outcome (p-value &lt; 0.001). With multivariate regression analysis neither TWA MAP below 70mmHg (OR 1.0, 95% CI 0.999 - 1.001, p-value 0.909) nor vasopressor load (OR 1.004, 95% CI 0.994 - 1.013, p-value 0.52) were independent predictors of long-term outcome. Conclusions: In this large prospective study of OHCA patients, we found no associations between MAP values during the first 48h and long-term outcome. Contrary to previous expectations, higher MAP values had no neuroprotective effect. Neither did vasopressor load associate with outcome.
Abstract 18687: PARP9 and PARP14 are Novel Regulators of Macrophage Activation
Authors: Hiroshi Iwata, Hideo Yoshida, Piero Ricchiuto, Takuya Hara, Iwao Yamada, Alexander Mojcher, Peter Libby, Mark Boothby, Elena Aikawa, Sasha Singh, Masanori Aikawa
Journal: Circulation (2014)

Background: Pro-inflammatory “M1” macrophages may promote atherogenesis, while “M2” macrophages may favor an anti-inflammatory milieu. Our global proteomics of M1 and M2 cells identified ADP-ribosylation enzymes PARP9 and PARP14 as novel regulators of macrophage activation. The present study has examined the underlying mechanisms and explored in vivo evidence for their role in vascular disease. Methods and Results: IFN gamma (M1) stimulation induced and IL-4 (M2) decreased PARP9 and PARP14 in mouse and human macrophages. siRNA silencing of PARP14 enhanced expression of M1 genes (e.g. TNFα, iNOS) and activation (phosphorylation) of pro-inflammatory STAT1 while suppressing M2 markers (e.g., Arginase 1) and anti-inflammatory STAT6. Conversely, PARP9 silencing suppressed M1 polarization and STAT1 activation. These results suggest that PARP14 inhibits and PARP9 promotes a pro-inflammatory macrophage phenotype. Co-immunoprecipitation indicated that PARP14 and PARP9 physically interact. ADP-ribosylation assays revealed that PARP9 impairs PARP14-induced ribosylation (Figure A). Targeted proteomics via high-resolution mass spectrometry demonstrated that PARP14 ADP-ribosylates at least two sites in STAT1α, which PARP9 suppressed. Mechanically injured arteries of Parp14-/- mice had accelerated lesion formation and macrophage accumulation. Peritoneal and plaque macrophages of PARP14-/- mice showed increased STAT1 phosphorylation, decreased STAT6 phosphorylation, enhanced M1 gene expression, and reduced M2 responses (Figure B, laser capture microdissection). More macrophages[[Unable to Display Character: &amp;#61472;]]were immunoreactive for PARP9 in human “unstable” plaques than in “stable” plaques (64.6±16.2% vs. 30.8±12.3%, p&lt;0.01, n=5). Conclusions: PARP14 and PARP9 reciprocally regulate the mechanisms of macrophage activation, offering the potential for new therapies for cardiovascular diseases and other conditions, in which macrophage activity impacts outcomes.
967. Angiotensinogen Inhibits Growth and Angiogenesis of Human Mammary Carcinoma and Prevents Pulmonary Metastasis of Murine Melanoma Cancer
Authors: Céline Bouquet, Noel Lamande, Jean-Marie Gasc, Franck Griscelli, Paule Opolon, Elisabeth Connault, Michel Perricaudet, Pierre Corvol
Journal: Molecular Therapy (2004)

It is now well established that a solid tumor cannot grow beyond a volume of a few mm3 without the formation of new capillaries to supply tumor cells with nutrients and oxygen, and to allow removal of waste products. We have already shown that recombinant human angiotensinogen (AGT) can inhibit endothelial cell proliferation and migration, capillary-like tube formation, and neovascularisation of the chick chorioallantoic membrane1. In order to determine whether these anti-angiogenic activities could impact tumor growth, we have delivered AGT by gene transfer into mice bearing experimental tumors using a replication defective adenovirus (AdAGT).
Abstract 3986: Characterization of prostaglandin signaling in primary neuroblastoma
Authors: Anna Kock, Karin Larsson, Linda Ljungblad, Helena Idborg, Marina Korotkova, Lotta Elfman, John-Inge Johnsen, Per-Johan Jakobsson, Per Kogner
Journal: Cancer Research (2014)

Abstract Neuroblastoma (NB) is an embryonic childhood tumor of the sympathetic nervous system. Despite intensive treatment patients in the high-risk group of NB shows a poor prognosis. We have shown the importance of inflammation in NB development and progression and that the pro-inflammatory lipid mediator prostaglandin E2 (PGE2) acts as a paracrine survival factor in NB. We have also shown that mPGES-1, essential for PGE2 synthesis, promotes growth and survival of several malignancies. In this study we focus on the abundance of prostaglandins and their specific enzymes in primary NB of different biological and clinical subsets in the aim of finding a more specific and targeted NB treatment. Levels of prostaglandins were assayed in 40 primary human NB tumors by mass spectrometry (MS) showing elevated levels of PGE2 in high risk 11q-deleted NB compared to low-risk NB whereas elevated levels of prostaglandin D2 (PGD2) could be coupled to NB with favorable clinical outcome. The expression of COX-1, COX-2, mPGES-1, L-PGDS, H-PGDS and 15-PGDH were analyzed in tumors by immunohistochemistry (IHC). Expression of mPGES-1 and L-PGDS was found in all analyzed tumors. Double stainings of mPGES-1 and the specific NB cell marker GD2 were performed on tumors with different biology using immunofluorescence. In low-risk tumors mPGES-1 is not expressed by the tumor cells whereas co-localization were found in 11q deleted high-risk tumors. To consider the level of inflammation and PGE2 signaling in these tumors we analyzed cell markers of both the innate and adaptive immune system together with mPGES-1. In all tumors mPGES-1 expressing cells are found in clusters closely together with T-cells, B-cells, dendritic cells and M1/M2 macrophages. Together this suggests an involvement of inflammatory prostaglandins in neuroblastoma development and tumor progression opening up new strategies for targeted therapies. Citation Format: Anna Kock, Karin Larsson, Linda Ljungblad, Helena Idborg, Marina Korotkova, Lotta Elfman, John-Inge Johnsen, Per-Johan Jakobsson, Per Kogner. Characterization of prostaglandin signaling in primary neuroblastoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3986. doi:10.1158/1538-7445.AM2014-3986
Abstract 752: Genetic and pharmacological FAK inhibition disrupt a β5 integrin signaling axis controlling anchorage-independent ovarian carcinoma growth
Authors: Isabelle Tancioni, Sean Uryu, Florian Sulzmaier, Nina Shah, Christine Lawson, Nichol L.G. Miller, Christine Jean, Xiao Lei Chen, Kristy K. Ward, David D. Schlaepfer
Journal: Cancer Research (2014)

Abstract Ovarian cancer spreads via cell shedding and growth within malignant ascites. Effective targeted therapies have not been developed for ovarian cancer. Ascites contains an abundance of matrix proteins, and spheroids maintain integrin receptor expression. Through databases analyses we find that elevated osteopontin (OPN), β5 integrin, and focal adhesion kinase (FAK) mRNA levels are associated with decreased overall survival of serous ovarian cancer patients treated with platinum and taxol. In ovarian tumor tissue arrays, increased FAK activation (FAK Y397 phosphorylation) correlated with elevated tumor grade in parallel with increased in β5 integin and OPN levels. FAK is a cytoplasmic tyrosine kinase that remains active in spheroids, and treatment of seven ovarian carcinoma cell lines with sub-micromolar levels of FAK inhibitor (PND-1186) identified sensitive (HEY and OVCAR8), intermediate (OVCAR3, ID8-IP, and IGROV1-IP), and resistant (SKOV3-IP and OVCAR10) cells to blockage of growth under anchorage-independent conditions. Genetic or pharmacological FAK inhibition within ID8-IP or HEY cells selectively prevents anchorage-independent growth in culture and tumor growth in mice with corresponding reductions in β5 integrin and OPN expression. β5 knockdown reduced HEY growth in soft agar, tumor growth in mice, FAK Y397 phosphorylation, and OPN expression in spheroids. Although FAK inhibitor resistant ovarian carcinoma cells (SKOV3-IP and OVCAR10) were associated with anchorage-independent Akt S473 phosphorylation, membrane-targeted and activated Akt expression in sensitive cells (HEY and OVCAR8) resulted in only a partial rescue of FAK inhibitor-associated growth block. These results support the hypothesis that OPN, αvβ5 integrins, and FAK may function as a signaling axis promoting ovarian tumor progression. Although Akt signaling pathway activation is a common event in serous ovarian cancer, our results suggest that this may not impart complete resistance to FAK inhibitor treatment. Supported by NIH CA102310 Citation Format: Isabelle Tancioni, Sean Uryu, Florian Sulzmaier, Nina Shah, Christine Lawson, Nichol L.G. Miller, Christine Jean, Xiao Lei Chen, Kristy K. Ward, David D. Schlaepfer. Genetic and pharmacological FAK inhibition disrupt a β5 integrin signaling axis controlling anchorage-independent ovarian carcinoma growth. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 752. doi:10.1158/1538-7445.AM2014-752
Lenalidomide−prednisone induction followed by lenalidomide−melphalan−prednisone consolidation and lenalidomide−prednisone maintenance in newly diagnosed elderly unfit myeloma patients
Authors: P Falco, F Cavallo, A Larocca, D Rossi, T Guglielmelli, A Rocci, M Grasso, M L M Siez, L De Paoli, S Oliva, S Molica, R Mina, F Gay, G Benevolo, P Musto, P Omedè, R Freilone, S Bringhen, A M Carella, G Gaidano, M Boccadoro, A Palumbo
Journal: Leukemia (2012)
Clusterin is induced by cancer chemotherapy and suppresses histone deacetylase inhibitor-induced apoptosis in breast cancer
Authors: Ikhlas Ahmed, Melissa Ranney, Rolf J. Craven
Journal: Clinical Cancer Research (2006)

B22  Background: Solid tumors are frequently treated with a combination of chemotherapy, radiation, and surgery. Highly malignant, p53-negative cancer cells induce the expression of clusterin in response to chemotherapy and radiation, and clusterin suppresses apoptosis and promotes drug resistance. Clusterin binds to Bax and can also promote apoptosis by binding to Ku70 in the nucleus. We have found that histone deacetylases regulate clusterin stability after chemotherapy.Experimental procedures: MDA-MB-231 human breast cancer cells were treated with doxorubicin in combination with pharmacological histone deacetylase inhibitors (HDIs), and clusterin expression was analyzed by western blot. Clusterin expression was then suppressed by RNAi, and its effect on apoptosis was analyzed by cleavage of PARP and pro-caspase 3.Results: Clusterin expression was induced by doxorubicin, and clusterin was hyper-expressed 2.4-fold following combined treatment with doxorubicin and the histone deacetylase inhibitors (HDIs) sodium butyrate or SAHA (suberoylanilide hydroxamic acid), suggesting that clusterin is inhibited by histone deacetylases. However, HDIs had a modest effect on clusterin transcription, suggesting that HDIs increase the post-transcriptional stability of clusterin. Clusterin was hyper-expressed following treatment with HDIs combined with etoposide or camptothecin, indicating that hyper-expression is not specific to doxorubicin, and doxorubicin/HDI treatment led to clusterin hyper-expression in multiple breast cancer cell lines. Using RNAi directed to clusterin, we determined that clusterin suppressed HDI-induced apoptosis. Clusterin suppressed polyADP ribose polymerase (PARP) cleavage, cytochrome c release, and caspase 3 activity (P
Reduced Intensity Hematopoietic Stem Cell Transplant Rescues Immune Function and Corrects Pulmonary Alveolar Proteinosis in DCML Deficiency/GATA 2 Mutation
Authors: Katherine Sturgess, Mary Slatter, Venetia Bigley, Muzlifah Haniffa, Xiao-Nong Wang, Rachel Dickinson, Naomi McGovern, Laura Jardine, Sarah Pagan, Ignatius Chua, Jonathan Wallis, Jim Lordan, Cliff Morgan, Andrew Cant, Andrew Gennery, Richard Edmondson, Chris Bacon, Fiona Black, Nigel Kirkham, Graham H Jackson, Sophie Hambleton, Matthew P. Collin
Journal: Blood (2011)
442. Novel cox-2 Driven Infectivity Enhanced CRAds for Treatment of Ovarian Cancer
Authors: Gerd J. Bauerschmitz, Anna Kanerva, Masato Yamamoto, Dirk Nettelbeck, Tanja Hakkarainen, Peter Dall, David T. Curiel, Akseli Hemminki
Journal: Molecular Therapy (2004)

CRAds are a promising strategy for adenoviral gene therapy of cancer. Although preclinical and the first clinical data with first generation CRAds show good results, more specificity of CRAd replication and an infectivity enhancement for target cells would be desirable. To this end we constructed a novel generation of CRAds specific for ovarian cancer treatment, containing the cox-2 promoter driving different mutations of E1A, combined with an adenovirus type 3 fiber-knob mutation on otherwise type 5 viruses. Two length variants of the cox-2 promoter were used, a shorter clone being more active in and a longer clone being more specific for ovarian cancer cells. The aim of this strategy is to investigate whether a more specific or a more active promoter for CRAds is more advantageous. E1A was used as wild type, as delta24-mutation and as delta2-delta24-mutation, testing the concept of specificity enhancement for cancer cells due to delta-mutations. These mutations inactivate Rb binding and thus allow replication only in cell deficient in the p16-Rb pathway, such as most human cancer cells, including ovarian cancers. Since the adenovirus type 3 receptor seems to be highly overexpressed in ovarian cancer cells resulting in a one to two log infectivity enhancement for these cells, we selected the adenovirus 5/3 chimera approach for enhanced transduction of tumor cells. Six different viruses were constructed, amplified and their constructs verified with PCR and restriction enzymes. The replication of all six viruses was one to two logs improved in cox-2 positive cells and one to two logs reduced in cox-2 negative cells compared to wild type adenovirus. In ovarian cancer cells the replication was improved up to three logs as result of the combination of specific replication in and infectivity enhancement for these cells. In addition, the liver-off phenotype of these viruses was tested with primary normal liver cells. Whereas the wild type virus replicated in and lysed the liver cells, our newly constructed CRAds replicated at least two logs lower than wild type. Further more, the cox-2 driven delta24-CRAds showed stronger oncolysis in ovarian tumor cells than an otherwise identical delta24-CRAd without cox2 promoter. Thus these viruses seem to replicate specifically and amplified in ovarian cancer cells while preserving cox-2 negative and especially liver cells. Therefore these viruses could improve the safety and efficacy profile of adenoviral gene therapy strategies for ovarian cancer.
Effectiveness of Managing Suspected Pulmonary Embolism Using an Algorithm Combining Clinical Probability, D-Dimer Testing, and Computed Tomography
Authors: Belle, A., van, H.R. Buller, M.V. Huisman, P.M. Huisman, K. Kaasjager, P.W. Kamphuisen, M.H.H. Kramer, M.J.H.A. Kruip, Erp, J.M., Kwakkel-van, F.W.G. Leebeek, M. Nijkeuter, M.H. Prins, M Sohne, L.W. Tick
Journal: JAMA (2006)

ContextPrevious studies have evaluated the safety of relatively complex combinations of clinical decision rules and diagnostic tests in patients with suspected pulmonary embolism.ObjectiveTo assess the clinical effectiveness of a simplified algorithm using a dichotomized clinical decision rule, D-dimer testing, and computed tomography (CT) in patients with suspected pulmonary embolism.Design, Setting, and PatientsProspective cohort study of consecutive patients with clinically suspected acute pulmonary embolism, conducted in 12 centers in the Netherlands from November 2002 through December 2004. The study population of 3306 patients included 82% outpatients and 57% women.InterventionsPatients were categorized as “pulmonary embolism unlikely” or “pulmonary embolism likely” using a dichotomized version of the Wells clinical decision rule. Patients classified as unlikely had D-dimer testing, and pulmonary embolism was considered excluded if the D-dimer test result was normal. All other patients underwent CT, and pulmonary embolism was considered present or excluded based on the results. Anticoagulants were withheld from patients classified as excluded, and all patients were followed up for 3 months.Main Outcome MeasureSymptomatic or fatal venous thromboembolism (VTE) during 3-month follow-up.ResultsPulmonary embolism was classified as unlikely in 2206 patients (66.7%). The combination of pulmonary embolism unlikely and a normal D-dimer test result occurred in 1057 patients (32.0%), of whom 1028 were not treated with anticoagulants; subsequent nonfatal VTE occurred in 5 patients (0.5% [95% confidence interval {CI}, 0.2%-1.1%]). Computed tomography showed pulmonary embolism in 674 patients (20.4%). Computed tomography excluded pulmonary embolism in 1505 patients, of whom 1436 patients were not treated with anticoagulants; in these patients the 3-month incidence of VTE was 1.3% (95% CI, 0.7%-2.0%). Pulmonary embolism was considered a possible cause of death in 7 patients after a negative CT scan (0.5% [95% CI, 0.2%-1.0%]). The algorithm was completed and allowed a management decision in 97.9% of patients.ConclusionsA diagnostic management strategy using a simple clinical decision rule, D-dimer testing, and CT is effective in the evaluation and management of patients with clinically suspected pulmonary embolism. Its use is associated with low risk for subsequent fatal and nonfatal VTE.
Study confirms that screening reduces deaths from breast cancer
Authors: Susan Mayor
Journal: BMJ (2001)

Screening with mammography reduces deaths from breast cancer by nearly two thirds, reported a Swedish study published last week which showed a much greater mortality reduction with “real life” screening than seen previously in randomised trials (Cancer 2001;91:1724-31).

Results from the study showed that mortality from incident breast carcinoma diagnosed in women aged 40-69 years fell by 63% (relative risk 0.37; 95% confidence interval 0.30 to …
Male Sexual Dysfunction
Authors: Sander J Breiner
Journal: JAMA (2004)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal