tbuckley/cabot-search huggingface dataset:
Abstract LB-226: Celecoxib synergizes human pancreatic ductal adenocarcinoma cells to sorafenib-induced growth inhibition involving p21 suppression
Authors: Ann H. Rosendahl, Chinmay Gundewar, Katarzyna Said, Roland Andersson
Journal: Cancer Research (2011)

Abstract Purpose: The aim of this study was to evaluate the potential for combining the multikinase inhibitor sorafenib and the specific cyclo-oxygenase 2 (COX-2) inhibitor celecoxib as therapy in pancreatic adenocarcinoma cells and to test the hypothesis that a synergistic or additive effect on the Ras/MAPK/ERK and related pathways might be obtained. Experimental design: COX-2 positive (BxPC-1) and low/negative (MIAPaCa-2, PANC-1 and AsPC-1) human pancreatic adenocarcinoma cells were exposed to sorafenib and celecoxib combined treatment in vitro, after which cell viability and various growth promoting and survival signaling pathways were monitored by MTT, flow cytometry and Western blotting. Results: Combined treatment with sorafenib and celecoxib resulted in synergistic inhibition of pancreatic adenocarcinoma cell proliferation through COX-2 independent mechanisms. This regimen produced combination index (CI) values between 0.67 and 0.92 for the various cell lines, suggesting significant synergistic interactions between sorafenib and celecoxib, which also markedly inhibited the migratory capacity. The growth inhibition was associated with a reduction of basal ERK1/2 activity, accumulation of cells in the G0/G1 phase of the cell cycle, induction of apoptosis and poly(ADP-ribose) polymerase cleavage. These changes were accompanied by a significant reduction of p21WAF1/Cip1 levels, where celecoxib sensitized the cells to sorafenib-mediated p21WAF1/Cip1 suppression. Conclusion: p21WAF1/Cip1 levels are elevated frequently in human pancreatic adenocarcinoma and increases with disease progression. In this study we demonstrate that combined treatment with sorafenib and celecoxib synergistically induce growth inhibition and apoptosis through a process involving phospho-ERK1/2 and p21WAF1/Cip1 suppression. These data suggest the combined treatment of sorafenib and celecoxib as potential therapy for clinical testing in patients with pancreatic adenocarcinoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-226. doi:10.1158/1538-7445.AM2011-LB-226
Primary Health Care at the Village Level
Authors: Robert A. Root
Journal: JAMA (1988)

The room was bare but for a mound of brown rice in the corner, a small wooden stool missing a leg, and two ceramic pots. The tiny infant lay snugly bundled on a straw mat beside its mother. For the woman, at age 24, this was her third baby. She smiled broadly as she spoke of the baby, who had been delivered at home the evening before, after she had gone into premature labor at 36 weeks. We examined the infant to make sure that there were no signs of umbilical sepsis—the cord had been cut by the grandmother with an unclean knife. The child looked healthy, although small for gestational age. We briefly reviewed with the mother proper breast-feeding technique. Then, touching our palms together in a farewell "namaste," we left the hut. I was accompanying two nurses in Tamil Nadu, South India, as they made their daily "home
Critically ill infants and children with influenza A (H1N1) in pediatric intensive care units in Argentina
Authors: Julio A. Farias, Analía Fernández, Ezequiel Monteverde, Nilda Vidal, Pilar Arias, María J. Montes, Gabriela Rodríguez, Mariela Allasia, Maria E. Ratto, Roxana Jaén, Claudia Meregalli, Karina Fiquepron, Ana R. Calvo, Alejandro Siaba, Lidia Albano, Rossana Poterala, Pablo Neira, Andrés Esteban
Journal: Intensive Care Medicine (2010)
Fat Necrosis Mimicking B-cell Lymphoma
Authors: Abdelfatihe Belakhlef, Chirag Jani, Clifford Church, Ron Fraser, Suresh Lakhanpal
Journal: Clinical Nuclear Medicine (2008)

F-18 fluoro-2-deoxyglucose positron emission tomography combined with computed tomography (FDG and PET/CT) is increasingly becoming the standard in staging and restaging patients with a range of malignancies including B-cell lymphoma. However, there are well-known pitfalls in PET/CT with FDG imaging, which comprise infection, inflammation, physiological variants, and benign pathologic conditions. Fat necrosis is the result of death of adipose tissue from disease, injury, or pathologic conditions. We describe a case of false positive PET/CT and FDG scan in a patient with fat necrosis mimicking B-cell lymphoma after 6 cycles of rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) treatment. In interpreting PET/CT and FDG images with inconsistency in lesion response, fat necrosis should be considered in the differential diagnosis.
RUPTURED PLAQUE WITH LARGE PLAQUE BURDEN IS PREDICTIVE OF DISTAL EMBOLIZATION IN ACS AND NON-ACS PATIENTS. ANGIOSCOPY AND VH-IVUS STUDY
Authors: Koshi Matsuo, Yasunori Ueda, Akio Hirata, Yasuhiro Akazawa, Kazuhisa Kodama
Journal: Journal of the American College of Cardiology (2011)
Long term structural effects of combination therapy in patients with early rheumatoid arthritis: five year follow up of a prospective double blind controlled study
Authors: J F Maillefert
Journal: Annals of the Rheumatic Diseases (2003)

<b>Objective:</b> To evaluate whether early combined therapy with methotrexate (MTX) and sulfasalazine (SSZ) during the first year in early rheumatoid arthritis (RA) induces long term beneficial effects, compared with monotherapy, when the further treatment strategy is a free choice. <b>Methods:</b> Study design: five year multicentre prospective longitudinal trial. Participants: 146/205 patients with RA previously included in a one year prospective randomised trial comparing the effects of treatment with MTX, SSZ, or a combination of both. Criteria for inclusion: patients with early RA (⩽1 year duration). Follow up: between the end of years 1 and 5, patients were followed up and treated by their own rheumatologist, who was allowed to indicate any treatment. Outcome measures: disease activity score (DAS), health assessment questionnaire (HAQ), and Sharp/van der Heijde radiological score at baseline and after five years of follow up. Analysis: comparison of the five year follow up DAS, HAQ, and radiological scores in patients given combined and single treatment during the first year. <b>Results:</b> At the end of the five years of follow up, the patients primarily receiving single or combined treatment had similar mean DAS, HAQ, and radiographic scores. <b>Conclusion:</b> Treatment of patients with early RA using combined therapy with MTX and SSZ during the first year did not influence the long term inflammatory status, or disability, or structural changes, compared with single disease modifying antirheumatic drug treatment.
Storing vaccines at the correct temperature.
Authors: A. Lipp
Journal: BMJ (1992)

transmission should therefore be explored.As cases in infants now seem to be making a consider- able contribution to endemic transmission (table ), one approach would be to offer infants early measles vaccination before giving measles, mumps, and rubella vaccine in the second year of life.Studies to determine the serological response to early vaccination in infants of vaccinated and naturally immune mothers and the accuracy of a clinical diagnosis of measles in infants and older age groups are under way, together with theoretical studies to explore the impact of such a strategy.An epidemiologically and logistically different approach to routinely offering two doses would be to attempt to vaccinate all subjects in a wide age range within a short time and thereby interrupt transmission.This has recently been done in the English speaking Caribbean, where over 95% of all children aged 1-15 in eight of the 17 islands were vaccinated within one month.'To ensure elimination this initiative must be repeated periodically, the interval and targeted age groups being decided on the basis of epidemiological data such as the age specific prevalence of the antibody,6 and results of theoretical studies.Clearly, further work is required to provide a sound scientific basis for deciding future policy.We suggest that in the short term the cost effectiveness of offering measles, mumps, and rubella vaccine to secondary school children should be decided locally on the basis of a district's previous uptake of measles vaccine and present age specific notification rates.
Immunosurveillance by Antiangiogenesis: Tumor Growth Arrest by T Cell–Derived Thrombospondin-1
Authors: Keri L. Schadler, Erika J. Crosby, Alice Yao Zhou, Dong Ha Bhang, Lior Braunstein, Kwan Hyuck Baek, Danielle Crawford, Alison Crawford, Jill Angelosanto, E. John Wherry, Sandra Ryeom
Journal: Cancer Research (2014)

Abstract Recent advances in cancer immunotherapy suggest that manipulation of the immune system to enhance the antitumor response may be a highly effective treatment modality. One understudied aspect of immunosurveillance is antiangiogenic surveillance, the regulation of tumor angiogenesis by the immune system, independent of tumor cell lysis. CD4+ T cells can negatively regulate angiogenesis by secreting antiangiogenic factors such as thrombospondin-1 (TSP-1). In tumor-bearing mice, we show that a Th1-directed viral infection that triggers upregulation of TSP-1 in CD4+ and CD8+ T cells can inhibit tumor angiogenesis and suppress tumor growth. Using bone marrow chimeras and adoptive T-cell transfers, we demonstrated that TSP-1 expression in the T-cell compartment was necessary and sufficient to inhibit tumor growth by suppressing tumor angiogenesis after the viral infection. Our results establish that tumorigenesis can be stanched by antiangiogenic surveillance triggered by an acute viral infection, suggesting novel immunologic approaches to achieve antiangiogenic therapy. Cancer Res; 74(8); 2171–81. ©2014 AACR.
Abstract 1406: Involvement of DNA repair pathways in DAG-lactone radiosensitization of human LNCaP cells
Authors: David J. Galvin, Tin H. Thin, Jean-Paul Truman, Larissa Shenker, Richard Kolesnick, Zvi Fuks, Adriana Haimovitz-Friedman
Journal: Cancer Research (2010)

Abstract We previously demonstrated that pre-treatment of human androgen-dependent prostate cancer cell line LNCaP with either 12-0-tetradecanoylphorbol 13-acetate (TPA, a known protein kinase C activator), or diacylglycerol-lactone (DAG-lactone) radiosensitized these cells. This effect was mediated by down-regulation of ATM protein levels, thus de-repressing the enzyme ceramide synthase (CerS), ceramide generation and apoptosis. Here we assessed whether ATM down-regulation affected DNA repair pathways. LNCaP cells were pretreated for 16 hr with 10μM DAG-lactone and irradiated with 20 or 40Gy. Pre-treatment with DAG-lactone significantly enhanced apoptosis at 48 hours from 1.1% to 13.9% (20Gy) and 19.9% (40Gy) respectively. γ-H2AX and BRCA1 foci formation at 1 and 8 hours post-radiation were scored. Immunofluorescent staining for γ-H2AX demonstrated a dose-dependent increase in γ-H2AX foci formation at 20Gy and 40Gy for both 1hr and 8 hr time points. Our data also shows that 40Gy alone produces the same amount of DNA double strand breaks (dsbs; as measured by γ-H2AX at 8 hr) as 20Gy+DAG-lactone, yet 40Gy alone does not induce apoptosis in LNCaP cells, while 20Gy+DAG-lactone does, indicating that ATM down-regulation is necessary for the apoptotic response. Similarly there was a dose-dependent response in the generation of BRCA1 foci at 20Gy and 40 Gy at 8hr post-radiation. There was no difference in the BRCA1 foci between pre-treatment with DAG-lactone either at 20Gy or at 40 Gy at both 1 hr or at 8 hr post-radiation. While apoptotic degradation is associated with γ-H2AX phosphorylation, in LNCaP cells these events would be expected at 24-48 hr. Therefore the foci observed here are unlikely to be associated with apoptotic DNA degradation and most likely result from DNA dsbs. Our recent data showed that unrepaired DNA dsbs trigger post-transcriptional activation of CerS via a mechanism that remains unknown. Accordingly MRE 11, ATM or DNA-PKcs (SCID) deficiencies sensitize mice towards CerS-mediated apoptosis in crypt stem cells clonogens. Although these studies indicate that HR is active, further experiments need to be carried out to explore whether non-homologous end-joining (NHEJ) is or is not functional in LNCaP treated with DAG-lactone and radiation. Hence, the trigger for CerS activation still needs to be established. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1406.
Responsiveness of bone marrow erythropoietic stem cells (CFU‐E and BFU‐E) to recombinant human erythropoietin (rh‐Ep) in vitro in aplastic anemia and myelodysplastic syndrome
Authors: Isao Aoki, Masashi Homori, Hiroo Chikazawa, Kyozo Ishikawa, Katsumi Higashi
Journal: American Journal of Hematology (1990)

Responsiveness of bone marrow erythropoietic stem cells (CFU-E and BFU-E) to recombinant human erythropoietin (rh-Ep) was examined in vitro in 23 patients with aplastic anemia and 14 with myelodysplastic syndrome (MDS) to investigate the clinical use of rh-Ep for these diseases. Bone marrow mononuclear cells were cultured by methylcellulose methods for CFU-E and BFU-E assays. In normals, the CFU-E numbers reached a plateau of increase at Ep doses of almost 2-5 units, and no further increase was observed with the addition of larger Ep doses. In aplastic anemia, the responses of CFU-E to Ep were relatively good in nonsevere type and generally poor in severe type. However, the CFU-E numbers increased with increasing doses of Ep in some of the patients with aplastic anemia. Among the patients with MDS, the responses of CFU-E to Ep were relatively good in primary acquired refractory anemia (PARA) and primary acquired sideroblastic anemia. On the other hand, the responses of CFU-E to Ep were poor in refractory anemia with an excess of blasts (RAEB) and RAEB in transformation among the MDS patients. BFU-E responses to Ep were poor in severe aplastic anemia, RAEB, and RAEB-T. However, there are Ep responsive patients in some of aplastic anemia and PARA. High titers of rh-Ep were suggested to be effective clinically in some patients with aplastic anemia and those with PARA.
RULES AND REGULATIONS FOR ORGANIZATION AND MAINTENANCE OF THE SOUTHERN MEDICAL COLLEGE ASSOCIATION.
Authors: M. T. Briggs
Journal: JAMA (1892)

This Association shall be composed of delegates from Southern Medical Colleges, whose Faculties have signified a desire to become members thereof, signed these rules of organization, and paid the membership fee of $5.00. The objects of the Association are to cultivate closer and more intimate relation between medical colleges and to elevate the standard of medical education by requiring a more thorough preliminary training and an increased length of medical study. The Association shall be composed of one or more from each Medical College, belonging thereto, who shall be elected annually by their respective faculties. Each college shall be entitled to one vote in the transactions of the Association. The officers shall consist of a President, Vice-President, Secretary and Treasurer, who shall be elected annually, just before the adjournment of the annual meetings, and shall perform the respective duties, pertaining to these offices in similar organizations. The meetings of the
IMPACT OF CORONARY CALCIFICATION ON ONE–YEAR OUTCOMES AFTER PCI IN STEMI AND NSTEMI: POOLED ANALYSIS FROM HORIZONS AND ACUITY TRIALS
Authors: Philippe Genereux, Akiko Maehara, Ajay Kirtane, Sorin Brener, Tullio Palmerini, Laura Lasalle, Tom McAndrew, Alexandra Lansky, Roxana Mehran, Gary Mintz, Gregg Stone
Journal: Journal of the American College of Cardiology (2013)
New drugs in respiratory disorders: I.
Authors: D C Flenley
Journal: BMJ (1983)

Trimethoprim, a selective antagonist of bacterial dihydro folate reduc?ase, is combined with sulphamethoxazole in co trimoxazole, which is of proved value in lower respiratory tract infections, in particular the mixed infection of Haemophilus influenzae and Streptococcus pneumoniae that occurs so commonly in patients with chronic bronchitis and emphysema.1 A compari? son of trimethoprim alone with co-trimoxazole showed no difference in outcome in adults with bronchitis, chronic bron? chitis, or pneumonia,2 but side effects (rashes, nausea, etc) were more common with co-trimoxazole. Trimethoprim is margin? ally cheaper than co-trimoxazole and should therefore be considered when treatment with co-trimoxazole is indicated. Co-trimoxazole in high doses remains the treatment of choice, however, in infection with Pneumocystis carinii in immune compromised patients.3
Finances in the Older Patient With Cognitive Impairment
Authors: Eric Widera
Journal: JAMA (2011)

Financial capacity can be defined as the ability to independently manage one's financial affairs in a manner consistent with personal self-interest. Financial capacity is essential for an individual to function independently in society; however, Alzheimer disease and other progressive dementias eventually lead to a complete loss of financial capacity. Many patients with cognitive impairment and their families seek guidance from their primary care clinician for help with financial impairment, yet most clinicians do not understand their role or know how to help. We review the prevalence and impact of diminished financial capacity in older adults with cognitive impairment. We also articulate the role of the primary care clinician, which includes (1) educating older adult patients and their families about the need for advance financial planning; (2) recognizing signs of possible impaired financial capacity; (3) assessing financial impairments in cognitively impaired adults; (4) recommending interventions to help patients maintain financial independence; and (5) knowing when and to whom to make medical and legal referrals. Clearly delineating the clinician's role regarding identification of financial impairment could establish for patients and families effective financial protections and limit the economic, psychological, and legal hardships of financial incapacity on patients with dementia and their families.
Long-term metered-dose inhaler adherence in a clinical trial. The Lung Health Study Research Group.
Authors: C S Rand, M Nides, M K Cowles, R A Wise, J Connett
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Poor adherence to medication regimens is a well-documented phenomenon in clinical practice and an ever-present concern in clinical trials. Little is known about adherence to inhaled medication regimens over extended periods. The present paper describes the 2-yr results of the Lung Health Study (LHS) program, which was developed to maintain long-term adherence to an inhaled medication regimen in 3,923 special intervention participants (as measured by self-report and medication canister weight). The LHS is a double-blind, multicenter, randomized controlled clinical trial of smoking intervention and bronchodilator therapy (ipratropium bromide or placebo) for early intervention in chronic obstructive pulmonary disease (COPD). At the first 4-mo follow-up visit, nearly 70% of participants reported satisfactory or better adherence. Over the next 18 mo, self-reported satisfactory or better adherence declined to about 60%. Canister weight classified adherence as satisfactory or better in 72% of participants returning all canisters at 1 yr, and in 70% of the participants returning all canisters at the 2-yr follow-up. Self-reporting confirmed by canister weight classified 48% of participants at 1 yr as showing satisfactory or better adherence. Overusers were 50% more likely than others to misrepresent their true smoking status, suggesting that canister weights indicating overuse may be deceptive. Results of multiple logistic regression analysis indicate that the best compliance was found in participants who were married, older, white, had more severe airways obstruction, less shortness of breath, and fewer hospitalizations, and who had not been confined to bed for respiratory illnesses.(ABSTRACT TRUNCATED AT 250 WORDS)
Secretoneurin gene therapy improves hind limb and cardiac ischaemia in Apo E−/− mice without influencing systemic atherosclerosis
Authors: Markus Theurl, Wilfried Schgoer, Karin Albrecht-Schgoer, Daniela Lener, Dominik Wolf, Maria Wolf, Egon Demetz, Piotr Tymoszuk, Ivan Tancevski, Reiner Fischer-Colbrie, Wolfgang-Michael Franz, Peter Marschang, Rudolf Kirchmair
Journal: Cardiovascular Research (2014)

Hypercholesterolaemia is a major risk factor for cardiovascular diseases and has been shown to influence angiogenesis in the hind limb ischaemia (HLI) model. The impaired up-regulation of angiogenic factors seems to be one of the underlying mechanisms for reduced vessel formation. Since we found that secretoneurin (SN) is up-regulated in hypoxic skeletal muscle cells and exerts beneficial effects in myocardial and HLI, we hypothesized that SN therapy might improve neovascularization in hypercholesterolaemic Apo E(-/-) (Apo E knockout) mice suffering from an impaired vascular response.For in vitro experiments, endothelial cells (ECs) were incubated with oxidized low-density lipoprotein (oxLDL) to mimic hypercholesterolaemia. EC function was impaired by oxLDL, but SN induced EC proliferation and in vitro tube formation under these conditions. In the HLI model, injection of SN plasmid resulted in a significant better outcome regarding blood flow recovery, amputation rate, and vessel density. In the myocardial infarction (MI) model, the SN group showed improvement in cardiac parameters. Aortic plaque area was not influenced by local SN injection. Interestingly, SN-induced recruitment of angiogenic monocytic cells was abolished under hypercholesterolaemia.SN gene therapy exerts beneficial effects in cardiovascular animal models in Apo E(-/-) mice without influencing atherosclerosis and might qualify as a promising therapy for cardiovascular disorders.
Selective activation of neurohormonal systems in post-infarction left ventricular dysfunction
Authors: Jean L. Rouleau, Gilles-R. Dagenais, Milton Packer, Bruce Sussex, J.Malcolm Arnold, Francois Sestier, John O. Parker, Patricia McEwan, Victoria Bernstein, Thomas E. Cuddy, Gervasio Lamas, Stephen S. Gottlieb, John McCans, Marc Klein, Daniel Bichet, Jacques de Champlain, Marc Pfeffer
Journal: Journal of the American College of Cardiology (1991)
Public health gets a boost in NHS streamlining
Authors: J Smith
Journal: BMJ (1994)

The last elements of the restructuring of the National Health Service in Britain were put in place last week with the publication of details of how the NHS Executive and its regional offices are to work. The proposals seem to strengthen the role of public health, but critics say that the Department of Health's report, Managing the New NHS, remains vague on crucial issues such as medical education and junior doctors' contracts.

The report follows last year's review of the functions of the NHS above district health authorities, which was prompted by the need to streamline central management as more responsibility was devolved to trusts and purchasing authorities. It recommended replacing the 14 English regional health authorities with eight regional offices of the NHS Executive (30 October, p 1091). When the secretary of state for health, Virginia Bottomley, accepted these recommendations last October she commissioned work to decide where the functions performed by the executive and the old regions should be done. She also set up a review of the work of the whole Department of Health. Its conclusions, together with a paper …