tbuckley/cabot-search huggingface dataset:
Postmenopausal Hormone Therapy and Atherosclerosis — Time Is of the Essence
Authors: John F. Keaney, Caren G. Solomon
Journal: New England Journal of Medicine (2016)

Multiple prospective cohort studies in the 1980s indicated that hormone therapy was associated with a nearly 50% lower risk of coronary heart disease in postmenopausal women,1 which prompted speculation that such therapy could be used to prevent coronary events. However, subsequent large-scale randomized trials that evaluated the effect of postmenopausal hormone therapy failed to support the presence of a cardiovascular benefit. Among women with established coronary heart disease, combined estrogen–progestin therapy resulted in an increased risk of coronary heart disease events at 1 year and had no significant effects on the risk of coronary heart disease events in longer-term follow-up. . . .
Correlation Between Serum IgE Concentration and Anti-IgE Mediated Histamine Release from Peripheral Blood Basophils in Allergic Rhinitis and Asthma Patients
Authors: Pawel Bielecki, Ilona V. DuBuske, Krzysztof Kowal, Lawrence M. DuBuske
Journal: Journal of Allergy and Clinical Immunology (2015)
Primary Mania Versus HIV-Related Secondary Mania in Uganda
Authors: Etheldreda Nakimuli-Mpungu, Seggane Musisi, Steven Kiwuwa Mpungu, Elly Katabira
Journal: American Journal of Psychiatry (2006)

The authors hypothesized that in the majority of HIV-positive patients presenting with mania, the mania is secondary to HIV infection and that its presentation and correlates differ from those of HIV-negative patients with primary mania.A comparative cross-sectional study was conducted with HIV-negative and HIV-positive patients admitted to psychiatric wards with acute mania. The authors compared the patients' psychiatric, physical, and immunological (CD4 cell counts) and other laboratory parameters. Pairwise comparisons were done for the two groups on a number of variables.Of 141 patients who presented with acute mania during a 6-month period and were eligible for the study, 61 met criteria for HIV-related secondary mania. Compared with HIV-negative patients with primary mania, they were older, more cognitively impaired less educated, and more likely to be female. Patients in this group had more manic symptoms: they were more irritable, more aggressive, more talkative, and had higher rates of paranoid delusions, visual hallucinations, and auditory hallucinations. More of the HIV-positive secondary mania group had CD4 counts below 350 cells/mm(3).Primary mania and HIV-related secondary mania are clinically and immunologically distinct. The relation between secondary mania and depressed CD4 counts suggests that in the setting of an HIV/AIDS epidemic in poor countries, secondary mania may be used as an indicator to initiate highly active antiretroviral therapy.
SP0139 Comorbidity and exercise therapy in patients with knee osteoarthritis
Authors: M. De Rooij
Journal: Annals of the Rheumatic Diseases (2013)

Osteoarthritis (OA) is one of the diseases with highest rates of comorbidity; rates between 68% to 85% have been reported. Comorbidity in patients with OA is associated with even more pain, greater limitations in daily activities, and worth functional prognosis in these activities. Highly prevalent comorbidities in knee OA are coronary diseases, heart failure, hypertension, type 2 diabetic, obesity, chronic obstructive pulmonary disease, chronic pain, non-specific low back pain, depression, and visual and hearing impairments. Exercise therapy is one of the key recommendations in current guidelines for the management of knee OA, being an effective intervention in pain relief and improvement of daily activities. Unfortunately, these guidelines do not offer guidance concerning comorbidity-associated adaptations. Therefore, there is a need to develop exercise therapy protocols for patients with knee OA and at least one highly prevalent comorbidity. We have developed comorbidity-adapted protocols for comorbidities that are common in OA and have impact on pain and/or affect daily functioning. These protocols provides guidance in clinical reasoning to direct diagnose and treatment phase of these patients. In this inter active session we will discuss the adaptations that have been made in the diagnostic and intervention phase in a patient with OA of the knee and comorbidities (diabetic type 2, hypertension and obesity). <h3>Disclosure of Interest</h3> None Declared
Effects of N-Rydroxy-N'-aminoguanidine Isoquinoline in Combination With Other Inhibitors of Ribonucleotide Reductase on L1210 Cells
Authors: G. Weckbecker, A. Weckbecker, E. J. Lien, J. G. Cory
Journal: JNCI Journal of the National Cancer Institute (1988)

The 1-isoquinolylmethylene derivative of N-hydroxy-N'-aminoguanidine (HAG) is the most potent agent of the recently synthesized series of HAG-derived ribonucleotide reductase inhibitors. To potentiate the effects of the HAG-isoquinoline drug [HAG-1-isoquinolylmethylene tosylate (HAG-IQ)], we combined it with other inhibitors of ribonucleotide reductase. Using mouse leukemia L1210 cell cultures, we tested drug combinations for their cytostatic and cytotoxic properties and for their effects on intracellular ribonucleotide reductase activity and nucleic acid synthesis. Deoxyguanosine or deoxyadenosine combined with HAG-IQ inhibited cell growth in an additive manner; three-drug combinations, HAG-IQ plus either deoxyguanosine/8-aminoguanosine or deoxyadenosine/deoxycoformycin, were strongly synergistic. When Desferal, an iron chelator, was added to these combinations, the four-drug combinations increased inhibition of cell growth and increased cytotoxicity. The intracellular target of these drug combinations in L1210 cells was the ribonucleotide reductase site. The formation of deoxycytidine from [14C]cytidine and incorporation into DNA were markedly inhibited by these drug combinations, while RNA synthesis was unaffected. These data show that the antiproliferative and cytotoxic effects of HAG-IQ, a potent inhibitor by itself, can be further potentiated in combinations with other ribonucleotide reductase inhibitors.
PTU-158 Coeliac disease investigation and follow-up: Abstract PTU-158 Table 1
Authors: I Nasr, M Austin, M Tarzi
Journal: Gut (2012)

<h3>Introduction</h3> Coeliac disease (CD) is an abnormal immune response to gluten affecting 1% of the UK population, resulting in small bowel villous atrophy, malabsorption and GI symptoms. A large number of patients are tested for CD and often repeat requests are made. This retrospective analysis looked at the prevalence of patients with positive CD serology in relation to subsequent gastroenterology referrals and/or small bowel biopsy. <h3>Methods</h3> The data were collected from patients who had undergone serological CD testing. All patients with a positive anti-tissue transglutaminase, or a positive endomysial antibody test were recorded and notes analysed for referral or endoscopy. We excluded patients under 18 years of age and those with known CD. The data were obtained from the laboratory database at Brighton and Sussex University Hospitals over a period of 1 year. <h3>Results</h3> We identified 7369 CD serology requests. The referral source for CD serology was a general practitioner, hospital specialist, gastrointestinal surgeon or gastroenterologist. Overall, 169 (2.3%) individuals had a positive result. From the total number of requests, 6.75% (498) were repeat requests. Of these, 8.23% (41) had a second positive test. 13.86% (69) of the patients who had a repeat serology done by a general practitioner or other hospital clinician were referred to gastroenterology. The overall prevalence of CD was 2.27% (167), of which 58% (97) were referred for a small bowel biopsy. Small bowel histology confirmed CD in 52% of the biopsy samples, that is, almost one third of the total number of cases with positive serology. <h3>Conclusion</h3> Positive CD serology was recorded in 2.3% of the study group. Although small bowel histology is the gold standard in the diagnosis of CD,<sup>1</sup> this was performed on 58% of the patients with positive serology. It is apparent that not all cases with positive serology are being referred to a specialist. We recommend that patients with suspected or incidental diagnosis of CD should be referred to a gastroenterologist for assessment, confirmation of the diagnosis with small bowel biopsy and advice on gluten-free diet. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Ciclitira PJ</b>, Dewar DH, McLaughlin SD, <i>et al.</i> The management of adults with coeliac disease. 2. <b>Crowe SE</b>. <i>Celiac Disease: When to Look and How? ACG 2011 Annual PG Course</i>.
Targeting Myocardial Reperfusion Injury — The Search Continues
Authors: Derek J. Hausenloy, Derek M. Yellon
Journal: New England Journal of Medicine (2015)

Timely reperfusion by means of primary percutaneous coronary intervention (PCI) is the most effective therapy for limiting myocardial infarct size in patients with ST-segment elevation myocardial infarction (STEMI). Although mortality in this patient population is falling, the number of patients in whom heart failure develops is increasing. As such, new treatments are needed to reduce myocardial infarct size and to preserve left ventricular function, so as to prevent the onset of heart failure.One neglected therapeutic target is myocardial reperfusion injury, the term given to the cardiomyocyte death that paradoxically results from reperfusion of ischemic myocardium.1 This phenomenon is mediated, . . .
Dr. Frank J. Rauscher, Jr.: An Appreciation
Authors: F. X. Mahaney
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Dr. Frank J. Rauscher, Jr.: An Appreciation Get access Francis X. Mahaney, Jr. Francis X. Mahaney, Jr. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 3, 3 February 1993, Pages 174–175, https://doi.org/10.1093/jnci/85.3.174 Published: 03 February 1993
The Use of β-Agonists and the Risk of Death and near Death from Asthma
Authors: Walter O. Spitzer, Samy Suissa, Pierre Ernst, Ralph I. Horwitz, Brian Habbick, Donald Cockcroft, Jean-François Boivin, Mary McNutt, A. Sonia Buist, Anthony S. Rebuck
Journal: New England Journal of Medicine (1992)

Morbidity and mortality from asthma appear to be increasing, and it has been suggested that medications used to treat asthma are contributing to this trend. We investigated a possible association between death or near death from asthma and the regular use of beta 2-agonist bronchodilators.Using linked health insurance data bases from Saskatchewan, Canada, we conducted a matched case-control study of subjects drawn from a cohort of 12,301 patients for whom asthma medications had been prescribed between 1978 and 1987. We matched 129 case patients who had fatal or near-fatal asthma with 655 controls (who had received medications for asthma but had not had fatal or near-fatal events) with respect to region of residence, age, receipt of social assistance, and previous hospitalization for asthma.The use of beta-agonists administered by a metered-dose inhaler was associated with an increased risk of death from asthma (odds ratio, 2.6 per canister per month; 95 percent confidence interval, 1.7 to 3.9) and of death or near death from asthma, considered together (odds ratio, 1.9; 95 percent confidence interval, 1.6 to 2.4). For death from asthma, use of the beta-agonist fenoterol was associated with an odds ratio of 5.4 per canister, as compared with 2.4 for the beta-agonist albuterol. On a microgram-equivalent basis, the odds ratio for this outcome with fenoterol was 2.3, as compared with 2.4 with albuterol.An increased risk of death or near death from asthma was associated with the regular use of inhaled beta 2-agonist bronchodilators, especially fenoterol. Regardless of whether beta-agonists are directly responsible for these adverse effects or are simply a marker for more severe asthma, heavy use of these agents should alert clinicians that it is necessary to reevaluate the patient's condition.
Abstract 2456: Discovery of orally active 4-amino-6-arylaminopyrimidine-5-carbaldehyde oximes with dual EGFR and HER2 inhibitory activity.
Authors: Peter J. Connolly, Mary Adams, Amanda K. Beck, Stuart L. Emanuel, Angel R. Fuentes-Pesquera, Lee M. Greenberger, Robert H. Gruninger, Terry V. Hughes, Stephen A. Middleton, Sandra Moreno-Mazza, Niranjan Pandey, Steven K. Wetter, Guozhang Xu
Journal: Cancer Research (2013)

Abstract Growth factor receptors of the ErbB family, especially ErbB1 (EGFR) and ErbB2 (HER2), have attracted considerable attention in recent years as therapeutic targets for the treatment of numerous malignancies including cancers of the lung, colon, and breast, either through blockade of the extracellular ligand binding site by monoclonal antibodies (e.g. anti-EGFR antibodies cetuximab and panitumumab, and anti-HER2 antibody trastuzumab) or inhibition of the intracellular tyrosine kinase domain by small molecule inhibitors (e.g. EGFR kinase inhibitors gefitinib and erlotinib, and dual EGFR/HER2 inhibitor lapatinib). The abundance of small molecule kinase inhibitors in clinical development or on the market attests to the acceptance of ErbB inhibition as a clinically relevant paradigm. Nevertheless, the emergence of resistance mechanisms in ErbB driven or dependent tumors indicates that continued research is required to discover more effective drugs. We previously reported the discovery of JNJ-28871063, a potent inhibitor of EGFR and HER2 kinases in vitro that also showed excellent antitumor efficacy in EGFR (A431 epidermoid carcinoma) and HER2 (N87 gastric carcinoma) overexpressing xenograft models and significant extension of survival in a mouse intracranial tumor model. This compound is a 4-amino-6-arylaminopyrimidine-5-carbaldehyde oxime, a monocyclic chemotype that mimics the traditional bicyclic quinazoline scaffold via an intramolecular hydrogen-bonded pseudocycle involving the adjacent 4-amino and 5-oximino groups. In this study, we present results of a structure-guided analog program designed to optimize in vitro kinase potency and in vivo antitumor efficacy of the pyrimidine-oximes. While substituents on the 6-arylamino group are critical for ErbB inhibitory potency and kinase selectivity, substitution on the oxime oxygen may be changed to modify physico-chemical properties and bioavailability. We will discuss structure-activity relationships for the 5-oximino and 6-arylamino groups as well as the important role played by O-aminoalkyl oxime substituents in improving in vivo activity. Citation Format: Peter J. Connolly, Mary Adams, Amanda K. Beck, Stuart L. Emanuel, Angel R. Fuentes-Pesquera, Lee M. Greenberger, Robert H. Gruninger, Terry V. Hughes, Stephen A. Middleton, Sandra Moreno-Mazza, Niranjan Pandey, Steven K. Wetter, Guozhang Xu. Discovery of orally active 4-amino-6-arylaminopyrimidine-5-carbaldehyde oximes with dual EGFR and HER2 inhibitory activity. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2456. doi:10.1158/1538-7445.AM2013-2456
III. Conditions for Discovery
Authors: Philip H. Abelson
Journal: JAMA (1965)

As I thought about Conditions for Discovery, it seemed desirable to relate some of my remarks to the new Institute for Biomedical Research, for in this venture reside opportunities to be especially creative in biomedical research. There also exists an opportunity to innovate with respect to mechanisms of achieving excellence through an optimal environment for research—in brief, creativity in being creative.  Let us consider first some fundamentals of the general environment in which this Institute will function. In order for a scientist to be productive he must work in fields in which there are opportunities for great discoveries. As one surveys the various fields of science, one can note great variation in their present potential.  Some areas show definite signs of being mined out. For instance, at one time a number of scientists were active in discovering all stable isotopes of the elements. That work is at least 99% complete.
Rainbow: A Global, Phase 3, Double-Blind Study of Ramucirumab Plus Paclitaxel Versus Placebo Plus Paclitaxel in the Treatment of Gastric Cancer Following Disease Progression: Western Population Subgroup
Authors: H. Wilke, P. Clingan, S. Ananda, G. Kurteva, T. Suuroja, G. Folprecht, A. Beny, D. Pastorelli, A. Cesas, C. Toganel, G. Bodoky, O. Lipatov, M. Limon, D. Cunningham, S. Cummins, Z. Wainberg, A. Ko, M. Emig, K. Chandrawansa, E. Van Cutsem
Journal: Annals of Oncology (2014)
Companion animals: Translational scientist’s new best friends
Authors: Amir Kol, Boaz Arzi, Kyriacos A. Athanasiou, Diana L. Farmer, Jan A. Nolta, Robert B. Rebhun, Xinbin Chen, Leigh G. Griffiths, Frank J. M. Verstraete, Christopher J. Murphy, Dori L. Borjesson
Journal: Science Translational Medicine (2015)

Knowledge and resources derived from veterinary medicine represent an underused resource that could serve as a bridge between data obtained from diseases models in laboratory animals and human clinical trials. Naturally occurring disease in companion animals that display the defining attributes of similar, if not identical, diseases in humans hold promise for providing predictive proof of concept in the evaluation of new therapeutics and devices. Here we outline comparative aspects of naturally occurring diseases in companion animals and discuss their current uses in translational medicine, benefits, and shortcomings. Last, we envision how these natural models of disease might ultimately decrease the failure rate in human clinical trials and accelerate the delivery of effective treatments to the human clinical market.
P610Akt-mediated cardioprotective effects of aldosterone in type 2 diabetic mice
Authors: L Fazal, F Azibani, G Coutance, N Birhy, E Polidano, R Merval, N Vodovar, JM Launay, C Delcayre, JL Samuel
Journal: Cardiovascular Research (2014)

Purpose: Studies have shown that aldosterone would have angiogenic effects, and therefore would be beneficial in the context of cardiovascular diseases. We thus investigated the potential involvement of aldosterone in triggering a cardiac angiogenic response in the context of type-2 diabetes, and the molecular pathways involved.
SP0045 What You Need to Know to Understand the Immune Targets in Biological Rheumatic Disease Treatment
Authors: R. Toes
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Many targeted therapies employing biologicals used in the treatment of patients with rheumatic disease are directed against molecules that play a dedicated role in the induction or propagation of immune responses. In the context of this presentation, the function of- and place in the immune system of several of the molecules targeted by different biologicals will be discussed in relation to their role in the immune response against invading pathogens as well as in relation to auto-immunity. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6323
Abstract 3384: The effects of mono- and combination-treatment of phytochemicals and antimicrotubule chemotherapeutic agents on prostate cancer cell proliferation and expression of EMT markers
Authors: Basil A. Smith
Journal: Cancer Research (2011)

Abstract PURPOSE: Treatment of androgen-independent metastatic prostate cancer with chemotherapeutic agent Estramustine showed diminishing success. Epidemiological studies showed an association between reduced cancer risk and dietary intake rich in phytochemicals from fruits and vegetables. We studied the molecular mechanisms through which phytochemicals muscadine grape skin extract (MSKE) and camalexin act individually, or in combination with Estramustine, to affect epithelial-mesenchymal transition (EMT), a process involved in prostate cancer progression. EMT can be induced by transcription factors such as Snail, and is associated with decrease in cell adhesion molecules like E-cadherin, and increase in mesenchymal markers such as vimentin. METHODOLOGY: MSKE, Camalexin, and Estramustine, were used in varying concentrations individually, and in combination, to conduct MTS proliferation assay on C4-2 and ARCaP prostate cancer EMT model overexpressing constitutively active Snail cDNA. EMT markers, E-cadherin and vimentin, were examined by Western Blot Analysis following treatments. RESULTS: MSKE or Camalexin with or without Estramustine significantly decreased cell proliferation of C4-2 cells. Surprisingly, ARCaP-Snail cells were more sensitive to MSKE and Estramustine treatments, and showed significant decrease in viability, as compared to control ARCaP-Neo cells. ARCaP-Snail cells treated with 5µg/ml MSKE showed a reversal in EMT as shown by increased E-cadherin and decreased vimentin levels. CONCLUSION: Both mono and combination treatments retarded prostate cancer cell proliferation and may show promise as a therapeutic agent to abrogate EMT and prostate cancer metastasis in the future. Supported by grants P20MD002285-01 &amp; G12RR003062-22. 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 3384. doi:10.1158/1538-7445.AM2011-3384
A Comparison of Four Methods of Weaning Patients from Mechanical Ventilation
Authors: Andrés Esteban, Fernando Frutos, Martin J. Tobin, Inmaculada Alía, José F. Solsona, Valverdú Valverdu, Rafael Fernández, Miguel A. de la Cal, Salvador Benito, Roser Tomás, Demetrio Carriedo, Santiago Macías, Jesús Blanco
Journal: New England Journal of Medicine (1995)

Weaning patients from mechanical ventilation is an important problem in intensive care units. Weaning is usually conducted in an empirical manner, and a standardized approach has not been developed.We carried out a prospective, randomized, multicenter study involving 546 patients who had received mechanical ventilation for a mean (+/- SD) of 7.5 +/- 6.1 days and who were considered by their physicians to be ready for weaning. One hundred thirty patients had respiratory distress during a two-hour trial of spontaneous breathing. These patients were randomly assigned to undergo one of four weaning techniques: intermittent mandatory ventilation, in which the ventilator rate was initially set at a mean (+/- SD) of 10.0 +/- 2.2 breaths per minute and then decreased, if possible, at least twice a day, usually by 2 to 4 breaths per minute (29 patients); pressure-support ventilation, in which pressure support was initially set at 18.0 +/- 6.1 cm of water and then reduced, if possible, by 2 to 4 cm of water at least twice a day (37 patients); intermittent trials of spontaneous breathing, conducted two or more times a day if possible (33 patients); or a once-daily trail of spontaneous breathing (31 patients). Standardized protocols were followed for each technique.The median duration of weaning was 5 days for intermittent mandatory ventilation (first quartile, 3 days; third quartile, 11 days), 4 days for pressure-support ventilation (2 and 12 days, respectively), 3 days for intermittent (multiple) trials of spontaneous breathing (2 and 6 days, respectively), and 3 days for a once-daily trial of spontaneous breathing (1 and 6 days, respectively). After adjustment for other covariates, the rate of successful weaning was higher with a once-daily trial of spontaneous breathing than with intermittent mandatory ventilation (rate ratio, 2.83; 95 percent confidence interval, 1.36 to 5.89; P < 0.006) or pressure-support ventilation (rate ratio, 2.05; 95 percent confidence interval, 1.04 to 4.04; P < 0.04). There was no significant difference in the rate of success between once-daily trials and multiple trials of spontaneous breathing.A once-daily trial of spontaneous breathing led to extubation about three times more quickly than intermittent mandatory ventilation and about twice as quickly as pressure-support ventilation. Multiple daily trials of spontaneous breathing were equally successful.