tbuckley/cabot-search huggingface dataset:
ProGem1: Phase I first-in-human study of the novel nucleotide NUC-1031 in adult patients with advanced solid tumors.
Authors: Essam Ahmed Ghazaly, Simon Joel, John G. Gribben, Tariq Mohammad, Oluwadunni Emiloju, Chara Stavraka, Tom Hopkins, Hani Gabra, Harpreet Wasan, Nagy A Habib, Robert C. F. Leonard, Christopher McGuigan, Magdalena Slusarczyk, Sarah Patricia Blagden
Journal: Journal of Clinical Oncology (2013)

2576 Background: NUC-1031 is a novel nucleotide (ProTide) that evades all three key cellular resistance mechanisms associated with gemcitabine (dFdC). NUC-1031 bypasses nucleoside transporters, is activated independent of deoxycytidine kinase and is resistant to cytidine deaminase-mediated degradation. NUC-1031 has demonstrated broad antiproliferative activity in vitro and in vivo. Methods: Patients with relapsed/refractory advanced solid tumors entered in sequential cohorts of up to 6 patients, with escalating doses of NUC-1031 administered as a 5-10 minute IV injection weekly or twice-weekly. Ongoing objectives are to determine recommended phase II dose, safety profile, pharmacokinetics (PK) and preliminary anti-tumor activity. Results: 8 patients (5 female, 3 male) with pancreatic (2), colorectal (2), breast (1), and ovarian (1) cancers; cholangiocarcinoma (1) and unknown primary (1) have been enrolled. Two dose levels - 500mg/m 2 (4) and 1000mg/m 2 (1) weekly and one dose level - 375 mg/m 2 (3) twice-weekly. No DLTs have been observed. Mean AUC (0 - 24 h) for NUC-1031 was 150.3 ± 84.8 µM/h (n=5). dFdC and dFdU were detected in plasma up to 24 h (range of 0 - 5.8 µM for dFdC and 0 - 14.9 µM for dFdU). NUC-1031 excreted in urine mainly as dFdU. The Table shows rapid elimination of NUC-1031 from plasma and high intracellular levels of the active gemcitabine triphosphate at 2 and 24 h. Stable disease achieved in 1 patient with rapidly progressing breast cancer. Two further patients had symptomatic relief and improved QOL, including a dramatic reduction in ascites and pain. Conclusions: PK data show NUC-1031 has ≥ 10x higher intracellular levels of the active compound, dFdCTP, and significantly lower plasma Cmax levels of the toxic metabolite, dFdU, compared to equivalent levels of gemcitabine. NUC-1031 has shown better intracellular delivery and toxicity profile than gemcitabine with some promising early indicators of clinical efficacy. Clinical trial information: NCT01621854. [Table: see text]
Enzyme discovery may help slow spread of antibiotic resistant bacteria
Authors: Judy Siegel-Itzkovich
Journal: BMJ (2000)

A group of enzymes capable of duplicating damaged DNA and creating new mutations has been discovered by scientists at Israel's Weizmann Institute of Science in Rehovot. The discovery could help researchers find ways to slow the spread of antibiotic resistant bacteria by suppressing the activity of these enzymes.

The research, conducted by Professor Zvi Livneh of the institute's biological chemistry department and colleagues, is reported in the latest issue of the …
Mechanisms of Recurrent Aortic Regurgitation After Aortic Valve Repair
Authors: Jean-Benoît le Polain de Waroux, Anne-Catherine Pouleur, Annie Robert, Agnès Pasquet, Bernhard L. Gerber, Philippe Noirhomme, Gébrine El Khoury, Jean-Louis J. Vanoverschelde
Journal: JACC. Cardiovascular imaging (2009)
Pulmonary hypertension in patients with lupus: Prevalence, etiology and risk factors
Authors: Fernando León, Gregorio Pérez-Peñate, J. Navarro, Gabriel Juliá, Antonio García, Carlos Cabrera, Pedro Cabrera, Nazario Ojeda, Juan Pulido, Iñigo Rúa Figueroa
Journal: European Respiratory Journal (2012)

Background: Pulmonary arterial hypertension has been reported between 0.5 and 14% in systemic lupus erythematosus (SLE).

Objectives: To assess PH prevalence, etiology and risk factors in a SLE cohort.

Methods: Prospective cross-sectional study of 158 SLE patients. Doppler echocardiographic (DE), diffusing capacity for CO (DLCO), NtproBNP and dyspnea (Borg scale) were performed in all patients. An echocardiographic exercise test (EE) was conducted in selected patients. When sPAP ≥ 45 mmHg (DE) or a positive EE (>20 mmHg increase in PAPs) a right heart catheterization (RHC) at rest or during exercise was performed. A rest mean pulmonary pressure (mPP) ≥25 mmHg was accepted as PH. When rest mPP was less than 25 mmHg, an exercise test was conducted. Patients with resting PH (sPAP ≥ 35 and < 45 mmHg) and obvious cardiac disease were excluded from RHC.

Results: Mean age: 45±12.9 years, 94.3% females. Twenty one patients (13.4%) had dyspnea (Borg scale ≥ 2). Eleven patients (6.9%) showed any degree of PH. Eight patients (out of 11) had PH of left cardiac origin. One patient had thromboembolic disease. Two patients had precapillary PH related with SLE. All 11 patients with PH had dyspnea (Borg scale ≥ 2) vs. those without PH (p<0.001). PH patients showed a significant decrease in DLCO and higher NtproBNP. There were no differences in SLE clinical characteristics between SLE patients and those without PH.

Conclusions: Our data confirm the low prevalence of precapillary PH in SLE. We found a preponderance of cardiac etiology. A PH screening program based on DE, NtproBNP and DLCO not seems to be cost-effective and should be restricted to SLE patients with unexplained dyspnea.
Abstract 21: Acute Rosiglitazone Treatment Activates Cardioprotective Signaling During Ischemia/Reperfusion in Non-Diabetic Mice
Authors: Alex Morrison, Ji Li
Journal: Circulation (2010)

Background: Rosiglitazone (RGZ), a PPAR-γ agonist, has been demonstrated to possess cardioprotective properties during ischemia/reperfusion (I/R), however, this notion remains controversial. In thi...
MEPs call for new alcohol strategy and calorie display on labels
Authors: R. Watson
Journal: BMJ (2015)

Members of the European Parliament are pressing the European Commission to produce a new wide ranging strategy to tackle alcohol related harm in Europe. The MEPs said that the strategy should include draft legislation to be tabled at the latest next year requiring the energy content of alcoholic beverages to be clearly labelled across the European Union. Alcohol is currently excluded from food labelling laws that apply to all other products.

The MEPs also gave their support to the possibility of using a minimum price on a unit of alcohol to curb the sale of very cheap alcohol. The Scottish government took a lead in …
Trends in the prescription of antidepressants by office-based psychiatrists
Authors: M Olfson, G L Klerman
Journal: American Journal of Psychiatry (1993)

This study was done in an effort to determine whether there was a change over the past decade in the number and proportion of patients prescribed antidepressants by psychiatrists in private practice.The authors analyzed data from the National Ambulatory Medical Care Survey for the years 1980, 1985, and 1989, focusing on visits by adults over the age of 18 years to physicians specializing in psychiatry and psychiatric subspecialties.The number of visits that included prescribing an antidepressant medication grew from approximately 2.5 million in 1980 to 4.7 million in 1989, or from 17.9% to 30.4% of all office-based psychiatric visits. Fluoxetine, which first became available in 1988, accounted for 29.6% of the prescriptions for antidepressants in 1989. Increases in prescriptions for antidepressants were particularly evident for male patients, young adult patients, and patients with neurotic disorders.There was an increase in the 1980s in the use of antidepressants in office-based psychiatric practice. The advent of new agents and the broadening of the clinical usefulness of existing agents may have contributed to this increase.
Early markers for protective mechanisms during rush venom immunotherapy
Authors: C. Bussmann, J. Xia, J.‐P. Allam, L. Maintz, T. Bieber, N. Novak
Journal: Allergy (2010)

Allergen-specific venom immunotherapy (VIT) represents the only rational-based option to treat allergic sensitizations against bee and wasp venom. So far, there is not much knowledge about early induction of protective and tolerogenic pathways during VIT.To identify the earliest markers for protective mechanisms against allergic reactions in the peripheral blood during the build-up phase of VIT.PBMC and monocytes were isolated, and serum samples were taken before and during a five day build-up phase from 65 hymenoptera venom allergic patients. Expression level of tolerogenic markers was analyzed on mRNA and protein level. Serum levels of different soluble tolerogenic factors were measured.We observed significantly enhanced tryptophan degradation, elevated ILT4 expression of monocytes as well as IL-10 production of CD3(+) T cells only a few hours after the first injection on day 1, followed by increased IL-10 serum levels, monocyte apoptosis and elevated intracellular cAMP levels of monocytes on day 3 combined with a higher ILT3 protein expression and IL-10 secretion of monocytes on day 5.From these data, we conclude that tryptophan depletion, ILT3/4-mediated inhibition, higher IL-10 production as well as intracellular cAMP might contribute to early induction of protective mechanisms against allergic reactions during the build-up phase of VIT.
Short-term analytically oriented psychotherapy versus behavior therapy
Authors: R B Sloane, F R Staples, A H Cristol, N J Yorkston
Journal: American Journal of Psychiatry (1975)

Ninety-four outpatients with anxiety neurosis or personality disorder were randomly assigned for four months to a waiting list, behavior therapy, or psychoanalytically oriented therapy. The target symptoms of all three groups improved significantly, but the two treated groups improved equally well and significantly more than those on the waiting list. There were no significant differences among the groups in work or social adjustment; however, the patients who received behavior therapy had a significant overall improvement at four months. One year and two years after the initial assessment, all groups were found to be equally and significantly improved.
Abstract 13760: Methamphetamine Use is Common Among Patients with Left Ventricular Systolic Dysfunction
Authors: Brandon M Wiley, Lucas Zier, Ann Bolger, Kirsten Bibbins-Domingo, Christopher F Barnett
Journal: Circulation (2012)

Background: Methamphetamine (meth) use is a major public health problem in the United States. Approximately 13 million Americans over age 12 have used meth at least once and 353,000 were current us...
Abstract 10171: Development and Validation of Risk-Adjustment Models for Long-Term Mortality and Myocardial Infarction Following Percutaneous Coronary Interventions
Authors: Mandeep Singh, David R Holmes, Ryan J Lennon, Charanjit S Rihal
Journal: Circulation (2010)

Background: Existing models for outcome after percutaneous coronary interventions (PCIs) lack assessment of long-term prognosis. Our goal was to derive 1- and 5-year mortality and mortality/myocard...
Human Secreted Stabilin-1−Interacting Chitinase-like Protein Aggravates the Inflammation Associated With Rheumatoid Arthritis and Is a Potential Macrophage Inflammatory Regulator in Rodents
Authors: Weichun Xiao, Geng Meng, Yanmei Zhao, Huihui Yuan, Tingting Li, Yanyan Peng, Yong Zhao, Ming Luo, Wenming Zhao, Zhanguo Li, Xiaofeng Zheng
Journal: Arthritis & Rheumatology (2014)

Objective To study the relationship between the human secreted protein stabilin‐1−interacting chitinase‐like protein (SI‐CLP) and rheumatoid arthritis (RA). Methods The expression of SI‐CLP in peripheral blood mononuclear cells (PBMCs) and synovial fluid from patients with RA and the effects of cytokines on SI‐CLP expression were examined by Western blotting. Fluorescence‐activated cell sorting analysis was performed to investigate the binding between SI‐CLP and cells. Bone marrow–derived macrophages were isolated from wild‐type and SI‐CLP −/− mice, and real‐time quantitative polymerase chain reaction was performed to detect the levels of messenger RNA for cytokines or SI‐CLP in SI‐CLP− or cytokine‐treated macrophages. Histologic studies were conducted to evaluate inflammation and the expression of interleukin‐12 (IL‐12), IL‐13, and SI‐CLP in lesions. Enzyme‐linked immunosorbent assays were used to detect the cytokine levels in bone marrow–derived macrophages. Rats or mice with collagen‐induced arthritis (CIA) and SI‐CLP −/− mice were used to study the function of SI‐CLP in RA. Results SI‐CLP expression was increased in PBMCs and detectable in synovial fluid from patients with RA. Administration of SI‐CLP to rats with CIA aggravated arthritis‐associated inflammation. SI‐CLP was specifically attached to the surface protein of macrophages, which elevated the expression of IL‐1β, IL‐6, IL‐12, and IL‐13 in macrophages and mouse bone marrow–derived macrophages, up‐regulating ERK phosphorylation. Moreover, SI‐CLP was up‐regulated by both IL‐12 and IL‐13 through JNK and JAK/STAT signaling, respectively. Knockout of SI‐CLP resulted in a decrease in the expression of IL‐1β, IL‐6, IL‐12, and IL‐13 and lower susceptibility to CIA compared with wild‐type mice. SI‐CLP treatment also aggravated arthritis‐related inflammation in wild‐type and SI‐CLP −/− mice. Conclusion SI‐CLP functions as a regulator of the inflammatory response by macrophages. The decrease in inflammation‐associated cytokine levels resulting from SI‐CLP knockout may explain the lower susceptibility to CIA in SI‐CLP −/− mice.
Validation of soluble mesothelin: design and preliminary results of a Belgian multicentric observational study
Authors: Kevin Hollevoet, Eliane Kellen, Kristiaan Nackaerts, Joel Thimpont, Paul Germonpre, Paul De Vuyst, Lionel Bosquee, Joris Delanghe, Catherine Legrand, Jan P. van Meerbeeck
Journal: Journal of Thoracic Oncology (2009)
Small‐bowel capsule endoscopy in patients with gastrointestinal food allergy
Authors: A. F. Hagel, T. M. de Rossi, Y. Zopf, A. S. Lindner, W. Dauth, M. F. Neurath, M. Raithel
Journal: Allergy (2011)

To cite this article: Hagel AF, de Rossi TM, Zopf Y, Lindner AS, Dauth W, Neurath MF, Raithel M. Small‐bowel capsule endoscopy in patients with gastrointestinal food allergy. Allergy 2012; 67 : 286–292. Abstract Background: Food allergy may present with a plethora of gastrointestinal and extraintestinal symptoms such as abdominal pain, diarrhea, cardiocirculatory symptoms, cutaneous reactions, or rhinitis. Macropathological lesions like lymphofollicular hyperplasia and erosive or ulcerative lesions have seldom been described in gastroscopy and colonoscopy previously. Methods: Fifteen patients presenting with unspecific abdominal symptoms in which food allergy was detected in due course were included. During the examination process, those patients showed various indications for small‐bowel capsule endoscopy, such as weight loss and anemia. Results: Fourteen (93.3%) of the 15 small‐bowel capsule endoscopies could be assessed, showing nonerosive lesions such as erythema, swelling, and lymphoid hyperplasia in 8 patients (57.1%) and erosive lesions such as aphthoid lesions, erosions, and petechiae in 4 patients (28.6%) with food allergy. Conclusion: In 15 patients with confirmed food allergy and after exclusion of other diseases, 12 (85.7%) showed various unspecific nonerosive or erosive mucosal lesions within the small bowel, resulting, however, partially in grave consequences such as anemia. Lymphoid hyperplasia was the most prominent finding in 7 patients (50%), albeit infectious disease had been excluded. Anemia improved within 1 year after adequate antiallergic treatment.
Cortical Hyperexcitability in Amyotrophic Lateral Sclerosis
Authors: Brian J. Wainger, Merit E. Cudkowicz
Journal: JAMA Neurology (2015)

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Abstract 12806: Under the Radar: Deaths From ST-Elevation Myocardial Infarction That Do Not Appear in Registries
Authors: Peter Bogaty, Yongling Xiao, Jim Nasmith, Eli Segal, Simon Kouz, Stephane Rinfret, Philippe L'Allier, Dave Ross, Alain Vanasse, Sebastien Maire, Laurie J Lambert
Journal: Circulation (2011)

Background: Medico-administrative data provides information on patients hospitalized with acute ST-elevation myocardial infarction (STEMI). However, patients who present to hospital emergency depar...
Adjuvant lymph-node field radiotherapy versus observation only in patients with melanoma at high risk of further lymph-node field relapse after lymphadenectomy (ANZMTG 01.02/TROG 02.01): 6-year follow-up of a phase 3, randomised controlled trial
Authors: Michael A Henderson, Bryan H Burmeister, Jill Ainslie, Richard Fisher, Juliana Di Iulio, B Mark Smithers, Angela Hong, Kerwin Shannon, Richard A Scolyer, Scott Carruthers, Brendon J Coventry, Scott Babington, Joao Duprat, Harald J Hoekstra, John F Thompson
Journal: The Lancet Oncology (2015)
Abstract 14854: Chronic Fish Oil Supplementation in Humans Reduces the Recurrence of Persistent Atrial Fibrillation after Cardioversion
Authors: Saurabh Kumar, Fiona Sutherland, Paul B Sparks
Journal: Circulation (2011)

Introduction: Pre clinical studies suggest that fish oils attenuate atrial structural remodelling in atrial fibrillation (AF) and thus may be anti-fibrillatory. Hypothesis: We hypothesised that chr...
Abstract 396: Role of Monocyte Chemotactic Protein-1 in Obesity Involves a Newly Discovered Transcription Factor MCPIP
Authors: Asim Azfer, Mingui Fu, Pappachan E Kolattukudy
Journal: Circulation (2007)

Monocyte chemotactic protein-1 (MCP) that is well known to play a major role in the development of cardiovascular diseases, was recently reported to be involved also in obesity. We recently discovered that MCP-1 treatment of human monocytes induces a novel CCCH zinc finger transcription factor designated MCP-induced protein (MCPIP). In the present study we report that in the white adipose tissue of high fat diet fed mice, MCPIP was induced when body mass and fasting glucose level were elevated, beginning at about 8 weeks on the diet. Six MCPIP-induced novel genes, with no previously known function, ltv , lzp , creld2 , ufm1 , cdh12 and cdh19, were induced in the white adipose tissue, starting at three months of high fat feeding; the increases in fasting glucose level, MCPIP transcript level and the transcript levels of the novel genes showed further progressive increases during the 5 months on the high fat diet. Similar molecular events were also observed during differentiation of NIH 3T3 -L1 cells into adipocytes in culture in the presence of dexamethasone and insulin. Under these conditions MCP-1 production was induced reaching a peak level at 24hr. MCPIP transcript level showed marked increase within 1 hr and reached a maximum at 2 days. ufm1 , lzp , and creld2 reached maximal levels at 4 hr, whereas ltv reached maximal level in 1–2 days, and cdh12 and cdh19 reached maximal levels in one day. Involvement of MCPIP in the differentiation process was indicated by the finding that transfection of 3T3 cells with MCPIP expression plasmid caused differentiation of these cells into adipocytes under non-inducing conditions in the absence of dexamethasone and insulin. This differentiation was accompanied by induction of the six novel MCPIP-induced genes. Knockdown of MCPIP with specific siRNA suppressed differentiation of 3T3 cells into adipocytes and induction of the six MCPIP-induced genes. These results indicate a role for MCP-1 in adipogenesis and that this role is mediated via the newly discovered transcription factor MCPIP.
Transient situational disturbances: course and outcome
Authors: John G. Looney, E. Eric Gunderson
Journal: American Journal of Psychiatry (1978)

The validity and usefulness of the diagnostic category transient situational disturbance were evaluated by studying the course and outcome for 2,078 hospitalized naval personnel. The condition was found to be less severe and disabling than other major psychiatric disorders in terms of chronicity, length of hospitalization, and disposition. Outcomes in terms of rehospitalization rates and work effectiveness also were relatively favorable. Based on three or more years of follow-up, a substantial proportion of patients originally diagnosed as having a transient situational disturbance subsequently manifested personality disorder problems. The results suggest that clearer criteria are needed to define situational disturbances operationally and to identify patients with underlying personality disorders.
Abstract 8728: Nitric Oxide Delivery During Cardiopulmonary Bypass Reduces Postoperative Morbidity in Children - A Randomized Trial
Authors: Paul A Checchia, Jared Muenzer, Ronald Bronicki, Steven Raithel, David Dixon, Sanjiv Gandhi, Charles Huddleston
Journal: Circulation (2011)

Background: Cardiac surgery leads to reperfusion injury and endothelial dysfunction causing fluid retention, coagulopathy, and myocardial dysfunction. Gaseous nitric oxide (gNO) has been demonstrated to have a myocardial protective effect and anti-reperfusion properties. We hypothesized that gNO administration during CPB would have similar beneficial effects. Methods: A prospective, randomized, blinded, placebo controlled study in which children undergoing repair of Tetralogy of Fallot received either 20 ppm of gNO or placebo delivered to the membrane oxygenator during CPB. Results: 16 children consented and randomized into 2 equal groups. There were no differences in age, cross clamp time, CPB time, or methemoglobin. The NO group had a shorter time on vent (8.4 +/- 7.6 vs 16.3 +/- 6.5 hrs, p&lt;0.05) and CICU LOS (53.8 +/- 19.7 vs 79.4 +/- 37.7 hrs, p=0.05). The NO group had lower troponin values at 12, 24, and 48 hours (p&lt;0.05) and lower BNP at 12 and 24 hours (p&lt;0.05) (graphs). There was a trend toward less positive fluid balance in the first 48hrs post op (+187mL vs +317mL) with significantly less diuretic usage (1.6 +/- 0.9 vs 4.0 +/- 1.0 of furosemide, and 0 vs 6.3 +/- 7.4 of chlorothiazide, both mean total dose (mg/kg) in first 48 hrs, both p&lt;0.05). NO patients had a higher mean Hgb at 48 hrs (11.8 vs 9.8, p&lt;0.05) despite no differences in chest tube output, PRBC transfusion, platelet counts or transfusion, FFP transfusion, or pT/pTT in the first 48hrs. There were no differences in IL6, IL8, TNF, or lactate. Conclusions: The delivery of gNO to the CPB circuit in children undergoing cardiac surgery results in myocardial protection, improved fluid balance, and improved postoperative ICU course.