tbuckley/cabot-search huggingface dataset:
Three in four Americans want major changes to healthcare system, survey finds
Authors: M. McCarthy
Journal: BMJ (2013)

Despite the fact that the United States spends $3000 (£1860; €2200) more per person on healthcare than Norway, the second highest spender, Americans are more likely to forgo care because of cost, a new survey has found. The results show that Americans face higher out-of-pocket expenses and are more likely than residents of 10 other developed nations to report trouble paying their medical bills.

The survey polled adults in Australia, Canada, France, Germany, the Netherlands, New Zealand, Norway, Sweden, Switzerland, the United Kingdom, and the US about their access to care, medical costs, and the complexity of their interactions with insurers.

The lead author of the study, published in Health Affairs ,1 was Cathy Schoen, senior vice president for …
Let's learn more in lectures
Authors: T. Greenhalgh
Journal: BMJ (1997)

“Dear Dr Greenhalgh, please will you give a lecture.” I have had three such requests this week, and around 25 so far this year. One person has asked me to lead a seminar, and one has tried hard to get me to speak in a debate. No requests for non-directive facilitation, role plays, brainstorming sessions, or reflections on prior experiential learning.

It is undoubtedly pedagogically correct to eschew the lecture as an anachronistic and ineffective educational medium. Please don't send me evidence–I already have it–that students gain around 50% more new ideas and twice as much information, as well as having more fun, when working in tutor facilitated small groups than when …
Abstract P2-12-02: Comorbidities and patient-reported cognitive function among women with stage I-II breast cancer randomized to hormonal therapy (HT) alone versus chemotherapy followed by hormonal therapy (C+HT) treated on the <i>Trial Assigning IndividuaLized Options</i>
Authors: Lynne I Wagner, Robert Gray, George Sledge, Tim Whelan, Daniel Hayes, Charles Geyer, E Claire Dees, David Cella, Joseph A Sparano
Journal: Cancer Research (2012)

Abstract Withdrawn by Author Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-12-02.
Definition of Volunteer Donor
Authors: J. Garrott Allen
Journal: JAMA (1976)

<h3>To the Editor.—</h3> The point that Drs Holley and Glenn (236:1117, 1976) raise about the American Association of Blood Bank's definition of a volunteer donor is well taken. However, if its clarity and purpose can be misconstrued with such ease, better the Association's definitions be redefined now than later.
Endothelin and ischaemic arrhythmias–antiarrhythmic or arrhythmogenic?
Authors: I Sharif
Journal: Cardiovascular Research (1998)

The aim of this study was to investigate the influence of endogenously released and exogenously applied endothelin-1 (ET-1) on ischaemia-induced arrhythmias.Ischaemia was induced in pentobarbitone-anaesthetised rats by ligation of a coronary artery for 30 min. To determine the role of endogenous ET-1 in ischaemic arrhythmias, either the ETA receptor antagonist BQ123 (50 micrograms/kg/min, i.v.; n = 10) or the ETB receptor antagonist PD161721 (0.1 or 1 mg/kg i.v.; n = 10 per group) was administered before the onset of ischaemia. To assess the influence of exogenous ET-1 on arrhythmias, ET-1 (1.6 nmol/kg i.v.) was administered 5 min before ischaemia in the absence (n = 12) or presence of BQ123 (n = 10) or PD161721 (n = 10). The total number of ventricular ectopic beats (VEB's) were counted and expressed as median (Q1-Q3) and the incidence of ventricular fibrillation (VF) and ventricular tachycardia (VT) in each group was determined. Mean arterial blood pressure (MABP) and heart rate (HR) were measured.In control animals (n = 20), the incidence of VF was 65% and the total VEB count was 2775 (1870-4041). Both BQ123 and the higher dose of PD161721 reduced the VEB count to 654 (348-1489; P < 0.05) and 782 (432-1153; P < 0.05) respectively. Only PD161721 reduced the incidence of VF (to 10%; P < 0.05). Administration of ET-1 reduced VEB's to 1530 (1204-2017); P < 0.05) and the incidence of VF to 17% (P < 0.05). Neither PD161721 nor BQ123 modified this antiarrhythmic effect of ET-1, but rather enhanced the reduction in arrhythmias. Before occlusion, ET-1 caused a transient fall in MABP (from 107 +/- 3 to 63 +/- 3 mmHg; P < 0.05). PD161721, but not BQ123, partially blocked this effect. Upon occlusion, MABP fell in control animals (from 106 +/- 4 to 67 +/- 4 mmHg at 1 min post-occlusion; P < 0.05). This was significantly attenuated by ET-1, although neither of the antagonists were able to block this effect of ET-1.ET-1 released endogenously during ischaemia is arrhythmogenic whereas exogenous application of ET-1 may, under certain conditions, be antiarrhythmic.
Bias toward use of a specific T cell receptor beta-chain variable region in a subgroup of individuals with sarcoidosis.
Authors: D R Moller, K Konishi, M Kirby, B Balbi, R G Crystal
Journal: Journal of Clinical Investigation (1988)

To evaluate the concept that biases in the usage of T cell antigen receptor beta variable (V) regions may be manifested in T lymphocytes that accumulate in nonmalignant, T cell-mediated human disorders, a V beta 8-specific antibody (anti-Ti3A, 5REX9H5) was used to evaluate lung and blood T cells in pulmonary sarcoidosis, a chronic granulomatous disorder of unknown etiology. Whereas normal patients had less than 5% Ti3A+ lung (n = 7) and/or blood (n = 9) lymphocytes, strikingly, a subgroup (8 of 21) with active pulmonary sarcoidosis had greater than 7% Ti3A+ lung and/or blood T cells and a higher proportion of Ti3A+ lymphocytes in the lung compared with blood. Dual-color flow cytometry demonstrated compartmentalization of Ti3A+ CD4+ lymphocytes to lung and Ti3A+ CD8+ lymphocytes to blood. Analysis with a 32P-labeled V beta 8 probe revealed that sarcoid lung T lymphocytes contained higher amounts of V beta 8+ mRNA than autologous blood T cells. However, Southern analysis of sarcoid lung and blood T cell DNA demonstrated no evidence of clonal rearrangements of V beta 8 genes. These observations demonstrate a clear bias toward the use of at least one V beta region in sarcoidosis, and suggests T cells accumulate secondary to external selective pressure, rather than in a random polyclonal fashion or by clonal expansion of one or few T cell clones.
Abstract B31: Aryl hydrocarbon receptor translocation, CYP1A1 induction and ROS formation: pharmacodynamic markers of sensitivity to antitumor Benzothiazole 5F203 in ovarian cancer
Authors: Mariana Alejandra Callero, Gabriela Luzzani, Diana De Dios, Bradshaw Tracey, Andrea Loaiza Perez
Journal: Clinical Cancer Research (2013)

Abstract Ovarian malignancies, the second cause of gynaecological cancer death in developed countries possess poor prognoses. Detected at advanced stages of disease (III and IV), the standard of care is cytoreductive surgery followed by platin- and taxane-based chemotherapy. Intrinsic- or acquired resistance to cytotoxic drugs result in significant risk of recurrence; therefore, the discovery of new molecular targets and more effective therapies remain vital. 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (5F203, NSC 703786) lysylamide belongs to a novel mechanistic class of antitumor agents. It elicits activity against ovarian, breast, kidney and colorectal cancer models. We have previously showed 5F203 activates aryl hydrocarbon receptor (AhR) signaling: enhanced CYP1A1 expression and AhR nuclear translocation in sensitive IGROV-1 ovarian cancer cells. This AhR modulation triggers an antiproliferative/pro-apoptotic activity evoking ROS formation, DNA damage and cell cycle arrest prior to apoptosis. In contrast, 5F203 failed to induce CYP1A1 expression, AhR translocation or oxidative stress in 5F203-resistant SKOV-3 cells. In this work we further investigated 5F 203 antitumor mechanism of action. We found that 5F203 ROS formation was accompanied by JNK, ERK and P38MAPK phosphorylation only in IGROV-1 sensitive cells. In addition, cancer cells have been isolated from ascites fluid of ovarian cancer patients; sensitivity to 5F203 and concurrent AhR signal transduction has been examined. 5F203 induced enhanced CYP1A1 expression, AhR translocation and ROS formation in ascites-isolated ovarian cancer cells that were sensitive to 5F203. We propose that AhR may represent a new molecular target in the treatment of ovarian tumors and 5F203 may exemplify a potential novel treatment. Finally, our studies demonstrate theranostic pharmacodynamic markers of 5F203 activity and provide additional insight into molecular targets of this novel anticancer agent, which may benefit ovarian cancer patients with limited therapeutic options. Note: This abstract was not presented at the conference. Citation Format: Mariana Alejandra Callero, Gabriela Luzzani, Diana De Dios, Bradshaw Tracey, Andrea Loaiza Perez. Aryl hydrocarbon receptor translocation, CYP1A1 induction and ROS formation: pharmacodynamic markers of sensitivity to antitumor Benzothiazole 5F203 in ovarian cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr B31.
Elevated levels of peripheral‐blood, naturally occurring aliphatic polyamines in bronchial asthmatic patients with active symptoms
Authors: M. Kurosawa, Y. Shimizu, H. Tsukagoshi, M. Ueki
Journal: Allergy (1992)

The levels of peripheral‐blood, naturally occurring aliphatic polyamines, such as putrescine, spermidine, and spermine, from 21 bronchial asthmatic patients (11 atopics and 10 nonatopics) were measured by postcolumn derivatization high‐performance liquid chromatography analysis. None of the patients, except the 44‐year‐old woman in the case report below, were given prednisolone, and they were instructed to take only regular medication during the tests. Blood was drawn from the patients in a fasting state, and the polyamine levels were compared between the times when they were free of asthmatic symptoms and when they had mild spontaneous attacks. Nine (5 atopics and 4 nonatopics), 6 (3 atopics and 3 nonatopics), and 4 (3 atopics and 1 nonatopic) out of 20 patients, when they had relatively mild asthmatic attacks, showed higher putrescine, spermidine, and spermine levels, respectively, than those of normal healthy control subjects. The levels of peripheral blood polyamines from a 44–year‐old atopic bronchial asthmatic woman, who was admitted to the hospital with severe asthmatic attacks, were measured serially, and the putrescine and spermidine levels were found to be elevated during the asthmatic attacks, returning to normal levels in parallel with the clinical course. These data may suggest a role for naturally occurring aliphatic polyamines in bronchial asthma.
Comprehensive Prognosis Assessment by CMR Imaging After ST-Segment Elevation Myocardial Infarction
Authors: Ingo Eitel, Suzanne de Waha, Jochen Wöhrle, Georg Fuernau, Phillipp Lurz, Matthias Pauschinger, Steffen Desch, Gerhard Schuler, Holger Thiele
Journal: Journal of the American College of Cardiology (2014)
Failure to Resolve a Diagnostic Inconsistency
Authors: George E. Thibault
Journal: New England Journal of Medicine (1992)

A 56-year-old obese white woman with a history of hypertension, diabetes mellitus, and lower-extremity deep venous thrombosis presented to the emergency room after experiencing sudden dizziness, diaphoresis, left-arm pain, and near syncope at work. She had had an inferior Q-wave myocardial infarction four years earlier and a non—Q-wave myocardial infarction a year earlier, at which time cardiac catheterization revealed two-vessel coronary artery disease with well-preserved left ventricular function.This information tells us that this woman has extensive vascular disease, having had two myocardial infarctions before the age of 56. With her left-arm pain and diaphoresis, I'd be concerned that she . . .
The Notch Pathway Inhibits TGFβ Signaling in Breast Cancer through HEYL-Mediated Crosstalk
Authors: Liangfeng Han, Adam Diehl, Nguyen K. Nguyen, Preethi Korangath, Weiwen Teo, Soonweng Cho, Scott Kominsky, David L. Huso, Lionel Feigenbaum, Alan Rein, Pedram Argani, Goran Landberg, Manfred Gessler, Saraswati Sukumar
Journal: Cancer Research (2014)

Acquired resistance to TGFβ is a key step in the early stages of tumorigenesis. Mutations in TGFβ signaling components are rare, and little is known about the development of resistance in breast cancer. On the other hand, an activated Notch pathway is known to play a substantial role in promoting breast cancer development. Here, we present evidence of crosstalk between these two pathways through HEYL. HEYL, a basic helix-loop-helix transcription factor and a direct target of Notch signaling, is specifically overexpressed in breast cancer. HEYL represses TGFβ activity by binding to TGFβ-activated Smads. HeyL(-/-) mice have defective mammary gland development with fewer terminal end buds. On the other hand, HeyL transgenic mice show accelerated mammary gland epithelial proliferation and 24% of multiparous mice develop mammary gland cancer. Therefore, repression of TGFβ signaling by Notch acting through HEYL may promote initiation of breast cancer.
Abstract 3369: Differential biotherapeutic advantages of honey in targeting the Warburg effect and survival of MRC-5 and A549 cell lines
Authors: Ibrahim O. Farah, Veshell L. Lewis, Wellington K. Ayensu, Joseph A. Cameron
Journal: Cancer Research (2014)

Abstract Lung cancer is a one of the most prevalent and deadly cancers in United States. Experimental evidence support that cancer cells do exhibit higher glycolytic rates than normal cells (Warburg effect). To exploit this unique cancer-dependent ATP generation phenomenon, we hypothesize that exposure of cancer cells to organic inhibitors of glycolysis would negatively impact their survival and alter their growth and viability resulting from the vast decrease in their essential glycolytic ATP production; no negative consequences will be seen on normal lung cells. The human lung fibroblast cell line MRC-5 and the human alveolar epithelial cell line A549 were used as models for normal lung and lung cancer in vitro in this study. Using standard methods, both cell lines were maintained and exposed to honey and D-glucose reagents at concentration levels ranging from 31.3-2,000 µg/ml in 96 well plates in quadruplets and experiments repeated at least three times using MTT, and cell counting (T4 Cellometer) assays as well as phase-contrast photo-imaging. Our results indicate that exposure of both cell lines to these natural nutraceutic organics resulted in concentration dependent cell destruction/cell survival depending on the cell line exposed. Honey and D-glucose showed statistically significant (p&amp;lt;0.05) differential negative effects on the A549 line in comparison to its unexposed control as well as to their effects on the MRC-5 cell line. Results show a promising role of honey and D-glucose as metabolites of interest for selective management of cancerous cells. Citation Format: Ibrahim O. Farah, Veshell L. Lewis, Wellington K. Ayensu, Joseph A. Cameron. Differential biotherapeutic advantages of honey in targeting the Warburg effect and survival of MRC-5 and A549 cell lines. [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 3369. doi:10.1158/1538-7445.AM2014-3369
Similarity of Bisphenol A Pharmacokinetics in Rhesus Monkeys and Mice: Relevance for Human Exposure
Authors: Julia A. Taylor, Frederick S. vom Saal, Wade V. Welshons, Bertram Drury, George Rottinghaus, Patricia A. Hunt, Pierre-Louis Toutain, Céline M. Laffont, Catherine A. VandeVoort
Journal: Environmental Health Perspectives (2010)

Daily adult human exposure to bisphenol A (BPA) has been estimated at <1 µg/kg, with virtually complete first-pass conjugation in the liver in primates but not in mice. We measured unconjugated and conjugated BPA levels in serum from adult female rhesus monkeys and adult female mice after oral administration of BPA and compared findings in mice and monkeys with prior published data in women.Eleven adult female rhesus macaques were fed 400 µg/kg deuterated BPA (dBPA) daily for 7 days. Levels of serum dBPA were analyzed by isotope-dilution liquid chromatography-mass spectrometry (0.2 ng/mL limit of quantitation) over 24 hr on day 1 and on day 7. The same dose of BPA was fed to adult female CD-1 mice; other female mice were administered 3H-BPA at doses ranging from 2 to 100,000 µg/kg.In monkeys, the maximum unconjugated serum dBPA concentration of 4 ng/mL was reached 1 hr after feeding and declined to low levels by 24 hr, with no significant bioaccumulation after seven daily doses. Mice and monkeys cleared unconjugated serum BPA at virtually identical rates. We observed a linear (proportional) relationship between administered dose and serum BPA in mice.BPA pharmacokinetics in women, female monkeys, and mice is very similar. By comparison with approximately 2 ng/mL unconjugated serum BPA reported in multiple human studies, the average 24-hr unconjugated serum BPA concentration of 0.5 ng/mL in both monkeys and mice after a 400 µg/kg oral dose suggests that total daily human exposure is via multiple routes and is much higher than previously assumed.
Effect of SQ 14225, an inhibitor of angiotensin I-converting enzyme, on the granulomatous response to Schistosoma mansoni eggs in mice.
Authors: J V Weinstock, M N Ehrinpreis, D L Boros, J B Gee
Journal: Journal of Clinical Investigation (1981)

Murine schistosomiasis is a granulomatous disease associated with high serum and granuloma angiotensin I-converting enzyme (ACE) activity. SQ 14225, a specific competitive inhibitor of ACE, was administered to normal mice and mice infected with Schistosoma mansoni to determine whether this compound could inhibit granuloma ACE activity and modify the size of the granulomatous response to schistosome eggs. Peroral administration of SQ 14225 for 5 wk to infected mice with peak granulomatous responses decreased ACE activity in isolated liver granulomas. Treated mice demonstrated a decrease in granuloma size in the liver, colon, and ileum, and hydroxyproline concentration of isolated liver granulomas was increased. Mean diameters of synchronous pulmonary granulomas, induced by the pulmonary embolization of schistosome eggs into normal and sensitized mice, were decreased by a similar dose of SQ 14225. Withdrawal of SQ 14225 from unsensitized mice with 2-wk-old synchronous pulmonary granulomas induced an increase in inflammation. Infected, but not normal mice receiving SQ 14225 demonstrated reduced portal pressure, liver weight, and body weight. Both normal and infected mice experienced dipsogenesis, expanded intravascular volume, and increased serum ACE. These observations suggest that SQ 14225 can partially inhibit the granulomatous response to schistosome eggs and the pathological manifestations of schistosomiasis. It is possible that ACE has an inflammatory role in granulomatous inflammation.
Interphase cytogenetics of workers exposed to benzene.
Authors: L Zhang, N Rothman, Y Wang, R B Hayes, W Bechtold, P Venkatesh, S Yin, Y Wang, M Dosemeci, G Li, W Lu, M T Smith
Journal: Environmental Health Perspectives (1996)

Fluorescence in situ hybridization (FISH) is a powerful new technique that allows numerical chromosome aberrations (aneuploidy) to be detected in interphase cells. In previous studies, FISH has been used to demonstrate that the benzene metabolites hydroquinone and 1,2,4-benzenetriol induce aneuploidy of chromosomes 7 and 9 in cultures of human cells. In the present study, we used an interphase FISH procedure to perform cytogenetic analyses on the blood cells of 43 workers exposed to benzene (median = 31 ppm, 8-hr time-weighted average) and 44 matched controls from Shanghai, China. High benzene exposure (> 31 ppm, n = 22) increased the hyperdiploid frequency of chromosome 9 (p < 0.01), but lower exposure (< or = 31 ppm, n = 21) did not. Trisomy 9 was the major form of benzene-induced hyperdiploidy. The level of hyperploidy in exposed workers correlated with their urinary phenol level (r = 0.58, p < 0.0001), a measure of internal benzene dose. A significant correlation was also found between hyperdiploidy and decreased absolute lymphocyte count, an indicator of benzene hematotoxicity, in the exposed group (r = -0.44, p = 0.003) but not in controls (r = -0.09, p = 0.58). These results show that high benzene exposure induces aneuploidy of chromosome 9 in nondiseased individuals, with trisomy being the most prevalent form. They further highlight the usefulness of interphase cytogenetics and FISH for the rapid and sensitive detection of aneuploidy in exposed human populations.
Circulating cell membrane microparticles transfer heme to endothelial cells and trigger vasoocclusions in sickle cell disease
Authors: Stéphane M. Camus, João A. De Moraes, Philippe Bonnin, Paul Abbyad, Sylvain Le Jeune, François Lionnet, Laurent Loufrani, Linda Grimaud, Jean-Christophe Lambry, Dominique Charue, Laurent Kiger, Jean-Marie Renard, Claire Larroque, Hervé Le Clésiau, Alain Tedgui, Patrick Bruneval, Christina Barja-Fidalgo, Antigoni Alexandrou, Pierre-Louis Tharaux, Chantal M. Boulanger, Olivier P. Blanc-Brude
Journal: Blood (2015)
The Third Degree. MMR: Can You Decide?
Authors: A. Berger
Journal: BMJ (2003)

BBC Three, 11 September, 9 pm Rating: ![Graphic][1]</img> I have a confession to make. I am entirely in favour of the MMR (measles, mumps, and rubella) vaccination, and actively support its use. I am for all vaccination programmes, because I believe in protecting our communities, and I have seen at first hand what happens in countries that do not enjoy the privileges that we have in the United Kingdom. That said, I find it quite tough being a general practitioner—getting caught in the middle between caring for individual patients while still defending the “masses.” And I find parents who happily support the general notion that our children should be vaccinated, yet withhold their own cherubs from doing their bit towards herd immunity, utterly selfish. So I was looking forward to watching this programme about how parents decide whether or not to have their children vaccinated. I was hoping … [1]: /embed/inline-graphic-1.gif