tbuckley/cabot-search huggingface dataset:
Abstract P3-03-07: Combination of eribulin and PI3K inhibitors in triple negative and HER2 expressing breast cancer cell lines results in synergistic growth inhibition and enhanced inhibition of the PI3K pathway
Authors: D Luyimbazi, T Luu, Q Xing, J Yan, D Tully, E Han, RML Yip, JH Yim
Journal: Cancer Research (2013)

Abstract Background. Patients with triple negative breast cancer (TNBC) have high levels of pAkt expression and activation of the PI3K-mTOR pathway. Eribulin is a microtubule-targeting agent with benefits in treating taxane and anthracycline refractory breast cancer. Our objective was to evaluate its efficacy in inhibiting PI3K pathway activity and cell growth both alone and in combination with PI3K/MTOR inhibitors BEZ 235 and BKM 120. Methods. TNBC cell lines MDA468, BT549, HS587T, MDA231, and HER2 expressing breast cancer cell line SKBR3 were used for this study. Both MDA468 and BT549 have PI3K- related mutations. The tetrazolium salt, 3-4,5 dimethylthiazol-2,5 diphenyl tetrazolium bromide (MTT) assays were used to assess growth inhibition after 72 hour treatment with eribulin, BEZ 235 and BKM 120 both alone and in combination. Combination indices (CI) generated by Chou-Talalay plots were used to quantify synergy. Western blots were used to evaluate the expression of phosphorylated Akt (pAkt), S6K1 (pS6K1) and S6 (pS6) from 30 min to 24 hours of treatment at different doses. Results. Eribulin has IC50 ranging from 60 pM to 300 pM, BEZ 235 has IC50 ranging from 50 nM to 80 nM, and BKM has IC50 ranging from 500 nM or higher. Standard dilutions of eribulin in combination with BEZ 235 resulted in synergistic growth inhibition (CI&amp;lt;1) in both MDA468 and BT549 cells at all doses tested, but required higher concentrations (500 to 2000 nM) for BKM 120. Western blot analysis for all cell lines treated with eribulin showed pAkt inhibition by eribulin alone with doses as low as 1 nM and as early as 4 hours. PI3K inhibitor alone confirmed inhibition of pAkt, pS6K1 and pS6 at early time points with feedback increase in pAkt at 24h. While both BEZ 235 and BKM 120 treatment increased pAkt in a dose dependent fashion at 24 hours, combination treatment with eribulin showed a dose dependent decrease in pAkt. Conclusion. Our study shows significant synergistic growth inhibition with the combination of eribulin and PI3K inhibitors. This may be related to inhibition by eribulin of the feedback increase in pAkt seen with PI3K inhibitors alone at later time points. These findings point to a potential role for combination therapy of both eribulin and PI3K inhibitors in treating refractory metastatic disease. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-03-07.
A New Bedside Test of Cognition for Patients with HIV Infection
Authors: Beverly N. Jones
Journal: Annals of Internal Medicine (1993)

Objective: To compare the Mental Alternation Test, a new 60-second bedside test of cognition, with the Mini-Mental State Exam (MMSE) and the Trailmaking Test, parts A and B, in patients with human immunodeficiency virus (HIV) infection. Design: Cohort study. Participants: Sixty-two inpatients with HIV infection. Setting: The AIDS service of a referral hospital. Measurements: Scores on the MMSE; the Trailmaking Test, parts A and B; and the Mental Alternation Test were compared using correlation calculations and analyses of variance. Receiver operating curves were constructed to identify the best cutoff score on the Mental Alternation Test for detecting impaired performance on the MMSE and the Trailmaking Test. Main Results: The Mental Alternation Test score correlated significantly with MMSE (r = 0.68, P < 0.01) and Trailmaking Test, part B, scores (r = 0.54,P < 0.01). The receiver operating curves showed that a Mental Alternation Test cutoff score of 15 yielded the best results for the detection of abnormal performance on the MMSE (sensitivity, 95% [95% CI, 90% to 100%]; specificity, 79% [CI, 69% to 89%]) and the Trailmaking Test, part B (sensitivity, 78% [CI, 68% to 88%]; specificity 93% [CI, 90% to 100%]). Patients making fewer than 15 alternations in 30 seconds were significantly more likely to have abnormal MMSE (P < 0.0001) and Trailmaking Test, part B, scores (P < 0.0001). The Mental Alternation Test had good reproducibility; analyses of reliability included test-retest correlation (r = 0.80) and inter-rater reliability (r = 0.85, = 0.84). Time of administration was approximately 60 seconds. Conclusions: The Mental Alternation Test of cognition has good sensitivity and specificity and is easily administered. It is a valuable test to identify patients who may need further cognitive evaluation.
Negotiating Equitable Access to Influenza Vaccines: Global Health Diplomacy and the Controversies Surrounding Avian Influenza H5N1 and Pandemic Influenza H1N1
Authors: David P. Fidler
Journal: PLoS Medicine (2010)

As part of the PLoS Medicine series on Global Health Diplomacy, David Fidler provides a case study of the difficult negotiations to increase equitable access to vaccines for highly pathogenic avian influenza A (H5N1) and pandemic 2009 influenza A (H1N1).
PNEUMOPERITONEUM AS AN AID IN THE DIAGNOSIS OF SUBDIAPHRAGMATIC CONDITIONS
Authors: L. R. SANTE
Journal: JAMA (1923)

Since the advent of pneumoperitoneum, or air inserted into the abdominal cavity, as an aid in roentgen-ray diagnosis, much has been done to simplify the technic, and a great deal of investigation has been carried out to determine the full range of possibilities of this method.  Early in our experience with pneumoperitoneum, it was pointed out that this method should prove of great avail in the diagnosis of subdiaphragmatic lesions. The full value of the method was not appreciated, however, until opportunity was afforded for its practical application. Pneumoperitoneum has been of such great aid to us on several occasions, in clearing up doubtful diagnoses, that a brief consideration of its use in these lesions seems advisable. While its application in subdiaphragmatic conditions is not as wide as in some of the other regions of the abdomen, because of the limited range of subdiaphragmatic lesions, the information that it gives
Functional alterations in NO, PGI<sub>2</sub> and EDHF pathways in the aortic endothelium after myocardial infarction in rats
Authors: Gabor Csanyi, Michael Bauer, Wolfgang Dietl, Magdalena Lomnicka, Tatiana Stepuro, Bruno K. Podesser, Stefan Chlopicki
Journal: European Journal of Heart Failure (2006)
Surgical treatment of cor triatriatum in a 41/2-month-old infant
Authors: H. Oelert, I. M. Breckenridge, G. Rosland, J. Stark
Journal: Thorax (1973)

Successful correction of cor triatriatum in a 4½-month-old infant is presented. Altogether six patients with cor triatriatum underwent surgical correction during the last eight years. All but one survived the operation. The clinical features and the surgical treatment are discussed.
Lactate threshold responses to a season of professional British youth soccer
Authors: K McMillan, J Helgerud, S J Grant, J Newell, J Wilson, R Macdonald, J Hoff
Journal: British Journal of Sports Medicine (2005)

To examine the changes in aerobic endurance performance of professional youth soccer players throughout the soccer season.Nine youth soccer players were tested at six different time points throughout the soccer season by sub-maximal blood lactate assessment, using an incremental treadmill protocol. Whole blood lactate concentration and heart frequency (Hf) were determined at each exercise stage. Running velocities at the first lactate inflection point (v-T(lac)) and at a blood lactate concentration of 4 mmol l(-1) (v-4mM) were determined.Running velocity at the two lactate thresholds increased from the start of pre-season training to the early weeks of the competitive season, from 11.67 (0.29) to 12.96 (0.28) km h(-1) for v-T(lac), and from 13.62 (0.25) to 14.67 (0.24) km h(-1) for v-4mM (p<0.001). However, v-T(lac )and v-4mM when expressed relative to maximum heart frequency (Hf(max)) remained unchanged. The Hf to blood lactate concentration relationship was unchanged after the pre-season training period. The two expressions of lactate threshold did not reveal differences between each other.Running velocity at v-T(lac )and v-4mM increased significantly over the pre-season period, but v-T(lac )and v-4mM were unchanged when expressed relative to Hf(max). This finding may indicate that increased endurance performance may be mainly attributable to alterations in Vo(2max). Although lactate assessment of soccer players is useful for determining endurance training adaptations in soccer players, additional assessment of the other two determinants of endurance performance (Vo(2max) and running economy) may provide more useful information for determining physiological adaptations resulting from soccer training and training interventions.
Dobutamine “Stress” Test and Latent Cardiac Susceptibility to Inhaled Diesel Exhaust in Normal and Hypertensive Rats
Authors: Mehdi S. Hazari, Justin Callaway, Darrell W. Winsett, Christina Lamb, Najwa Haykal-Coates, Q. Todd Krantz, Charly King, Daniel L. Costa, Aimen K. Farraj
Journal: Environmental Health Perspectives (2012)

Background: Exercise "stress" testing is a screening tool used to determine the amount of stress for which the heart can compensate before developing abnormal rhythm or ischemia, particularly in susceptible persons. Although this approach has been used to assess risk in humans exposed to air pollution, it has never been applied to rodent studies.Objective: We hypothesized that a single exposure to diesel exhaust (DE) would increase the risk of adverse cardiac events such as arrhythmia and myocardial ischemia in rats undergoing a dobutamine challenge test, which can be used to mimic exercise-like stress.Methods: Wistar-Kyoto normotensive (WKY) and spontaneously hypertensive (SH) rats implanted with radiotelemeters and a chronic intravenous catheter were whole-body exposed to 150 μg/m3 DE for 4 hr. Increasing doses of dobutamine, a β1-adrenergic agonist, were administered to conscious unrestrained rats 24 hr later to elicit the cardiac response observed during exercise while heart rate (HR) and electrocardiogram (ECG) were monitored.Results: A single exposure to DE potentiated the HR response of WKY and SH rats during dobutamine challenge and prevented HR recovery at rest. During peak challenge, DE-exposed SH rats had lower overall HR variability when compared with controls, in addition to transient ST depression. All DE-exposed animals also had increased arrhythmias.Conclusions: These results are the first evidence that rats exhibit stress-induced cardiac dysrhythmia and ischemia sensitivity comparable to humans after a single exposure to a toxic air pollutant, particularly when in the presence of underlying cardiovascular disease. Thus, exposure to low concentrations of air pollution can impair the heart's ability to respond to stress and increase the risk of subsequent triggered dysfunction.
Effects of Killed and Live Attenuated Influenza Vaccine on Symptoms and Specific Airway Conductance in Asthmatics and Healthy Subjects
Authors: T. KAVA, L. A. LAITINEN
Journal: Allergy (1985)

Killed and live influenza virus vaccines were given to asthmatics and healthy subjects to investigate symptoms and alterations in their respiratory performance after vaccination. Polyvalent killed influenza virus vaccine was given to 16 asthmatics and live attenuated influenza virus vaccine to 23 asthmatics and 21 healthy subjects. Fourteen of the 16 asthmatics vaccinated with the killed vaccine displayed a significant rise in serum antibody level as measured by a single radial haemolysis in gel (SRH test). 11 of the 23 asthmatics and 14 of the 21 healthy subjects vaccinated with the live attenuated vaccine displayed a significant rise in the SRH test. Among the subjects with no measurable initial antibodies and with a significant rise in the SRH test, one asthmatic vaccinated with the killed vaccine experienced symptoms of common cold with fever and dyspnoea 1 week after vaccination. Three asthmatics and four healthy subjects vaccinated with live attenuated vaccine experienced mild symptoms, mainly rhinorrhoea, cough and sore throat 2 to 3 days after vaccination. No alterations in specific airway conductance in asthmatics or in healthy subjects were observed. We conclude that both killed and live attenuated influenza virus vaccines are tolerated well by asthmatics and appear to be safe for asthma patients.
Quantitative analysis of synovial membrane inflammation: a comparison between automated and conventional microscopic measurements
Authors: G. Cunnane, L. Bjork, A.-K. Ulfgren, S. Lindblad, O. FitzGerald, B. Bresnihan, U. Andersson
Journal: Annals of the Rheumatic Diseases (1999)

The objective of this study was to quantify selected features of chronic synovial tissue inflammation by computerised image analysis and to validate the results by comparison with conventional microscopic measurements.Synovial biopsy samples were obtained from the knee joints of patients with chronic arthritis and prepared for immunohistochemical analysis using standard techniques. Following the development of special software, four parameters of chronic synovial inflammation were evaluated: intimal layer thickness, CD3+ cell infiltration, CD8+ cell infiltration and vascularity. Intimal layer thickness was expressed in microns. The intensity of CD3+ and CD8+ cell infiltration was expressed as the percentage area of the tissue section occupied by positively stained cells. Vascularity was expressed as the percentage area occupied by blood vessels. Conventional quantitative microscopic analysis was also undertaken and the results from both methods compared.Seventy eight tissue sections were selected for study. Measurements of intimal layer thickness by both techniques correlated strongly: r = 0.85, p = 0.0006. Measurements of CD8+ cell infiltration, usually widely dispersed, also correlated well: r = 0.64, p = 0.005. Measurements of CD3+ cell infiltration, often densely aggregated, correlated less well: r = 0.55, p = 0.02. Measurements of vascularity demonstrated no statistically significant correlation: r = 0.41, p = 0.07. Proficiency in the use of computerised image analysis was readily acquired.Computerised image analysis was successfully applied to the measurement of some features of synovial tissue inflammation. Further software development is required to validate measurement of blood vessels of variable size.
Average Coronary Blood Flow Per Unit Weight of Left Ventricle in Patients With and Without Coronary Artery Disease
Authors: FRANCIS J. KLOCKE, IVAN L. BUNNELL, DAVID GREENE, STEPHEN M. WITTENBERG, JOHN P. VISCO
Journal: Circulation (1974)

Average left ventricular flow per unit mass (F/W) has been evaluated at rest in 20 normal individuals and 26 patients with arteriographically proven, advanced coronary artery disease, using inert gas techniques modified to take into account methodological problems presented by heterogeneous perfusion within the ventricle. Preliminary studies in a canine model in which corornary flow could be measured directly before and after coronary occlusion indicated (1) that inert gas techniques utilizing venous sampling are suitable for abnormal situations when appropriately long periods of saturation and desaturation, and careful resolution of prolonged venous-arterial differences, are employed; and (2) that traditional inert gas methods are not adequate when F/W is abnormally heterogeneous. Using helium as a tracer, coronary disease patients showed a systematic reduction, in comparison to normal individuals, in average left ventricular F/W at rest (54 ± 11 vs 70 ± 13 ml/min/100 g, P &lt; 0.01). Simultaneous studies with traditional nitrous oxide and krypton techniques did not show this difference because of the methodological limitations of these techniques in the presence of abnormally heterogeneous F/W. We conclude: (1) that useful, accurate measurements of F/W can be obtained in coronary disease if appropriate methodological precautions are taken; and (2) that appreciable portions of the left ventricle have an abnormally low F/W, even at rest, in patients with advanced coronary disease.
Role of the Parasympathetic System in Airway Obstruction Due to Emphysema
Authors: Nicholas J. Gross, Morton S. Skorodin
Journal: New England Journal of Medicine (1984)

To study the relative contributions of parasympathetic and sympathetic mechanisms in airway obstruction in patients with emphysema, we gave supramaximal doses of anticholinergic and adrenergic agents in sequence and in combination. Serial doses of one agent were administered to achieve a plateau of bronchodilatation; after that the other agent was administered. The plateau achieved with the anticholinergic agent (atropine methonitrate) was significantly higher than that achieved with the adrenergic agent (salbutamol). When the adrenergic agent was given first, additional bronchodilatation was achieved with subsequent use of the anticholinergic agent. When the anticholinergic agent was given first, no additional bronchodilatation was achieved with subsequent administration of the adrenergic agent. When both agents were given simultaneously, the degree of bronchodilatation was virtually identical to that obtained with the anticholinergic agent alone. Tests sensitive to small-airway and large-airway function and lung volumes gave essentially the same results. Thus, all achievable bronchodilatation was obtained with the anticholinergic agent alone. These results suggest that the two classes of agents produce bronchodilatation through a common cholinergic pathway in emphysema, and support the concept that parasympathetic activity is the dominant reversible component of airway obstruction in this disease. (N Engl J Med 1984; 311:421–5.)
Myocardial insulin resistance in patients with syndrome X.
Authors: H E Botker, N Moller, O Schmitz, J P Bagger, T T Nielsen
Journal: Journal of Clinical Investigation (1997)

Insulin resistance is common in patients with angina pectoris, a positive exercise electrocardiogram, and normal coronary angiograms (syndrome X). It is still not known whether insulin resistance affects the cardiac muscle itself and, if so, whether insulin resistance involves myocardial hemodynamics and energy metabolism. We investigated hemodynamics as well as metabolite exchanges across the heart and the forearm in eight patients with syndrome X and eight control subjects during a baseline period after an overnight fast and during a hyperinsulinemic-euglycemic clamp. Myocardial hemodynamics and metabolism were studied at rest, during pace stress, and in the recovery period after pacing. Neither coronary sinus blood flow nor forearm blood flow differed between the groups before and during the clamp. Whole body insulin-stimulated glucose uptake was decreased in the patients (15.6+/-2.1 vs. 23.1+/-2.0 micromol x kg-1 x min-1). Insulin-stimulated glucose uptake in the forearm and the cardiac muscle was equally reduced in the patients (46+/-5 and 48+/-5%). Myocardial glucose uptake correlated with total arterial delivery in the control subjects (r = 0.63, P < 0.01), but not in patients (r = 0.22, P = 0.13). Carbohydrate and lipid oxidation was similar in the two groups at rest, and changes during the clamp were not different in control subjects and patients either at rest, during pacing, or in the recovery period. Patients with syndrome X exhibit myocardial insulin resistance, but cardiac energy metabolism remains unaffected. In patients with syndrome X, insulin-stimulated glucose uptake is independent from myocardial blood flow.
Residents' Prescription Writing for Nonpatients
Authors: Brian M. Aboff
Journal: JAMA (2002)

Context Writing prescriptions is one of the most tangible new responsibilities that residents acquire after graduating from medical school.During their regular duties, house officers' prescription writing is carefully monitored.Little is known, however, about residents' patterns of prescription writing outside of supervision or about residents' knowledge of the ethical and legal guidelines that regulate prescription writing. ObjectiveTo study what factors influence residents' decision to write prescriptions for nonpatients.Design, Setting, and Participants Survey distributed in December 1997 to 92 internal medicine and family practice residents at a US community-based teaching hospital.Eighty percent responded.Main Outcome Measures Self-reported prescribing activities for nonpatients and for individuals in 12 hypothetical vignettes. ResultsEighty-five percent of respondents reported having written prescriptions for nonpatients.Based on their responses to the vignettes, under certain circumstances, up to 95% of residents would write a prescription for an individual who is not their patient (eg, a sibling).Thirteen percent of residents believed that some ethical guidelines on prescription-writing activity existed.Only 4% of residents reported being aware of federal or state laws addressing the appropriateness of physician prescription writing for nonpatients.None of the residents were able to describe the circumstances that make prescription writing for nonpatients illegal or unethical based on legal statutes or ethical guidelines, respectively. ConclusionsIn a sample of community-based internal medicine and family practice residents, unsupervised prescription writing by residents for individuals who are not their patients is a common occurrence.Since residency training is a time when practice habits are established, it is important that all residents learn about the ethical, legal, and liability implications of writing prescriptions for nonpatients.
Pretreatment Antibody Titers in Repeated Rabies Prophylaxis
Authors: Larry I. Lutwick
Journal: JAMA (1980)

SINCE the number of animal bites in the United States exceeds 1 million each year,<sup>1</sup>practicing physicians will at times be forced to make a decision whether to initiate postexposure rabies prophylaxis. The basic guidelines for the treatment of individuals bitten by animals have been outlined by the Center for Disease Control (CDC).<sup>2</sup>However, unusual circumstances not well covered by these guidelines occasionally arise. We have recently seen two cases involving animal bites in which the person had previously received one or more courses of rabies prophylaxis. Because the recommendations for repeated rabies prophylaxis in previously unimmunized individuals seem somewhat arbitrary, we are reporting these incidences to stress the importance of the pretreatment rabiesneutralizing antibody titer in directing the length of treatment. <h3>Report of Cases</h3><h3>Case 1.—</h3> A 16-year-old high school student was referred to the University of Iowa, Iowa City, because of a recent potential rabies exposure.