tbuckley/cabot-search huggingface dataset:
Abstract 1716: FGFR1 gene amplification predicts the antitumor response of FGFR inhibitor LY2874455 in human lung cancer cells
Authors: Chen Bi, Genshi Zhao, Jessica A. Baker, James J. Starling, Wenjuan Wu
Journal: Cancer Research (2012)

Abstract Lung cancer is the leading cause of cancer-related death for both men and women in the world. FGFR receptor tyrosine kinase signaling pathway has been implicated in tumor cell growth, survival, angiogenesis, and metastasis. Activation of the FGFR pathway via FGFR over-expression, and chromosomal amplification and translocation as well as genetic mutation contributes to the tumor progression and the resistance to anti-EGFR and -VEGF treatment in lung cancer. Targeting FGFR pathway is therefore an attractive therapeutic strategy for lung cancer. We have discovered and developed a novel, ATP competitive and orally active small molecule inhibitor of FGFR, LY2874455, currently in clinic development. LY2874455 is a potent inhibitor against four FGFRs, and demonstrates a broad-spectrum of anti-tumor activity in a number of tumor xenograft models. In the current study, we evaluated the anti-tumor activity of LY2874455 in lung tumor cells with or without FGFR1 gene amplification. FGFR1 is known to be amplified in human lung cancer cells NCI-H1581, NCI-H520 and DMS-114, but not in NCI-H460, A549 and NCI-H1299. The mRNA expression levels of FGFR1 are shown to be higher in the FGFR1 amplified cells than those in the FGFR1 non-amplified cells. Consistent with this, the FGFR1 amplified cells exhibited the much more robust b-FGF-induced phosphorylation of FRS2 and ERK, which are also more sensitive to the inhibition by LY2874455 than that in the FGFR1 non-amplified cells. Furthermore, the FGFR1 amplified cells exhibit the better responses to the growth inhibition and apoptosis induction by LY2874455 than those in the FGFR1 non-amplified cells. Therefore, these findings suggest that FGFR1 plays an important role in lung cancer cell growth and survival, and that LY2874455 may provide a promising treatment option for some lung cancer patients whose tumor harbors FGFR1 gene amplification. The in vivo anti-tumor response of LY2874455 is being further investigated in the tumor xenograft models derived from these FGFR1 amplified or non-amplified human lung cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1716. doi:1538-7445.AM2012-1716
Amiodarone and Ventricular Arrhythmia Suppression
Authors: James R. Cook
Journal: Annals of Internal Medicine (1993)

Letters15 February 1993Amiodarone and Ventricular Arrhythmia SuppressionJames R. Cook, MDJames R. Cook, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-118-4-199302150-00024 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:In their interesting report on the “rapid and dramatic” reduction in ventricular arrhythmias in patients treated with oral amiodarone, Kim and colleagues [1] correctly point out the possible confounding effects of other antiarrhythmics administered early in the course of amiodarone loading. Despite this caveat, the graphs and P values presented appear impressive. However, several problems in the analysis may render the conclusion erroneous. First, use of analysis of variance (ANOVA) requires an implicit assumption of normally distributed data. No mention was made of data transformation (that is, logarithms), often used to reduce the influence of extreme values ...References1. Kim SG, Mannino MM, Chou R, Roth S, Roth JA, Desai B, et al. Rapid suppression of spontaneous ventricular arrhythmias during oral amiodarone loading. Ann Intern Med. 1992; 117:197-201. Google Scholar2. Fleiss JL. The design and analysis of clinical experiments. New York: John Wiley & Sons; 1986:78. Google Scholar3. Glantz SA, Slinker BK. Primer of applied regression and analysis of variance. New York: McGraw-Hill, Inc.; 1990:292. Google Scholar4. Marchlinski FE, Buxton AE, Flores BT, Doherty JU, Waxman HJ, Josephson ME. Value of Holter monitoring in identifying risk for sustained ventricular arrhythmia recurrence on amiodarone. Am J Cardiol. 1985; 55:709-12. Google Scholar5. Pratt CM, Hallstrom A, Theroux P, Romhilt D, Coromilas J, Myles J. Avoiding interpretive pitfalls when assessing arrhythmia suppression after myocardial infarction: insights from the long-term observations of the placebo-treated patients in the Cardiac Arrhythmia Pilot Study (CAPS). J Am Coll Cardiol. 1991; 17:1-8. Google Scholar Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 February 1993Volume 118, Issue 4Page: 316KeywordsAnalysis of varianceArrhythmiaStatistical dataStatistical distributions Issue Published: 15 February 1993 CopyrightCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Neurology at a Crossroads
Authors: Timothy A. Pedley
Journal: JAMA (2014)

Neurology was once derided as a field known for the diagnostic skills of its practitioners but also for its inability to offer effective treatments for a majority of patients. Today, neurologists have an increasing number of available therapeutic options, many of which substantially improve physical well-being and quality of life. Rapid and transformative advances in understanding the underlying neurobiology of the diseases neurologists treat and in development of increasingly targeted and effective therapies are altering the course and outcome of many diseases. Several examples include recognition of autoantibody-mediated diseases1; availability of oral and parenteral new drugs to treat multiple sclerosis based on increased knowledge of the condition’s fundamental immunopathogenesis2; deep brain stimulation for Parkinson disease; intravenous thrombolysis and intra-arterial therapy for treatment of acute ischemic stroke; and the development of neurological intensive care units.
Principles and Practice of Physiologic Acupuncture
Authors: Ralph M. Coan
Journal: JAMA (1983)

Dr Ulett is one of a few hundred physicians in the United States who have thoroughly mastered the art of acupuncture. From my own experience with 10,000 patients at the Acupuncture Center of Washington, I agree with Dr Ulett that acupuncture is the treatment of choice for pain. He presents data that over 50% of patients will receive relief from disabling pain of long duration. From his own research and that of others, he also presents data that acupuncture is not hypnosis nor does it work by a placebo effect. Dr Ulett has excellent chapters on the mechanisms of pain within the peripheral and central nervous systems. He explains in detail several presumed ways in which acupuncture modifies pain, including the gate and neurotransmitter theories. For example, he explains the mechanism of blocking dental pain by the use of a needle placed into the web space between the thumb and
Mild traumatic brain injury among a cohort of rugby union players: predictors of time to injury: Figure 1
Authors: Stephanie J Hollis, Mark R Stevenson, Andrew S McIntosh, Ling Li, Stephane Heritier, E Arthur Shores, Michael W Collins, Caroline F Finch
Journal: British Journal of Sports Medicine (2011)

This study reports the time to sustain a mild traumatic brain injury (mTBI) among a cohort of community rugby union players. Demographic and player characteristics were collected and players followed up for between one and three playing seasons. 7% of the cohort sustained an mTBI within 10 h of game time, increasing twofold to 14% within 20 h. The mean time to first mTBI was 8 h with an SD of 6.2 (median 6.8 h; IQR: 2.9–11.7 h). Players reporting a recent history of concussion were 20% more likely to sustain an mTBI after 20 h of game time compared with those with no recent history of concussion. Players were likely to sustain an mTBI in shorter time if they trained for &lt;3 h/week (HR=1.48, p=0.03) or had a body mass index &lt;27 (HR=1.77, p=0.007). The findings highlight modifiable characteristics to reduce the likelihood of shortened time to mTBI.
Myelomatosis presenting as dermatomyositis.
Authors: P. Beck
Journal: BMJ (1968)

Communications Dwn= 747 DIscussIoNThese experiments show that platelet factor 4, like platelet factor 3, is not normally available in intact platelet and that it can be released by the same agents that cause release of platelet factor 3. These agents may merely expose heparincombining sites on the platelet or, alternatively, they may actually release the antiheparin factor into the surrounding plasma.The finding that most of the platelet factor 4 activity remains in the supernatant after deposition of the platelets would suggest that this factor is actually released, and in this way it differs from the behaviour of platelet factor 3, which appears to remain largely associated with the platelets (Hardisty and Hutton, 1966).Findings essentially similar to ours have been reported by Niewiarowski d al. (1967, 1968).It has been observed that little or no heparin is inactivated in citrated blood, whereas significant amounts are activated in blood mixed directly with heparin but not containing citrate (Barkhan, 1964).Our findings would suggest that this differ- ence may be due to the prevention by citrate of aggregation of platelets, which are then unable to release platelet factor 4.
Lipoprotein(a) and Diabetes: An update
Authors: Steven M Haffner
Journal: Diabetes Care (1993)

On the basis of the available data (much of which is contradictory), I suggest that the following might summarize the role of Lp(a) in diabetes currently. 1. Lp(a) in IDDM: Concentrations are probably elevated. Concentrations are probably related to metabolic control. Concentrations are increased with microalbuminuria. 2. Lp(a) in NIDDM: Concentrations are not elevated. Concentrations do not change with metabolic control. Too few data exist to make an assessment of relation of Lp(a) to microalbuminuria in NIDDM. 3. Lp(a) and CHD in diabetes: Little current evidence shows that Lp(a) is a risk factor for CHD in diabetes. More studies--especially prospective studies with larger numbers of subjects--need to be done.
Effect of Short Call Admission on Length of Stay and Quality of Care for Acute Decompensated Heart Failure
Authors: Jennifer L. Schuberth, Tom A. Elasy, Javed Butler, Robert Greevy, Theodore Speroff, Robert S. Dittus, Christianne L. Roumie
Journal: Circulation (2008)

Background— In response to residency work hour restrictions, programs restructured call schedules, increasing the use of short call (daytime admitting teams). Few data exist on the effect of short call on quality of patient care. Our objective was to examine the effect of short call admission on length of stay and quality of care for patients with acute decompensated heart failure. Methods and Results— We conducted a retrospective cohort study of 218 patients admitted with acute decompensated heart failure to the Nashville VA Medical Center between July 1, 2003, and June 30, 2005. The primary exposure was short call, and the primary outcome was length of stay. The secondary outcomes—diuretic dosing, weight monitoring, and hospital complications—were determined through a combination of administrative data and chart review. Patients admitted to short call had a longer median length of stay than patients admitted to long call (5.2 days [25% to 75%, 3.2 to 8 days] versus 3.9 days [interquartile range, 2.7 to 6.5 days]; P =0.0004). After adjustment for covariates, short call had a 44% increase in length of stay (95% CI, 15 to 80) compared with long call. Short call patients received fewer diuretic doses in the first 24 hours of hospitalization (1.80 versus 2.12; P =0.014) and had a longer median time to the second dose of loop diuretics compared with long call patients (17.9 hours versus 16.2 hours; P =0.044). Conclusions— Admission to short call is predictive of increased length of stay, a decreased number of diuretic doses, and delays in the timing of diuretics among patients with acute decompensated heart failure. Additional studies are needed to clarify the impact of short call admission on inpatient quality of care.
Melatonin, Circadian Rhythms, and Sleep
Authors: Josephine Arendt
Journal: New England Journal of Medicine (2000)

Disturbances in circadian rhythms often result in disturbances in sleep. Examples include syndromes in which sleep time is delayed or advanced, the sleeping problems associated with jet lag and shift work, and the sleep disorders that occur in totally blind persons with free-running circadian rhythms (i.e., rhythms that are not synchronized to the 24-hour day).1 The hormone melatonin can be used both to characterize and to treat such disorders.The circadian rhythm of melatonin secretion is generated by the central pacemaker, or “clock,” in the suprachiasmatic nuclei of the hypothalamus, and like many other circadian rhythms, it is synchronized to . . .
Points: Patient information booklets
Authors: P J M Sloan
Journal: BMJ (1984)

<b>Objectives:</b> To describe the implementation, use of, and outputs from an assault patient questionnaire (APQ) introduced in accident and emergency (A&amp;E) departments to determine Crime &amp; Disorder and Community Safety priorities on Merseyside, a metropolitan county in north west England, UK. <b>Methods:</b> Why and how the APQ was implemented, data collected, and information obtained. The subsequent incorporation of the APQ into the Torex Patient Administration System (PAS) at the Royal Liverpool University Hospital A&amp;E department and its routine completion by trained reception staff. <b>Results:</b> Analysis is based upon anonymised data—for example, patient ID and date of birth information is suppressed. A summary of “baseline” information obtained from the data collected is provided. <b>Conclusions:</b> It is possible for the APQ to be implemented at no extra cost in a large A&amp;E department in an acute general teaching hospital. Valuable intelligence can be obtained for Crime &amp; Disorder Act and Community Safety processes. The APQ forms part of a medium to long term strategy to prevent and reduce violent assaults in the community that subsequently require treatment in an A&amp;E department. Such incidents include assaults both inside and outside licensed premises, attacks by strangers on the street, and domestic violence. Emphasis is also placed upon the feedback of results to staff in A&amp;E departments.
Serum alanine aminotransferase flares during interferon treatment of chronic hepatitis B: Is sustained clearance of HBV DNA dependent on levels of pretreatment viremia?
Authors: Satheesh Nair, Robert P. Perrillo
Journal: Hepatology (2001)

During interferon treatment of chronic hepatitis B, an alanine aminotransferase (ALT) flare may herald a sustained loss of viral replication, but the relationship between virologic response, the extent of a flare, and pretreatment hepatitis B virus (HBV) DNA level has not been defined. We retrospectively examined the impact of an ALT flare on sustained virologic response in 121 interferon-treated patients and 42 untreated controls with either low-level (&lt;100 pg/mL) or high-level (≥100 pg/mL) viremia. The degree of ALT flare was classified as mild (increase in ALT of 86-171 IU/L above baseline), moderate (increase of 172 to 343 IU/L above baseline), and severe (increase of ≥344 IU/L above baseline). Undetectable serum HBV DNA and hepatitis B e antigen (HBeAg) loss were significantly more likely at the end of follow-up in patients having a flare ( P = .0001 and .001, respectively). In the high viremia group, a proportionate increase in virologic response was observed as the degree of flare increased. By multivariate analysis, high baseline HBV DNA, high pretreatment ALT, and both moderate and severe ALT flare were independently predictive of a virologic response with severe flare being the most powerful predictor for a sustained loss of serum HBV DNA (odds ratio, 5.3; P = .004). Severe flare was predictive of a virologic response in the high but not low viremia group. We conclude that a virologic response in patients with high-level viremia is dependent on the degree of ALT flare. Induction of a robust flare may enhance virologic response when high-level viremia is detected.
Comparison of Change in Quality of Care Between Safety-Net and Non–Safety-Net Hospitals
Authors: Rachel M. Werner, L. Elizabeth Goldman, R. Adams Dudley
Journal: JAMA (2008)

Safety-net hospitals (ie, those that predominantly treat poor and underserved patients) often have lower quality of care than non-safety-net hospitals. While public reporting and pay for performance have the potential to improve quality of care at poorly performing hospitals, safety-net hospitals may be unable to invest in quality improvement. As such, some have expressed concern that these incentives have the potential to worsen existing disparities among hospitals.To examine trends in disparities of quality of care between hospitals with high and low percentages of Medicaid patients.Longitudinal study of the relationship between hospital performance and percentage Medicaid coverage from 2004 to 2006, using publicly available data on hospital performance. A simulation model was used to estimate payments at hospitals with high and low percentages of Medicaid patients.Changes in hospital performance between 2004 and 2006, estimating whether disparities in hospital quality between hospitals with high and low percentages of Medicaid patients have changed.Of the 4464 participating hospitals, 3665 (82%) were included in the final analysis. Hospitals with high percentages of Medicaid patients had worse performance in 2004 and had significantly smaller improvement over time than those with low percentages of Medicaid patients. Hospitals with low percentages of Medicaid patients improved composite acute myocardial infarction performance by 3.8 percentage points vs 2.3 percentage points for those with high percentages, an absolute difference of 1.5 (P = .03). This resulted in a relative difference in performance gains of 39%. Larger performance gains at hospitals with low percentages of Medicaid patients were also seen for heart failure (difference of 1.4 percentage points, P = 0.04) and pneumonia (difference of 1.3 percentage points, P <.001). Over time, hospitals with high percentages of Medicaid patients had a lower probability of achieving high-performance status. In a simulation model, these hospitals were more likely to incur financial penalties due to low performance and were less likely to receive bonuses.Safety-net hospitals tended to have smaller gains in quality performance measures over 3 years and were less likely to be high-performing over time than non-safety-net hospitals. An incentive system based on these measures has the potential to increase disparities among hospitals.
A SEARCH FOR THE AFFECTIVE DETERMINANTS OF CHRONIC URTICARIA
Authors: ROBERT J. SHOEMAKER, MACY I. LEVINE, WILLIAM G. SHIPMAN, MARY A. MALLY
Journal: American Journal of Psychiatry (1962)

1. Medical study of 40 patients failed to produce evidence of an allergic mechanism or a causative physical agent in the etiology of their chronic urticaria. 2. Chronic urticaria may be viewed as a regressive, physiological expression of unconscious conflict when previously operating mechanisms of defense have become inadequate to bind strong affect. Anxiety is the dominant affect in this disorder. 3. Regression from a predominate action level of tension discharge to an organ level of expression is dynamically crucial to the formation of chronic urticaria. 4. The prime affective force in chronic urticaria stems from a revival of abandonment fear and companion rage, called up in a state of helplessness engendered by a particular set of life circumstances. 5. The conversion process offers the most satisfactory explanation for the physical reaction of chronic urticaria among the patients in this series.
UK trial of policy of neonatal ECMO provides most reliable information so far
Authors: D. Elbourne, A. Grant, D. Field, C. Skeoch, A. Johnson
Journal: BMJ (1999)

EDITOR—Shann suggests that striking advantages ascribed to extracorporeal membrane oxygenation in the United Kingdom trial of this treatment versus conventional ventilatory management may have been due to “better” care in the extracorporeal membrane oxygenation centres rather than to the treatment itself.1 2 As principal investigators for the trial, we disagree.

The trial was designed to be pragmatic in the sense that, as much as possible, it reflected the then-current clinical policies and practices; results were therefore likely to be applicable outside the trial. In …
PPAR[gamma ]2 gene Pro12Ala polymorphism may influence serum level of an adipocyte-derived protein, adiponectin, in the Japanese population
Authors: Yukihiro Yamamoto, Hiroshi Hirose, Kiichi Miyashita, Kanako Nishikai, Ikuo Saito, Matsuo Taniyama, Motowo Tomita, Takao Saruta
Journal: Metabolism (2002)
Abstract P4-01-05: 3’-deoxy-3’-[18F]fluoro-thymidine (18F-FLT) positron emission tomography (PET): An accurate and effective tool for assessing tumor response in breast cancer
Authors: O Couturier, C Rousseau, J-Y Pierga, A Berriolo-Riedinger, J-L Alberini, S Girault, P Fumoleau, E Brain, S Abadie-Lacourtoisie, P Vera, J-C Liehn, P Olivier, L Uwer, F Cachin, C Sagan, F Bouchet, N Lebas, C Mesleard, E Fourme, A-L Martin, P Lovinfosse, F Lacœuille, M Campone
Journal: Cancer Research (2013)

Abstract Objectives : A French multicenter study was promoted by the national French cancer federation (Unicancer R&amp;D) to assess the potential of [18F]FLT (positron emission tomography (PET) biomarker of proliferation)to manage breast cancer neoadjuvant chemotherapy (NAC). The main objective was to compare changes in tumor [18F]FLT uptake to histopathological changes induced by NAC, assuming an arrest of tumor growth related to the effectiveness of NAC. Methods : 97 patients (age 48.6 +/- 10.2 y.) were included in 13 nuclear medicine centers. All patients were eligible to anthracycline-based NAC for a de novo unifocal breast cancer (ductal n = 84, lobular = 11, other type = 2; stage II n = 75, stage III n = 21 et stage IV n = 1). 90 patients underwent a baseline PET before the onset of NAC (PET1) and a final PET after the end of NAC and before surgery (PET3). PET acquisitions were performed 60±7min after FLT injection. SUVmax (maximum standardized uptake value), SUVpeak (1 cm3 ROI including pixel max) and SUV41 (isocontour 41% of pixel max) were computed. Changes in SUV on PET3 vs PET1 were analyzed in relation to histopathological findings at the end of NAC (Sataloff criteria). Results : Tumor FLT uptake decreased markedly between TEP1 and TEP3 (SUVmax = 6.2±4.8 vs 1.3±1.2 respectively; SUVpeak = 4.6±3.2 vs 0.9±0.9; SUV41 = 3.6±2.8 vs 0.8±0.7). Total or near-total therapeutic effect (grade A) were obtained in 20 patients, more than 50% therapeutic effect but less than total or near-total effect (grade B) in 37 patients, less than 50% therapeutic effect but visible effect (grade C) in 22 patients, or no therapeutic effect (grade D) in 11 patients. SUVmax decreased dramatically (87.5%) to background levels in all patients with a complete response (grade A). Overall, changes in SUV differed depending on the type of histological response (p&amp;lt;0.01) i.e. SUVmax changes were more pronounced as pathological responses were good: 61% for grade D; 65.7% grade C and 69.8% grade B. The same results were obtained with the two other SUV types. Conclusions : Pathologic response to NAC in breast cancer can be assessed accurately by FLT. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-01-05.