tbuckley/cabot-search huggingface dataset:
Ongoing Attention to Injurious Inpatient Falls and Pressure Ulcers
Authors: Joanne Spetz, Diane S. Brown, Carolyn S. Aydin
Journal: JAMA Internal Medicine (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
PLCγ-1 and c-Src mediate epidermal growth factor receptor stimulated head and neck squamous cell carcinoma invasion
Authors: Hiroshi Nozawa, Gina Howell, Qing Zhang, Alan Wells, Jennifer Rubin Grandis, Sufi Mary Thomas
Journal: Cancer Research (2006)

3519   Most head and neck squamous cell carcinoma (HNSCC) tumors rapidly invade the surrounding normal stroma and metastasize to regional and distant lymph nodes. Understanding the molecular mechanisms responsible for the highly invasive nature of HNSCC tumors is vital in developing effective strategies to manage this disease. We previously reported that PLCγ-1 is a mediator of cellular migration and invasion downstream of EGFR where PLCγ-1 modulates HNSCC cell motility but does not affect cell proliferation indicating specificity of function. In addition, we also reported that c-Src plays a role in HNSCC invasion downstream of EGFR. However, the mechanisms whereby EGFR mediates HNSCC invasion via PLCγ-1 and c-Src activation are incompletely understood. The present study was undertaken to test the hypothesis that levels of PLCγ-1 and c-Src are elevated in metastatic tumor compared with levels in primary tumor, we used matched tissues derived from metastatic and primary HNSCC tumors. We found that the expression levels of PLCγ-1 and c-Src were increased in metastatic tumors compared to levels in primary tumors. To test the hypothesis that inhibition of PLCγ-1 or c-Src activation abrogates EGF stimulated HNSCC cell invasion, we used HNSCC cells expressing a dominant-negative PLCγ-1 or c-Src construct for their response to EGF stimulation in Matrigel coated invasion chambers. We found that inhibition of PLCγ-1 or c-Src abrogated EGF stimulated invasion in these cells. To determine the interaction between PLCγ-1 and c-Src in HNSCC cells stimulated with EGF, we carried out immunoprecipitation of PLCγ-1 from EGF stimulated or unstimulated cells followed by immunoblotting for c-Src and PLCγ-1. EGF stimulation increased the association between PLCγ-1 and c-Src in HNSCC cells. Combined inhibition of PLCγ-1 and c-Src resulted in further abrogation of HNSCC cell invasion, using the PLC inhibitor (U73122) and the c-Src family inhibitor (AZD0530). These cumulative results suggest that PLCγ-1 and c-Src activation contribute to HNSCC invasion, interact with each other on EGF stimulation, and combined targeting of both these molecules inhibit HNSCC invasion.
A comparison of fluticasone propionate, 1 mg daily, with beclomethasone dipropionate, 2 mg daily, in the treatment of severe asthma. International Study Group
Authors: NC Barnes, G Marone, GU Di Maria, S Visser, I Utama, SL Payne
Journal: European Respiratory Journal (1993)

We wanted to compare the efficacy and safety of fluticasone propionate, a new topically active inhaled corticosteroid, to that of high dose beclomethasone dipropionate, in severe adult asthma. Patients currently receiving between 1.5-2.0 mg.day-1 of an inhaled corticosteroid were treated for six weeks in a double-blind, randomized, parallel group study with 1 mg.day-1 fluticasone propionate (n = 82), or 2 mg.day-1 beclomethasone dipropionate (n = 72). Mean morning peak expiratory flow rates (PEFR) increased from 303 to 321 l.min-1 with fluticasone propionate, and from 294 to 319 l.min-1 with beclomethasone dipropionate. There was an increase in evening PEFR, asthma symptoms improved, and rescue beta 2-agonist use decreased for both treatment groups. None of these differences between treatments were statistically significant. However, diurnal variation was significantly reduced with fluticasone propionate, when compared with beclomethasone dipropionate (difference = 7 l.min-1; p = 0.038). Clinic lung function also improved with both treatments and, apart from % predicted PEFR, which showed no difference after beclomethasone dipropionate but increased from 73 to 78% with fluticasone propionate, there were no differences between treatments. Forced expiratory volume in one second (FEV1) increased with both treatments. The geometric mean plasma cortisol concentration rose after treatment with fluticasone propionate (from 293 to 309 nmol.l-1) and fell after beclomethasone dipropionate (from 256 to 224 nmol.l-1); the difference between treatments was significant. The incidence of adverse events was low in both treatment groups. In conclusion, 1 mg.day-1 fluticasone propionate was as effective as 2 mg.day-1 beclomethasone dipropionate in the control of severe asthma.(ABSTRACT TRUNCATED AT 250 WORDS)
Caspofungin for the treatment of candidaemia in patients with haematological malignancies
Authors: L. Pagano, L. Fianchi, R. Fanci, A. Candoni, M. Caira, B. Posteraro, M. Morselli, C.G. Valentini, G. Farina, M.E. Mitra, M. Offidani, M. Sanguinetti, M.E. Tosti, A. Nosari, G. Leone, P. Viale
Journal: Clinical Microbiology and Infection (2009)
A Novel Chromosomal Translocation t(4; 14)(p16.3; q32) in Multiple Myeloma Involves the Fibroblast Growth-Factor Receptor 3 Gene
Authors: Raffaella Richelda, Domenica Ronchetti, Luca Baldini, Lilla Cro, Luigi Viggiano, Rosalia Marzella, Mariano Rocchi, Takemi Otsuki, Luigia Lombardi, Anna Teresa Maiolo, Antonino Neri
Journal: Blood (1997)
Abstract #5678: Overexpression of ALK correlates with poor prognosis neuroblastoma patients regardless of activating mutations
Authors: Luca Longo, Paola Collini, Andrea Gregorio, Claudio Gambini, Alberto Garaventa, Vito Pistoia, Federica Del Grosso, Raffaella Defferrari, Marilena De Mariano, Gian Paolo Tonini, Mangeng Cheng, Andrea Anichini, Franca Fossati-Bellani, Roberto Luksch, Lorena Passoni
Journal: Cancer Research (2009)

ALK (Anaplastic Lymphoma Kinase) is a receptor tyrosine kinase mainly expressed in fetal neuronal tissues that likely plays a role in neuronal differentiation. Activating mutations in the tyrosine kinase domain were recently identified as predisposing to familial neuroblastoma (NB) and associated with high risk patients indicating ALK as a crucial oncogene in NB. To gain more insights into the oncogenic potential and clinical relevance of ALK, we sought for a correlation between ALK genetic alterations, protein expression/activation and clinical outcome both in a panel of 17 NB cell lines expressing different protein levels and in 82 NB patients. Our results showed ALK constitutive activation in NB cell lines with high levels of ALK protein, regardless of its mutational status. Conversely, no activation was observed in NB cell lines with low expression of ALK protein. Treatment with small molecule ALK inhibitor CEP-14083 (60nM) induced growth arrest and cell death in NB cells overexpressing both wild-type (wt) and mutated ALK but not in NB cells expressing low amount of ALK (average viability: ALKhigh, 12,8%; ALKlow, 73%, CI= 37 to 83% P   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5678.
Psychological stress and cardiovascular disease
Authors: M. Hotopf
Journal: BMJ (2002)

Editor—Macleod et al's paper on stress and cardiovascular disease tells us two things.1 Firstly, the Rose angina questionnaire rather inconveniently does not just measure angina in the sense understood by cardiologists.2 Instead it measures chest pain as understood by everyone else.

Most cases of chest pain in the general population are not due to heart disease, and even in middle aged Scottish men the prevalence of coronary heart disease is low, so the positive predictive value of the Rose questionnaire will be poor.3 The relation between stress and chest pain that the questionnaire measures is only a “bias” in as much as it does not fit into the view of cardiovascular epidemiologists. The effect is real (and has important clinical implications to cardiologists) in that the Rose questionnaire is a superb measure of anxiety in young people but will mislead those who interpret its results too credulously.3 The effect probably accounts for anomalies such as the higher rates of angina in women despite their lower rates of coronary heart disease.4

The second thing the paper tells us is that a weak measure of stress is a poor predictor of cardiovascular events many years later. Contrary to the statement in “This week in the BMJ,” the findings of the study do not do much to “cast doubt over the associations between psychosocial measures and disease outcomes.”

Many studies indicate a higher mortality for people with depression and other psychiatric disorders.5 Though there may be important residual confounders (or explanatory pathways) to explain these effects, they still need explaining.
Increased uric acid levels in bronchoalveolar lavage fluid of mice infected with H1N1 influenza
Authors: Maria Kuipers, Maria Hegeman, Hamid Aslami, Geartsje Jongsma, Catharina Wieland, Marcus Schultz, Koenraad van der Sluijs
Journal: European Respiratory Journal (2011)

Rationale: Lower respiratory tract infections with influenza are associated with severe inflammatory responses, which may result in ALI/ARDS. Tissue injury results in the release of damage-associated molecular patterns (DAMPs), such as uric acid and ATP, leading to NLRP3/inflammasome activation and IL-1β release.

Hypothesis: We hypothesized that influenza-induced lung injury is associated with the release of DAMPs into the airway lumen.

Methods: C57Bl/6 mice were inoculated with 10TCID50 influenza A/PR/8/34 (H1N1) and sacrificed 4, 8 and 14 days later to collect BALF to determine uric acid, extracellular ATP and markers of inflammation and lung injury. Non-infected mice were sacrificed on day 0 for control measurements.

Results: Influenza virus infection resulted in bodyweight loss between day 6 and day 11 (p<0.05) and returned to normal values on day 14 after infection. Uric acid levels in BALF were significantly increased on day 8 after viral infection (52.7-115.9 μM vs 12.2-25.8 μM in control mice, 95% CI, p<0.01), while ATP was undetectable. Uric acid in BALF was associated with increased levels of inflammatory markers (IL-6, KC and IFN-γ) as well as markers of lung injury (sRAGE and total protein in BALF). However, increased IL-1β levels, indicative for inflammasome activation, were only observed on day 4 after influenza infection (p<0.01).

Conclusion: Uric acid in BALF is increased during influenza infection and associates with biomarkers of inflammation and lung injury, but not with markers of inflammasome activation. Whether uric acid fails to activate NLRP3/inflammasome or that IL-1β is scavenged by IL-1 receptor antagonist during influenza infection remains to be determined.
Demystifying neurology
Authors: M. Menken
Journal: BMJ (2002)

See Reviews p 1528 

Muhammad Ali, Dudley Moore, Ronald Reagan, and Christopher Reeve have in common that they suffered from degenerative and traumatic disorders of the nervous system, the prevalence of which will increase greatly during the next 20 years.1 Although neurological and psychiatric disorders account for only 1.4% of all deaths, they account for a remarkable 28% of all years of life lived with a disability. Thus all doctors must be prepared to meet the needs of patients with such disorders and refer appropriately for specialised care and investigations, bearing in mind that neurologists often function as consultants for other physicians. Yet do medical students and house officers believe they are being adequately prepared for independent practice, and do general doctors have confidence in their ability to diagnose and treat patients with disorders of the nervous system?

Apparently not. Schon et al …
Abstract 18699: Negative Predictive Value of Transthoracic Echocardiography for Infective Endocarditis in the Modern Era
Authors: Joseph A Sivak, Amit N Vora, Ann Marie Navar-Boggan, Anna L Crowley, Joseph Kisslo, Eric J Velazquez, Zainab Samad
Journal: Circulation (2014)

BACKGROUND: Transesophageal echocardiography (TEE) is often recommended to exclude infective endocarditis (IE) in patients presenting with bacteremia despite a negative transthoracic echocardiogram (TTE). Previous studies showing inadequate sensitivity of TTE for native valve endocarditis are dated, and do not reflect modern advances in ultrasound image optimization technology. We hypothesized that with current generation echocardiography technology, a TTE absent mobile echo targets and without significant valvular abnormalities would have sufficient negative predictive value to exclude IE. METHODS: The Duke Echocardiographic Database was queried from 1/1/2007 [[Unable to Display Character: &amp;#8211;]] 2/28/2014 for TTEs performed within 7 days prior to a TEE ordered for bacteremia/endocarditis. The dominant imaging platform used for both TTE and TEE during this era was the Philips IE33, with frequent use of fundamental frequencies to enhance spatial resolution beyond that of harmonic imaging alone. TTE studies identified as having poor sound transmission were excluded. A normal TTE was defined by the demonstration of normal cardiac anatomy, at most trivial valvular regurgitation, and absence of valvular stenosis, mobile/oscillating echo targets on valves, and hardware including catheters. The demonstration of an oscillating target on TEE along with clinical criteria based on chart review defined IE. RESULTS: A total of 974 unique patients had a TTE followed by a TEE within a week. IE was suggested in 209 of these patients by TEE. Among 107 patients meeting the a priori normal criteria on TTE, 3 patients had an abnormal TEE consistent with IE. These results correspond to a negative predictive value (NPV) of 97.2% (95% C.I. 91.4% - 99.3%) for a normal TTE to exclude IE. CONCLUSIONS: In this retrospective analysis from an academic medical center echocardiography laboratory, we demonstrated that an adequate quality TTE alone in a patient with a structurally normal heart without indwelling hardware has a high NPV for IE. Current TTE image optimization approaches may obviate the need to pursue TEE in patients after a recent preceding normal TTE.
Low dosage tricyclic antidepressants in depression
Authors: H. M Jones
Journal: BMJ (2003)

# Giving low dose tricyclics is not justified by evidence {#article-title-2} EDITOR—The meta-analysis by Furakawa et al must be considered downright naughty.1 While masquerading as a contribution to an academic debate about appropriate antidepressant treatment it actually does little more than endorse the widely held prejudice in favour of using low dose tricyclics in depression. Published in a widely read UK general medical journal, it will inevitably encourage a practice that is not encouraged by either the Royal College of Psychiatrists or the American Psychiatric Association. The subject of optimal dosage of tricyclics remains controversial, but the value of treatment with tricyclic antidepressants at standard dosage compared with placebo is abundantly clear. As Furakawa et al concede but perhaps do not emphasise sufficiently, the evidence for low dose tricyclic antidepressants is of generally poor quality. Many of the trials used in their analysis took place before standardised diagnostic or outcome criteria were commonplace. What is less clear is the motivation for their undertaking. Fluoxetine is now available in generic preparations for about £7 per month, significantly reducing the financial advantage of older antidepressants. Some evidence supports the use of tricyclics in severe depression, but presumably the authors would not recommend low dose tricyclics in such patients. The chronic severe nature of depression would make it unethical to recommend a treatment without a secure evidence base. Being charitable, one can only hope that the therapeutic advice was added to add colour to an otherwise unexceptional meta-analysis. 1. 1.↵1. Furukawa AT, 2. McGuire H, 3. Barbui C . Meta-analysis of effects and side-effects of low dosage tricyclics antidepressants in depression: systematic review. BMJ 2002; 325: 991–995 [OpenUrl][1][Abstract/FREE Full Text][2] # Evidence to change current guidelines is insufficient {#article-title-4} EDITOR—The study by Furukawa et al consists of two separate analyses looking at quite different things so it is difficult to draw any firm conclusions.1 The first meta-analysis of 35 … [1]: {openurl}?query=rft.jtitle%253DBMJ%26rft.stitle%253DBMJ%26rft.issn%253D0007-1447%26rft.aulast%253DFurukawa%26rft.auinit1%253DT.%2BA%26rft.volume%253D325%26rft.issue%253D7371%26rft.spage%253D991%26rft.epage%253D991%26rft.atitle%253DMeta-analysis%2Bof%2Beffects%2Band%2Bside%2Beffects%2Bof%2Blow%2Bdosage%2Btricyclic%2Bantidepressants%2Bin%2Bdepression%253A%2Bsystematic%2Breview%26rft_id%253Dinfo%253Adoi%252F10.1136%252Fbmj.325.7371.991%26rft_id%253Dinfo%253Apmid%252F12411354%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=ABST&journalCode=bmj&resid=325/7371/991&atom=%2Fbmj%2F326%2F7387%2F499.2.atom
Prognostic Value of Stress Myocardial Perfusion Positron Emission Tomography
Authors: Sharmila Dorbala, Marcelo F. Di Carli, Rob S. Beanlands, Michael E. Merhige, Brent A. Williams, Emir Veledar, Benjamin J.W. Chow, James K. Min, Michael J. Pencina, Daniel S. Berman, Leslee J. Shaw
Journal: Journal of the American College of Cardiology (2012)
Abstract 13041: An Updated Meta-Analysis and Meta-Regression of Niacin in Cardiovascular Prevention
Authors: Daniel Siniawski, Walter Masson, Cesar Belziti
Journal: Circulation (2014)

Introduction:  AIM-HIGH trial and Heart Protection Study 2 (HPS 2) THRIVE failed to demonstrate a significant reduction in cardiovascular (CV) events when niacin was added to statins (with or without ezetimibe) in high risk patients that achieved low cholesterol levels. These results were discordant with previous randomized trials and meta-analyses that showed the clinical benefit of niacin as monotherapy or combined to lipid-lowering therapy.   Hypothesis:  The purpose of this meta-analysis was to assess the efficacy of niacin for reducing cardiovascular events, adding clinical data from the Harvard Atherosclerosis Reversibility Project (HARP) and HPS 2 THRIVE to revised outcomes of trials included in two previous meta-analyses.   Methods:  Odds ratios (ORs) for four cardiovascular disease endpoints were calculated with a random-effects meta-analysis. Random meta-regression analyses were done to model the relationship between differences in on-treatment low-density cholesterol (LDL-C) and high-density cholesterol (HDL-C) and the size of effect of niacin on CV risk.   Results:  Thirteen eligible trials, including 35,723 subjects were identified. Niacin use was associated with a significant reduction in the composite endpoints of any CV event (OR: 0.73; 95% CI: 0.59 to 0.89; p=0.003; I2 =65%), major coronary heart disease events (OR: 0.80; 95% CI: 0.65 to 0.98; p=0.03; I2 =54%) and any revascularization (OR: 0.59; 95% CI: 0.40 to 0.86; p=0.006; I2 = 58%). No significant association was observed between niacin therapy and stroke incidence (OR: 0.93; 95% CI: 0.70 to 1.24; p=0.64). Meta-regression analysis showed no significant relationship between the difference in on-treatment HDL-C and the natural log-adjusted OR for any CV event (p =0.36). The relationship between the amount of on-treatment LDL-C difference between arms and the effect of niacin on outcomes showed a positive trend that did not reach statistical significance.   Conclusions:  This meta-analysis strongly suggests that niacin reduces CV events and that this may occur through a mechanism not reflected by changes in HDL-C and not fully explained by LDL-C reduction. Niacin could be useful for CV prevention in patients who do not respond adequately to intensive doses of statins.
Abstract 5045: Characterization of estrogen receptor alpha phosphorylation sites as a marker for tamoxifen resistant breast cancer
Authors: Wayne A. Speckmann, Robert Brockett, Chun Yang, Chandra Mohan, Kevin Long, Michele Hatler, Xiaoyi Xu
Journal: Cancer Research (2015)

Abstract A major focus of breast cancer research is to understand the mechanisms responsible for disease progression and drug resistance. Most treatment options target endocrine therapy, however, the processes that modulate these signaling pathways are poorly understood. Here, we seek to gain additional understanding about the phosphorylation status of the estrogen receptor as it relates to tamoxifin drug treatment. Tamoxifen, a selective ER inhibitor, was the first targeted breast cancer therapy developed. Unfortunately, tamoxifen therapy was shown to be ineffective for certain kinds of cancers and even in affected tumors an acquired resistance was eventually seen. Previous research has shown that the estrogen receptor protein is phosphorylated at more than 20 different sites and some of these sites are linked with poor prognosis in tamoxifen treated patients. For example, phosphorylation at the S305 site may lead to an activation of ERα and to transcription of ERα-responsive gene after tamoxifen treatment, leading to tamoxifen resistance. In addition, other phosphorylation sites have also been found to correlate with poor prognosis of tamoxifen treated patients. Thus, differential phosphorylation of ERα may serve as a biomarker to identify patients unlikely to respond to tamoxifen treatment. Here, utilizing a newly developed medium throughput IHC test system we have interrogated multiple sites of ERα for phosphorylation status by screening an extensive panel of different breast cancer patient samples and other non-breast cancer tissue microarray (TMA) samples. These patient samples were classified according to their clinical grade (ER positive or negative, Her2, progesterone positive or negative, and Ki67 index) and tamoxifen treatment and then screened for their ERα phosphorylation status. The results show unique staining patterns depending upon the tumor classification and conclusions about the utilization of this information as a potential for diagnostic applications will be discussed. Citation Format: Wayne A. Speckmann, Robert Brockett, Chun Yang, Chandra Mohan, Kevin Long, Michele Hatler, Xiaoyi Xu. Characterization of estrogen receptor alpha phosphorylation sites as a marker for tamoxifen resistant breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5045. doi:10.1158/1538-7445.AM2015-5045