tbuckley/cabot-search huggingface dataset:
Abstract 1793: Imatinib treatment for gefitinib-resistant lung cancer harboring epidermal growth factor receptor mutation
Authors: Tatsuro Fukuhara, Cezary Jan Treda, Tomohiro Sakakibara, Akira Inoue, Masahito Ebina, Toshihiro Nukiwa
Journal: Cancer Research (2012)

Abstract Background: Epidermal growth factor receptor (EGFR) mutant-lung cancer showed significant response to EGFR-tyrosine kinase inhibitor (TKI) treatment, however, treatment failure due to acquired resistance to EGFR-TKI become important clinical problem for long-term survivors. Our purpose is to develop the new treatment for EGFR-TKI resistance. Methods: We used PC9 human lung cancer cell line harboring EGFR exon 19 deletion (E746-A750). When PC9 cells were cultured with 2 μM gefitinib solved in dimethylsulfoxide (DMSO), most of cells died and surviving cells proliferated slowly. By 90 days-culture with 2 μM gefitinib, PC9 gefitinib resistant cells (PC9GR90) were established and confirmed that EGFR-T790M resistance-related mutation was negative. In PC9GR90, an immunoblot assay revealed MET (hepatocyte growth factor receptor) amplification and alternative EGFR3 tyrosine phosphorylation, which is known as one of the major resistant mechanisms. Results: When PC9GR90 were cultured with 2 μM gefitinib and one inhibitor (histone deacetylase inhibitor, insulin-like growth factor receptor inhibitor, gamma secretase inhibitor, or imatinib known as bcr-abl, c-kit and platelet derived growth factor receptor inhibitor), 10 μM imatinib treatment with gefitinib showed significant suppression of cell growth. The ratio of cell count of 2 μM gefitinib/DMSO and 10 μM imatinib with 2 μM gefitinib/DMSO were 91.7% and 6.0%, respectively. When imatinib concentration was decreased to 1 μM known as appropriate concentration for chronic myeloid leukemia treatment, there was no effect. The imatinib effect was not shown for NCI-H1975 lung cancer cells harboring both EGFR-L858R and -T790M. By immunoblot, we found EGFR3 phosphorylation was inhibited by imatinib treatment. Conclusion: It is the first report that imatinib inhibits EGFR3 phophorylation and induce cell death in the EGFR-TKI resistant lung cancer with MET amplification and EGFR3 phophorylation. Although further studies are required to apply this strategy to a clinical setting, we demonstrate a hopeful data to conquer one important resistant mechanism. 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 1793. doi:1538-7445.AM2012-1793
The Role of Radiotherapy and Radioactive Phosphorus (32P)
Authors: John Storaasli
Journal: JAMA (1969)

ABSTRACT Little attention has been given to the beneficial results of radiation therapy in the treatment of localized carcinoma of the prostate or for palliative treatment of patients with metastatic disease,29,30 in contrast to orchiectomy or the administration of estrogenic hormones.31 The majority succumbing to the disease will ultimately exhibit clinical evidence of osseous metastases, and almost invariably, the symptomatic relief of pain becomes important. Patients in whom the diagnosis of carcinoma of the prostate was made even after the appearance of metastases have a median survival of three years with proper treatment.31 In fact, it is not uncommon to see patients who have had extensive osseous involvement of more than five years' duration. Although prolongation of life does not occur, the judicious use of radiation therapy can play an important part in improving the life of the patient by alleviating pain.A survey of the recent literature
Coordinate gene expression during neonatal rat heart development. A possible role for the myocyte in extracellular matrix biogenesis and capillary angiogenesis
Authors: G. L Engelmann
Journal: Cardiovascular Research (1993)

Objective: Neonatal heart development is a period of active extracellular matrix deposition and capillary angiogenesis which follows the cessation of ventricular myocyte proliferation The aim was to determine whether coordinate expression of growth factors by the ventricular myocyte could function to inhibit myocyte proliferation directly as well as indirectly by paracrine stimulation of non-myocyte extracellular matrix deposition and capillary angiogenesis. Methods: Immunohistochemistry and northern blot hybridisations were performed on ventricular samples from fetal to mature animals of the spontaneously hypertensive (SHR) and normotensive control Wistar Kyoto (WKY) strains. Results: Ventricular expression of types I, III, and IV collagen genes reached their "maximum" within the first 2-3 postnatal weeks and then rapidly declined. Expression of TGFβ3 and SPARC were found to precede and accompany the changes in extracellular matrix gene expression during this same developmental period. TGFβ3 was immunolocalised to fetal cardiomyocytes with very limited expression in neonatal/adult non-myocytes. Associated with the neonatal expression of TGFβ variants, transcripts for the type 2 IGF receptor gradually declined over the first three postnatal weeks. Myocyte TGFβ gene expression, latent TGFβ release, and paracrine mechanisms of action could be facilitated by residual type 2 IGF receptor expression to help mediate stimulation of non-myocyte extracellular matrix synthesis and deposition. Conclusions: Expression of select growth factors, growth factor receptors, and components of the extracellular matrix appear to be highly coordinated during ventricular remodelling which occurs during neonatal heart development. A paradigm is presented which integrates the expression patterns of various myocyte derived stimuli and their postulated impact on formation of the structural components of the neonatal heart by modulation of myocyte and non-myocyte cell types. Abbreviations used: TGFβ=transforming growth factor-beta; SPARC=Secreted Protein, Acidic and Rich in Cysteine; FGF=fibroblast growth factor; Flg=fibroblast growth factor receptor-1; IGF=insulin-like growth factor. Cardiovascular Research 1993;27:1598-1605
Cellular and molecular actions of Methylene Blue in the nervous system
Authors: Murat Oz, Dietrich E. Lorke, Mohammed Hasan, George A. Petroianu
Journal: Medicinal Research Reviews (2009)

Abstract Methylene Blue (MB), following its introduction to biology in the 19th century by Ehrlich, has found uses in various areas of medicine and biology. At present, MB is the first line of treatment in methemoglobinemias, is used frequently in the treatment of ifosfamide‐induced encephalopathy, and is routinely employed as a diagnostic tool in surgical procedures. Furthermore, recent studies suggest that MB has beneficial effects in Alzheimer's disease and memory improvement. Although the modulation of the cGMP pathway is considered the most significant effect of MB, mediating its pharmacological actions, recent studies indicate that it has multiple cellular and molecular targets. In the majority of cases, biological effects and clinical applications of MB are dictated by its unique physicochemical properties including its planar structure, redox chemistry, ionic charges, and light spectrum characteristics. In this review article, these physicochemical features and the actions of MB on multiple cellular and molecular targets are discussed with regard to their relevance to the nervous system. © 2009 Wiley Periodicals, Inc. Med Res Rev, 31, No. 1, 93–117, 2010
Authors' reply to Ellis and Yates
Authors: N. Kapur, T. Kendall, C. Taylor, M. Chan, H. Bhatti
Journal: BMJ (2012)

Ellis and Yates highlight the recommendations on risk scales.1 2 3 A central question is whether healthcare professionals should be able to accurately predict adverse outcomes after self harm. The literature review carried out for the guideline suggests that this is not a realistic aim.4 After a first self harm episode, most people will not repeat self harm or die by suicide.5 Identifying those who will have a poor outcome …
Extracorporeal membrane oxygenation for severe influenza A (H1N1) acute respiratory distress syndrome: a prospective observational comparative study
Authors: Antoine Roch, Renaud Lepaul-Ercole, Dominique Grisoli, Jacques Bessereau, Olivier Brissy, Matthias Castanier, Stephanie Dizier, Jean-Marie Forel, Christophe Guervilly, Vlad Gariboldi, Frederic Collart, Pierre Michelet, Gilles Perrin, Remi Charrel, Laurent Papazian
Journal: Intensive Care Medicine (2010)
Reduced expression of the prostaglandin E2 receptor E-prostanoid 2 on bronchial mucosal leukocytes in patients with aspirin-sensitive asthma
Authors: Chris J. Corrigan, Rahilya L. Napoli, Qiu Meng, Cailong Fang, Huifen Wu, Keri Tochiki, Victoria Reay, Tak H. Lee, Sun Ying
Journal: Journal of Allergy and Clinical Immunology (2012)
Experts Explore Emerging Information Technologies' Effects on Medicine
Authors: Andrew A. Skolnick
Journal: JAMA (1996)

MOST PEOPLE probably don't realize it, but Congress has just passed the most significant health care system reform legislation since the Medicare programs and Medicaid were adopted back in the 1960s, says former US Surgeon General C. Everett Koop, MD, ScD. Speaking at a University of Vermontsponsored conference on emerging information technologies in Burlington, Koop said that the telecommunications bill just signed into law is likely to do more to change the US health care system than has anything within the last generation. "In the past few years, as I have spoken around the nation about health care reform and telecommunication," said the former surgeon general, who is now director of the C. Everett Koop Institute at Dartmouth, Hanover, NH, "I have implied that health care reform is going to force us to change the way we exchange information in the health care system. But now we are going to
ACUTE TOTAL VOLVULUS OF THE STOMACH
Authors: MAX THOREK
Journal: JAMA (1923)

Volvulus of the stomach is rare. The first case was reported by Berti 1 in 1866. Berti's case was a total volvulus found at necropsy.  The first reported case in which operation was performed was that of Berg, 2 in 1895. Berg reported two cases, one of a total, the other a partial, volvulus. Since then, several total and partial cases have been reported, the partial being the more common.  Kocher, 3 who in 1914 reported a case of total idiopathic volvulus of the stomach in a woman, aged 53, found twenty-eight cases in the literature. Cases of total volvulus have since been reported by Niosi 4 and Siegel, 5 the latter case being in a child, aged 2 years.  REPORT OF CASE  I have recently observed and operated in the case of volvulus here reported:  History.  —Mrs. A. P., a widow, aged 77, had pneumonia during 1895 and again
Allied Health Manpower — Solution or Problem?
Authors: Anthony Robbins
Journal: New England Journal of Medicine (1972)

Abstract Although there are over 3 1/2 million health workers in the United States, effective use of these workers is compromised by several factors. Manpower analysis and inventories have produced an inappropriate concern with numbers rather than with actual job content, flexibility and development. Decisions about manpower have too often been influenced by physicians, who are more aware of individual rather than broad institutional needs. The customs of the health professions and licensure and certification rules have combined to leave administrators little leeway to manipulate the work force. If nonphysician medical manpower is to improve the health system, tasks rather than numbers must be studied, management must be given more authority, and professionalism must be curtailed.
Inorganic nitrate and nitrite and control of blood pressure
Authors: Mark Gilchrist, Angela C. Shore, Nigel Benjamin
Journal: Cardiovascular Research (2010)

Continual nitric oxide (NO) synthesis is important in the regulation of vascular tone and thus blood pressure. Whereas classically NO is provided by the enzymatic oxidation of l-arginine via endothelial NO synthase, it is now clear that NO can also be generated in mammals from the reduction of nitrite and nitrate. Thus inorganic nitrate derived either from NO oxidation or from dietary sources may be an important storage form of reactive nitrogen oxides which can be reduced back to nitrite and NO when physiologically required or in pathological conditions. The very short half-life of NO and the ready availability of stored nitrite and nitrate make for a very sensitive and responsive blood pressure control system. This review will examine processes by which these storage forms are produced and how augmentation of dietary nitrate intake may have a beneficial effect on blood pressure and other vascular function in humans.
Serum lipoprotein(a) levels before and after subtotal thyroidectomy in subjects with hyperthyroidism
Authors: Kyosuke Yamamoto, Iwata Ozaki, Noriko Fukushima, Yoichi Setoguchi, Susumu Kajihara, Toshihiko Mizuta, Teruyoshi Yanagita, Takahiro Sakai
Journal: Metabolism (1995)
Arginine dependence of acute myeloid leukemia blast proliferation: a novel therapeutic target
Authors: Francis Mussai, Sharon Egan, Joseph Higginbotham-Jones, Tracey Perry, Andrew Beggs, Elena Odintsova, Justin Loke, Guy Pratt, Kin Pong U, Anthony Lo, Margaret Ng, Pamela Kearns, Paul Cheng, Carmela De Santo
Journal: Blood (2015)
Unusually Intense FDG Uptake in a Hypertrophied Adenoid
Authors: Yen-Kung Chen, Rayleigh Ping-Ying Chiang, Chung-Huei Hsu
Journal: Clinical Nuclear Medicine (2007)

The adenoids, or pharyngeal tonsils, are located in the posterior aspect of the midline of the roof of the nasopharynx. The lingual (floor), pharyngeal (roof), and palatine (lateral) tonsils compose the bulk of the lymphoid tissue of Waldeyer's ring. They play important roles in host defense against locally invading pathogens and induction of secretory immunity for upper respiratory tract infections. Intense uptake of 18-fluoro-2-deoxyglucose (FDG) in the adenoids is seldom found in adults. A 34-year-old woman who had chronic sinusitis and acute rhinitis at presentation underwent an FDG-positron emission tomographic (PET) study for a whole-body cancer screening. The PET images revealed focally intense uptake of FDG in the adenoids. A coregistered CT scan also revealed a soft tissue lesion in the corresponding region and vegetation of the adenoids were identified by an ear, nose and throat doctor. After symptomatic treatment and follow up for over 1 year, no malignancy was detected.
Derivation and validation of a risk adjustment model for predicting seven day mortality in emergency medical admissions: mixed prospective and retrospective cohort study
Authors: S. Goodacre, R. Wilson, N. Shephard, J. Nicholl
Journal: BMJ (2012)

<b>Objectives</b> To derive and validate a risk adjustment model for predicting seven day mortality in emergency medical admissions, to test the value of including physiology and blood parameters, and to explore the constancy of the risk associated with each model variable across a range of settings. <b>Design</b> Mixed prospective and retrospective cohort study. <b>Setting</b> Nine acute hospitals (n=3 derivation, n=9 validation) and associated ambulance services in England, Australia, and Hong Kong. <b>Participants</b> Adults with medical emergencies (n=5644 derivation, n=13 762 validation) who were alive and not in cardiac arrest when attended by an ambulance and either were admitted to hospital or died in the ambulance or emergency department. <b>Interventions</b> Data were either collected prospectively or retrospectively from routine sources and extraction from ambulance and emergency department records. <b>Main outcome measure</b> Mortality up to seven days after hospital admission. <b>Results</b> In the derivation phase, age, ICD-10 code, active malignancy, Glasgow coma score, respiratory rate, peripheral oxygen saturation, temperature, white cell count, and potassium and urea concentrations were independent predictors of seven day mortality. A model based on age and ICD-10 code alone had a C statistic of 0.80 (95% confidence interval 0.78 to 0.83), which increased to 0.81 (0.79 to 0.84) with the addition of active malignancy. This was markedly improved only when physiological variables (C statistic 0.87, 0.85 to 0.89), blood variables (0.87, 0.84 to 0.89), or both (0.90, 0.88 to 0.92) were added. In the validation phase, the models with physiology variables (physiology model) and all variables (full model) were tested in nine hospitals. Overall, the C statistics ranged across centres from 0.80 to 0.91 for the physiology model and from 0.83 to 0.93 for the full model. The rank order of hospitals based on adjusted mortality differed markedly from the rank order based on crude mortality. ICD-10 code, Glasgow coma score, respiratory rate, systolic blood pressure, oxygen saturation, haemoglobin concentration, white cell count, and potassium, urea, creatinine, and glucose concentrations all had statistically significant interactions with hospital. <b>Conclusion</b> A risk adjustment model for emergency medical admissions based on age, ICD-10 code, active malignancy, and routinely recorded physiological and blood variables can provide excellent discriminant value for seven day mortality across a range of settings. Using risk adjustment markedly changed hospitals' rankings. However, evidence was found that the association between key model variables and mortality were not constant. Supplementary data appendix
Hypothermic arrest and potassium arrest: metabolic and myocardial protection during elective cardiac arrest.
Authors: D J Hearse, D A Stewart, M V Braimbridge
Journal: Circulation Research (1975)

Hypothermic arrest, potassium arrest, and ischemic arrest, either singly or in combination, with or without coronary perfusion were studied in an isolated perfused rat heart preparation. Procedures that permitted the maintenance of high cellular levels of adenosine triphosphate (ATP) and creatine phosphate during arrest, e.g., coronary perfusion with hypothermic solutions or solutions containing 16.0 mM potassium, produced a fully reversible arrest with complete cardiac recovery. Cardiac arrest and coronary flow were related to the degree of hypothermia and the concentration of potassium in the coronary perfusate, and the minimum conditions required to induce complete cardiac arrest were ascertained. The effects of hypothermia and potassium were additive; total cardiac arrest could be obtained by combining small evaluations of potassium with moderate hypothermia. Under these conditions, cellular high-energy phosphates were maintained, and complete recovery was possible. Under conditions in which arrest was obtained without maintaing coronary perfusion, e.g., ischemic arrest, cellular high-energy phosphates declined rapidly, and the hearts exhibited poor recoveries. Some protection could be afforded to the ischemic myocardium by topical hypothermia or by combining the ischemia with potassium arrest. In both instances, ATP and creatine phosphate were maintained at higher levels, and improved recoveries were observed.
A Piece of My Mind: A Collection of Essays From The Journal of the American Medical Association
Authors: Tony Miksanek
Journal: JAMA (1989)

<i>A Piece of My Mind</i>is a collection of 80 offerings selected from the weekly column of the same name that has animated the pages of<i>JAMA</i>and aroused its readers since 1980. The content of these diverse stories varies from whimsical to profound, and they evoke feelings that span inspirational to hysterical. These narratives, however, are fused by their stark medical realism, and whether the setting is Vietnam, a pediatric emergency room, an ICU, or a doctor's office, it is apparent that the authors have labored in the trenches of medicine. Their special experiences have engendered these stories. In poignant paragraphs, doctors share their search for the soul of medicine and, perhaps not surprisingly, discover it is prismatic. Where one physician finds meaning through running "in a cloud of memories of failures, of lost lives and abandoned hopes," another doctor uncovers fulfillment "from the sudden intimacies with total strangers."
Delay in transition from segmental contraction to relaxation activity (TT) reliably predicts changes in myocardial perfusion during dobutamine stress
Authors: Gabriel W.K. Yip, Bijoy Khandheria, Cristina Pislaru, Peter Anagnostopoulos, Marek Belohlavek, Patricia Pellikka, James Seward, Theodore P. Abraham
Journal: Journal of the American College of Cardiology (2003)
Libel threat delays UK publication of book on campaigns against vaccines
Authors: C. Dyer
Journal: BMJ (2011)

<h3>Objective</h3> To assess the variation in bleeding risk estimates and risk stratification among Web and mobile applications for patients with atrial fibrillation. <h3>Design</h3> Cross-sectional study. <h3>Setting</h3> Simulated patient population. <h3>Participants</h3> Hypothetical patient cohorts that encompassed all possible binary risk factor combinations for each clinical prediction model. <h3>Interventions</h3> Twenty-five bleeding risk calculators (18 Web and 7 mobile apps), each of which used 1 of 4 clinical prediction models to predict an individual’s 12-month bleed risk: ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation), HAS-BLED (hypertension [systolic blood pressure &gt;160 mm Hg], abnormal renal or liver function, stroke [caused by bleeding], bleeding, labile international normalized ratio, elderly [age &gt;65 years], drugs [acetylsalicylic acid or nonsteroidal anti-inflammatory drugs] or alcohol [≥8 drinks per week]), HEMORR<sub>2</sub>HAGES (hepatic or renal disease, ethanol abuse, malignancy, older [age &gt;75 years], reduced platelet count or function, rebleeding risk [history of past bleeding], hypertension [uncontrolled], anemia, genetic factors, excessive fall risk, and stroke), and mOBRI (modified Outpatient Bleeding Risk Index). <h3>Main outcome measures</h3> Four simulated cohorts were constructed. The coefficient of variation, relative difference (RD), and 95% CI for annual bleeding risk estimates were calculated for all hypothetical patient cohorts. Additionally, pairwise agreement between calculators across low- (&lt;10%), moderate- (10% to 20%), and high-risk (&gt;20%) categories of patients was determined. <h3>Results</h3> The risk estimates the calculators generated were imprecise, with coefficients of variation ranging from 14% for HEMORR<sub>2</sub>HAGES to 64% for mOBRI. Wide variation was observed in annual risk estimates for calculators using the mOBRI (maximum RD=4.3) and HAS-BLED (maximum RD=3.1) models. The 95% CI of mean annual bleeding risk varied among models; 1 calculator using the HAS-BLED model had a 95% CI of mean annual risk estimates of 5.4% to 6.2%, while another HAS-BLED calculator reported a 95% CI of 17.7% to 18.5%. Concordance for risk category stratification among calculators was high for those based on mOBRI and ATRIA (=1 for both). Poor agreement was observed in 1 calculator using HEMORR<sub>2</sub>HAGES (=0.54) and another using HAS-BLED ( range=-0.11 to 0.35). <h3>Conclusion</h3> Inconsistencies and a lack of precision were observed in annual risk estimates and risk stratification produced by Web and mobile bleeding risk calculators for patients with atrial fibrillation. Clinicians should refer to annual bleeding risks observed in major randomized controlled trials to inform risk estimates communicated to patients.
Preoperative Serum Sex Hormone-Binding Globulin as a Predictive Marker for Extraprostatic Extension of Tumor in Patients with Clinically Localized Prostate Cancer
Authors: Sang Eun Lee, Jae Seung Chung, Byung Kyu Han, Chan Soo Park, Ki Hyuk Moon, Seok-Soo Byun, Gheeyoung Choe, Sung Kyu Hong
Journal: European Urology (2008)