tbuckley/cabot-search huggingface dataset:
Bush plans to screen whole US population for mental illness: Is road of initiative paved with good intentions?
Authors: Woody Caan
Journal: BMJ (2004)

Editor—The grandiose scale of George W Bush's mental health initiative makes it difficult to comment on the “road” he wishes to take, or to relate this American proposal to the recent British report on mental health and social exclusion.1 2 The devil is in the detail. Because of the longstanding …
Selective beta-1 receptor blockade with oral practolol in man. A dose-related phenomenon.
Authors: J J Lertora, A L Mark, J Johannsen, W R Wilson, F M Abboud
Journal: Journal of Clinical Investigation (1975)

The purpose of this study was to test the hypothesis that oral administration of a low dose of practolol in man produces selective beta-1 receptor blockade, whereas oral administration of a high dose blocks both beta-1 and beta-2 receptors. Normal men were studied 2-4 h after a single oral dose of practolol (1.5 or 12 mg/kg) and after placebo. Effects on beta-1 receptors were studied by measuring heart rate responses to exercise. Effects on beta-2 receptors were tested by measuring forearm vascular responses to brachial arterial infusions of isoproterenol. Neither dose of practolol altered base-line heart rate, forearm vascular resistance, and arterial pressure, Both low and high doses significantly attenuated heart rate responses to exercise. Forearm vasodilator responses to isoproterenol were attenuated by the high dose, but not the low dose, of practolol. Serum concentrations of practolol 2 h after administration of the drug and at the time of the studies of forearm vascular responses averaged 0.5+/-0.1 (SE) and 5.9+/-1.0 mug/ml for low and high doses of practolol, respectively. The results indicate that the phenomenon of selective beta-1 receptor blockade in man is related to the dose and serum concentration of practolol selectively block beta-1 receptors; a high dose and serum concentrations block both beta-1 and beta-2 receptors.
Abstract 1451: Lipid-based Akt inhibitors preferentially kill lung cancer cells with mesenchymal features
Authors: Chunyu Zhang, Koffi S. Messan, Evthokia Hobbs, Chun-Te Chiang, Barbara Saber, Joell J. Gills, Phillip A. Dennis
Journal: Cancer Research (2010)

Abstract Most solid tumors are epithelial in origin. A loss of epithelial-cell markers and gain of mesenchymal-cell markers (epithelial mesenchymal transition, EMT) has been observed in patient tumor samples, particularly at the leading edge or invasive front of solid tumors such as non-small cell lung cancer (NSCLC). Pathological EMT is often associated with tumor metastasis and can confer a poor prognosis. EMT is promoted by Akt activation, which contributes to the formation, maintenance, and therapeutic resistance of cancer. In this study, we found that lipid-based Akt inhibitors (LBAI) such as phosphatidylinositol ether lipid analogues (PIAs) and alkylphospholipids (perifosine and miltefosine) preferentially kill tumor cells with mesenchymal features. NSCLC cell lines that exhibited epithelial, intermediate and mesenchymal phenotypes (H322, A549 and H157, respectively) were increasingly sensitive to the cytotoxic effects of LBAI. Prolonged treatment of A549 cells with TGFbeta induced a mesenchymal phenotype and increased sensitivity to LBAI. Because EMT can be controlled by the tumor suppressor RhoB, which we previously showed was transcriptionally activated by LBAI, we investigated the role of RhoB in these cell lines. An inverse relationship between Akt activation and RhoB expression was observed in the parental cell lines as well as A549 cells treated with TGFbeta, which correlated with LBAI cytotoxicity. Stable knockdown of RhoB in A549 cells induced features of EMT including loss of E-cadherin expression, induction of vimentin expression and Akt activation, and increased cellular migration. Stable knockdown of RhoB also increased sensitivity to LBAI. These studies show that lung cancer cells with a mesenchymal phenotype are preferentially sensitivity to LBAI, and that RhoB is a critical mediator of EMT. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1451.
Photodynamic Therapy: A Light in the Darkness?
Authors: Alexander Lin, Stephen M. Hahn
Journal: Clinical Cancer Research (2009)

Photodynamic therapy (PDT) is used to treat localized premalignant or early malignant disease. This study reports the enhanced, systemic antitumor immune response from PDT, suggesting that it may have a potential role as a therapy to address both local and disseminated disease.
Initiation of Tumor Necrosis Factor-α Antagonists and the Risk of Hospitalization for Infection in Patients With Autoimmune Diseases
Authors: Carlos G. Grijalva, Lang Chen, Elizabeth Delzell, John W. Baddley, Timothy Beukelman, Kevin L. Winthrop, Marie R. Griffin, Lisa J. Herrinton, Liyan Liu, Rita Ouellet-Hellstrom, Nivedita M. Patkar, Daniel H. Solomon, James D. Lewis, Fenglong Xie, Kenneth G. Saag, Jeffrey R. Curtis
Journal: JAMA (2011)

Although tumor necrosis factor (TNF)-α antagonists are increasingly used in place of nonbiologic comparator medications, their safety profile remains incomplete.To determine whether initiation of TNF-α antagonists compared with nonbiologic comparators is associated with an increased risk of serious infections requiring hospitalization.Within a US multi-institutional collaboration, we assembled retrospective cohorts (1998-2007) of patients with rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis, psoriatic arthritis, or ankylosing spondylitis (psoriasis and spondyloarthropathies) combining data from Kaiser Permanente Northern California, New Jersey and Pennsylvania Pharmaceutical Assistance programs, Tennessee Medicaid, and national Medicaid/Medicare. TNF-α antagonists and nonbiologic regimens were compared in disease-specific propensity score (PS)-matched cohorts using Cox regression models with nonbiologics as the reference. Baseline glucocorticoid use was evaluated as a separate covariate.Infections requiring hospitalization (serious infections) during the first 12 months after initiation of TNF-α antagonists or nonbiologic regimens.Study cohorts included 10,484 RA, 2323 IBD, and 3215 psoriasis and spondyloarthropathies matched pairs using TNF-α antagonists and comparator medications. Overall, we identified 1172 serious infections, most of which (53%) were pneumonia and skin and soft tissue infections. Among patients with RA, serious infection hospitalization rates were 8.16 (TNF-α antagonists) and 7.78 (comparator regimens) per 100 person-years (adjusted hazard ratio [aHR], 1.05 [95% CI, 0.91-1.21]). Among patients with IBD, rates were 10.91 (TNF-α antagonists) and 9.60 (comparator) per 100 person-years (aHR, 1.10 [95% CI, 0.83-1.46]). Among patients with psoriasis and spondyloarthropathies, rates were 5.41 (TNF-α antagonists) and 5.37 (comparator) per 100 person-years (aHR, 1.05 [95% CI, 0.76-1.45]). Among patients with RA, infliximab was associated with a significant increase in serious infections compared with etanercept (aHR, 1.26 [95% CI, 1.07-1.47]) and adalimumab (aHR, 1.23 [95% CI, 1.02-1.48]). Baseline glucocorticoid use was associated with a dose-dependent increase in infections.Among patients with autoimmune diseases, compared with treatment with nonbiologic regimens, initiation of TNF-α antagonists was not associated with an increased risk of hospitalizations for serious infections.
Delay in Treatment Does Not Predict Outcome in Inflammatory Breast Cancer.
Authors: P. Levine, J. Schenfeld, H. Hoffman, H. Young
Journal: Cancer Research (2009)

Abstract Aim: Inflammatory breast cancer (IBC) is an extremely aggressive form of breast cancer that fortunately has proven to be increasingly controlled by modern multimodal chemotherapy. Many doctors consider the immediate use of chemotherapy as critical to the outcome, and delays in treatment due to diagnostic issues have on occasion led to law suits. One such law suit led us to examine the relative importance of delay in diagnosis and other potential prognostic factors in a series of well documented IBC patients.Methods: 134 patients reported to the North American IBC Registry were evaluated for prognostic factors related to disease outcome. Relevant information included the time intervals between onset of symptoms and first medical visit, first medical visit to onset of chemotherapy, and progression free survival (PFS). Other parameters included initial response to chemotherapy, cell surface receptors and extent of disease at diagnosis. Patients were categorized according to the extent of clinical breast involvement and the presence or absence of dermal lymphatic invasion (DLI).Results: Patients with a delay of diagnosis of 60 days or less had a mean PFS of 4.41 years (N=62) while those with a delay &amp;gt;60 days had a mean PFS of 4.58 years (N=58). Initial response to chemotherapy was an important predictor of outcome: 31 patients with a complete clinical response had a median PFS of 5.12 years vs. 4.38 years for 71 patients that had a partial clinical response and 4.01 years for 15 patients with no significant response or progression of disease. The detection of dermal lymphatic invasion (RR: 2.77; 95%CI: 1.4-5.46) and clinical metastases at diagnosis (RR 2.81. 95% CI:1.16-6.80) were also significantly associated with a poorer outcome. The presence or absence of hormone receptors and HER2-neu markers were not predictive of outcome.Conclusion: Delay in initiating chemotherapy was not a significant factor in determining outcome of IBC. Initial extent of disease and response to chemotherapy were the two most imnportant factors in predicitng outcome of treated patients. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2012.
Vesnarinone Limits Infarct Size via Adenosine-Dependent Mechanisms in the Canine Heart
Authors: Masafumi Kitakaze, Tetsuo Minamino, Hiroharu Funaya, Koichi Node, Yoshiro Shinozaki, Hidezo Mori, Masatsugu Hori
Journal: Circulation (1997)

Background Recently, vesnarinone, a synthetic inotropic agent, was reported to inhibit adenosine transport into cells, which may increase adenosine levels in the heart and in turn mediate cardioprotection. Thus, vesnarinone may also have protective effects in sustained ischemia-reperfusion, because adenosine limits infarct size. Methods and Results In open-chest dogs, the left anterior descending coronary arteries were occluded for 90 minutes followed by 6 hours of reperfusion. Vesnarinone limited infarct size compared with controls (6.8±2.2% versus 44.7±3.9%), which was completely reversed by a nonselective adenosine receptor antagonist, 8-sulfophenyltheophylline (44.1±6.8%), and partially blunted by an inhibitor of ecto-5′-nucleotidase, α,β-methyleneadenosine 5′-diphosphate (AMP-CP, 28.9±4.7%). Dipyridamole, an inhibitor of adenosine uptake into cells, only modestly limited infarct size (27.4±5.5%). Furthermore, vesnarinone increased adenosine release during coronary hypoperfusion, which was attenuated by AMP-CP. In vitro, vesnarinone increased the activity of ecto-5′-nucleotidase of the myocardium. Conclusions We conclude that vesnarinone potently limits infarct size via adenosine-dependent mechanisms, mainly through activation of ecto-5′-nucleotidase.
Lack of support for an association between CLEC4M homozygosity and protection against SARS coronavirus infection
Authors: Nelson Leung-Sang Tang, Paul Kay-Sheung Chan, David Shu-Cheong Hui, Ka-Fai To, Weimin Zhang, Francis K L Chan, Joseph Jao-Yiu Sung, Yuk Ming Dennis Lo
Journal: Nature Genetics (2007)

Lack of support for an association between  CLEC4M  homozygosity and protection against SARS coronavirus infection
SURGICAL TRADE CODE FORBIDS REBATES
Authors: Fred B. Hovey
Journal: JAMA (1934)

<h3>To the Editor:—</h3> As secretary of the American Surgical Trade Association, which sponsored the Code of Fair Competition for the Surgical Distributors Trade, approved on Aug. 24, 1934, I wish to call the attention of the members of the medical profession to certain provisions of this code, which are of special interest to members of the medical profession. This code contains the trade practice provisions prohibiting what is generally called commercial bribery which are found in almost all codes of fair competition. These provisions are contained in section 1 of article VIII of the Code of Fair Competition for the Surgical Distributors Trade and read as follows: Section 1. No member of the trade shall give, permit to be given, or offer to give, anything of value for the purpose of influencing or rewarding the action of any employee, agent or representative of another in relation to the business of
Radioiodine in human thyroid glands and incidence of thyroid cancer in Cumbria.
Authors: C. Bowlt, P. Tiplady
Journal: BMJ (1989)

may take large amounts of laxatives for postoperative constipation, leading to the "cathartic colon."If this had been so in our study we would have expected more use of laxatives by the women who had had hysterectomy than we found, although such use might have been underreported deliberately.Another possible mechanism is pelvic autonomic denervation due to an intraoperative manoeuvre,5 traction during the operation, or realignment of the pelvic organs after removal of the uterus.Urinary dysfunction is a well recognised complication of hysterectomy and is thought to be due to disruption of the nerve supply to the bladder.We found a highly significant association between persistently reduced bowel frequency and persistently increased urinary frequency after hysterectomy.This supports the hypothesis that they may have a common aetiology-namely, autonomic denervation of both viscera, which have a closely related nerve supply in the pelvis.We thank Dr A A Robertson, Dr A Donald and partners, Dr M A Eastwood, and Mr J
Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes
Authors: John A Todd, Neil M Walker, Jason D Cooper, Deborah J Smyth, Kate Downes, Vincent Plagnol, Rebecca Bailey, Sergey Nejentsev, Sarah F Field, Felicity Payne, Christopher E Lowe, Jeffrey S Szeszko, Jason P Hafler, Lauren Zeitels, Jennie H M Yang, Adrian Vella, Sarah Nutland, Helen E Stevens, Helen Schuilenburg, Gillian Coleman, Meeta Maisuria, William Meadows, Luc J Smink, Barry Healy, Oliver S Burren, Alex A C Lam, Nigel R Ovington, James Allen, Ellen Adlem, Hin-Tak Leung, Chris Wallace, Joanna M M Howson, Cristian Guja, Constantin Ionescu-Tîrgovişte, Matthew J Simmonds, Joanne M Heward, Stephen C L Gough, David B Dunger, Linda S Wicker, David G Clayton
Journal: Nature Genetics (2007)
US links motor neurone disease with Gulf war service
Authors: F. Charatan
Journal: BMJ (2002)

US secretary of veterans affairs Anthony Principi has declared that motor neurone disease is connected with service in the Gulf war.

He is the first to connect a specific illness with service in the Gulf war, and his decision will lead to full disability and survivor benefits for those with the disease, the cause of which is unknown.

Last month the Department of Veterans Affairs described preliminary results of a government sponsored study involving 2.5 million …
Comparison of Adenosine, Dipyridamole, and Dobutamine in Stress Echocardiography
Authors: Timothy W. Martin, John F. Seaworth, Joseph P. Johns, Lawrence E. Pupa, William R. Condos
Journal: Annals of Internal Medicine (1992)

Objective: To compare adenosine, dipyridamole, and dobutamine in stress echocardiography with regard to sensitivity, specificity, accuracy, and side effects. ▪Design: Crossover, blinded comparison, with coronary angiography serving as the criterion standard. ▪Setting: U.S. Army tertiary care hospital. Participants: Forty participants, 25 with coronary disease and 15 without coronary disease. Patients were eligible if they had coronary angiography within 6 weeks of stress testing or if they had a risk for coronary disease of less than 5%. Measurements: Left ventricular wall motion was recorded after dobutamine (0.38 mg/kg body weight), adenosine (0.84 mg/kg body weight), and dipyridamole (0.84 mg/kg body weight) stress testing. Stress echocardiographic evaluation was considered to be abnormal if the patient developed new or progressive wall motion abnormalities. The rate of side effects for the types of echocardiography and the patient preference were recorded. Main Results: The sensitivity of dobutamine stress echocardiography (76%; 95% Cl, 59% to 93%) was significantly higher than that of adenosine echocardiography (40%; Cl, 21 % to 59%; P〈0.001) and that of dipyridamole echocardiography (56%; Cl, 37% to 75%; P = 0.019). The specificity of adenosine testing (93%; Cl, 80% to 100%) was significantly higher than that of dobutamine echocardiography (60%; Cl, 35% to 85%; P = 0.008) and that of dipyridamole echocardiography (67%; Cl, 43% to 91%; P= 0.028). Symptoms were more frequent with adenosine echocardiography (100%) than with dipyridamole (88%; P〈0.001) or dobutamine (80%; P〈0.001) echocardiography. Treatmentfor persistent symptoms was required in more patients after dipyridamole echocardiography (40%) than after dobutamine (12%; P〈0.001) or adenosine (0%; P〈.001) echocardiography. More patients preferred dobutamine (48%) or dipyridamole (40%) echocardiography to adenosine echocardiography (12%; P〈0.001). Conclusions: Dobutamine stress echocardiography is more sensitive and is better tolerated than adenosine or dipyridamole stress echocardiography. Adenosine echocardiography is more specific than dobutamine or dipyridamole echocardiography and is less likely to cause persistent symptoms.
Effect of an Intensive Educational Program for Minority College Students and Recent Graduates on the Probability of Acceptance to Medical School
Authors: Joel C. Cantor
Journal: JAMA (1998)

Context.—Increasing the number of minority physicians is a long-standing goal of professional associations and government.Objective.—To determine the effectiveness of an intensive summer educational program for minority college students and recent graduates on the probability of acceptance to medical school.Design.—Nonconcurrent prospective cohort study based on data from medical school applications, Medical College Admission Tests, and the Association of American Medical Colleges Student and Applicant Information Management System.Setting.—Eight US medical schools or consortia of medical schools.Participants.—Underrepresented minority (black, Mexican American, mainland Puerto Rican, and American Indian) applicants to US allopathic medical schools in 1997 (N=3830), 1996 (N=4654), and 1992 (N=3447).Intervention.—The Minority Medical Education Program (MMEP), a 6-week, residential summer educational program focused on training in the sciences and improvement of writing, verbal reasoning, studying, test taking, and presentation skills.Main Outcome Measure.—Probability of acceptance to at least 1 medical school.Results.—In the 1997 medical school application cohort, 223 (49.3%) of 452 MMEP participants were accepted compared with 1406 (41.6%) of 3378 minority nonparticipants (P=.002). Positive and significant program effects were also found in the 1996 (P=.01) and 1992 (P=.005) cohorts and in multivariate analysis after adjusting for nonprogrammatic factors likely to influence acceptance (P<.001). Program effects were also observed in students who participated in the MMEP early in college as well as those who participated later and among those with relatively high as well as low grades and test scores.Conclusions.—The MMEP enhanced the probability of medical school acceptance among its participants. Intensive summer education is a strategy that may help improve diversity in the physician workforce.
Targeting the Androgen Receptor Confers In Vivo Cross-resistance Between Enzalutamide and Docetaxel, But Not Cabazitaxel, in Castration-resistant Prostate Cancer
Authors: Robert J. van Soest, Ellen S. de Morrée, Charlotte F. Kweldam, Corrina M.A. de Ridder, Erik A.C. Wiemer, Ron H.J. Mathijssen, Ronald de Wit, Wytske M. van Weerden
Journal: European Urology (2014)
Notes on the Action of Medicines, Old and New
Authors: J. K. Spender
Journal: BMJ (1872)

rently the lining membrane of the lateral ventricle had given way, and the fluid had macerated the corpus callosum, and performed the natural dissection above described-a dissection which I at once re- cognised, from having repeatedly made it in hardened brains.The optic commissure and tracts were embedded in solid yellow exudation, but apparently normal when extracted.The right optic nerve near the eye was expanded into a bulb of considerable size, evidently formed by distension of the outer sheath by fluid; it was quite translucent.The disc was fairly defined, not papillated, not so pale as usual.The retinal vein was extremely large and distinct, issuing from the centre of the disc.The left optic nerve had no bulbous expansion, and no appearance of having been distended.Longitudinal vessels of considerable size were visible on its exterior.The disc was not well de- fined, but had a sort of halo round it.The retinal veins were rather large; the arteries small, but distinctly visible.Both vessels were
Eotaxin in induced sputum of asthmatics: relationship with eosinophils and eosinophil cationic protein in sputum
Authors: H. Yamada, M. Yamaguchi, K. Yamamoto, T. Nakajima, K. Hirai, Y. Morita, Y. Sano, H. Yamada
Journal: Allergy (2000)

Background: Eosinophilic inflammation is a crucial aspect of allergic diseases such as bronchial asthma. An eosinophil‐active chemokine, eotaxin, may play a role in the pathogenesis of the tissue eosinophilia accompanying asthma. Methods: Induced sputa were obtained from 53 patients with atopic asthma and six healthy subjects, and the concentration of eotaxin in the sputum was measured by ELISA. We investigated whether the sputum content of eotaxin is related to 1) asthma status or corticosteroid therapy, and 2) other sputum indices, including percentage of eosinophils and concentration of eosinophil cationic protein (ECP). Results: The patients with stable or unstable asthma showed significantly higher concentrations of sputum eotaxin than the normal controls. The level of sputum eotaxin demonstrated a positive correlation with the percentage of eosinophils in stable asthmatics not receiving corticosteroid therapy, but not in stable patients treated with corticosteroids, or in unstable patients. Sputum eotaxin demonstrated a positive correlation with ECP in asthmatic patients who were either in a stable state or not receiving steroid therapy. Conclusions: The elevated level of eotaxin detected in association with increased eosinophils and ECP in the sputum of asthmatics suggests that eotaxin is involved in the pathogenesis of eosinophilic airway inflammation. The relationship of eotaxin to airway eosinophilia may be modified by the stability status of asthma and corticosteroid therapy.
UTILIDAD DE LA AMILASA SERIADA A LAS 6 Y LAS 24 HORAS PARA PREDICIR LA PANCREATITIS POSTCPRE
Authors: R Díez Rodríguez, J Espinel Díez, AB Dominguez Carbajo, G Rascarachi, M García Alvarado, L Vaquero Ayala, S Vivas Alegre
Journal: Endoscopy (2011)

Objetivo: Analizar el rendimiento de la amilasa medida 6horas y 24 horas después de la CPRE, en el diagnóstico de la pancreatitis post CPRE.