tbuckley/cabot-search huggingface dataset:
EU legislation threatens clinical trials
Authors: R. Watson
Journal: BMJ (2003)

European Union legislation due to take effect next year could seriously reduce the scope for non-commercial clinical trials, says Cancer Research UK.

The new rules are designed to simplify and harmonise the many different national provisions now in force relating to good practice in the conduct of clinical trials of medicinal products. Their aim is to ensure good care of patients and to make it easier to conduct pan-European research.

But, as governments now prepare the enabling legislation to implement the EU rules in domestic …
Resurgence of Tuberculosis Prompts US Search for Effective Drugs, Expanded Research Effort
Authors: Charles Marwick
Journal: JAMA (1993)

FEWER THAN 10 years ago, the (then) director of what now is the Centers for Disease Control and Prevention (Atlanta, Ga), James O. Mason, MD, DrPH, told Congress that tuberculosis could be eradicated in the United States for an annual cost of about $30 million. In recent months, the same physician—now assistant secretary for health and head of the Public Health Service in Washington, DC—has had to ask for $540 million just to attempt to control tuberculosis. So notes David E. Rogers, MD, Cornell University Medical College, New York, NY, who spoke on the first day of the World Congress on Tuberculosis recently in Bethesda, Md. <h3>Lost Opportunity</h3> Says Rogers: "The opportunity to eliminate one of humankind's most persistent scourges has been lost and we are paying dearly for it." That opportunity has been discussed many times in recent years. Nearly 30 years ago, the International Union Against Tuberculosis was
BLACK HAIRY TONGUE ASSOCIATED WITH PENICILLIN THERAPY
Authors: SAMUEL A. WOLFSON
Journal: JAMA (1949)

Local reactions from the use of oral penicillin (glossitis, stomatitis and vesicular cheilitis) have frequently been described. However, another type of reaction has been reported in the foreign literaure<sup>1</sup>but not in the American journals. The condition itself, black hairy tongue, has been known for many years, but its association with penicillin therapy is of recent note. I have observed this reaction to penicillin and believe that it is of sufficient interest to be documented. <h3>REPORT OF CASES</h3><h3>Case 1.—</h3> In January 1948 a white woman aged 37 had been using penicillin lozenges for a sore throat. Discoloration of the tongue was observed a few days later. She was examined on the eighth day, at which time the tongue presented a velvety appearance and was brownish black on its medial and posterior portions. The filiform papillae were hypertrophied and bent like the nap of wet, heavy velvet when stroked
G-Quartet Oligonucleotides
Authors: Naijie Jing, Yidong Li, Weijun Xiong, Wei Sha, Ling Jing, David J. Tweardy
Journal: Cancer Research (2004)

Abstract Stat3 is a signaling molecular and oncogene activated frequently in many human malignancies including the majority of prostate, breast, and head and neck cancers; yet, no current chemotherapeutic approach has been implemented clinically that specifically targets Stat3. We recently developed G-rich oligodeoxynucleotides, which form intramolecular G-quartet structures (GQ-ODN), as a new class of Stat3 inhibitor. GQ-ODN targeted Stat3 protein directly inhibiting its ability to bind DNA. When delivered into cells using polyethyleneimine as vehicle, GQ-ODN blocked ligand-induced Stat3 activation and Stat3-mediated transcription of antiapoptotic genes. To establish the effectiveness of GQ-ODN as a potential new chemotherapeutic agent, we systemically administered GQ-ODN (T40214 or T40231) plus polyethyleneimine or polyethyleneimine alone (placebo) by tail-vein injection into nude mice with prostate and breast tumor xenografts. Whereas the mean volume of breast tumor xenografts in placebo-treated mice increased &amp;gt;7-fold over 18 days, xenografts in the GQ-ODN-treated mice remained unchanged. Similarly, whereas the mean volume of prostate tumor xenografts in placebo-treated mice increased 9-fold over 10 days, xenografts in GQ-ODN-treated mice increased by only 2-fold. Biochemical examination of tumors from GQ-ODN-treated mice demonstrated a significant reduction in Stat3 activation, levels of the antiapoptotic proteins Bcl-2 and Bcl-xL, and an 8-fold increase in the number of apoptotic cells compared with the tumors of placebo-treated mice. Thus, GQ-ODN targeting Stat3 induces tumor cell apoptosis when delivered into tumor xenografts and represents a novel class of chemotherapeutic agents that holds promise for the systemic treatment of many forms of metastatic cancer.
Abstract 606: Inhibition of epithelial to mesenchymal transition and advancement of therapeutic effect in oral cancer by the flavonoid compound, Quercetin: pivotal roles of Snail repression and RKIP induction.
Authors: Yun-Ching Chang, Shih-Hwa Chiou, Shin Nieh
Journal: Cancer Research (2013)

Abstract Oral squamous cell carcinoma (OSCC) is prevalent worldwide, and survival in OSCC has not improved significantly in the last few decades. Cancer prevention using natural products has become an integral part of cancer control. Quercetin is a plant-derived flavonoid known to possess anti-inflammatory property, but its use as a chemopreventive substance has been reviewed quite recently. Several reports have assessed the pro-apoptotic action of Quercetin in cancer cells similar to many other flavonoids, although the mechanisms involved are not clear. We here reported that Quercetion-mediated sensitization may result from modulation of the EMT inducer Snail and the EMT suppressor/ immunosurveillance cancer gene product Raf-1 kinase inhibitory protein (RKIP). Quercetin regulated EMT, invasion, cell survival and apoptosis via inhibition of NF-κB inactivation as well as leaded to the induction of RKIP through downregulation of its transcriptional repressor Snail. Quercetin-induced RKIP upregulation potentiates further modulated mitochondria-mediated apoptosis, thus leading to enhance therapeutic effect. These findings demonstrate the role of Quercetin in the regulation of EMT via inhibition of NF-κB and Snail and induction of RKIP and also identified Quercetin as targets for resistance via NF-κB/Snail/RKIP circuitry. Citation Format: Yun-Ching Chang, Shih-Hwa Chiou, Shin Nieh. Inhibition of epithelial to mesenchymal transition and advancement of therapeutic effect in oral cancer by the flavonoid compound, Quercetin: pivotal roles of Snail repression and RKIP induction. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 606. doi:10.1158/1538-7445.AM2013-606
Pattern and Clinical Predictors of Lymph Node Involvement in Nonfunctioning Pancreatic Neuroendocrine Tumors (NF-PanNETs)
Authors: Stefano Partelli, Sebastien Gaujoux, Letizia Boninsegna, Rim Cherif, Stefano Crippa, Anne Couvelard, Aldo Scarpa, Philippe Ruszniewski, Alain Sauvanet, Massimo Falconi
Journal: JAMA Surgery (2013)

Nonfunctioning pancreatic neuroendocrine tumors (NF-PanNETs) are often indolent neoplasms without lymph node (LN) metastasis at diagnosis. Therefore, in patients with low risk of LN metastasis, the extent of surgery and lymphadenectomy could be limited and follow-up adjusted to the very low risk of relapse.To construct a predicting model to assess the risk of pN+ prior to surgical resection for NF-PanNETs using preoperative retrievable variables.Retrospective review using multiple logistic regression analysis to construct predictive model of pN+ based on preoperatively available data.The combined prospective databases of the Surgical Departments of the University of Verona, Verona, Italy, and Beaujon Hospital, Clichy, France, were queried for clinical and pathological data.All patients with resected (R0 or R1), pathologically confirmed NF-PanNETs between January 1, 1993 and December 31, 2009.Risk of lymph node metastases in patients with pancreatic neuroendocrine tumors.Among 181 patients, nodal metastases were reported in 55 patients (30%) and were associated with decreased 5-year disease-free survival (70% vs 97%, P < .001). Multivariable analysis showed that independent factors associated with nodal metastasis were radiological nodal status (rN) (odds ratio [OR], 5.58; P < .001) and tumor grade (NET-G2 vs NET-G1: OR, 4.87; P < .001) (first model). When the tumor grade was excluded, rN (OR, 4.73; P = .001) and radiological tumor size larger than 4 cm (OR, 2.67; P = .03) were independent predictors of nodal metastasis (second model). The area under the receiver operating characteristic curve for the first and second models were 80% and 74%, respectively.Patients with NF-PanNET-G1 have a very low risk of pN+ in the absence of radiological signs of node involvement. When preoperative grading assessment is not achieved, the radiological size of the lesion is a powerful alternative predictor of pN+. The risk of pathological nodal involvement in patients with NF-PanNETs can be accurately estimated by a clinical predictive model.
THE COMBINED ACTIONS OF CHLORAMPHENICOL AND OF BACTERICIDAL ANTIBODY PLUS COMPLEMENT ON SALMONELLA TYPHOSA
Authors: Henry P. Treffers, Louis H. Muschel
Journal: The Journal of Experimental Medicine (1954)

Quantitative determinations, employing turbidimetric growth assays, have been made of the inhibitory actions of choramphenicol, and of specific antibody plus complement, separately, and in combination. In experiments with the Ty2 strain of S. typhosa the combined activities of the two groups of reagents have been predicted, within 3 per cent, from the activities of the separate components, on the hypothesis of joint, independent action (additive inhibitions). A fourfold increase in resistance to chloramphenicol of the 0901 strain of S. typhosa has been shown to have little, if any, effect on its susceptibility to the bactericidal action of anti-O antibody and complement. Indirect evidence indicates that the latter may not be a general effect but may vary with the particular strain.
Allied Health Education and Accreditation
Authors: John T. Boberg
Journal: JAMA (1985)

<h3>COOPERATION AMONG THE HEALTH PROFESSIONS</h3> The term<i>allied health</i>describes a large cluster of health care personnel who fulfill necessary functions in the health provision system, including assisting, facilitating, and complementing the work of physicians and other medical specialists. For more than 50 years the American Medical Association (AMA) has participated extensively in activities to promote quality in the education of allied health personnel and in the accreditation review processes of allied health educational programs. In collaboration with the AMA, more than 48 allied health organizations and related medical specialty societies have developed educational standards for allied health professions that presently number 25 (Appendix IV, Table 1). Using these standards, the Committee on Allied Health Education and Accreditation (CAHEA) accredits more than 3,000 allied health educational programs, with more than 86,000 students and 39,000 graduates in 1983-1984 (Table), at nearly 1,800 institutions, including hospitals and clinics, junior and community colleges,
AIDS IN THE MEASUREMENT OF REFRACTION.
Authors: EDWARD JACKSON
Journal: JAMA (1900)

The two instruments that I herewith present have proved of sufficient value, in facilitating the testing of the refraction of the eye, to justify me in calling the attention of the members of the Section to them. The first is <h3>A TRIAL-FRAME FOR SKIASCOPY.</h3> It is simply a light trial-frame, in each cell of which is fixed a metal disc, with a central opening large enough to allow the application of the shadow-test through it. Upon the disc are enameled bands of black and white, each occupying an angle of 30 degrees of the disc. In the center of each band is marked a point, white in the black bands, and black in the white bands. This constitutes a graduation to 15 degrees spaces. The center of a white band marks 90 degrees, and the center of a black band, 180 degrees, of the usual graduation of the trial-frame. This
Up-regulation of inositol 1,4,5 trisphosphate receptor expression in atrial tissue in patients with chronic atrial fibrillation
Authors: Jutaro Yamada, Tomoko Ohkusa, Tomoko Nao, Takeshi Ueyama, Masafumi Yano, Shigeki Kobayashi, Kimikazu Hamano, Kensuke Esato, Masunori Matsuzaki
Journal: Journal of the American College of Cardiology (2001)
Threshold of trichloroethylene contamination in maternal drinking waters affecting fetal heart development in the rat.
Authors: Paula D Johnson, Stanley J Goldberg, Mary Z Mays, Brenda V Dawson
Journal: Environmental Health Perspectives (2002)

Halogenated hydrocarbons such as trichloroethylene (TCE) are among the most common water supply contaminants in the United States and abroad. Epidemiologic studies have found an association but not a cause-and-effect relation between halogenated hydrocarbon contamination and increased incidence of congenital cardiac malformations or other defective birth outcomes. Avian and rat studies demonstrated statistically significant increases in the number of congenital cardiac malformations in those treated with high doses of TCE, either via intrauterine pump or in maternal drinking water, compared with controls. This study attempts to determine if there is a threshold dose exposure to TCE above which the developing heart is more likely to be affected. Sprague-Dawley rats were randomly placed in test groups and exposed to various concentrations of TCE (2.5 ppb, 250 ppb, 1.5 ppm, 1,100 ppm) in drinking water or distilled water (control group) throughout pregnancy. The percentage of abnormal hearts in the treated groups ranged from 0 to 10.48%, with controls having 2.1% abnormal hearts, and the number of litters with fetuses with abnormal hearts ranged from 0 to 66.7%, and the control percentage was 16.4%. The data from this study indicate not only that there is a statistically significant probability overall of a dose response to increasing levels of TCE exposure, but also that this trend begins to manifest at relatively low levels of exposure (i.e., < 250 ppb). Maternal rats exposed to more than this level of TCE during pregnancy showed an associated increased incidence of cardiac malformations in their developing rat fetuses.
Sézary syndrome: Diagnosis, prognosis, and critical review of treatment options
Authors: Janet S. Wieselthier, Howard K. Koh
Journal: Journal of the American Academy of Dermatology (1990)

Sézary syndrome is a form of leukemia-lymphoma characterized clinically by erythroderma, pruritus, adenopathy, and circulating atypical cells with cerebriform nuclei. Histologically, atypical lymphocytes in the dermis and Pautrier's microabscesses are often present in skin biopsy specimens. Immunologic findings that support a diagnosis of Sézary syndrome include a predominance of CD4+ lymphocytes in both skin biopsy specimens and peripheral blood. Cytogenetic studies that demonstrate aneuploidy and DNA probe analysis that shows gene rearrangement for the β-subunit of the T cell receptor are the latest, most sensitive, and specific methods for identifying the clonal nature of the disease. Various staging systems are used. We review the various treatments for Sézary syndrome, including the newer, biologically based investigational therapies, (e.g., antithymocyte globulin, monoclonal antibodies and other immunostimulants, retinoids, cyclosporine, interferon, and extracorporeal photopheresis). Extracorporeal photopheresis and some chemotherapeutic agents appear to produce the best results in terms of response and remission duration with minimal toxicity. However, more multicenter controlled clinical trials are needed to determine the most effective single or combined therapeutic regimen. Sézary syndrome is a form of leukemia-lymphoma characterized clinically by erythroderma, pruritus, adenopathy, and circulating atypical cells with cerebriform nuclei. Histologically, atypical lymphocytes in the dermis and Pautrier's microabscesses are often present in skin biopsy specimens. Immunologic findings that support a diagnosis of Sézary syndrome include a predominance of CD4+ lymphocytes in both skin biopsy specimens and peripheral blood. Cytogenetic studies that demonstrate aneuploidy and DNA probe analysis that shows gene rearrangement for the β-subunit of the T cell receptor are the latest, most sensitive, and specific methods for identifying the clonal nature of the disease. Various staging systems are used. We review the various treatments for Sézary syndrome, including the newer, biologically based investigational therapies, (e.g., antithymocyte globulin, monoclonal antibodies and other immunostimulants, retinoids, cyclosporine, interferon, and extracorporeal photopheresis). Extracorporeal photopheresis and some chemotherapeutic agents appear to produce the best results in terms of response and remission duration with minimal toxicity. However, more multicenter controlled clinical trials are needed to determine the most effective single or combined therapeutic regimen.
The Oldest but Latest Fad—Hypnotism.
Authors: W. P. Howle
Journal: JAMA (1895)

<h3>To the Editor:</h3> —You will agree with me that it is a difficult matter to make<i>one cause</i>explain all phenomena. Sometime in the past I wrote an article for theJournalunder the heading, " Modern Insanity" and in a jocular way put it as a cause of many unique acts. At that time I had not "read up" on "Hypnotism." Since reading the last number of theJournalI have reason to modify some of my views. Hypnotism in its latest phase assists wonderfully in explaining a phenomena heretofore not understood. For instance.<i>One</i>who is a<i>multiplex personality</i>can say in regard to his unusual acts, that Number 2 or Number 3, did the act, and therefore Number<i>one</i>is excusable. Whether or not he could make a court or jury believe him is another question. The average juror looks upon himself as a<i>unit</i>and may be
Staging of Hodgkin Disease by Laparotomy
Authors: S. Frederick Rabiner
Journal: JAMA (1973)

To the Editor.—  In their retrospective report, Smith et al (224:1026, 1973) concluded that ... with stage I or II disease above the diaphragm, laparotomy is not necessary if extended field and splenic irradiation is administered. I would surely agree with this conclusion and congratulate the authors on their logic. At the present state of the art, the only chance for cure with patients with Hodgkin disease resides in intensive x-ray therapy. If one intends to irradiate the abdomen, it is not necessary to have the patient undergo a laparotomy merely for the sake of reclassifying patients from stage II to III or IV.  However, the authors recommend laparotomy for patients who initially have stage II or IV disease. They justify this on the basis of several false positive lymphangiograms on patients originally classified as stage III, and the false conclusion that two patients were stage IV because of either an
Carotid 'whirlpool' sweeps in new atherogenesis theory
Authors: W. A. Check
Journal: JAMA (1982)

A hydraulic engineer could tell you that unusual flow patterns are likely where a rapidly moving fluid diverges into two streams—at the carotid bifurcation, for example. But it was only during the last year, and only with a very advanced ultrasonic scanning system, that scientists demonstrated for the first time a phenomenon predicted by theoreticians: an area of reverse blood flow just beyond the carotid bifurcation. This phenomenon, called a "boundary layer" or "flow separation" in hydraulic engineering parlance, is the basis for a newly emerging theory of how and why atherosclerosis develops. The finding of a boundary layer was reported at the recent Joint International Conference on Stroke and Cerebral Circulation in New Orleans by Christopher P. L. Wood, MB, BS, of the British Medical Research Council's Clinical Research Centre in Harrow, England. While a visiting fellow in the neurology department at the Bowman Gray School of Medicine in
Cardiac Angiotensin-(1-7) in Ischemic Cardiomyopathy
Authors: David B. Averill, Yuichiro Ishiyama, Mark C. Chappell, Carlos M. Ferrario
Journal: Circulation (2003)

Accumulating evidence suggests that angiotensin-(1-7) (Ang-[1-7]) may play an important role in counteracting the pressor, proliferative, and profibrotic actions of angiotensin II in the heart. Thus, we evaluated whether Ang-(1-7) is expressed in the myocardium of normal rats and those in which myocardial infarction was produced 4 weeks beforehand.The left coronary artery in 10-week-old Lewis rats was either ligated (n=5) or exposed but not occluded in age-matched controls (sham; n=5). Left ventricular end-diastolic pressures were significantly elevated 4 weeks after myocardial infarction (25+/-1 versus 5+/-1 mm Hg for sham; P<0.001), whereas left ventricular systolic pressures were significantly reduced (ligated 86+/-4 versus sham 110+/-5 mm Hg; P<0.01). Hemodynamic effects of coronary artery ligation were accompanied by significant cardiac hypertrophy (heart weight to body weight: ligated 4.3+/-0.1 versus sham 2.9+/-0.1 mg/g; P<0.001). In both ligated and sham rats, Ang-(1-7) immunoreactivity was limited to cardiac myocytes and absent in interstitial cells and coronary vessels. Ang-(1-7) immunoreactivity was significantly augmented in ventricular tissue surrounding the infarct area in the heart of rats with myocardial infarction.Development of heart failure subsequent to coronary artery ligation leads to increased expression of Ang-(1-7),which was restricted to myocytes.
Expression of GM-CSF in the airway drives Th2 differentiation and effector function in mice exposed to ragweed intranasally
Authors: Elizabeth C Cates, Ramzi Fattouh, David Alvarez, Meghan J Cundall, Susanna Goncharova, Martin R Stampfli, Monika Cwiartka, Anthony J Coyle, Jose-Carlos GutierrezRamos, Susan Waserman
Journal: Journal of Allergy and Clinical Immunology (2002)