tbuckley/cabot-search huggingface dataset:
EWTD has negative impact on training for surgeons
Authors: Mohiemen Anwar, Shabina Irfan, Niall Daly, Furrat Amen
Journal: BMJ (2005)

Rationing in response to NHS deficits: rural patients are likely to be affected most See News, p 1426Editor-News that pressing financial problems have caused NHS trusts in Suffolk to set new "thresholds" to treatments such as joint replacements reinforces concerns raised by a recent BMA survey of medical directors of trusts in which over a third of respondents anticipated reductions of key services in response to funding shortfalls. 1 2 What has hitherto escaped comment is how cuts in services are far more likely to be felt in some parts of the country than others.Deficits in the NHS are invariably presented as a problem of financial mismanagement, but the pattern of deficits shows that the current resource allocation model discriminates against particular communities.According to the recently published accounts for 2004-5, 3 89 out of 303 (30%) English primary care trusts ended the year in deficit.The table shows how 301 of these trusts are distributed accorded to fifths of deprivation and rurality.Primary care trusts serving populations that are in both the most rural and the least deprived fifth were most likely to be in financial difficulties.Seventeen of the 25 (68%) in this category were in deficit.These trusts received the lowest funding allocation per head (£995).By contrast, only 3% (one of 34) of the primary care trusts serving populations that are in both the most urban and the most deprived fifths failed to break even in 2004-5.These trusts received the highest funding allocations per head (£1405).This shows that poor financial management can at best only partly explain why some trusts are in deficit.The pattern of deficits implies that NHS funding provides insufficient resources for rural areas, for comparatively affluent areas, and, most particularly, for areas that are both rural and affluent.The risk is that such measures will result in NHS services being subject to a new postcode lottery, in which rural residents are more likely to lose out.
Treatment of New Growths by Fluorescein and X Rays
Authors: C. Gouldesbrough
Journal: BMJ (1933)

<h3>Objectives</h3> National and international guidelines recommend prompt referral of patients presenting with inflammatory arthritis (IA), but general practitioners (GPs) feel uncertain in their proficiency to detect synovitis through joint examination, the method of choice to identify IA. Our objective was to develop and validate a rule composed of clinical characteristics to assist GPs and other physicians in identifying IA when in doubt. <h3>Design</h3> Split-sample derivation and validation study. <h3>Setting</h3> The Leiden Early Arthritis <i>Recognition</i> Clinic (EA<i>R</i>C), a screening clinic for patients in whom GPs suspected but were unsure of the presence of IA. <h3>Participants</h3> 1288 consecutive patients visiting the EA<i>R</i>C. <h3>Primary and secondary outcome measures</h3> Associations of clinical characteristics with presence of IA were determined using logistic regression in 644 patients, while validating the results in the other 644 patients (split-sample validation). To facilitate application in clinical practice, a simplified rule (with scores ranging from 0 to 7.5) was derived and validated. <h3>Results</h3> IA was identified by a rheumatologist in 41% of patients. In univariable analysis, male gender, age ≥60 years, symptom duration &lt;6 weeks, morning stiffness &gt;60 min, a low number of painful joints (1–3 joints), presence of patient-reported joint swelling and difficulty with making a fist were associated with IA in the derivation data set. Using multivariable analysis, a simplified rule consisting of these seven items was derived and validated, yielding an area under the receiver operator characteristic curve (AUC) of 0.74 (95% CI 0.70 to 0.78) in the derivation data set. Validation yielded an AUC of 0.71 (95% CI 0.67 to 0.75). Finally, the model was repeated to study predicted probabilities with a lower prevalence of inflammatory arthritis to simulate performance in primary care settings. <h3>Conclusions</h3> Our rule, composed of clinical parameters, had reasonable discriminative ability for IA and could assist physicians in decision-making in patients with suspected IA, increasing appropriateness of healthcare utilisation.
Abstract LB-290: Tranilast inhibits breast cancer stem cells
Authors: Gerald J. Prud'homme, Yelena Glinka, Anna Toulina, Venkateswaran Subramaniam, Rabindranath Chakrabarti, Serge Jothy
Journal: Cancer Research (2010)

Abstract Cancer stem cells (CSCs) have increased resistance to anti-cancer drugs, and may be responsible for chemotherapeutic failure. CSCs can be enriched from cancer cell lines by growth with anti-cancer drugs (e.g., doxorubicin, mitoxantrone), and form mammospheres in low-adherence, serum-free cultures. We are studying tranilast, a non-toxic orally active drug in clinical use for allergic diseases in Japan, but that we found also targets cancer cells. Previously, we reported that tranilast exerts multiple anti-cancer effects and protects against breast cancer metastasis. Our recent studies show that tranilast strongly inhibits breast CSCs in several assays, at pharmacologically relevant concentrations. We enriched CSCs from breast cancer cell lines by cell sorting for ALDH-1 positive cells (ALDEFLUOR+), or by growth in mitoxantrone-containing medium to select drug-surviving CSCs. In both cases, CSCs readily formed mammospheres in vitro. Tranilast inhibited mammosphere formation,’ and dissociated formed mammospheres. It was more effective than paclitaxel or etoposide. We recently identified molecular targets of this drug. We found it has aryl hydrocarbon receptor (AHR) agonist activity and this might explain its anti-cancer effects. The AHR is a receptor for toxins such as dioxin and polycyclic aromatic hydrocarbons. It is a transcription factor that exerts a number of ligand-dependent effects, such as cell-cycle arrest, reduced RB phosphorylation, and decreased cytokine and growth factor production. Unlike many AHR ligands, tranilast has very low toxicity (LD50 &amp;gt; 1 gm/kg in rats), and is well tolerated by patients. In accord with a role for the AHR, breast CSCs expressed higher levels of this receptor than the main population of cancer cells, and the effects of tranilast were markedly diminished by an AHR antagonist (alpha-naphthoflavone). Moreover, we found tranilast inhibits some ATP-binding cassette (ABC) multiple drug resistance transporters, and it enhances the effects of other anti-cancer drugs. Our studies show that tranilast is a drug of low toxicity that has potential as an anti-CSC drug. 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 LB-290.
Gallium SPECT Detection of Lymphomatous Involvement of the Cervical Dens
Authors: ROY J. FERTAKOS, LAWRENCE C. SWAYNE, THADDEUS M. YABLONSKY
Journal: Clinical Nuclear Medicine (1995)

Isolated osseous metastases to the odontoid process of C2 are rare with only a few cases reported in the literature. The authors report a rare case of lymphomatous involvement of the cervical dens, initially detected with skeletal and SPECT gallium scintigraphy.
FOCAL INFECTION—THE SEMINAL VESICLES
Authors: Charles Miner Cooper
Journal: JAMA (1923)

<h3>To the Editor:</h3> —During the last two years I have seen a number of men who suffered from toxic fibrositis, patients who obtained temporary relief from acetylsalicylic acid, but who failed to get the expected permanent relief from removal of infected teeth and tonsils, or from the clearing up of other evidently infected areas. For some years I had recognized that my finger was not long enough to enable me to elicit satisfactory findings concerning the condition of the seminal vesicles, and I had been in the habit of depending on the well recognized genitourinary specialists for this information. It finally occurred to me that perhaps the physical limitations of these specialists might similarly be a bar to their efficiency in this respect, and so I sent a number of these patients to a surgeon whom nature had endowed with unusually long fingers. The results have been highly gratifying, many
Abstract 3208: Semaphorin 3F suppresses telomerase activity
Authors: Christina D. Drenberg, Yira Bermudez, Santo V. Nicosia, Patricia A. Kruk
Journal: Cancer Research (2010)

Abstract Objectives: Telomerase is a ribonucleoprotein that is active in more than 90% of human tumors, including ovarian cancers. We have previously demonstrated that vascular endothelial growth factor (VEGF) stimulates telomerase activity in ovarian cancer cell lines through cellular VEGF receptors and the ERK1/2 pathway targeting Sp1 sites within the hTERT promoter. Since semaphorin 3F (S3F), a proposed tumor suppressor, has been shown to antagonize VEGF, the purpose of this study was to determine whether S3F inhibits telomerase Methods: Telomerase-positive ovarian cancer cell lines (OV2008, C-13, SW626) and telomerase-negative non-tumorigenic, SV-40 large-T antigen-transfected human ovarian surface epithelium (HOSE) cell lines were evaluated for endogenous RNA and protein expression of S3F, VEGF, and their shared receptors. Cultured cells were either treated with recombinant S3F protein or transiently transfected with cDNA to over-express S3F. Conversely, these cells were transiently transfected with siRNA targeting S3F ± specific receptor inhibitors. RT-PCR and western blot confirmed S3F over-expression, knock-down of S3F, or inhibition of receptors. Telomerase activity was measured by telomerase PCR-ELISA, while RT-PCR and western immunoblotting were utilized to detect S3F as well as to explore the signaling pathway involved in S3F-mediated telomerase regulation. Results: Telomerase activity was suppressed in ovarian cancer cell lines following treatment with S3F recombinant protein or S3F over-expression by transient transfection. Furthermore, siRNAs targeting S3F and NP-2 or treatment with the VEGF receptor inhibitor, CBO-P11, abrogated S3F mediated telomerase inhibition. Over-expression of S3F resulted in up-regulation of phosphorylation of Erk1/2. Conclusions: These data suggest that telomerase is a novel molecular target of S3F. Since, angiogenic and angiostatic factors play an important role in ovarian cancer tumorigenesis, S3F-mediated inhibition of telomerase represents a potential novel target for therapeutic intervention. 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 3208.
Treatment of Refractory Disseminated Nontuberculous Mycobacterial Infection With Interferon Gamma: A Preliminary Report
Authors: Steven M. Holland, Eli M. Eisenstein, Douglas B. Kuhns, Maria L. Turner, Thomas A. Fleisher, Warren Strober, John I. Gallin
Journal: New England Journal of Medicine (1994)

Studies conducted in vitro and in animals suggest that cytokine signals to monocytes or macrophages by interferon gamma are important in the containment and clearance of disseminated nontuberculous mycobacterial infections.
Amyloid deposits in the knee joint at autopsy.
Authors: C Ladefoged
Journal: Annals of the Rheumatic Diseases (1986)

Joint capsule, meniscus, and cartilage from the patella and medial femoral condyle from 30 non-selected autopsies have been investigated for amyloid deposits with light and electron microscopy. Both right and left knee joints from 28 of the 30 autopsy specimens contained amyloid deposits (93%). The amyloid characteristically showed green dichroism in polarised light after staining with alkaline Congo red. The ultrastructural features were also characteristic of amyloid. Amyloid in capsule tissue was found in a subsynovial location, as well as deeper in the capsule tissue, while in the cartilage amyloid was localised along the surface. The meniscus tissue, in particular, contained heavy deposits of amyloid--mainly along the inner margin. Osteoarthritic changes, with fibrillation of the cartilage, were significantly related to amyloid deposition. No pathogenetic correlation between the osteoarthritic changes and amyloid deposition could be shown in the present investigation.
WHAT IS THE IMPACT OF NEW OR PRESUMED NEW LEFT BUNDLE BRANCH BLOCK ON IN-HOSPITAL MORTALITY COMPARED TO KNOWN LEFT BUNDLE BRANCH BLOCK IN PATIENTS PRESENTING WITH SUSPECTED ACUTE CORONARY SYNDROME?
Authors: Pranav Kansara, Subba Reddy Vanga, Sandra Weiss, William S. Weintraub, Ehsanur Rahman
Journal: Journal of the American College of Cardiology (2014)
THE WELFARE OF THE COMMUNITY DEMANDS THAT MARRIAGE SHOULD BE REGULATED.
Authors: DANIEL R. BROWER
Journal: JAMA (1896)

The closing hours of the nineteenth century are full of marvelous results in science and art, and of wonderful progress in medicine and surgery, but in the midst of these brilliant achievements may be seen on every side insanity, pauperism, criminality and the degenerating effects of various vices of nutrition so rapidly increasing that they will overwhelm the race unless they can be arrested. These melancholy effects are produced, at least in part, by the violation of the laws of heredity, constantly taking place in unregulated marriages. Under our higher civilization abnormal man, be he defective, dependent or delinquent, is propagated, cultivated and protected, his feeble and crippled offspring are nursed to manhood and sent forth to produce their kind. Under savage and semi-civilized conditions these abnormalities are speedily extinguished, the deformed and the weaklings have no place in their system, and some way or other are soon cut off.
LG-03 * RADIATION THERAPY IS ASSOCIATED WITH INCREASED LATE MORTALITY IN LONG-TERM ADULT SURVIVORS OF CHILDHOOD LOW GRADE GLIOMA: A POPULATION BASED STUDY
Authors: R. Krishnatry, N. Zhukova, A. G. Stucklin, J. Pole, M. Mistry, V. Ramaswamy, U. Bartels, A. Huang, N. Laperriere, P. Dirks, S. Zelcer, M. Silva, D. L. Johnston, K. Scheinemann, C. Hawkins, P. Bandopadhayay, M. W. Kieran, P. E. Manley, E. Bouffet, U. Tabori
Journal: Neuro-Oncology (2015)

To uncover clinical risk factors and the impact of radiotherapy on children and adult survivors of childhood low grade glioma (PLGG).
ANALYSIS OF METHODS OF MODERN MEDICAL EDUCATION
Authors: WILLIAM COGSWELL CLARKE
Journal: JAMA (1923)

The dilemma which confronts us today in any consideration of medical education is two horned. On the one hand we have the vast and ever-increasing fund of information that must be given to the student, and on the other, the shortness of the allotted time in which to give it to him. Methods of teaching must be found that are best suited to the majority of students, and that will serve to prepare them for the practice of medicine or for a life of research. What should be taught must also be decided. The good and the bad in past and present medical education must be remembered in order to solve this problem. Present methods have failed to deal adequately with the difficulties of the situation, and, if they are persisted in, the purposes of the medical school will be increasingly defeated.  The day of the morphologic ultramechanical impress on
Opposing Effects of Apolipoprotein M on Catabolism of Apolipoprotein B–Containing Lipoproteins and Atherosclerosis
Authors: Christina Christoffersen, Tanja Xenia Pedersen, Philip L.S.M. Gordts, Anton J.M. Roebroek, Björn Dahlbäck, Lars Bo Nielsen
Journal: Circulation Research (2010)

Plasma apolipoprotein (apo)M is mainly associated with high-density lipoprotein (HDL). HDL-bound apoM is antiatherogenic in vitro. However, plasma apoM is not associated with coronary heart disease in humans, perhaps because of a positive correlation with plasma low-density lipoprotein (LDL).We explored putative links between apoM and very-low-density (VLDL)/LDL metabolism and the antiatherogenic potential of apoM in vivo.Plasma apoM was increased approximately 2.1 and approximately 1.5 fold in mice lacking LDL receptors (Ldlr(-/-)) and expressing dysfunctional LDL receptor-related protein 1 (Lrp1(n2/n2)), respectively, but was unaffected in apoE-deficient (ApoE(-/-)) mice. Thus, pathways controlling catabolism of VLDL and LDL affect plasma apoM. Overexpression (approximately 10-fold) of human apoM increased (50% to 70%) and apoM deficiency decreased ( approximately 25%) plasma VLDL/LDL cholesterol in Ldlr(-/-) mice, whereas apoM did not affect plasma VLDL/LDL in mice with intact LDL receptors. Moreover, plasma clearance of apoM-enriched VLDL/LDL was slower than that of control VLDL/LDL in mice lacking functional LDL receptors and LRP1, suggesting that apoM impairs the catabolism of VLDL/LDL that occurs independently of the LDL receptor and LRP1. ApoM overexpression decreased atherosclerosis in ApoE(-/-) (60%) and cholate/cholesterol-fed wild-type mice (70%). However, in Ldlr(-/-) mice the antiatherogenic effect of apoM was attenuated by its VLDL/LDL-raising effect.The data suggest that defect LDL receptor function leads to increased plasma apoM concentrations, which in turn, impairs the removal of VLDL/LDL from plasma. This mechanism opposes the otherwise antiatherogenic effect of apoM.
Long-Term Anticoagulants for Myocardial Infarction
Authors: Vernon E. Martens
Journal: JAMA (1965)

<h3>To the Editor:—</h3> In "Long-term Anticoagulant Therapy After Myocardial Infarction" (<i>JAMA</i><b>193</b>:929, 1965), a Veterans Administration Cooperative Study omitted reference to the significant follow-up studies of Benjamin Manchester, MD, reported in<i>Angiology</i>(<b>15</b>: 19, 1964), "Continuous Anticoagulant Therapy Following Myocardial Infarction." Previous communications by this author were also significant and I feel that the authors of the report inThe Journalmade a serious omission in not referring to them.
Abstract 4949: Epigenetic silence of <i>ASPP1</i> and <i>ASPP2</i> genes promotes tumor growth in HBV-positive hepatocellular carcinoma
Authors: Jian Zhao, Yajun Guo
Journal: Cancer Research (2010)

Abstract The Ankyrin-repeat-, SH3-domain- and proline-rich-region containing protein (ASPP) family of proteins regulates apoptosis through interaction with p53 and its family members. This study evaluates the epigenetic regulation of ASPP1 and ASPP2 in HBV-positive hepatocellular carcinoma (HCC) and explores the effects of down-regulation of ASPP1 and ASPP2 on the development of HCC. The expression of ASPP1 and ASPP2 was diminished in HCC cells by epigenetic silence owing to hypermethylation of ASPP1 and ASPP2 promoters as detected by methylation-specific PCR (MS-PCR) and 5-Aza-2′-Deoxycytidine treatment. Analyses of 51 paired HCC and surrounding non-tumor tissues revealed that methylation of ASPP1 and ASPP2 was associated with the decreased expression of ASPP1 and ASPP2 in tumor tissues (38.1% vs 6.7% in ASPP1, P = 0.018, and 50% vs 15% in ASPP2, P = 0.012). The correlations of the expression and the methylation of ASPP1 and ASPP2 with p53 gene status were further analyzed. HCCs harboring wild type p53 gene were more frequent to have decreased ASPP2 expression (P = 0.028). Whereas no statistic significance was found between down-regulation of ASPP1 and p53 gene status (P = 0.704). Methylation of ASPP1 and/or ASPP2 in the surrounding non-tumor tissues was closely related with the tumor size (P = 0.031) and the tumor stage (P = 0.010). This result indicates that methylation of ASPP1 and ASPP2 may participate in the early stage of neoplasia. Moreover, ASPP2 became methylated upon HBV X protein (HBx) expression. The expression of HBx enhanced the recruitment of DNMT1 and DNMT3A on ASPP2 promoter to initiate DNA methylation, and subsequent increased the binding of methyl-CpG binding proteins on its promoter to suppress ASPP2 expression. The suppressive effects on tumor growth by ASPP1 and ASPP2 were examined with RNA interference mediated gene silence. Down-regulation of ASPP1 and ASPP2 promoted the growth of HCC cells in soft agar and in nude mice, and decreased the sensitivity of HCC cells to apoptotic stimuli. In conclusion, ASPP1 and ASPP2 genes are frequently down-regulated by DNA methylation in HBV-positive HCC, which may play important roles in the development of HCC. These findings provide a new insight into the molecular mechanisms leading to hepatocarcinogenesis and may have potent therapeutic applications. 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 4949.
Preventing tobacco-caused cancer: a call to action.
Authors: C T Orleans
Journal: Environmental Health Perspectives (1995)

Nicotine addiction is the most common serious medical problem in the country. Tobacco use is responsible for 30% of cancer deaths in the United States and 90% of all lung cancer deaths. The physical addiction to nicotine explains why over 30% of Americans continue to smoke or use tobacco despite their desires and efforts to quit. The testimony summarized in this paper recommends four broad strategies for preventing tobacco-caused cancers in the United States: a) mandating and reimbursing effective treatments for nicotine addiction; b) increasing Federal and state tobacco excise taxes and earmarking a fraction of tax revenues for tobacco prevention and cessation; c) enacting other policy changes to prevent tobacco use and addiction among children, including expanded clean indoor air legislation, comprehensive youth tobacco access legislation, and the regulation of tobacco products and their advertising and promotion; and d) expanding tobacco control research and critical Federal research support. Specific recommendations are given for each broad strategy.
Injuries to Research Subjects
Authors: Philippe V. Cardon, F. William Dommel, Robert R. Trumble
Journal: New England Journal of Medicine (1976)

Abstract A task force of the Department of Health, Education, and Welfare conducted a survey aimed at estimating the incidence of research-related injuries, with a view to determining the feasibility of compensating subjects injured during research. The data were obtained by telephone from 331 investigators conducting research on nearly 133,000 human subjects over the past three years. Eighty-five investigators reported at least one injury. Of the 4957 reported injuries, 3926 were classified as trivial, and 974 as temporarily disabling; of 57 injuries resulting in death or permanent disability, one disabling stroke, not clearly related to the research, occurred three days after a nontherapeutic procedure; the rest resulted from treatments expected to benefit the patients directly, usually cancer chemotherapy. The data suggest that the risks of participation in nontherapeutic research may be no greater than those of everyday life, and in therapeutic research, no greater than those of treatment in other settings. (N Engl J Med 295:650–654, 1976)