tbuckley/cabot-search huggingface dataset:
Abstract LB-60: Long-term use of hormone therapy and breast cancer incidence and mortality
Authors: Wendy Y. Chen, Walter C. Willett, Susan E. Hankinson, Bernard A. Rosner
Journal: Cancer Research (2012)

Abstract Background: The risk of breast cancer associated with longer-term use of both estrogen (ET) or estrogen + progesterone (E+P) hormone therapy (HT) cannot be determine from existing randomized controlled trials. Methods: The Nurses’ Health Study included 121,700 female registered nurses aged 30-55 in 1976 who have been followed with biennial questionnaires to medication use, risk factors and cancer incidence. Only postmenopausal women were included in this analysis. The main outcome was incidence of invasive breast cancer. We additionally evaluated the risk of fatal breast cancer (breast cancer diagnosis that resulted in breast cancer death). Results: During 1.57 million person-years of follow-up from 1980 through 2008, 5631 incident invasive breast cancers were diagnosed and 884 died of breast cancer. Breast cancer risk increased with duration of current E+P use without evidence for a plateau (e.g. RR 1.88 (95% CI 1.64-2.16) for 10-14.9 years and RR 2.35 (95% CI 1.90-2.92) for 15-19.9 years of use). More than 10 years of current ET use was also associated with increased breast cancer risk (RR 1.22 (95% CI 1.06-1.40) for 10-14.9 years and RR 1.43 (95% CI 1.22-1.68) for 15-19.9 years of use). Past E+P was also weakly associated with breast cancer risk. When the population was restricted to the same entry criteria as the Women's Health Initiative trial, we also observed a non-significant deceased risk of breast cancer HT with current ET use similar in magnitude to that seen in the trial (RR 0.61 (95% CI 0.63-1.05) for &amp;lt; 5 years and RR 0.93 (95% CI 0.76-1.14) for 5-9.9 years), but still observed an increased risk with current ET users of 15-19.9 years (RR 1.30 (95% CI 1.07-1.59). Effects were stronger for ER positive tumors and among thinner women. Results were similar when limited to women who underwent regular screening. Although breast cancer incidence was increased in these groups, there was no increase in the risk of fatal breast cancer with either E+P or ET use (RR 1.05 (95% CI 0.67-1.68) and RR 1.08 (0.80-1.46) for 10-19.9 years of current use respectively). Conclusions: Both past and current E + P users and current long-term ET users were at increased breast cancer risk. We did not observe an increase in fatal breast cancer with HT use. 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 LB-60. doi:1538-7445.AM2012-LB-60
Osseous Localization of Non-Hodgkin Lymphoma Shown on Tc-99m HMPAO-Labeled Leukocyte Scintigraphy
Authors: Christianne S J  Duchateau, Patrick A Brouwer, Marcel P M Stokkel
Journal: Clinical Nuclear Medicine (2003)

J. DUCHATEAU, CHRISTIANNE S. M.D.; BROUWER, PATRICK A. M.D.; STOKKEL, MARCEL P. M. M.D., Ph.D. Author Information
Comparison of the Transcriptional Response to Fulvestrant and Oestrogen Deprivation in ER-Positive Breast Cancer in Vitro and in Vivo
Authors: N. Patani, A. Dunbier, H. Anderson, E. Anderson, Q. Gao, A. Mackay, Z. Ghazoui, I. Kuter, L. Martin, M. Dowsett
Journal: Annals of Oncology (2013)
Vincent James Marmion
Authors: Emma Prower
Journal: BMJ (2015)

Vincent James Marmion was born in Birkenhead. His medical training started in Edinburgh with premedical studies, after which he went to Queen’s University Belfast, where he qualified in December 1950. He was awarded the Magrath clinical scholarship in obstetrics and gynaecology in his final MB.

His first job was in Belfast, where he spent five years in general practice as well as demonstrating in physiology at Queen’s University, and working part time as a clinical assistant in ophthalmology. He became a member of the Royal College of Physicians, Edinburgh, in 1960 and a fellow of the Royal College …
FRI0117 Diabetes in rheumatoid arthritis: Incidence and association with RA treatment
Authors: M. Holmqvist, F. Wolfe, K. Michaud
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Studies indicate that different RA-treatments are associated with a decreased risk of type 2 diabetes mellitus (DM), a strong risk factor for cardiovascular disease in the general population.ion. <h3>Objectives</h3> To estimate the incidence rate and standardized morbidity ratio (SMR) of DM in RA, and to assess the influence of RA-treatment on DM risk in RA. <h3>Methods</h3> We identified RA-patients participating in a longitudinal prospective observational study of rheumatic diseases in the US from 2000 through 2010. All were diagnosed by a rheumatologist and completed at least two semi-annual questionnaires. DM was determined by patient self-report or use of any DM-specific medication. Patients with DM at enrollment were excluded from analyses. Participants provided all treatments taken. SMRs were estimated using the Centers for Disease Control and Prevention reported incidence rate of DM for the US stratified by calendar year, sex and age. Cox proportional hazard models were used to estimate hazard ratios (HR) to compare the 6-month lagged association of treatment with DM risk. Adjustments were made for baseline age, sex, RA-duration, ethnicity, employment status, total income, smoking status, comorbidity index, HAQ and body mass index (BMI). <h3>Results</h3> In total, 10,853 RA-patients were included with 695 (6.4%) having DM during followup.At baseline, mean (SD) RA duration was 13.6 (11.3) years and age was 59.5 (13.2) years. Baseline mutually exclusive treatment groups included 24.6% on at least hydroxychloroquine (HCQ), 30.0% on methotrexate (MTX) alone or with TNF-inhibitor, and 42.4% on other or no DMARDs. The incidence rate (95% CI) for DM was 1.34 (1.2-1.5) per 100 person-years, and the corresponding SMR was 1.2 (1.1-1.3). After adjustments, the only individual treatments significantly associated with DM were HCQ, HR 0.59 (0.48-0.73); MTX, HR 0.8 (0.7-0.9); golimumab, HR 12.3 (3.6-41.5); and prednisone, HR 1.3 (1.1-1.5). Mutually exclusive treatment groups showed a differential effect of MTX and TNF based on being on prednisone or not; protective effects of MTX with or without TNF (HR 0.8, 0.7-1.0) in individuals not on prednisone, but not in individuals on prednisone (HR 1.1, 0.8-1.3). HCQ with prednisone was still protective, HR 0.6 (0.4-0.9). Of all risk factors tested, BMI had the greatest association with DM followed by HCQ usage. <h3>Conclusions</h3> HCQ usage in RA patients was associated with a decrease in DM incidence independent of other treatment and covariate adjustments while MTX alone and MTX with anti-TNF therapy was similarly protective when prednisone was not concomitant. <h3>Disclosure of Interest</h3> None Declared
AB0171 Improved radiological outcome of rheumatoid arthritis (ra): evidence for early treatment with methotrexate (mtx) as a key prognostic factor
Authors: E. Belke-Voss, C. Fiehn, D. Krause, S. Wassenberg, R. Rau
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To compare the rate of radiological progression in patients with RA firstly diagnosed in the 1980s with those of the late 1990s until the era of biologic drugs and to evaluate key factors for differences in prognosis. <h3>Methods</h3> 92 RA patients who were firstly seen in our clinic from 1997 to 2005 were identified. As a control group, 89 RA patients from 1986 to 1990 were matched for the criteria disease duration, age and number of x-ray controls from hands and forefeet. Radiological erosivity was measured by the Ratingen-Score (RS). <h3>Results</h3> The initial RS was significantly lower in the 1997-2005 group in comparison to the 1986-1990 group (mean 3.8 ± 8.7 versus 7.7 ± 13.0 respectively, p&lt;0.0001). Moreover, in the follow-ups the group 1997-2005 showed significantly less radiological progression than the group 1986-1990 (maximum mean Ratingen-Score 7.9 ± 13.3 versus 29.3 ± 27.9 respectively, p&lt;0.0001). The most marked difference in treatment characteristics was a higher rate of patients who received MTX prior to the first consultation (35% versus 1%) and during follow-ups (73% versus 28%) in the 1997-2005 group compared to the 1986-1990 group. In 63 patients firstly seen from 2000 on, 21 (23%) patients received biologic drugs, mainly TNF-inhibitors during follow-ups. However, in comparison to those from 1997-1999 (n=25), therefore directly before approval of TNF-inhibitors, no difference in radiological erosivity was seen. Multivariant analysis showed that early start of MTX was a significant predictor of low radiographic progression (p&lt;0.005), as were low ESR at baseline and belonging to the later group. In contrast, neither treatment with glucocorticoids or biologic drugs nor the overall rate of MTX-use were predictive. <h3>Image/graph</h3> <h3>Conclusions</h3> The results of this study indicate that radiological erosivity of RA patients is markedly diminished since mid of the 1990s. The high rate of early treatment with MTX seems to be a key factor for this improved prognosis. <h3>Disclosure of Interest</h3> None Declared
Hospitals and care homes that fail to provide basic care will face prosecution, says UK regulator
Authors: C. White
Journal: BMJ (2013)

The performance of hospitals and care homes is to be subject to a new tier of inspection criteria that will include basic standards of care, such as whether an individual has been given adequate food and drink, a senior adviser at the Care Quality Commission has said.

Alan Rosenbach, special policy adviser at the CQC, said that providers that fail to deliver the basics will be fast tracked to prosecution under new powers awarded to the regulator. The new powers will include the ability to place providers into a “quality failure regime.” 

In what he described as “a shocking indictment” of the system, Rosenbach told delegates at the National Ageing Population Conference in London on 24 September that the government …
Medical Problems of Musicians
Authors: Alan H. Lockwood
Journal: New England Journal of Medicine (1989)

Abstract Surveys of performing musicians indicate that almost half of them experience playing-related medical problems, some of which threaten or end their careers. Overuse injuries involving the muscle—tendon unit are the most common problem, with symptoms ranging from mild pain while the musician is playing to pain severe enough to preclude any use of the affected hand. String players are the most commonly affected, and percussionists the least. The most important predisposing characteristic is the use of repetitive movements during long hours of practice, but awkward body positions man-dated by the shape and weight of the instrument, the technical difficulty of the repertoire, and unfamiliar instruments may also play a part. Women are more commonly affected than men. Rest is the cornerstone of therapy. Neural impingement syndromes affecting the median or ulnar nerves or the thoracic outlet affect many musicians. Focal dystonias may involve part or all of a hand or the muscles forming the embouchure (the position of the lips in wind players). These are very resistant to therapy and may terminate or drastically alter a career. Stress, especially performance anxiety, may impede performance. Beta-adrenergic blocking agents prevent the symptoms of performance anxiety and are frequently used by musicians without medical supervision. A recognition of the unique problems of musician-patients has led to the formation of successful specialty clinics in a number of cities. (N Engl J Med 1989; 320:221–7.)
Maternal-Fetal Relation
Authors: Ross E. Rocklin, John L. Kitzmiller, Charles B. Carpenter, Marvin R. Garovoy, John R. David
Journal: New England Journal of Medicine (1976)

We investigated an immunologic mechanism that might explain the apparent "tolerant" state of the mother during pregnancy. Cellular-immune reactivity in vitro to paternal alloantigens was demonstrated in multigravid women by production of lymphocyte migration inhibitory factor. Serum from normal multigravid women contained a factor that blocked production of migration inhibitory factor by maternal lymphocytes to paternal antigens in a specific manner. The blocking factor was an IgG antibody whose activity was removed by absorption with paternal lymphocytes but not with pooled human platelets. We tested the biologic importance of this blocking factor in women who have difficulty maintaining a normal term pregnancy. Our observations indicate that women who experience idiopathic spontaneous abortions produce lymphocyte migration inhibitory factor to paternal alloantigens, but their serums lack the blocking factor. The presence of the serum blocking factor during pregnancy may contribute to the success of the fetus as an allograft.
Abstract 4535: MDM2 inhibitor MI-319 in combination with cisplatin/oxaliplatin is an effective treatment for pancreatic cancer independent of p53 function
Authors: Asfar S. Azmi, Philip A. Philip, Amro Aboukameel, Sanjeev Banerjee, Zhiwei Wang, Shaomeng Wang, Dajun Yang, Fazlul H. Sarkar, Ramzi M. Mohammad
Journal: Cancer Research (2010)

Abstract Pancreatic cancer (PC) is considered to be among the most intractable malignancies as it is refractory to chemotherapy and radiation. Among the various genetic alterations in PC, mutation in the tumor suppressor p53 (mut-p53) gene has been reported to be about 50%. In the remaining 50%, the p53 is normal, but its function is inhibited by MDM2 protein which plays a key role in promoting ubiquitination and proteasomal-dependent degradation of p53. An attractive approach to p53 activation is the use of MDM2 inhibitors that disrupt the MDM2-p53 interaction and restore the p53 function. However, these small molecule inhibitors (SMIs) are not effective against tumors with mut-p53. Our group has designed a new class of SMI of MDM2 that is different from Nutlin-3. Here we are reporting, for the first time, that MI-319 can induce cell growth inhibition and apoptosis in PC irrespective of p53 mutational status when combined with cisplatin/oxaliplatin. MI-319-cisplatin or oxaliplatin combination synergistically suppressed cell growth (MTT CI&amp;lt;1), colony formation (clonogenic assay) and induced apoptosis in both mut-p53 Colo-357, BxPC-3 and Panc-28 or wt-p53 Capan-2 cells. Western blot analysis and siRNA silencing studies in mutant as well as p53 null cells highlighted a mechanism involving p73 which is under the regulation of MDM2, and unlike p53, it is rarely mutated in PC. In order to substantiate its in vivo relevance we tested this potent combination in mice xenograft models carrying Capan-2 and BxPC-3 tumors. 4 groups, each containing 8 animals were treated either with; Control (Vehicle only), MI-319 treated 200mg/Kg orally twice a day for three weeks, Cisplatin treated 4 mg/kg (i.v.) twice a week for two weeks and combination treated (MI-319 200 mg/Kg orally + Cisplatin 4 mg/kg). The combination effectively reduced tumor growth in both wt-p53 and mut-p53 tumor xenograft models (50% Capan-2 animals were tumor free). Consistent with our in vitro results, remnant tumor tissue analysis showed up-regulation of p73 and the cell cycle regulator p21. In conclusion, this study highlights a new role of MDM2 inhibitors in combination with cisplatin or oxaliplatin, and thus warrants further clinical investigation in human pancreatic tumors containing both wt-p53 and mut-p53. 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 4535.
Phenytoin Therapy of Recessive Dystrophic Epidermolysis Bullosa
Authors: Eugene A. Bauer, Thomas W. Cooper, Dolores R. Tucker, Nancy B. Esterly
Journal: New England Journal of Medicine (1980)

We administered phenytoin (diphenylhydantoin) by mouth to 17 unselected patients to assess its ability to reduce blistering in recessive dystrophic epidermolysis bullosa (RDEB). Therapeutic response was correlated with blood levels of the drug. Although there was a decrease in blistering of 53 +/- 6 per cent (mean +/- S.E.) among all patients at levels of more than 8 microgram of phenytoin per milliliter, the response was variable, with 12 of 17 patients having a decrease in blistering of more than 40 per cent. Since increased collagenase in human skin has been implicated in the pathogenesis of blistering in RDEB, we examined the effect of phenytoin on this enzyme. Although the drug did not inhibit collagenase activity directly, its addition to human-skin explant and fibroblast cultures produced a 50 to 60 per cent decrease in collagenase activity and immunoreactive protein concentrations. These in vitro studies suggest that phenytoin inhibits synthesis or secretion of collagenase of both, and that the favorable clinical response can be explained by this inhibition.
Book: Patients, Power and Politics: From Patients to Citizens
Authors: S. Ellis
Journal: BMJ (1999)

Christine Hogg Sage, £16.99, pp 219 ISBN 0 7619 5878 9 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> For most of the time for most people, health services are not important, and yet, as Christine Hogg reminds us, "Everyone of us is at some time or another a patient." This fate is as inevitable as death and taxes, and, like their attitude to these other eternal verities, people often feel powerless when confronted by it. In the 20 years that I have been involved with campaigning about healthcare issues I have continually had to struggle with … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
Study of nonionizing microwave radiation effects upon the central nervous system and behavior reactions.
Authors: M G Shandala, U D Dumanskiĭ, M I Rudnev, L K Ershova, I P Los
Journal: Environmental Health Perspectives (1979)

The biologic effect of an electromagnetic field of a frequency of 2375 +/- 50 MHz was studied in rats and rabbits in specially constructed absorbant chambers. The results of the investigations have shown that microwave radiation of 10, 50, 500 mu W/cm2 for 30 days, 7 hr/day, causes a number of changes in bioelectric brain activity and also in behavioral immunological, and cytochemical reactions. It was found that levels of 10 and 50 mu W/cm2 stimulate the electric brain activity at the initial stage of irradiation, while a level of 500 mu W/cm2 causes its suppression, as seen from the increase of slow, high amplitude delta-waves. At 500 mu W/cm2 a decrease in capacity of work, in value of unconditioned feeding stimulus, in investigating activity, electronic irradiation threshold, and in inhibition of cellular and humoral immunity were also observed.
COARCTATION MAY BE ASSOCIATED WITH MORE RAPID AORTIC DILATION IN INDIVIDUALS WITH BICUSPID AORTIC VALVE: INSIGHTS FROM THE GENTAC REGISTRY
Authors: Maria Yates, Claudia Pedroza, Weilu Han, Federico Asch, GenTAC Consortium, Siddharth Prakash
Journal: Journal of the American College of Cardiology (2015)
SP0010 Autoreactive B Cells in RA - What do Cloned ACPA Tell Us
Authors: V. Malmström
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Approximately 2/3 of RA patients develop antibodies towards a common posttranslational modification - citrullination. Such anti-citrullinated protein antibodies, ACPA, are strongly associated with the HLA-DR locus but consist of multiple fine specificities towards several different proteins. The strongest HLA association is seen for autoantibodies to citrullinated a-enolase and vimentin, while ACPA also targets additional proteins such as fibrinogen. Whether ACPA represents a cause or a consequence remains a matter of discussion. Especially given the appearance of such autoantibodies many years prior to clinical onset, which suggests dissociation from joint disease. Also, many of the proteins that ACPA target are not joint-restricted, but of ubiquitous nature. In order to dissect the contribution of ACPA to disease manifestations, we have established a technology to clone and express the immunoglobulin genes from patient-derived B cells. The molecular information generated from the sequences gives clues to the mutation and maturation processes the B cell has undergone. This may prove useful to address the issue whether some ACPA may be the result of innate rather than adaptive immune responses. The generated recombinant monoclonal antibodies represents tools to dissect pathogenic effects mediated by ACPA in vitro as well as in experimental systems. We are utilizing this approach to study B cells from different anatomical sites, with synovial fluid being the proof-of-principle study (Amara et al J Exp Med 2013, 210:455-55). <h3>Disclosure of Interest</h3> None Declared
Abstract 4057: Negative regulation of prostate specific membrane antigen by androgen is mediated by <i>TMPRSS2-ERG</i> gene fusion in VCaP prostate cancer cells
Authors: Lihong Yin, Pravin Rao, Jianghua Wang, Michael Ittmann, Warren D.W. Heston
Journal: Cancer Research (2010)

Abstract Prostate specific membrane antigen (PSMA) is a type II transmembrane glycoprotein over-expressed in prostate carcinoma. Elevated PSMA expression has been correlated with aggressive disease and risk of early recurrence after radical prostatectomy. This molecule is also expressed in the neovasculature of multiple nonprostate solid tumors. Consequently, this unique cell marker has been targeted for diagnosis and therapy of prostate cancer (PCa) and other malignancies. Recently studies have shown that a significant fraction of PCa harbor a signature gene fusion between the androgen-responsive TMPRSS2 gene and transcription factors in the ETS family - most commonly ERG. The TMPRSS2-ERG fusion is likely the cause for over-expression of ERG in PCa. PSMA, unlike ERG, is negatively regulated by androgen. Elucidation of the relationship between TMPRSS2 gene fusions and PSMA expression could reveal mechanisms to alter PSMA expression and disease course. The purpose of this investigation was to determine whether PSMA gene expression could be regulated by the TMPRSS2-ERG fusion in prostate cancer cells. We employed VCaP cells, which harbor TMPRSS2-ERG fusion, and LNCaP cells, which lack the fusion. Our data showed that after 24h androgen R1881 treatment, ERG and TMPRSS2-ERG mRNA level were increased in VCaP cells and unchanged in LNCaP cells. PSMA and androgen receptor (AR) mRNA level were dramatically decreased in VCaP cells and only modestly decreased in LNCaP cells. Treatment with the androgen antagonist flutamide partially restored PSMA and AR expression in androgen-treated VCaP cells. Knocking down ERG by siRNA in VCaP cells enhances PSMA expression both in the presence and absence of R1881. When LNCaP cells transfected with TMPRSS2-ERG fusion transcripts, PSMA was down-regulated both in the presence or absence of R1881. Using PSMA-based luciferase reporter assays, we found TMPRSS2-ERG fusion can inhibit PSMA activity at the transcriptional level. Our data indicated that negative regulation of PSMA by androgen is mediated by TMPRSS2-ERG gene fusion in VCaP prostate cancer cells. 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 4057.