tbuckley/cabot-search huggingface dataset:
Abstract 1385: PPARδ promotes mammary tumorigenesis through mTOR activation.
Authors: Robert I. Glazer, Hongyan Yuan, Geeta Upadhyay, Yuzhi Yin, Levy Kopelovich
Journal: Cancer Research (2013)

Abstract Background: Peroxisome proliferator-activated receptorδ (PPARδ) regulates a multitude of physiological processes associated with glucose and lipid metabolism, inflammation and proliferation. One or more of these processes are potential risk factors for the ability of PPARδ agonists to promote tumorigenesis in the mammary gland. In the present study, we describe a new transgenic mouse model in which activation of PPARδ by endogenous or synthetic ligands results in mammary neoplasia. Methods: Transgenic mice were generated in which expression of PPARδ was directed to the mammary gland under the control of the MMTV long terminal repeat. Results: Multiparous MMTV-PPARδ mice presented with infiltrating ductal carcinomas after a latency of 12 months. When transgenic animals were maintained on a diet supplemented with the PPARδ ligand GW501516, rapid progression to ductal and alveolar hyperplasia, dysplasia and ductal carcinoma in situ occurred within three months, and multifocal ductal carcinomas occurred after 5 months. Histopathological changes occurred in concert with a marked increase in phosphatidylcholine (PC) and lysoPC levels. Gene array profiling revealed an inflammatory, invasive, metabolic and proliferative signature denoted by enhanced expression of Saa1/2, S100a8, Klk6/7, Acsl4 and Plac1, and increased mTOR signaling. Treatment with the mTOR inhibitor, everolimus, dramatically reversed many of the histopathological and gene expression abnormalities. Conclusion: MMTV-PPARδ mice demonstrate a direct role for PPARδ in breast tumorigenesis that is linked to several previously unknown signaling processes. These findings suggest a rationale for new therapeutic approaches to prevent and treat this disease. Supported by 1N01CN43302-WA19 and 1P30CA51008 1st Choice Category: TB1 Cell Culture and Animal Models of Cancer Citation Format: Robert I. Glazer, Hongyan Yuan, Geeta Upadhyay, Yuzhi Yin, Levy Kopelovich. PPARδ promotes mammary tumorigenesis through mTOR activation. [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 1385. doi:10.1158/1538-7445.AM2013-1385
Progesterone and the premenstrual syndrome: a double blind crossover trial.
Authors: L Dennerstein, C Spencer-Gardner, G Gotts, J B Brown, M A Smith, G D Burrows
Journal: BMJ (1985)

A double blind, randomised, crossover trial of oral micronised progesterone (two months) and placebo (two months) was conducted to determine whether progesterone alleviated premenstrual complaints. Twenty three women were interviewed premenstrually before treatment and in each month of treatment. They completed Moos9s menstrual distress questionnaire, Beck et al9s depression inventory, Spielberger et al9s state anxiety inventory, the mood adjective checklist, and a daily symptom record. Analyses of data found an overall beneficial effect of being treated for all variables except restlessness, positive moods, and interest in sex. Maximum improvement occurred in the first month of treatment with progesterone. Nevertheless, an appreciably beneficial effect of progesterone over placebo for mood and some physical symptoms was identifiable after both one and two months of treatment. Further studies are needed to determine the optimum duration of treatment.
Gallium-67 Scintigraphy and F-18 Fluorodeoxyglucose Position Emission Tomography in Posttransplant Lymphoproliferative Disorder
Authors: Mei-Hsiu Pan, Yih-Leong Chang, Yen-Wen Wu, Chia-Hung Kao, Ruoh-Fang Yen
Journal: Clinical Nuclear Medicine (2004)

A 21-year-old man, who underwent heart transplantation 5 years earlier because of dilated cardiomyopathy, was admitted for recent onset of intermittent abdominal pain and poor appetite. Whole-body Ga-67 scintigraphy showed intense gastrointestinal uptake. Fluorodeoxyglucose position emission tomography (FDG PET) revealed hypermetabolism in the left lower neck, mediastinum, stomach, and extensively in a bowel loop. The histologic findings of a gastric biopsy through endoscopy disclosed the typical “starry sky” appearance of Burkitt’s lymphoma. Based on these findings, the patient was diagnosed as having a posttransplant lymphoproliferative disorder. Chemotherapy was then arranged for subsequent treatment.
Recent asthma exacerbations predict future exacerbations in children with severe or difficult-to-treat asthma
Authors: Tmirah Haselkorn, Robert S. Zeiger, Bradley E. Chipps, David R. Mink, Stanley J. Szefler, F. Estelle R. Simons, Marc Massanari, James E. Fish
Journal: Journal of Allergy and Clinical Immunology (2009)
Pathogenesis of experimental neonatal woodchuck hepatitis virus infection: Chronicity as an outcome of infection is associated with a diminished acute hepatitis that is temporally deficient for the expression of interferon gamma and tumor necrosis factor-alpha messenger RNAs
Authors: Ikuo Nakamura, James T. Nupp, Matthew Cowlen, William C. Hall, Bud C. Tennant, John L. Casey, John L. Gerin, Paul J. Cote
Journal: Hepatology (2001)

Surgical biopsies of the liver were obtained from woodchuck hepatitis virus (WHV)–infected neonatal woodchucks at 2 time points before the self–limited or chronic outcomes became obvious by serologic criteria. Following segregation of outcomes, livers were analyzed for intrahepatic type 1 cytokine messenger RNAs (mRNAs) (interleukin 2 [IL–2], interferon gamma [IFN–γ], tumor necrosis factor–alpha [TNF–α]) and leukocyte inflammatory phenotype (IgG + plasma cells, lysozyme + macrophages, CD3 + T cells). Baselines were assessed using age–matched uninfected control livers. At week 8 (early acute phase), intrahepatic type 1 cytokine mRNAs were similarly low in both outcome settings and no different from age–matched uninfected controls. This was consistent with the minimal initial viral loads and lack of histologic inflammation at this time. At week 14 (mid–acute phase), changes in viral load between outcome groups related inversely to the intrahepatic inflammatory responses. Animals that eventually became resolved had increased intrahepatic expression of IFN–γ and TNF–α mRNAs and robust inflammation by CD3 + T cells, plasma cells, and macrophages. At the same time point of infection, animals that eventually became chronic carriers had an acute hepatitis involving the same cell types, but at diminished levels, and markedly deficient intrahepatic expression of IFN–γ and TNF–α mRNAs. IL–2 mRNA remained at baseline control levels in both outcome groups. These cotemporal comparisons map a critical deviation in host response to the acute stage of an evolving chronic infection. They strongly suggest that increasing viral load and chronicity as an outcome of neonatal WHV infection result from a temporal deficiency in the acute intrahepatic effector mechanisms mediated by IFN–γ and TNF–α.
Treating homosexuality as a sickness: Summary of responses
Authors: Birte Twisselmann
Journal: BMJ (2004)

The two papers detailing the experiences of former patients and health professionals and the ensuing conflict between psychiatry and sexual orientation, accompanied by the Editor's choice on medicine's shameful past and the obituary of Judd Marmor, sparked a lively debate on bmj.com.1–4

Correspondents point out errors: it was not Marmor who declassified homosexuality but gay and lesbian …
BASEM revisited: getting to grips with the future
Authors: Eleanor J Tillett
Journal: British Journal of Sports Medicine (2013)

In this year's BASEM issue of BJSM we are reflecting back and looking forward; reflecting back on our 2012 congress and looking forward organisationally and educationally.

After a couple of challenging years, we were pleased that our 2012 congress received such good feedback from the delegates. One area which we were particularly glad to see so strongly represented were submissions for both the BASEM/Institute of SEM Prize for Sport and Exercise Medicine and the Tom Donaldson Poster Prize for Students. We displayed posters from across the breadth of research in sport and exercise medicine, and included in this issue are the abstracts from four of the prize winners ( see page 1133 ). It was particularly good to see exercise medicine so well represented in the posters.

On the second day, we …
Vascular Targeting as a Strategy for Cancer Therapy
Authors: J E Schnitzer
Journal: New England Journal of Medicine (1998)

New molecular techniques have yielded a battery of potential therapies for many diseases, but the clinical fruits of these methods have not been abundant, in part because in vitro models used for screening often do not duplicate in vivo conditions. For example, in vivo the microvascular wall prevents many intravenous agents with in vitro activity from reaching target cells in the tissue. Moreover, the magic bullet of cancer immunotherapy — antibodies conjugated to a drug or toxin — do not consistently hit their mark, because the bull's-eye on the other side of the vascular endothelium remains largely inaccessible to the . . .
Relationship between biochemical, virological, and histological response during interferon treatment of chronic hepatitis C
Authors: M L Shiffman, C M Hofmann, E B Thompson, A Ferreira-Gonzalez, M J Contos, A Koshy, V A Luketic, A J Sanyal, A S Mills, C T Garrett
Journal: Hepatology (1997)

The present study was conducted to evaluate the relationship between biochemical, virological, and histological response during the course of interferon therapy. Ninety consecutive patients with well-documented chronic hepatitis C virus (HCV) were treated with 5 MU of interferon alfa-2b three times weekly for 6 months. Liver biopsy was performed, and serum HCV RNA titer was measured before and at the completion of interferon treatment. Normalization of serum alanine transaminase (ALT) concentration (biochemical response) was observed in 50% of patients. In these patients, Knodell score declined significantly from 9.6 ± 0.5 to 5.0 ± 0.5 ( P &lt; .01), and 75% became HCV RNA negative. The remaining patients (50%) were biochemical nonresponders; mean Knodell score declined from 9.6 ± 0.5 to 7.7 ± 0.5 ( P &lt; .01), and 11% became HCV RNA negative. For both biochemical responders and nonresponders, the decline in Knodell score was confined to the components of hepatic inflammation (piecemeal necrosis + lobular + portal inflammation); no change in fibrosis was observed. Hepatic inflammation declined by 5 points or more in 69% of biochemical responders and 48% of biochemical nonresponders, and by at least 50% from pretreatment values in 74% and 38% of biochemical responders and biochemical nonresponders, respectively. For all patients (both biochemical responders and nonresponders) who remained viremic at the conclusion of interferon therapy, the reduction in hepatic inflammation was a linear function of the decline in HCV RNA titer. We conclude that more than one third of patients who had no biochemical response after 6 months of interferon therapy achieved a similar improvement in hepatic histology as was observed in patients with biochemical response. This improvement in hepatic histology appeared to correlate with a reduction in HCV RNA titer, especially in patients who remained viremic.
Long-term complications of valve replacement.
Authors: C M Oakley
Journal: BMJ (1982)

Long-term complications of valve replacementThe main long-term complications of heart valve replacement are valve failure, myocardial failure, thromboembolism, and prosthetic endocarditis.With the exception of endocarditis these risks differ greatly with the prosthesis, the implantation site, and the original disease.Most mechanical valves have a good record of reliability,' 2 and tissue valves have a low risk of embolism3-6; but the durability of the latter7-9 and the embolic risks of the former10 remain major causes for concern.The operative mortality for elective replacement of the aortic valve is usually under 500, and in general the results are excellent even though many of the patients are elderly."Almost no patient is unsuitable.Calcific aortic stenosis of well because there is little room in the right ventricle for a cage or for a pivoting disc, and tricuspid stenosis is sometimes
Thresholds for taking antihypertensive drugs in different professional and lay groups: questionnaire survey
Authors: N. Steel
Journal: BMJ (2000)

Hypertension is a common risk factor for cardiovascular disease, but patients' compliance with medication is low. Patients may be less likely to take antihypertensive drugs if they have accurate information about their levels of risk.1 Doctors who estimate the risk more accurately are less likely to recommend treatment.2 It is not known whether a patient's professional background affects his or her threshold for complying with treatment.

The study compared the threshold at which consultant physicians, general practitioners, nurses attached to a general practice, and the general population would start taking antihypertensive drugs.

A postal questionnaire asked whether or not respondents would take drugs if one life would be saved for every 12, 33, 50, 100, or 250 people treated for five years. This gave six thresholds of numbers needed to treat (<12 to 250).

A pilot study showed that a sample …
Boundaries in the Physician-Patient Relationship-Reply
Authors: Carol Nadelson
Journal: JAMA (1995)

<h3>In Reply.</h3> —Based on the comments of Dr Fay and Dr Lazarus, we can only conclude that they have misread our article. We do not believe that all forms of physician self-disclosure are harmful. In our article, we are quite clear that we are referring to the physician's disclosure of personal problems to the patient in a manner that burdens the patient. If Fay will review the references he cites on outcome data when therapist self-disclosure was used, he will discover that these studies did not involve the revelation of serious personal problems to the patient. While Fay accuses us of errors in fact and logic, we can assure him from our extensive clinical experience evaluating and treating physicians charged with boundary violations that the slippery slope phenomenon is pervasive in these cases. We agree that all instances of overstepping boundaries do not lead to more serious violations such as
Medicaid Payments and Access to Care
Authors: Sara Rosenbaum
Journal: New England Journal of Medicine (2014)

Interview with Prof. Sara Rosenbaum on Medicaid payments, physician participation, and access to care. (17:38)Download Medicaid has long faced relatively low physician participation, at least in part because of low payment rates. Some beneficiaries and providers have turned to litigation claiming inadequate access to care, but there may be no remedy in the courts.
The Use of Cancer Registry Data to Study Preoperative Carcinoembryonic Antigen Level as an Indicator of Survival in Colorectal Cancer
Authors: S. F. Sener, J. P. Imperato, J. Chmiel, A. Fremgen, J. Sylvester
Journal: CA A Cancer Journal for Clinicians (1989)

A retrospective analysis of survival results for colorectal cancer patients in Illinois was performed by the Cancer Incidence and End Results Committee of the Illinois Division of the American Cancer Society. Cancer registry data on 1,774 patients from 63 hospitals were used to investigate whether the preoperative level of serum carcinoembrvonic antigen (CEA) was a prognostic indicator of survival for cancers diagnosed between 1976 and 1978. A direct relationship was found between the preoperative level of serum CEA and both the thickness and stage of the tumor at initial diagnosis. For Stage B2/3 colorectal cancer, the actuarial survival curves corresponding to normal, elevated, and markedly elevated CEA levels were significantly different (p < 0.0001). The five-year survival rates for these patients were 61. 50, and 32 percent, respectively. Similar trends for patients with Stage C2/3 cancer were observed (p = 0.0058). The corresponding five-year survival rates were 44, 30, and 26 percent, respectively. Using a statewide cancer registry system, the analysis suggested that the pre-operative level of serum CEA was an indicator of survival in patients with colorectal cancer, independent of the stage of disease at diagnosis.
Biliary stenting of an iatrogenic esophageal perforation following corrosive esophagitis in a 5-year-old child
Authors: O. Ruthmann, S. Richter, A. Fischer, K. Rückauer, U. Hopt, H. Schrag
Journal: Endoscopy (2009)

Most esophageal perforations are iatrogenic in origin (0.01 % – 55 %) [1] [2] [3], and traumatic defects are still associated with high mortality, ranging between 12 % and 50 % [4]. Clinically, early identification and treatment of the problem is necessary, but guidelines for effective management have not been established.
Bone marrow examination has limited value in the staging of patients with an anaplastic large cell lymphoma first presenting in the skin. Retrospective analysis of 107 patients
Authors: M.F. Benner, R. Willemze
Journal: British Journal of Dermatology (2008)

According to criteria of the World Health Organization-European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas a diagnosis of primary cutaneous CD30-positive anaplastic large cell lymphoma (C-ALCL) should be made only when systemic localizations have been excluded by adequate staging procedures, including a bone marrow biopsy. It has recently been questioned whether or not bone marrow examination should be performed routinely in indolent cutaneous lymphomas such as C-ALCL. Studies addressing this issue have never been performed.To determine the incidence of bone marrow involvement in patients with an ALCL first presenting in the skin to find out if the current policy to advise bone marrow examination should be maintained or whether a bone marrow biopsy should be performed only in selected cases.All patients presenting with skin lesions with histological and immunophenotypical features of an ALCL were retrieved from the database of the Dutch Cutaneous Lymphoma Group. Patients with a history of systemic ALCL and patients without bone marrow examination were excluded from the study. The final study group included 107 patients with an ALCL first presenting in the skin, who had been staged completely.Staging procedures showed the presence of extracutaneous disease in 20 patients, but bone marrow involvement was not detected in any of the 107 patients. Moreover, only one patient developed bone marrow involvement during follow up (median follow-up period 69 months).Bone marrow examination has limited value in the staging of patients with an ALCL first presenting in the skin, and should be performed only in selected cases.
In Time of Change, USSR Seeks to End Tradition of Extensive Alcohol Use by Majority of Citizens
Authors: Timothy F. Kirn
Journal: JAMA (1987)

"NYET, NYET," said Daniel J. Anderson, PhD, leaning over a small table, pounding his fist through the air above it. He was predicting the reaction of the visiting delegation of Soviet alcohol-abuse officials to an upcoming presentation of the Hazelden Foundation's (Center City, Minn) new model of "chemical health." Anderson, the foundation's president emeritus, was both dreading a contretemps and itching for a lively debate. As its name implies, the model is a blueprint for promoting healthy and responsible alcohol/chemical use by preventing abuse, responding to problems, and encouraging healthy life-styles. It works at two levels, both as a prescription for treating the alcohol/chemical abuser and as a rough outline for society-wide efforts, says Anderson (whose work in the alcoholism field was recognized a few weeks ago by the University of Minnesota, which presented him with an honorary doctorate). Anderson's Soviet guests, three members of the All-Union Voluntary Temperance Promotion
10-minute consultation: Rhinitis
Authors: S. Walker
Journal: BMJ (2002)

A woman presents in early summer with a history of progressively worsening symptoms of a constant runny nose and frequent sneezing bouts.She was prescribed antihistamine tablets many years ago, which were helpful but made her drowsy.Lately, she has used "over the counter" decongestant nasal sprays, which, although initially helpful, now do not relieve symptoms.Tired and upset, she wants to know what else might help.
Systemic lupus erythematosus and invasive thymoma: report of two cases.
Authors: M.M Steven, M.L Westedt, F Eulderink, H.M Hazevoet, J.H Dijkman, A Cats
Journal: Annals of the Rheumatic Diseases (1984)

Two cases of invasive thymoma in patients with systemic lupus erythematosus (SLE) are described. In both instances the suspected diagnosis of a mediastinal tumour proved difficult to confirm. Neither surgical removal of the thymoma in one case nor irradiation in the other had any apparent clinical or serological effect on the course of the SLE. Both patients subsequently suffered from respiratory problems and the distinction between recurrent tumour and pulmonary involvement by SLE proved difficult. One patient had a good response, however, to pulse methylprednisolone, but the other later developed recurrence of tumour and died of Pneumocystis carinii infection following cytotoxic therapy three years after discovery of the tumour.
Convulsions during Delirium Ebriosum
Authors: W. Griffith
Journal: BMJ (1843)

as to the power thc patient has to contend against thc depressinig effccts of suppuratioii and irritationi; thc surgconi feclinlg satisfied that, if thlcrc be sufficient stamnina to withstand the effects of thc discharge, the p)aticilt will recover.Where, however, thc injury is of suclh a character as to preclude the possibility of :3aving tllh limb, anid amputation becomes a mere quiestion of time, the first favorablc opportunlity must be embraced for the operation. CONVULSIONS DURINCG
All applicants to medical school should be interviewed
Authors: Des Spence
Journal: BMJ (2012)

I manipulate online self testing questionnaires for attention deficit hyperactivity disorder, bipolar 2, oppositional defiant disorder, and the rest. I guess the answers to get my diagnosis. I have never failed yet. Likewise, I pore over the Diagnostic and Statistical Manual (DSM) definitions of personality disorders—narcissistic, antisocial, histrionic, and paranoid—recognising all these traits in myself. Obviously these are to be expected in a columnist. These psychological and psychiatric descriptions are interesting and to some extent useful, but are in reality just inadequate cardboard cut-out caricatures, failing to encapsulate even a …
Let’s wave goodbye to “transplant tourism”
Authors: Leigh Turner
Journal: BMJ (2008)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Let’s wave goodbye to “transplant tourism” Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
How dangerous are falls in old people at home?
Authors: D Wild, U S Nayak, B Isaacs
Journal: BMJ (1981)

From a survey in six general practices information was obtained on 125 people aged 65 and over who fell in their own homes. Three fractured their femurs and 15 had other fractures; most of the rest suffered only trivial injuries. Twenty lay on the floor for more than one hour; none were known to have suffered hypothermia. One-quarter of these patients died within one year of the fall, five times as many as in an age- and sex-matched control group; while of those who lay on the floor for more than one hour, half died within six months of the fall. Factors associated with mortality from falls were impaired mobility, abnormal balance, and a disturbed pattern of gait. Falls at home in old age are often indicative of the presence of severe ill health.