tbuckley/cabot-search huggingface dataset:
Abstract 549: Role of the glucocorticoid receptor in skin carcinogenesis and stem cell maintenance: Implication for the use of selective GR activators (SEGRA) as anti-cancer drugs
Authors: Gleb Baida, Joyce Rundhaug, Pankaj Bhalla, Irina Budunova
Journal: Cancer Research (2012)

Abstract Glucocorticoids are important physiological and pharmacological regulators of epidermal proliferation, differentiation and skin tumorigenesis. The glucocorticoid effects are mediated via the glucocorticoid receptor (GR), a transcription factor that regulates genes expression by DNA-binding dependent transactivation, and DNA-binding independent transrepression through negative interaction with other transcription factors. Our previous studies demonstrated that keratin5.GR transgenic animals are resistant to skin carcinogenesis. We also found that GR diminishes the number of follicular epithelial stem cells (SC), reduces their proliferative and survival potential and affects the expression of follicular SC “signature” genes. To further explore the tumor suppressor role of GR in skin carcinogenesis we generated skin-specific GR knockout animals by breeding of GRflox/flox animals with Keratin5.Cre recombinase animals in C57Bl genetic background. Skin-specific GR KO (Cre/GRfl/fl) mice do not have gross skin or hair phenotype. However, the detailed analysis of keratinocyte markers revealed decreased expression of some intermediate/late markers of differentiation including Keratin 10 and loricrin. We also found that Cre/GRfl/fl mice are more sensitive to the effects of UV irradiation and tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA). The ongoing DMBA/TPA skin carcinogenesis experiment showed that Cre/GRfl/fl mice are more prone to skin carcinogenesis: they have higher tumor incidence and tumor multiplicity compared to GRfl/fl littermates. The analysis of global effect of the GR overexpression and GR silencing on gene expression in follicular epithelial SC, basal keratinocytes, and mouse skin tumors 1) revealed important GR targets in keratinocytes including STAT3 and REDD1 - the major regulator of mTOR; 2) provided an unexpected evidence that gene transrepression by GR plays critical role in the maintenance of SC and in inhibition of skin carcinogenesis. It is well understood that therapeutic effects of glucocorticoids are mediated by GR transreprssion, while many adverse metabolic effects are mediated by GR transactivation. Thus, our findings are important in light of drug discovery programs focused on the development of selective GR acivators (SEGRA) that preferentially induce GR transrepression. Some of SEGRA entered preclinical studies or clinical trials as anti-inflammatory GR ligands with reduced side effects. Our results suggest that SEGRA could be also used for skin cancer prevention/treatment. 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 549. doi:1538-7445.AM2012-549
Bilateral Breast Uptake Demonstrated on FDG PET/CT Scans in 3 Male Patients With Hepatocellular Carcinomas
Authors: Yu-Chin Wu, Te-Chun Hsieh, Shung-Shung Sun, Kuo-Yang Yen, Chia-Hung Kao
Journal: Clinical Nuclear Medicine (2012)

We reported 3 male patients with hepatocellular carcinoma who underwent FDG PET/CT for systemic survey before liver transplantation. All of their scans demonstrated obvious FDG uptake in bilateral breasts. These uptakes might be owing to gynecomastia caused by an increase in free estrogen related to the cirrhotic liver.
Plasma phospholipids identify antecedent memory impairment in older adults
Authors: Mark Mapstone, Amrita K Cheema, Massimo S Fiandaca, Xiaogang Zhong, Timothy R Mhyre, Linda H MacArthur, William J Hall, Susan G Fisher, Derick R Peterson, James M Haley, Michael D Nazar, Steven A Rich, Dan J Berlau, Carrie B Peltz, Ming T Tan, Claudia H Kawas, Howard J Federoff
Journal: Nature Medicine (2014)
Thinking about teaching?
Authors: Z.-J. Playdon
Journal: BMJ (1999)

Consider the distinction between training and teaching. The concept of training has application when (a) there is some specifiable performance that has to be mastered, (b) practice is required for the mastery of it, and (c) little emphasis is placed on the underlying rationale. The typical term for the educational process by which people are brought to understand principles is teaching, for teaching - unlike training or instructing - implies that a rationale is to be grasped behind the skill or body of knowledge..1

If I ask someone how to do something and their answer begins with the words “Always and only,” then I know that I am in a training environment. The matter is not up for discussion, there are not exceptional circumstances; just do it and do it like this. Some of medicine is like this: the disposal of sharps, scrubbing up, keeping patient records. But to understand not just what is done but why it is done we must turn to teaching, to the rationale behind professional action.

### Summary points

Teaching postgraduate doctors the sensitivity and discrimination required in the complex process of making clinical judgments cannot be done through the checklists and competence bases used in training. Action is provisional to the context in which the doctor must act, rather than being pre-specified. Discussing and exploring the reasons why a particular procedure has been chosen opens up the whole vista of medicine in all of its excitement, uncertainty, and …
Is childhood asthma being underdiagnosed and undertreated?
Authors: A N Speight
Journal: BMJ (1978)

Thirty-four cases of asthma in children referred to outpatient clinics in Newcastle upon Tyne (16 cases) and London (18 cases) were reviewed. In both cities there was evidence of inappropriate diagnosis and treatment by general practitioners. One of the main factors seemed to be doctors9 reluctance to use the word "asthma," even when a history of episodic wheezing strongly suggested the diagnosis. Freer use of the word "asthma" might help parents to co-operate in managing asthmatic children and allow them to be better prepared to cope with severe asthmatic attacks if they occur.
Cytochrome P-450 Polymorphisms and Response to Clopidogrel
Authors: Jessica L. Mega, Sandra L. Close, Stephen D. Wiviott, Lei Shen, Richard D. Hockett, John T. Brandt, Joseph R. Walker, Elliott M. Antman, William Macias, Eugene Braunwald, Marc S. Sabatine
Journal: New England Journal of Medicine (2008)

Clopidogrel requires transformation into an active metabolite by cytochrome P-450 (CYP) enzymes for its antiplatelet effect. The genes encoding CYP enzymes are polymorphic, with common alleles conferring reduced function.We tested the association between functional genetic variants in CYP genes, plasma concentrations of active drug metabolite, and platelet inhibition in response to clopidogrel in 162 healthy subjects. We then examined the association between these genetic variants and cardiovascular outcomes in a separate cohort of 1477 subjects with acute coronary syndromes who were treated with clopidogrel in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial Infarction (TRITON-TIMI) 38.In healthy subjects who were treated with clopidogrel, carriers of at least one CYP2C19 reduced-function allele (approximately 30% of the study population) had a relative reduction of 32.4% in plasma exposure to the active metabolite of clopidogrel, as compared with noncarriers (P<0.001). Carriers also had an absolute reduction in maximal platelet aggregation in response to clopidogrel that was 9 percentage points less than that seen in noncarriers (P<0.001). Among clopidogrel-treated subjects in TRITON-TIMI 38, carriers had a relative increase of 53% in the composite primary efficacy outcome of the risk of death from cardiovascular causes, myocardial infarction, or stroke, as compared with noncarriers (12.1% vs. 8.0%; hazard ratio for carriers, 1.53; 95% confidence interval [CI], 1.07 to 2.19; P=0.01) and an increase by a factor of 3 in the risk of stent thrombosis (2.6% vs. 0.8%; hazard ratio, 3.09; 95% CI, 1.19 to 8.00; P=0.02).Among persons treated with clopidogrel, carriers of a reduced-function CYP2C19 allele had significantly lower levels of the active metabolite of clopidogrel, diminished platelet inhibition, and a higher rate of major adverse cardiovascular events, including stent thrombosis, than did noncarriers.
Testing with Antineutrophil Cytoplasmic Antibody To Diagnose Wegener Granulomatosis
Authors: Jaya K. Rao
Journal: Annals of Internal Medicine (1996)

Letters1 October 1996Testing with Antineutrophil Cytoplasmic Antibody To Diagnose Wegener GranulomatosisJaya K. Rao, MD and Nancy B. Allen, MDJaya K. Rao, MDRoudebush Veterans Affairs Medical Center, Indianapolis, IN 46202Duke University Medical Center, Durham, NC 27710Search for more papers by this author and Nancy B. Allen, MDRoudebush Veterans Affairs Medical Center, Indianapolis, IN 46202Duke University Medical Center, Durham, NC 27710Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-125-7-199610010-00020 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We appreciate Dr. Hoffman's comments and clarification regarding the utility of c-ANCA titers to assess disease activity in patients with Wegener granulomatosis. As we stated in the Discussion section of our paper, previous studies that address the utility of c-ANCA as a disease-monitoring tool have provided mixed results. We mentioned the NIH study [1] primarily because these data provided a marked contrast to the temporal relation between changes in disease activity and c-ANCA titers noted by Cohen Tervaert and colleagues [2]. Furthermore, several studies have also shown that 1) some patients with active Wegener granulomatosis may have negative ...References1. Kerr GS, Fleisher TA, Hallahan CW, Leavitt RY, Fauci AS, Hoffman GS. Limited prognostic value of changes in antineutrophil cytoplasmic antibody titer in patients with Wegener's granulomatosis. Arthritis Rheum. 1993; 36:365-71. Google Scholar2. Cohen Tervaert JW, van der Woude FJ, Fauci AS, Ambrus JL, Velosa J, Keane WF, et al. Association between active Wegener's granulomatosis and anticytoplasmic antibodies. Arch Intern Med. 1989; 149:2461-5. Google Scholar3. Davenport A, Lock RJ, Wallington TB, Feest TG. Clinical significance of antineutrophil cytoplasm antibodies detected by a standardized assay. Q J Med. 1994; 87:291-9. Google Scholar4. Davenport A, Lock RJ, Wallington TB. Clinical relevance of testing for antineutrophil cytoplasm antibodies with a standard indirect immunofluorescence ANCA test in patients with upper or lower respiratory tract symptoms. Thorax. 1994; 49:213-7. Google Scholar5. Jayne DR, Gaskin G, Pusey CD, Lockwood CM. ANCA and predicting relapse in systemic vasculitis. Q J Med. 1995; 88:127-33. Google Scholar Author, Article, and Disclosure InformationAffiliations: Roudebush Veterans Affairs Medical Center, Indianapolis, IN 46202Duke University Medical Center, Durham, NC 27710 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 October 1996Volume 125, Issue 7Page: 622-623KeywordsAntibody productionReactive arthritisWegener granulomatosis Issue Published: 1 October 1996 Copyright & PermissionsCopyright © 1996 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
IMPACT OF UNCORRECTED CONCOMITANT MODERATE FUNCTIONAL MITRAL REGURGITATION ON SURVIVAL IN PATIENTS UNDERGOING AORTIC VALVE REPLACEMENT
Authors: Halit Yerebakan, Robert Sorabella, Marc Najjar, John Vandenberge, Catherine Wang, Hiroo Takayama, Yoshifumi Naka, Mathew Williams, Michael Argenziano, Craig Smith, Isaac George
Journal: Journal of the American College of Cardiology (2014)
The Problems of the "Problem-Oriented Medical Record"
Authors: ALVAN R. FEINSTEIN
Journal: Annals of Internal Medicine (1973)

The greatest virtues of the new "problem-oriented medical record" are a flexible nomenclature for describing problems, specified details of "patient profile" and "patient education," and an easily applied method for arranging complex medical data. Many other apparent advantages arise not from the problem-structured format but from the associated enthusiasm and supervision with which the new system is applied. In particular, certain apparent contributions to the delivery, coordination, or evaluation of patient care seem attributable more to supervisory attention than to the structure used in the record. The new procedure is not concerned with outstanding scientific problems in patient care and has some major disadvantages, including a reduced emphasis on basic skills in diagnostic judgment. The many desirable features of the problem-structured record may ultimately be more valuable for augmenting and revising the standard record than for radical replacement.
821 RELATIONSHIP BETWEEN PLASMACYTOID AND MYELOID DENDRITIC CELLS AND RESPONSE TO ANTIVIRAL THERAPY
Authors: M. Andrieu, E. Middendorp, V. Mallet, J. Gaston, L. Vimeux, M. Ahloulay, S. Fernandes, A. Vallet-Pichard, M. Nascimbeni, B. Nalpas, S. Pol
Journal: Journal of Hepatology (2008)
Value for money in the Health Service.
Authors: K Young
Journal: BMJ (1973)

The prosperity of a nation depends less upon its size, geo graphical position, or natural resources than on the industry and resourcefulness of its people, which cannot be developed to their potential if they are handicapped by ill health. This is why the United Kingdom currently spends about ?2,000 million per annum on the National Health Service (N.H.S.), roughly 5% of the gross national product, and, though some other countries devote proportionally more to health services, the differences among them in this proportion are small. It is the responsibility of everyone working in the health service to ensure that the country gets the best value for its money. Clearly the aims of the N.H.S. are not confined to providing a service for sick people, but include the prevention of disease, the care of groups of people at particular risk, training of staff, and research into the cause and treatment of disease. The dramatic change in incidence and pattern of disease in the population over the last 30 years is a result more of rising standards of living and of preventive rather than of curative medicine. In the middle of the last century Sir Edwin Chadwick, a Poor Law Commissioner, concluding that poverty was a result of ill health and that ill health was a result of bad environ mental conditions, succeeded in setting in train the systematic cleaning up of the environment, so that today we take for granted the provision of clean food and water, and the safe disposal of waste. His systematic inquiry into the physical state of the population, reinforced half a century later by the dis covery (at the beginning of the Boer War) that a high proportion of volunteers for military service in South Africa were medically unfit, led to the setting up of the Interdepartmental Committee on Physical Deterioration, whose recommendations had far reaching effects on the rapid growth of the personal health services. The effect of other preventive measures such as immunization against infectious diseases on the health of the country needs no emphasis, but it is difficult to foresee that a similarly dramatic pay-off from prevention could occur over the next 50 years.
Burn Scar Carcinoma
Authors: J. Castillo, H. S. Goldsmith
Journal: CA A Cancer Journal for Clinicians (1968)

Although Celsus was the first to ob serve cancer in a burn scar, it was Marjolin whose name is eponymous with cancer arising in a burn scar, following his description in 1828 of neoplastic degeneration in scars. IncidenceThe true incidence of burn scar car cinoma is difficult to establish.Clini cal studies carried out years ago es timated that 9 percent of all skin can cers originate in burn scars.' Treves and Pack, in their comprehensive re view of 2,465 patients with skin can cer at Memorial Hospital, New York City, reported 2 percent of epider moid carcinomas and 0.3 percent of basal cell carcinomas originating in skin which had been previously sub jected to thermal injury.2Conway, in a recent review of five independent stud ies, estimated 1.2 percent of all skin carcinomas develop in burns.3The pro gressive decrease in the incidence of burn scar carcinoma is most likely a reflection of both improved safety fac tors associated with burn prevention and improved local treatment of burns, with fewer being allowed to heal by secondary intention.
Reply: Prognostic Value of Functional Decline in Middle-Aged Smokers
Authors: M. Bradley Drummond, Robert A. Wise
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

To the Editor:Drummond and colleagues (1) report that smokers with mild to moderate chronic obstructive pulmonary disease (COPD) and worse initial FEV 1 /FVC have a more rapid decrease of FEV 1 and higher rate of death.Only subjects with lower than 70% FEV 1 /FVC ratio are at risk for excessive lung function decline.The main limitation of their study is the only 5 years of followup, so their conclusion that spirometry predicts long-term outcome is not warranted.The authors refer to the previous study by Burrows and colleagues (2) of 13 smokers, with initial FEV 1 /FVC less than 70%, followed for 10 years, but omit another study of 56 middle-aged smokers, followed for 13 years (3), including besides spirometry, airway resistance, maximal expiratory flow rates, and small-airway disease tests such as closing volume and N 2 slope.Both studies showed that subjects with a low FEV 1 /FVC or a low FEV 1 /VC at the entry had a subsequent accelerated loss of FEV 1 .In the article by Burrows and colleagues (2) on 141 male smokers, with an FEV 1 greater than 60% of predicted, followed by spirometry for at least 6 years, initial normal FEV 1 /FVC explained only about 16% of the subsequent decrease of FEV 1 .Similarly, in our study, 79% of smokers with a normal FEV 1 /VC still had normal values (more than 70%) 13 years later (3).Conversely, a decreased FEV 1 /VC has no necessarily serious implication in itself.Indeed, only a minority of our subjects, with lower than 60% FEV 1 /VC, showed an accelerated loss of FEV 1 , reaching end FEV 1 /VC values lower than 45%.An associated high N 2 slope adds the necessary information to predict a low FEV 1 /VC.In agreement with our data, the analysis of Drummond and colleagues (1) showed that excessive lung function decline occurred only below FEV 1 /FVC of 0.65.Both figures of Drummond and colleagues (1) and ours (3) are lower than current thresholds used to define COPD.Our data suggest that a subgroup of smokers in their 50s with a low FEV 1 /VC and a high N 2 slope are probably the susceptible smokers at high risk to develop COPD.Recently it was reported that in some subjects, the progressive decrease with age of FEV 1 is not the rule.In them, FEV 1 remains stable or even increased (4, 5).However, these results were obtained from follow-ups of only 3 to 5 years, too short a time.In 7 out of 56 subjects, over 13 years, FEV 1 either did not change or even increased (3).
THE VALUE OF THIS SECTION'S WORK AND HOW TO ADVANCE IT.
Authors: EDWIN ROSENTHAL
Journal: JAMA (1900)

I was so deeply grateful for the honor done me, when I was chosen your chairman, that I promised myself, whatever work I might undertake, it should not only meet your approbation, but also enlist your interest to that extent as to make the work yours. The opening of the sessions with an address carries with it a certain reponsibility, for in a measure, I am but the spokesman, and my utterances are but yours. Therefore, in presenting the result of my labors, I shall briefly preface my remarks with my reasons for pursuing such a topic. The By-Laws say that the Chairman of each section shall prepare an address on the recent advances in the branches belonging to his Section, including such suggestions in regard to improvements or methods of work as he may regard important, and present the same to the Section over which he presides on the
PREOPERATIVE RIGHT VENTRICULAR VOLUMES DETERMINE RIGHT VENTRICULAR NORMALIZATION AND EVENTS LATE AFTER PULMONARY VALVE REPLACEMENT IN PATIENTS WITH TETRALOGY OF FALLOT
Authors: Jouke Bokma, Michiel Winter, Thomas Oosterhof, Hubert Vliegen, Barbara Mulder, Berto Bouma
Journal: Journal of the American College of Cardiology (2014)
No evidence for increased risk
Authors: G. Heiss, J. Hsia, M. Pettinger, B. V. Howard, G. Anderson
Journal: BMJ (2010)

Bolland and colleagues contrast the results of their meta-analysis with those of the women’s health initiative (WHI) randomised controlled trial of calcium/vitamin D supplementation with 254 000 subject years of follow-up.1 2 Cardiovascular events in the WHI study were pre-specified end points …
Interstitial granulomatous drug reaction following intravenous ganciclovir
Authors: A. Marcollo Pini, K. Kerl, J. Kamarachev, L.E. French, G.F.L. Hofbauer
Journal: British Journal of Dermatology (2008)

Journal Article Interstitial granulomatous drug reaction following intravenous ganciclovir Get access A. Marcollo Pini, A. Marcollo Pini Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland Search for other works by this author on: Oxford Academic Google Scholar K. Kerl, K. Kerl Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland Search for other works by this author on: Oxford Academic Google Scholar J. Kamarachev, J. Kamarachev Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland Search for other works by this author on: Oxford Academic Google Scholar L.E. French, L.E. French Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland Search for other works by this author on: Oxford Academic Google Scholar G.F.L. Hofbauer G.F.L. Hofbauer Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland Correspondence: Günther Hofbauer. E‐mail: hofbauer@usz.ch Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 158, Issue 6, 1 June 2008, Pages 1391–1393, https://doi.org/10.1111/j.1365-2133.2008.08560.x Published: 01 June 2008
Neurodevelopment After In Utero Exposure to Phenytoin and Carbamazepine
Authors: David W. Loring
Journal: JAMA (1994)

<h3>To the Editor.</h3> —Dr Scolnik and colleagues<sup>1</sup>report a "clinically important negative effect of phenytoin on neurobehavioral development" and "recommend that whenever clinically possible, switching therapy to carbamazepine should be considered." However, we question whether their experimental design and data analysis support such a strong conclusion. The authors used a case-control design in which mothers receiving either phenytoin or carbamazepine were paired to control mothers who were not receiving antiepileptic drugs (AEDs). The IQs of children exposed to AEDs in utero were compared with IQs of nonexposed children for their respective control group. However, we calculate a -10.3 point (phenytoin-phenytoin control) difference and a -3.4 (carbamazepine-carbamazepine control) difference rather than -10.6 and -1.8 as reported in Table 3. The principal conclusion was based on informally contrasting a significant (phenytoin-phenytoin control) IQ difference with a nonsignificant (carbamazepine-carbamazepine control) IQ difference. However, the appropriate statistical analysis is to compare directly the