tbuckley/cabot-search huggingface dataset:
Androgen Deprivation Causes Epithelial–Mesenchymal Transition in the Prostate: Implications for Androgen-Deprivation Therapy
Authors: Yuting Sun, Bu-Er Wang, Kevin G. Leong, Peng Yue, Li Li, Suchit Jhunjhunwala, Darrell Chen, Kyounghee Seo, Zora Modrusan, Wei-Qiang Gao, Jeffrey Settleman, Leisa Johnson
Journal: Cancer Research (2011)

Androgen deprivation is currently a standard-of-care, first-line therapy for prostate cancer in the United States. Although this regimen effectively regresses androgen-dependent disease, relapse often occurs in an androgen-independent manner and is associated with poor prognosis. Such castration-resistant prostate cancer represents a major clinical challenge, and the mechanisms underlying castration resistance are not fully understood. Epithelial-mesenchymal transition (EMT) is a key developmental process and has also been implicated in cancer metastasis and therapeutic resistance in recent years. However, the factors contributing to EMT in human cancers remain unclear. Here, we show that both normal mouse prostate tissue and human LuCaP35 prostate tumor explants display an EMT as well as increased stem cell-like features following androgen deprivation. Importantly, we observed similar changes in mesenchymal features in prostate tumors from patients treated with androgen-deprivation therapy. In addition, we have delineated a feedback loop involving the androgen receptor and the Zeb1 transcription factor that seems to mediate this transition. In summary, we show for the first time that androgen deprivation induces EMT in both normal prostate and prostate cancer, revealing a potentially important consequence of a standard-of-care treatment for prostate cancer. This finding could have significant implications for second-line treatment strategies in this clinical setting.
Disputes over payments for short stay patients are wasting NHS time, says watchdog
Authors: N. Hawkes
Journal: BMJ (2012)

The NHS in England is wasting time, distorting budgets, and reducing data quality because it does not follow a consistent policy for classifying short stay patients.

The same patient might be classified as an outpatient at one hospital and an inpatient at another, costing five to six times as much, although the treatment is identical, says the Audit Commission in a report. It blames poor guidance rather than deliberate manipulation for such discrepancies, and says that the classifications are a frequent cause of dispute between commissioners and providers, tying up managers who have better things to do.

Payment by results demands that each episode of care should be recorded appropriately in order that the right payment is made. But there is an area of confusion over short …
Phase II Trial of Carboxyamidotriazole in Patients With Relapsed Epithelial Ovarian Cancer
Authors: Mahrukh M. Hussain, Herbert Kotz, Lori Minasian, Ahalya Premkumar, Gisele Sarosy, Eddie Reed, Suoping Zhai, Seth M. Steinberg, Miranda Raggio, Vyta Kulpa Oliver, William D. Figg, Elise C. Kohn
Journal: Journal of Clinical Oncology (2003)

Carboxyamidotriazole (CAI) is a cytostatic inhibitor of nonvoltage-operated calcium channels and calcium channel-mediated signaling pathways. It inhibits angiogenesis, tumor growth, invasion, and metastasis. We hypothesized that CAI would promote disease stabilization lasting >/= 6 months in patients with relapsed ovarian cancer.Patients with epithelial ovarian cancer, good end-organ function, measurable disease, and three or fewer prior regimens were eligible. Oral CAI was given daily using a pharmacokinetic-dosing approach to maintain plasma concentrations between 2 and 4 microg/mL. Radiographic imaging to assess response was performed every 8 weeks. Positive outcome included stabilization or improvement of disease lasting >/= 6 months. Plasma vascular endothelial growth factor (VEGF), interleukin (IL)-8, and matrix metalloproteinase (MMP)-2 were measured.Thirty-six patients were assessable for primary end point analysis, and 38 were assessable for toxicity. Forty-four percent of patients had three prior regimens, more than 50% had four or more disease sites, and 48% had liver metastases. Thirty-three patients reached the targeted concentration range during the first cycle. Eleven patients (31%) attained the >/= 6-month outcome end point, with one partial response (8 months) and three minor responses (8, 12+, and 13 months). Median time to progression was 3.6 months (range, 1.6 to 13.3 months). CAI was well tolerated, with mostly grade 1 to 2 toxicity. Grade 3 events included fatigue (5%), vomiting (2%), neutropenic fever (2%), and neutropenia (2%). There were no grade 4 adverse events. No associations between VEGF, IL-8, and MMP-2 with CAI concentration or clinical outcome were observed.CAI is a potential agent for additional study in the stabilization of relapsed ovarian cancer. Given a limited toxicity profile, it may have utility as a maintenance therapeutic agent for this disease.
Medical Student Burnout and Professionalism—Reply
Authors: Liselotte N. Dyrbye
Journal: JAMA (2011)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Choosing tomorrow's doctors
Authors: S. Goldbeck-Wood
Journal: BMJ (1996)

The national debate on medical school selection criteria continues. The underlying assumption at a recent gathering of students, patients' representatives, the chief medical officer, and admissions deans from Britain and abroad at St George's Hospital Medical School in London was that we are getting it wrong. But are we? Just what do we want from the doctors of the future? To what extent are we achieving it now, and how, if at all, will selection criteria help us improve things?

The only clear answer was that, with 2.8 applicants for every medical school place in Britain, we do need to select. We currently use academic achievement, in the form of A level grades, as a filter—a requirement of three “A” grades, or two “A”s and a “B”, reduces numbers sufficiently to make individual interviews practicable. Average A level grades among medical school entrants have increased over the past 10 years,1 even though selectors themselves agree that these academic requirements far exceed what is needed to be able to complete the course. Whether driven or followed by selection policy, being good at science is now far more likely to be quoted as a reason for applying to medical school than in 1966.2

Is academic achievment at 18 too blunt a discriminator? It is certainly unfair, since it excludes people who are able …
Infarct-Sparing Effect of A <sub>2A</sub> -Adenosine Receptor Activation Is Due Primarily to Its Action on Lymphocytes
Authors: Zequan Yang, Yuan-Ji Day, Marie-Claire Toufektsian, Susan I. Ramos, Melissa Marshall, Xin-Qun Wang, Brent A. French, Joel Linden
Journal: Circulation (2005)

A2A-adenosine receptor (A2AAR) activation on reperfusion after ischemia reduces the size of myocardial infarction, but the mechanism of action has not been fully defined.We created chimeric mice by bone marrow transplantation from A2AAR-knockout or green fluorescent donor mice to irradiated congenic C57BL/6 (B6) recipients. In the GFP chimeras, we were unable to detect green fluorescent-producing cells in the vascular endothelium, indicating that bone marrow-derived cells were not recruited to endothelium at appreciable levels after bone marrow transplantation and/or acute myocardial infarction. Injection of 5 or 10 microg/kg of a potent and selective agonist of A2AAR, ATL146e, had no effect on hemodynamic parameters but reduced infarct size in B6 mice after 45 minutes of left anterior descending artery occlusion followed by 24 hours of reperfusion to 42.5+/-3.0% and 39.3+/-4.7% of risk region, respectively, compared with 61.0+/-2.3% in vehicle-treated B6 mice (P<0.05). Myocardial myeloperoxidase activity in the risk region measured at 4 hours after reperfusion was significantly reduced by ATL146e. The salutary effects of ATL146e were absent in A2AAR-knockout mice or in mice treated with a selective A2AAR antagonist, ZM241385. ATL146e also reduced infarct size and myeloperoxidase in B6/B6 (donor/recipient) chimeras (P<0.05) but not in A2AAR-knockout/B6 chimeras. In immunocompromised Rag-1-KO mice, infarct size was significantly reduced compared with B6 mice but was not further reduced by ATL146e.The results indicate that A2AAR activation on bone marrow-derived cells, specifically T or B lymphocytes, is responsible for the infarct-sparing and antiinflammatory effects of ATL146e administered at the time of reperfusion after coronary occlusion.
Isolated Mitral Valve Replacement With St Jude Medical Prosthesis
Authors: J. P. Remadi, O. Baron, C. Roussel, P. Bizouarn, Al Habasch, P. Despins, J. L. Michaud, D. Duveau
Journal: Circulation (2001)

In this retrospective study, approximately 440 patients received mitral valve replacements with the St Jude Medical prosthesis. The last patient was operated on 10 years before the beginning of the follow-up. The extended follow-up was 19 years.Four hundred forty patients (sex ratio, 1.32 [men to women]; age, 60+/-11.4 years; age range, 7 to 75 years) were operated on from 1979 to 1987. All patients underwent isolated mitral valve replacement. Tricuspid plasty was the only associated procedure. The follow-up at 19 years was 98% complete. The overall actuarial survival rate was 63+/-3.3% at 19 years, and the actuarial survival rate (only valve related) was 83+/-2.7%. The operative mortality rate (0 to 30 days) was 4.09%. We found that 89.4% of the patients alive at 19 years were in NYHA class I/II. Multivariate analysis showed that age and sex were significantly correlated with valve-related mortality and that age, sex, NYHA class, and atrial fibrillation were significantly correlated with overall mortality. The linearized rates (percent patient-years) of thromboembolism, thrombosis, and hemorrhage were 0.69, 0.2, and 1, respectively. At 19 years, freedom from endocarditis and reoperation was 98.6+/-1% and 90+/-3%, respectively.In this study, the very-long-term results confirm the excellent durability of the St Jude Medical prosthesis in the mitral position and show the difficulty of adjusting the anticoagulation protocol, even after long-term treatment.
Abstract 4668: Antitumor efficacy of AZD1480 in head and neck squamous cell carcinoma.
Authors: Malabika Sen, John Black, Sarah Wheeler, Maria L. Freilino, Sonali Joyce, Vivian Lui, Yan Zeng, Korey Marshall, Jennifer R. Grandis
Journal: Cancer Research (2013)

Abstract Aberrant activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway has been implicated in cancer cell proliferation and survival. AZD1480, a pharmacologic inhibitor of JAK2, has been tested in several cancer models including glioblastoma, lung, renal, prostate, breast, and ovarian cancer. However JAK inhibitors, including AZD1480 has not been evaluated in head and neck squamous cell cancer (HNSCC). In the present study, the in vitro and in vivo efficacy of AZD1480 was evaluated in HNSCC preclinical models. AZD1480 decreased HNSCC proliferation in cell lines with varying levels of pJAK2 and pSTAT3 with an IC50 ranging from 0.9μM - 4μM. Further evaluation demonstrated downmodulation of pJAK2 and pSTAT3 in HNSCC cell lines by AZD1480. Furthermore, in vivo antitumor efficacy of AZD1480 was tested in heterotopic xenograft tumor models derived from 2 HNSCC patient tumors. AZD1480 at a dose of 30mg/kg, was given twice daily via oral gavage and compared with vehicle (0.5% Hypromellose) control. Tumors treated with AZD1480 exhibited significant growth inhibition relative to the tumors treated with vehicle (p=0.0037). In addition, significant decrease in pSTAT3Tyr705 expression was observed in both the patient tumors treated with AZD1480 compared to vehicle alone indicating that AZD1480 targets pSTAT3 and may be considered for study in the treatment of HNSCC patients. Citation Format: Malabika Sen, John Black, Sarah Wheeler, Maria L. Freilino, Sonali Joyce, Vivian Lui, Yan Zeng, Korey Marshall, Jennifer R. Grandis. Antitumor efficacy of AZD1480 in head and neck squamous cell carcinoma. [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 4668. doi:10.1158/1538-7445.AM2013-4668
Henry VIII and the Barber Surgeons — Keeping Warm — Patient's Association
Authors: John Lister
Journal: New England Journal of Medicine (1963)

A MOST interesting exhibition has recently been held at the National Portrait Gallery to mark the rediscovery of Holbein's original cartoon for his famous portrait group, "Henry VIII and the Barber Surgeons." In 1786, the Company of Surgeons, who were then independent of the Barbers, purchased from a Monsieur Desenfans for 50 guineas "a large and capital picture being a cartoon by Hans Holbein representing King Henry VIII delivering the Charter to the Barber Surgeons." Shortly after the purchase the picture was transformed into what appeared to be an oil painting on canvas. This painting closely resembled the Holbein painting . . .
Can Broader Diffusion of Value-Based Insurance Design Increase Benefits from US Health Care without Increasing Costs? Evidence from a Computer Simulation Model
Authors: R. Scott Braithwaite, Cynthia Omokaro, Amy C. Justice, Kimberly Nucifora, Mark S. Roberts
Journal: PLoS Medicine (2010)

Background Evidence suggests that cost sharing (i.e.,copayments and deductibles) decreases health expenditures but also reduces essential care. Value-based insurance design (VBID) has been proposed to encourage essential care while controlling health expenditures. Our objective was to estimate the impact of broader diffusion of VBID on US health care benefits and costs. Methods and Findings We used a published computer simulation of costs and life expectancy gains from US health care to estimate the impact of broader diffusion of VBID. Two scenarios were analyzed: (1) applying VBID solely to pharmacy benefits and (2) applying VBID to both pharmacy benefits and other health care services (e.g., devices). We assumed that cost sharing would be eliminated for high-value services (<$100,000 per life-year), would remain unchanged for intermediate- or unknown-value services ($100,000–$300,000 per life-year or unknown), and would be increased for low-value services (>$300,000 per life-year). All costs are provided in 2003 US dollars. Our simulation estimated that approximately 60% of health expenditures in the US are spent on low-value services, 20% are spent on intermediate-value services, and 20% are spent on high-value services. Correspondingly, the vast majority (80%) of health expenditures would have cost sharing that is impacted by VBID. With prevailing patterns of cost sharing, health care conferred 4.70 life-years at a per-capita annual expenditure of US$5,688. Broader diffusion of VBID to pharmaceuticals increased the benefit conferred by health care by 0.03 to 0.05 additional life-years, without increasing costs and without increasing out-of-pocket payments. Broader diffusion of VBID to other health care services could increase the benefit conferred by health care by 0.24 to 0.44 additional life-years, also without increasing costs and without increasing overall out-of-pocket payments. Among those without health insurance, using cost saving from VBID to subsidize insurance coverage would increase the benefit conferred by health care by 1.21 life-years, a 31% increase. Conclusion Broader diffusion of VBID may amplify benefits from US health care without increasing health expenditures. Please see later in the article for the Editors' Summary
Audit Commission recommends home nursing shake up
Authors: P. Anderson
Journal: BMJ (1999)

The NHS's home nursing service needs radical change in order to meet rising demand, according to the Audit Commission.

The commission, which is responsible for overseeing the use of public money in England and Wales, says district nursing services are overstretched and need modernisation, in a report published last week.

Demand for professional nursing care at home is increasing because the population of elderly people in the United Kingdom is growing, hospitals are discharging patients earlier, and more patients …
Estrogen Replacement Therapy in Breast Cancer Survivors
Authors: Leonard R. Prosnitz
Journal: JAMA (1995)

To the Editor.  —Dr Cobleigh and colleagues 1 have done a fine job in reviewing the issues associated with the use of ERT in breast cancer survivors. Although the article is subtitled A Time for Change, I looked in vain for a specific statement that the prescription of estrogens for women with a history of breast cancer and severe postmenopausal symptoms is justified. They clearly state that clinical trials are justified, but equally clearly the answers from such trials are at least 10 years away. Since one of the issues is medical-legal and since JAMA is an authoritative publication, I would ask Cobleigh and colleagues to indicate what they think is a reasonable position for clinicians to take until the definitive trials are available.
THE EXISTENCE OF TWO FORMS OF HYPERTENSIN
Authors: Leonard T. Skeggs, Walton H. Marsh, Joseph R. Kahn, Norman P. Shumway
Journal: The Journal of Experimental Medicine (1954)

Two types of hypertensin have been demonstrated by means of counter-current distribution. The first type is the product of the action of the enzyme, renin, upon its substrate and has been designated hypertensin I. It can be rapidly converted to a second approximately equally pressor compound, hypertensin II, apparently through the action of an enzyme in the plasma which requires halide or nitrate for activation. A highly purified preparation containing horse hypertensins I and II caused an elevation of blood pressure when injected into human beings.
Competition between normal [674C] and mutant [674R]GPIIb subunits: role of the molecular chaperone BiP in the processing of GPIIb-IIIa complexes
Authors: Elena G. Arias-Salgado, Nora Butta, Consuelo González-Manchón, Susana Larrucea, Matilde S. Ayuso, Roberto Parrilla
Journal: Blood (2001)

Abstract This work aimed at investigating the function of the [C674R] mutation in GPIIb that disrupts the intramolecular 674 to 687 disulfide bridge. Individuals heterozygous for this mutation show a platelet GPIIb-IIIa content approximately 30% of normal controls, which is less than expected from one normal functioning allele. Coexpression of normal [674C]GPIIb and mutant [674R]GPIIb with normal GPIIIa produced a [674R]GPIIb concentration-dependent inhibition of surface exposure of GPIIb-IIIa complexes in Chinese hamster ovary (CHO) cells, suggesting that [674R]GPIIb interferes with the association and/or intracellular trafficking of normal subunits. Mutation of either 674C or 687C had similar effects in reducing the surface exposure of GPIIb-IIIa. However, substitution of 674C for A produced a much lesser inhibition than R, suggesting that a positive-charged residue at that position renders a less efficient subunit conformation. The mutant [674R]GPIIb but not normal GPIIb was found associated with the endoplasmic reticulum chaperone BiP in transiently transfected CHO cells. BiP was also found associated with [674R]GPIIb-IIIa heterodimers, but not with normal GPIIIa or normal heterodimers. Overexpression of BiP did not increase the surface exposure of [674R]GPIIb-IIIa complexes, indicating that its availability was not a limiting step. Platelets from the thrombasthenic patient expressing [674R]GPIIb-IIIa were found to bind soluble fibrinogen in response to physiologic agonists or dithiothreitol treatment. Thus, the [674R]GPIIb mutation leads to a retardation of the secretory pathway, most likely related to its binding to the molecular chaperone BiP, with the result of a defective number of functional GPIIb-IIIa receptors in the cell surface.
THE PATHOLOGY AND TREATMENT OF SYCOSIS.Read in the Section of Dermatology and Syphiligraphy at the Forty-first Annual Meeting of the American Medical Association, at Nashville, Tenn., May, 1890.
Authors: JOHN V. SHOEMAKER
Journal: JAMA (1890)

<i>Pathology</i>.—In order clearly to comprehend the pathology of sycosis it is of advantage to consider the structure of hair, the mode of its growth and nutrition. Hair is a modification of the epithelial layer of the integument. The root of each hair is lodged in a little pit called the hair follicle. The follicle descends through the substance of the skin into the subcutaneous connective tissue. Its orifice is shaped like a funnel, the narrower and lower end of the funnel being known as the neck. Below the neck the follicle widens and terminates in a bulbous expansion. The proper wall of the hair follicle belongs to the corium and is divided into three layers: an outer, a middle and an internal. The outer is the thickest and consists of connective tissue fibres disposed parallel to the long axis of the follicle. It supports a small artery and vein and
Potassium concentrations in irradiated blood.
Authors: J. Duguid, J. Cunningham, N. Pender
Journal: BMJ (1992)

James O'Brien and colleagues' approach was too simplistic.'The premise that primary treatment of the symptoms of stress, urge, and mixed incontinence is simple is unfounded.In controlled trials the objective cure rate after pelvic floor exercise in women with genuine stress incontinence is low2; similarly, in women with detrusor instability bladder retraining is associated with a high long term relapse rate.3In O'Brien and colleagues' study patients were treated on the basis of symptoms alone and no attempt was made to diagnose the cause of incontinence.As the correlation between urinary symptoms and urodynamic diagnosis is poor4 many patients will have been incorrectly treated, resulting in an apparent reduction in the efficacy of treatment.It is not surprising that patients with mixed symptoms had the poorest outcome, with only half reporting symptomatic improvement.Patients who remain incontinent will become disillusioned and may seek no further medical advice, thinking that nothing can be done to help them.It is already difficult to convince patients that most of them can be cured, or their incontinence can at least be improved, by appropriate investigation and management.The nature and duration of follow up were inadequate; no objective measures of severity of leakage were used, and no assessment of the results of treatment was continued beyond 12 weeks.We believe that, with few exceptions (notably elderly people), incontinent patients require some basic investigation, often including urodynamic assessment, before treatment.Outcome should be carefully monitored and assessed objectively whenever possible.