tbuckley/cabot-search huggingface dataset:
Phosphorylation of Akt (Ser473) is an Excellent Predictor of Poor Clinical Outcome in Prostate Cancer
Authors: Jeffrey I. Kreisberg, Shazli N. Malik, Thomas J. Prihoda, Roble G. Bedolla, Dean A. Troyer, Suzanne Kreisberg, Paramita M. Ghosh
Journal: Cancer Research (2004)

Abstract We previously showed, by immunohistochemistry with phospho-specific antibodies, increased phosphorylation (activation) of Akt (Ser473) [phosphorylated Akt (pAkt)] in high-Gleason grade prostate cancer (Malik SN, et al., Clin Cancer Res 2002;8:1168–71). Elevation of pAkt was accompanied by decreased phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 (Thr202/Tyr204) [phosphorylated ERK (pERK)], indicative of inactivation. In this report, we determined whether increased pAkt and decreased pERK predicted clinical outcome. Prostate-specific antigen (PSA) failure (detectable and rising PSA) versus PSA non-failure (undetectable PSA 5 years after prostatectomy) was used as a surrogate for clinical outcome. Prostate tumors from cases of PSA failure versus non-failure were stained for pAkt and pERK. A significant increase in mean pAkt staining (P &amp;lt; 0.001) in the PSA failures versus non-failures was seen based on the Wilcoxon signed ranks test [222.18 ± 33.9 (n = 37) versus 108.79 ± 104.57 (n = 16)]. Using the best-fitting multiple logistic regression equation, a 100-point increase in pAkt staining resulted in a 160% increase in the odds of being a PSA failure. There was decreased staining for pERK in PSA failures versus non-failures: a 100-point decrease resulted in an 80% increase in the odds of being a PSA failure. Each of these effects assumed the other biomarker was held constant. The area under the receiver-operating characteristic curve for these two biomarkers predicting PSA failure was 0.84, indicating excellent discrimination between PSA failure and non-failure cases. These data indicate that increased pAkt, alone or together with decreased pERK, is an important predictor of probability of PSA failure. However, pERK alone was not a significant predictor of PSA failure.
Cost Effectiveness of Colorectal Cancer Screening in the Elderly
Authors: Judith L. Wagner, Roger C. Herdman, Sandeep Wadhwa
Journal: Annals of Internal Medicine (1991)

To assess the cost effectiveness of a periodic program of colorectal cancer screening in the elderly.A model was constructed of four strategies for the periodic screening of persons 65 to 85 years of age. The effect of each strategy on life expectancy and health care costs was estimated under assumptions that were uniformly unfavorable to screening. Cost and added years of life were discounted at 5% per year. Cost per year of life gained from screening was calculated for each screening strategy.Assumptions used in the model were based on a review of pertinent studies; those studies with results more unfavorable to screening were given more weight. Strengths and weaknesses of studies are discussed.A program of annual fecal occult blood testing (FOBT) in the elderly would detect at least 17% of the expected cases of cancer and could cost $35,000 per year of life saved. Screening schedules that include periodic sigmoidoscopy would prevent more cases of cancer but could cost between $43,000 and $47,000 per year of life gained. These estimates are based on uncertain assumptions, but results were not extremely sensitive to further relaxation of the values of the most uncertain assumptions. In no case did the cost per year of life gained from annual FOBT exceed $55,000 or did the cost per year of life gained from FOBT with sigmoidoscopy every 5 years exceed $61,000.Although colorectal cancer screening is costly in the aggregate, its potential medical benefits make it a reasonably cost-effective preventive intervention for the elderly.
Comparison of Radiation Exposure and Cost Between Dynamic Computed Tomography and Sestamibi Scintigraphy for Preoperative Localization of Parathyroid Lesions
Authors: Catherine A. Madorin, Randall Owen, Brian Coakley, Hannah Lowe, Kee-Hyun Nam, Kaare Weber, Leon Kushnir, Jose Rios, Eric Genden, Puneet S. Pawha, William B. Inabnet
Journal: JAMA Surgery (2013)

Dynamic computed tomography (CT) is emerging as a first-line alternative to sestamibi scintigraphy for preoperative localization of parathyroid lesions. In recent years, there has been increased concern over the impact of radiation exposure from medical imaging, as well as on the cost of diagnostic medical procedures. An ideal diagnostic procedure would be cost effective while minimizing hazardous exposures and complication rates.To compare the radiation dose and financial cost of dynamic CT with sestamibi scintigraphy.A retrospective review of 263 patients at a large, urban, tertiary referral center who underwent either dynamic parathyroid CT or sestamibi scintigraphy for any etiology of hyperparathyroidism from 2006 through 2010.The 2 primary study outcomes were radiation exposure measured in millisieverts (mSv) and medical charges for the respective diagnostic procedures. The study was conducted with the hypothesis that dynamic parathyroid CT would have slightly greater radiation exposure with similar cost to sestamibi scintigraphy.Dynamic parathyroid CT and sestamibi scintigraphy delivered mean radiation doses of 5.56 and 3.33 mSv, respectively (P < .05). Charges totaled $1296 for thin-cut dynamic parathyroid CT and a mean of $1112 for sestamibi scintigraphy, depending on the type and amount of radiotracer injected. Although multiphase CT scanning took less than 5 minutes, sestamibi scintigraphy lasted a mean time of 306 minutes. A total of 62 of 119 patients (52%) in the CT group have undergone operative treatment to date, whereas all patients in the sestamibi arm underwent operative treatment of their hyperparathyroidism. Of the patients who underwent a surgical procedure, CT correctly identified the side of the parathyroid adenoma in 54 of 62 patients (87%), while sestamibi scintigraphy only correctly lateralized 90 of 122 adenomas (74%) as confirmed by exploratory surgery, intraoperative parathyroid hormone levels, and pathologic features. A dynamic parathyroid CT correctly predicted multiglandular disease in 1 of 7 patients (14%), while sestamibi scintigraphy correctly predicted multiglandular disease in 8 of 23 patients (35%).In patients who underwent directed parathyroid surgery, dynamic CT is comparable to sestamibi scintigraphy in patients with hyperparathyroidism. Although CT delivers a higher dose of radiation, the average background radiation exposure in the United States is 3 mSv/y, and added exposures of less than 15 mSv are considered low risk for carcinogenesis. Overall, dynamic parathyroid CT is a safe, cost-effective alternative to sestamibi scintigraphy.
Sensitization of Human Atrial 5-HT <sub>4</sub> Receptors by Chronic β-Blocker Treatment
Authors: Louise Sanders, James A. Lynham, Brian Bond, Federica del Monte, Sian E. Harding, Alberto J. Kaumann
Journal: Circulation (1995)

Background Chronic treatment of patients with β-blockers induces β 2 -adrenergic receptor hyperresponsiveness in atrium and sinoatrial node. To investigate whether other atrial G s protein–coupled receptors also become hyperresponsive after chronic treatment with β-blockers, we investigated 5-HT 4 receptors in tissues and myocytes, which mediate serotonin-evoked increases of both contractile force and cAMP levels. Methods and Results Isolated right atrial strips from patients who had been chronically treated or not treated with a β-blocker were set up to contract. In tissues from β-blocker–treated patients (n=27), the maximum inotropic response to serotonin was 56±3% (mean±SEM) of the effect elicited by (−)-isoproterenol (200 μmol/L) compared with a response of 19±6% in tissues from non–β-blocker–treated patients (n=13) ( P &lt;.001). The responsiveness of the tissues to Ca 2+ was unchanged by chronic β-blocker treatment. Serotonin (1 and 10 μmol/L) increased tissue cAMP levels, the increase with 10 μmol/L being significantly greater ( P &lt;.05) in tissues from β-blocker–treated (n=9) than in non–β-blocker–treated (n=7) patients. In paced atrial myocytes, serotonin caused concentration-dependent increases in contraction. Myocytes obtained from atria of β-blocker–treated patients were more sensitive ( P &lt;.01) to the effects of serotonin (−log EC 50 , 7.9±0.2 mol/L; n=12) than myocytes obtained from non–β-blocker–treated patients (−log EC 50 , 7.3±0.2 mol/L, n=12). Chronic β-blocker treatment had no effect on forskolin-evoked myocyte responses. Carbachol (1 μmol/L) suppressed the effects of both serotonin (n=6) and (−)-isoproterenol (n=6) in the same atrial myocyte. Conclusions Chronic treatment of patients with β-blockers causes atrial 5-HT 4 receptor inotropic hyperresponsiveness and enhanced serotonin-evoked increases in cAMP levels. This may be due to modified cross talk between 5-HT 4 receptors, β-adrenergic receptors, and muscarinic receptors.
Coronary disease and personality.
Authors: E. Frankel
Journal: BMJ (1969)

TABLE I.-Case 2. Investigations Day Day 2 Day 3 Day 4 Day 6 Day 8 Day 10 Day 18 Haemoglobin (g./100 ml.) 16-2 14-6 13 9 14-6 W.B.C./c.mm.6,600 7,200 9,400 7,
A controlled study of the autonomic changes produced by habitual cigarette smoking in healthy subjects
Authors: D. Lucini, F. Bertocchi, A. Malliani, M. Pagani
Journal: Cardiovascular Research (1996)

Objectives: An increased sympathetic drive, in view of its proarrhythmic, proatherosclerotic, and prothrombotic actions, could contribute to the elevated cardiovascular risk of habitual smokers. However, the underlying mechanisms are still debated. In this study we address the hypothesis that spectral analysis of RR interval and systolic arterial pressure short-term variabilities may be used to assess the complex autonomic changes produced by habitual cigarette smoking. Methods: A cross-sectional design compared heavy (> 20 cigarettes/day) habitual smokers (n = 20; 40 ± 3 years), with similar age controls. Spectral analysis of RR interval variability provided markers of the sympatho-vagal balance modulating the SA node, by way of the normalised low frequency (LF ≅ 0.10 Hz) and high frequency (HF ≅ 0.25 Hz) components. The LF component of systolic arterial pressure (SAP) variability assessed the sympathetic vasomotor modulation. The frequency domain index (α) measured the baroreflex gain of the SA node. Subjects were studied at rest, and during the sympathetic excitation produced by active standing. Results: In smokers LFRR was, at rest, greater than in controls (70.6 ± 3.8 vs 46.0 ± 2.5 normalised units, nu); concurrently HFRR was reduced (22.1 ± 3.2 vs 42.0 ± 2.8 nu). Baroreflex gain and RR variance were also smaller in smokers. LFSAP was, instead, similar in the smokers and control groups. The standing induced increase in LFRR was blunted (P < 0.001) in smokers. Conclusions: Spectral analysis of RR interval and systolic arterial pressure variability indicates that habitual cigarette smoking induces selective alterations in neural control of the SA node. An increase at rest in markers of sympathetic modulation is accompanied by signs of reduced vagal drive and depressed baroreflex gain; while sympathetic vasomotor modulation appears similar in controls and smokers. Data are consistent with the hypothesis that autonomic alterations may contribute to the increased cardiovascular risk present in smokers.
Trypanosoma cruzi trans-sialidase initiates a program independent of the transcription factors RORγt and Ahr that leads to IL-17 production by activated B cells
Authors: Daniela A Bermejo, Shaun W Jackson, Melisa Gorosito-Serran, Eva V Acosta-Rodriguez, Maria C Amezcua-Vesely, Blythe D Sather, Akhilesh K Singh, Socheath Khim, Juan Mucci, Denny Liggitt, Oscar Campetella, Mohamed Oukka, Adriana Gruppi, David J Rawlings
Journal: Nature Immunology (2013)
The science of life as seen through Rose-coloured glasses
Authors: Mike Anderson
Journal: Behavioral and Brain Sciences (1999)

This commentary takes issue with two of Rose's central themes from the perspective of the psychology of intelligence. In the case of reductionism, I argue that Rose fails to live up to his own rhetoric by claiming a veto from his own discipline (biology) over facts of the matter in another (psychology). In the case of “ Lifelines, ” Rose's argument is contradicted by evidence from both individual differences and developmental change in intelligence.
Comparison of matched unrelated and matched related donor myeloablative hematopoietic cell transplantation for adults with acute myeloid leukemia in first remission
Authors: R B Walter, J M Pagel, T A Gooley, E W Petersdorf, M L Sorror, A E Woolfrey, J A Hansen, A I Salter, E Lansverk, F M Stewart, P V O'Donnell, F R Appelbaum
Journal: Leukemia (2010)
Isoenzyme Patterns and Pathogenicity in Amebic Infection
Authors: Donald J. Krogstad
Journal: New England Journal of Medicine (1986)

Entamoeba histolytica was first identified as a human pathogen in the 19th century,1 and it was subsequently given its species name because of its ability to lyse human tissue. Since that time, the approach to this important pathogen has been based primarily on its morphologic characteristics. Although Diamond and his colleagues have developed an in vitro culture system,2 it is unavailable in most clinical microbiology laboratories. Thus, the diagnosis of intestinal amebic infection is typically based on stool examination alone. However, this method is insensitive because the parasite cannot replicate under these conditions, and it is subject to error because . . .
Lupus cor pulmonale with electron microscope and immunofluroescent antibody studies.
Authors: P P Yeo, R Sinniah
Journal: Annals of the Rheumatic Diseases (1975)

A case of systemic lupus erythemaosus with an unusual complication of pulmonary hypertension leading to cor pulmonale is reported. Lung biopsy showed an interstitial pneumonitis with pulmonary vascular narrowing causing pulmonary hypertension. These changes appeared to be immunologically mediated by the utilization of IgG and C3. Microtubular virus-like particles were present in the endothelial cell cytoplasm of both lung and kidney.
Ventricle Devices, Artificial Hearts in Near Future?
Authors: Charles Marwick
Journal: JAMA (1991)

NOW THAT the government's artificial heart program has the green light from the National Academy of Sciences' Institute of Medicine, clinicians might even have long-term or permanent ventricular assist devices by the middle of this decade. But long-term, fully implantable artificial hearts are at least a decade away and probably won't be in general clinical use for still another decade. The National Heart, Lung, and Blood Institute (part of the National Institutes of Health, Bethesda, Md) presently has contracts with two clinical centers for development of long-term ventricular assist devices and with four groups to develop fully implantable artificial hearts. In its report, the Institute of Medicine (Washington, DC) recommends that these contracts, when
Inhibition of Src Tyrosine Kinase as Treatment for Human Pancreatic Cancer Growing Orthotopically in Nude Mice
Authors: Maksim V. Yezhelyev, Gudrun Koehl, Markus Guba, Thomas Brabletz, Karl-Walter Jauch, Anderson Ryan, Alan Barge, Tim Green, Michael Fennell, Christiane J. Bruns
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The Src family comprises a family of nonreceptor intracellular tyrosine kinases that mediate a variety of cellular pathways. Src kinases are overexpressed in a variety of human tumors, including cancer of the colon, breast, and pancreas, and they are an integral part of tumor cell signaling pathways associated with migration, proliferation, adhesion, and angiogenesis. Experimental Design: We investigated whether the blockade of Src kinase by daily oral administration of the novel Src tyrosine kinase inhibitor AZM475271 [kindly provided by AstraZeneca (Macclesfield, United Kingdom)], alone or in combination with intraperitoneal gemcitabine, can inhibit growth and metastasis of orthotopically implanted human pancreatic carcinoma cells in nude mice. Results: Treatment with AZM475271 alone reduced the primary pancreatic tumor volume by approximately 40%, whereas AZM475271 plus gemcitabine reduced tumor volume by 90%. Furthermore, treatment with AZM475271 and gemcitabine significantly reduced metastasis: none of eight animals who received the combination treatment had lymph node or liver metastases, compared with five of five and three of five animals, respectively, in the control group (P = 0.001). Src inhibition by AZM475271 (alone or with gemcitabine) was associated with significantly reduced tumor cell proliferation, decreased tumor microvessel density, and increased apoptosis in vivo. Moreover, these effects were all significantly increased when gemcitabine was combined with AZM475271 compared with gemcitabine alone. Conclusions: Src inhibition by AZM475271, either alone or in combination with gemcitabine, demonstrated significant antitumor and antimetastatic activity in an orthotopic nude mouse model for human pancreatic cancer. The combination of AZM475271 with gemcitabine sensitized tumor cells to the cytotoxic effect of gemcitabine.
The Politics of Transplantation of Human Fetal Tissue
Authors: G J Annas, S Elias
Journal: New England Journal of Medicine (1989)

Research involving human fetal tissue has been the subject of intense political debate in this country for almost two decades, and the use of fetal tissues in transplantation continues this controversy in another forum. Since Roe v. Wade,1 the landmark decision on abortion by the U.S. Supreme Court in 1973, the federal government has focused public attention on fetal research by creating panels of experts. For example, in 1974 Congress created the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research and made the formulation of regulations on fetal research the first item on its . . .
Fertility Preservation Strategies for Breast Cancer Patients
Authors: Lucia Del Mastro, Marco Venturini
Journal: Journal of Clinical Oncology (2006)

reviewed in Donskov et al 17 ).In the study by Fumagalli et al, 1 blood neutrophils were available from the differential WBC automatic counter.The reason why Fumagalli did not include blood neutrophils in the multivariate analysis, but only included blood lymphocytes, is unknown.Our present study 2 validates and strengthens the impact of neutrophil count as a poor prognostic factor in mRCC by identifying both blood neutrophils and intratumoral neutrophils as independent poor prognostic factors.As we assessed a large number of blood and tumor immune cells, dichotomy by the median value is correct from a statistical point of view.Our current study 2 suggests a prognostic model based on clinical factors supplemented with independent immunological prognostic factors.Patients in the good prognostic groups had 5-year survival rates of 60% and 25%.In contrast, all patients in the poor prognostic group died within 3 years.We suggest IL-2-based immunotherapy restricted to patients who most likely will benefit, while referring other patients to alternative investigational modalities.We also are clinicians treating patients and patients in the poor prognostic group do not seem to benefit from IL-2-based immunotherapy, but all suffer from treatment-related toxicity.This view is in line with the conclusion in a recent Cochrane review, 3 that for the large majority of patients with mRCC, the disease parameters are more powerful determinants of outcome than any treatment modality.Finally, validation of our prognostic model, 2 based on clinical factors supplemented with immunological factors, is of high priority as validation of these features may help to select patients more likely to benefit from IL-2-based immunotherapy.
Extended Transgene Expression From a Nonintegrating Adenoviral Vector Containing Retroviral Elements
Authors: Changyu Zheng, Joseph M Vitolo, Weitian Zhang, Fumi Mineshiba, John A Chiorini, Bruce J Baum
Journal: Molecular Therapy (2008)

We studied the effects of specific retroviral elements in a first-generation serotype 5 adenoviral (Ad5) vector, AdLTR(2)EF1alpha-hEPO. This vector contains 858 base pair (bp) [251-bp envelope sequence plus 607-bp long-terminal repeat (LTR)] from Moloney murine leukemia virus (MoMLV), upstream of the human elongation factor-1alpha (EF1alpha) promoter and human erythropoietin (hEPO) cDNA, with the LTR sequence downstream of the polyadenylation signal. We compared expression of AdLTR(2)EF1alpha-hEPO with corresponding expressions of two conventional Ad5 vectors, AdEF1alpha-hEPO and AdCMV-hEPO, in vivo in submandibular glands in rats. Both the conventional vectors yielded low serum hEPO levels by day 7, and little change in hematocrits. In contrast, after receiving AdLTR(2)EF1alpha-hEPO, the rats showed elevated hEPO levels and hematocrits for 1-3 months. In vitro studies showed that the integration efficiencies of all the vectors were similar (approximately 10(-3)). Approximately 0.1% of the vector genomes were present 1 year after delivery in the case of each of the three vectors, primarily as intact linear double-strand DNA. The unique results seen with AdLTR(2)EF1alpha-hEPO are partly because of LTR enhancer activity. However, other cis-acting activity, which is not immunomodulatory but nevertheless influences promoter methylation, appears to be involved. A vector such as AdLTR(2)EF1alpha-hEPO may prove useful in clinical applications in which extended, but not "permanent," transgene expression is desirable.
Intersectoral Action for Health: The Role of Intersectoral Cooperation in National Strategies for Health for All
Authors: Milton I. Roemer
Journal: JAMA (1987)

It has long been known that health is determined by many conditions in the physical and social environment much more than by the specific actions of physicians or other health professionals. In 1790, Johann Peter Frank told the graduating class of the University of Pavia Medical School that "Poverty is the mother of disease." He spoke dramatically of the misery of a bare subsistence diet, of backbreaking manual labor, of grim and inhuman housing, and so on. In 1978 at Alma-Ata, when the World Health Organization and UNICEF, with representatives of almost all nations on earth, set out to revitalize the world movement for improved health, they spoke of the same relationships. In the language of contemporary international health work, they said: Primary health care... involves, in addition to the health sector, all related sectors and aspects of national and community development, in particular agriculture, animal husbandry, food, industry, education,