tbuckley/cabot-search huggingface dataset:
Should Colorectal Cancer Screening Be Considered in Elderly Persons Without Previous Screening?
Authors: Frank van Hees, J. Dik F. Habbema, Reinier G. Meester, Iris Lansdorp-Vogelaar, Marjolein van Ballegooijen, Ann G. Zauber
Journal: Annals of Internal Medicine (2014)

Background: The U.S. Preventive Services Task Force recommends against routine screening for colorectal cancer (CRC) in adequately screened persons older than 75 years but does not address the appropriateness of screening in elderly persons without previous screening. Objective: To determine at what ages CRC screening should be considered in unscreened elderly persons and to determine which test is indicated at each age. Design: Microsimulation modeling study. Data Sources: Observational and experimental studies. Target Population: Unscreened persons aged 76 to 90 years with no, moderate, and severe comorbid conditions. Time Horizon: Lifetime. Perspective: Societal. Intervention: One-time colonoscopy, sigmoidoscopy, or fecal immunochemical test (FIT) screening. Outcome Measures: Quality-adjusted life-years gained, costs, and costs per quality-adjusted life-year gained. Results of Base-Case Analysis: In unscreened elderly persons with no comorbid conditions, CRC screening was cost-effective up to age 86 years. Screening with colonoscopy was indicated up to age 83 years, sigmoidoscopy was indicated at age 84 years, and FIT was indicated at ages 85 and 86 years. In unscreened persons with moderate comorbid conditions, screening was cost-effective up to age 83 years (colonoscopy indicated up to age 80 years, sigmoidoscopy at age 81 years, and FIT at ages 82 and 83 years). In unscreened persons with severe comorbid conditions, screening was cost-effective up to age 80 years (colonoscopy indicated up to age 77 years, sigmoidoscopy at age 78 years, and FIT at ages 79 and 80 years). Results of Sensitivity Analyses: Results were most sensitive to assuming a lower willingness to pay per quality-adjusted life-year gained. Limitation: Only persons at average risk for CRC were considered. Conclusion: In unscreened elderly persons CRC screening should be considered well beyond age 75 years. A colonoscopy is indicated at most ages. Primary Funding Source: National Cancer Institute.
A Brief History of Great Discoveries in Pharmacology: In Celebration of the Centennial Anniversary of the Founding of the American Society of Pharmacology and Experimental Therapeutics
Authors: Ronald P. Rubin
Journal: Pharmacological Reviews (2007)

When the American Society of Pharmacology and Experimental Therapeutics (ASPET[1][1]) Centennial Committee began considering ways to celebrate the Society's 100th anniversary in 2008, an early interest was expressed in having a publication that presented the research history of the discipline.
Targeted Delivery of Paclitaxel to EphA2-Expressing Cancer Cells
Authors: Si Wang, Roberta Noberini, John L. Stebbins, Swadesh Das, Ziming Zhang, Bainan Wu, Sayantan Mitra, Sandrine Billet, Ana Fernandez, Neil A. Bhowmick, Shinichi Kitada, Elena B. Pasquale, Paul B. Fisher, Maurizio Pellecchia
Journal: Clinical Cancer Research (2012)

Abstract Purpose: YSA is an EphA2-targeting peptide that effectively delivers anticancer agents to prostate cancer tumors. Here, we report on how we increased the drug-like properties of this delivery system. Experimental Design: By introducing non-natural amino acids, we have designed two new EphA2 targeting peptides: YNH, where norleucine and homoserine replace the two methionine residues of YSA, and dYNH, where a D-tyrosine replaces the L-tyrosine at the first position of the YNH peptide. We describe the details of the synthesis of YNH and dYNH paclitaxel conjugates (YNH-PTX and dYNH-PTX) and their characterization in cells and in vivo. Results: dYNH-PTX showed improved stability in mouse serum and significantly reduced tumor size in a prostate cancer xenograft model and also reduced tumor vasculature in a syngeneic orthotopic allograft mouse model of renal cancer compared with vehicle or paclitaxel treatments. Conclusion: This study reveals that targeting EphA2 with dYNH drug conjugates could represent an effective way to deliver anticancer agents to a variety of tumor types. Clin Cancer Res; 19(1); 128–37. ©2012 AACR.
Blasts from the past
Authors: Paul A. Insel, Stuart Kornfeld, Philip W. Majerus, Andrew R. Marks, Paul A. Marks, Arnold S. Relman, Bruce F. Scharschmidt, Thomas P. Stossel, Ajit P. Varki, Stephen J. Weiss, Jean D. Wilson
Journal: Journal of Clinical Investigation (2004)

With this issue of the JCI, we celebrate the 80th anniversary of the Journal. While 80 years is not a century, we still feel it is important to honor what the JCI has meant to the biomedical research community for 8 decades. To illustrate why the JCI is the leading general-interest translational research journal edited by and for biomedical researchers, we have asked former JCI editors-in-chief to reflect on some of the major scientific advances reported in the pages of the Journal during their tenures.
Modulation of DNA Repair <b> <i>In vitro</i> </b> after Treatment with Chemotherapeutic Agents by the Epidermal Growth Factor Receptor Inhibitor Gefitinib (ZD1839)
Authors: Benjamin Friedmann, Martyn Caplin, John A. Hartley, Daniel Hochhauser
Journal: Clinical Cancer Research (2004)

The epidermal growth factor receptor (EGFR) is commonly expressed in human tumors and provides a target for therapy. Gefitinib (Iressa, ZD1839) is a quinazoline derivative that inhibits EGFR tyrosine kinase activity. Gefitinib demonstrated anticancer efficacy in vivo, and although experiments in vitro have suggested that inhibition of EGFR modulates the activity of chemotherapeutic agents, the mechanism of this interaction is unclear. We investigated mechanisms for this modulation.The antiproliferative effect of gefitinib alone or combined with cisplatin, melphalan, and etoposide was determined in a human breast (MCF-7) cancer cell line. Using the alkaline single-cell gel electrophoresis (comet) assay, we investigated kinetics of DNA damage and repair after treatment with the chemotherapeutic drugs combined with gefitinib. To investigate whether the phosphatidylinositol 3'-kinase pathway was contributing to repair-inhibition produced by gefitinib, cells were exposed to chemotherapy in combination with the phosphatidylinositol 3'-kinase inhibitor LY294002.A superadditive (synergistic) increase in growth inhibition for combined treatment with gefitinib was found for cisplatin and etoposide, but not with melphalan. There was delayed repair of DNA strand breaks after treatment with etoposide combined with gefitinib, and repair of DNA interstrand cross-links produced by cisplatin is delayed in combination with gefitinib. Inhibition of cell proliferation and DNA repair was identical in cells treated with LY294002. Immunoprecipitation of cell extracts demonstrated that after exposure to gefitinib, there was an association between EGFR and DNA-PK(CS).Gefitinib acts through inhibition of repair of cisplatin and etoposide-induced DNA damage; this effect is mimicked by inhibitors of the phosphatidylinositol 3'-kinase suggesting similar mechanisms of action.
Exercise Is Medicine
Authors: Thijs M. H. Eijsvogels, Paul D. Thompson
Journal: JAMA (2015)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Therapeutic equivalence between bambuterol, 10 mg once daily, and terbutaline controlled release, 5 mg twice daily, in mild to moderate asthma
Authors: AM Fugleholm, TB Ibsen, L Laxmyr, UG Svendsen
Journal: European Respiratory Journal (1993)

Bambuterol is the first long-acting oral beta 2-agonist with a 24 h effective duration. In order to investigate the possibility of replacing established treatment modalities with bambuterol once daily, we wanted to compare the bronchodilating and tremorogenic effects of bambuterol, 10 mg once daily, and terbutaline, 5 mg controlled-release (CR) tablets twice daily. The study was of a double-blind, double-dummy, randomized, cross-over design and involved two, two week treatment periods, separated by a one week wash-out period. Peak expiratory flow (PEF) recorded in patients' diaries was the primary efficacy variable. Seventy adult, asthmatic out-patients with mild to moderate asthma were included (forced expiratory volume in one second (FEV1) > or = 50% predicted). After treatment with bambuterol, mean morning and evening PEF (SD) were 347 (122) and 365 (121) l.min-1, respectively and 346 (121) and 365 (122) l.min-1, respectively, after treatment with terbutaline. FEV1 (SD) was 2.21 (0.91) l and 2.27 (0.93) l after bambuterol and terbutaline treatments, respectively. Tremor scores tended to be lower during treatment with bambuterol, although not significantly so. Tremor scores were low, in general. In conclusion, no difference in the bronchodilating effect was demonstrated between bambuterol, 10 mg once daily, and controlled release terbutaline, 5 mg twice daily. A tendency towards less tremor was seen with bambuterol.
Neuropathological assessment of Parkinson's disease: refining the diagnostic criteria
Authors: Dennis W Dickson, Heiko Braak, John E Duda, Charles Duyckaerts, Thomas Gasser, Glenda M Halliday, John Hardy, James B Leverenz, Kelly Del Tredici, Zbigniew K Wszolek, Irene Litvan
Journal: The Lancet Neurology (2009)
Cellular and molecular basis of human gamma delta T cell activation. Role of accessory molecules in alloactivation.
Authors: M Takamizawa, F Fagnoni, A Mehta-Damani, A Rivas, E G Engleman
Journal: Journal of Clinical Investigation (1995)

Although gamma delta T cell receptor-bearing lymphocytes (gamma delta T cells) constitute a significant minority of circulating and tissue-associated T lymphocytes, the mechanism responsible for the activation of these cells is unknown. To address this question, resting gamma delta TCR+, CD3+, CD4-, CD8- cells isolated from the blood of healthy volunteers were cultured with allogeneic dendritic cells (DC) or monocytes, and their proliferative response measured. DC alone induced gamma delta T cells to proliferate, with a peak response on the sixth day of culture. Pretreatment of DC with an anti-HLA-DR mAb, but not anti-HLA class I or anti-CD1 mAbs, inhibited the response of gamma delta T cells. Antibodies to gamma delta T cell receptor, CD2, CD3, or CD11a were also inhibitory, whereas antibodies to alpha beta T cell receptor, CD4, CD5, and CD8 had no effect. Although only 40-60% of freshly isolated gamma delta T cells expressed CD28, mAbs directed against CD28 or its ligand, CD80, were markedly inhibitory. Moreover, removal of CD28+ cells from the gamma delta T cell population nearly abrogated the response to DC. These results demonstrate that resting gamma delta T cells recognize and respond to MHC class II determinants on allogeneic DC in a manner that is highly dependent on the CD28 activation pathway as well as molecules such as CD2 and CD11a that mediate cell-to-cell adhesion.
Alienation-Reduction in Brief Group Therapy
Authors: WILLIAM B. DONOVAN, ROBERT C. MARVIT
Journal: American Journal of Psychiatry (1970)

The authors describe a controlled study of patients in brief group therapy that was designed to determine whether this kind of therapy reduces alienation. They found that while alienated attitudes were not reduced, the participants became more sociable and content; affective and behavioral, but not attitudinal, components of alienation were affected.
Induction of Mammary Neoplasms in the Sprague-Dawley Rat by 430-keV Neutrons and X-Rays&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Claire J. Shellabarger, Danielle Chmelevsky, Albrecht M. Kellerer
Journal: JNCI Journal of the National Cancer Institute (1980)

Female noninbred Sprague-Dawley rats were exposed to single doses of 0.28, 0.56, and 0.85 gray (Gy = 1 J/kg or 100 rads) of X-rays or 0.001, 0.004, 0.016, and 0.064 Gy of 430-keV neutrons at 62 +/- 1 days of age and were then observed over the rest of their lives for the appearance of mammary neoplasia. As mammary neoplasms were detected, they were removed and given a classification of adenocarcinoma(s) (AC) or fibroadenoma(s) (FA) after microscopic study. All irradiated groups exhibited an increased incidence of mammary neoplasia. The tumor rate increased steeply with age of the animals, and the effect of the irradiation could be adequately described as a forward shift in time of the spontaneous incidence. The cumulative prevalence was derived from first neoplasms only, and a formalism was presented that makes it possible to derive the integral tumor rate from all neoplasms in all animals. Mortality-corrected cumulative prevalences and integral tumor rates as a function of age were given for the different doses and separately for FA and AC. The mammary FA response and the total mammary neoplastic response (including both FA and AC) were approximately proportional to the absorbed dose of X-rays or the square root of the neutron dose. The relative biological effectiveness (RBE) of the neutrons increased with decreasing dose and reached values exceeding 100 at a neutron dose of 1 mGy; the single dose of 1 mGy of neutrons produced a significant increase of the tumor rate that corresponded to a foward shift or roughly 35 days of the spontaneous incidence. The AC, taken separately, were subject to considerable statistical uncertainties due to their small numbers. However, their RBE-dose dependence was consistent with that for the FA and, even at the highest dose studied, the RBE value exceeded 10. The nonrandom development of multiple FA within individual animals appeared to be the result of differences in susceptibility to radiation. However, mammary FA and AC within individual animals were not statistically correlated.
Human hepatic stellate cells secrete adrenomedullin: potential autocrine factor in the regulation of cell contractility
Authors: M Nieves Görbig, Pere Ginès, Ramón Bataller, Josep M Nicolás, Eva Garcia-Ramallo, Pilar Cejudo, Pau Sancho-Bru, Wladimiro Jiménez, Vicente Arroyo, Juan Rodés
Journal: Journal of Hepatology (2001)
What should undergraduate medical students know about psoriasis? Involving patients in curriculum development: modified Delphi technique
Authors: Abdelaziz Alahlafi, Susan Burge
Journal: BMJ (2005)

To identify the content of a psoriasis curriculum for medical students.Literature review and modified Delphi technique.Primary and secondary care in Oxfordshire and Buckinghamshire.19 dermatologists (7 teaching hospital consultants; 6 consultants in district general hospitals; 6 registrars); 2 general practitioner senior house officers working in dermatology, 5 dermatology nurses, 7 rheumatologists, 25 general practitioner tutors, and 25 patients with chronic psoriasis.Percentage of agreement by participants to items derived from literature and our existing psoriasis syllabus.71 (84.5%) of 84 questionnaires were returned. A 75% level of consensus was reached on key items that focused on the common presentations of psoriasis, impact, management, and communication skills. Students should be aware of the psychosocial impact of psoriasis, examine the skin while showing sensitivity, and be able to explain psoriasis to patients in a way that enables patients to explain the condition to others.The panels identified the important items for a psoriasis curriculum. The views of patients were particularly helpful, and we encourage educators to involve patients with chronic diseases in developing curriculums in the future. The method and results could be generalised to curriculum development in chronic disease.
CRUISE: can routine intravascular ultrasound influence stent expansion? Analysis of outcomes
Authors: P.J. Fitzgerald, M. Hayase, G.S. Mintz, R. Kuntz, J.W. Moses, D.J. Diver, E. Deutsch, C.A. Simonton, D.S. Baim, M.B. Leon, P.G. Yock
Journal: Journal of the American College of Cardiology (1998)
Amputation Prevention Initiative in South India
Authors: Vijay Viswanathan, Sivagami Madhavan, Seena Rajasekar, Snehalatha Chamukuttan, Ramachandran Ambady
Journal: Diabetes Care (2005)

To determine whether intensive treatment and education strategies for type 2 diabetic patients with high-risk diabetic foot disease helps in preventing foot amputations.Participants included 4,872 consecutive type 2 diabetic patients (male-to-female ratio 3,422:1,450, mean (+/-SD) age 60.5 +/- 8.8 years, mean duration of diabetes 13.7 +/- 7.6 years) with high-risk diabetic foot disease. The patients were categorized as high-risk subjects according to the International Consensus on the Diabetic Foot. The three study groups were subjects with diabetes and neuropathy (group 1; n = 2,871), diabetic neuropathy with deformity (group 2; n = 235), and diabetic neuropathy with deformity and foot ulceration or peripheral vascular disease (group 3; n = 1,766). Neuropathy was diagnosed by biothesiometry. Peripheral vascular disease was diagnosed as an ankle brachial index <0.8. All the subjects were educated regarding diabetic foot disease and its complications and prevention. They were also instructed to visit the center if any sign of new lesions appeared.Among the 1,259 group 3 subjects who came for follow-up, 718 (57%) strictly followed the advice given and 541 (43%) did not. Ulcers present during the recruitment had healed in 585 (82%) subjects who followed the advice, but in only 269 (50%) subjects who did not. A significantly larger proportion of subjects who did not follow the advice developed new problems (26%) and required surgical procedures (14%) compared with those who followed the advice (5 and 3%, respectively).Strategies such as intensive management and foot care education are helpful in preventing newer problems and surgery in diabetic foot disease.
Statin Use and Survival After Colorectal Cancer: The Importance of Comprehensive Confounder Adjustment
Authors: Michael Hoffmeister, Lina Jansen, Anja Rudolph, Csaba Toth, Matthias Kloor, Wilfried Roth, Hendrik Bläker, Jenny Chang-Claude, Hermann Brenner
Journal: JNCI Journal of the National Cancer Institute (2015)

Statins have been associated with moderate reductions in mortality among colorectal cancer (CRC) patients, but these studies lacked adjustment for some potentially relevant factors associated with statin use. We aimed to provide more detailed results on this association from a population-based patient cohort study. Use of statins and other risk or protective factors were assessed in standardized interviews with 2697 patients from southern Germany with a diagnosis of incident CRC between 2003 and 2009 (Darmkrebs: Chancen der Verhütung durch Screening [DACHS] study). Follow-up included assessment of therapy details, recurrence, vital status, and cause of death. Information about molecular pathological subtypes of CRC was available for 1209 patients. Cox proportional hazard regression models were used to estimate adjusted hazard ratios (HRs) and their 95% confidence intervals (CIs). All statistical tests were two-sided. Patients were age 68 years on average, 412 used statins (15%), and 769 died during follow-up (29%). After a median follow-up time of 3.4 years, use of statins was not associated with overall (HR = 1.10, 95% CI = 0.85 to 1.41), CRC-specific (HR = 1.11, 95% CI = 0.82 to 1.50), or recurrence-free survival (HR = 0.90, 95% CI = 0.63 to 1.27). Analyses in relevant subgroups also showed no association of statin use with overall and CRC-specific survival, and no associations were observed after stratifying for major pathological subtypes. Among stage I and II patients, statin use was associated with better recurrence-free but not with better CRC-specific survival. Statin use was not associated with reduced mortality among CRC patients. Effects reported in previous studies might reflect incomplete control for stage at diagnosis and other factors associated with the use of statins.
Physiologic study of the terminal digestive tract in chronic painful constipation.
Authors: P Meunier
Journal: Gut (1986)

A manometric study of the sigmoid colon and of the anorectum was undertaken in 65 chronically constipated patients complaining of abdominal pain, and in a control group of 23 healthy volunteers. Rectal compliance was tested in both groups. The sigmoid motility study allowed for the segregation of the constipated patients into three groups: hypokinesia (12 cases), normokinesia (34 cases), hyperkinesia (19 cases). Rectal manometry showed anal hypertony in 24 patients, impaired rectal conscious sensitivity in 12 subjects, and normal functions in the remaining cases. The rectal compliance study disclosed a decreased compliance in 15 cases and increased compliance in 13 other patients. In 12 cases disordered sigmoid motility was the only abnormality; in 10 cases only a rectoanal abnormality was found. Most of the patients (52%) exhibited miscellaneous disorders. In contrast, all parameters were normal in nine subjects. No consistent pattern of motility disorders was thus demonstrated in this clinically homogeneous group of patients with chronic, painful, constipation.
Structural Basis for the Restoration of TCR Recognition of an MHC Allelic Variant by Peptide Secondary Anchor Substitution
Authors: Michael J. Miley, Ilhem Messaoudi, Beatrix M. Metzner, Yudong Wu, Janko Nikolich-Žugich, Daved H. Fremont
Journal: The Journal of Experimental Medicine (2004)

Major histocompatibility complex (MHC) class I variants H-2Kb and H-2Kbm8 differ primarily in the B pocket of the peptide-binding groove, which serves to sequester the P2 secondary anchor residue. This polymorphism determines resistance to lethal herpes simplex virus (HSV-1) infection by modulating T cell responses to the immunodominant glycoprotein B498-505 epitope, HSV8. We studied the molecular basis of these effects and confirmed that T cell receptors raised against Kb–HSV8 cannot recognize H-2Kbm8–HSV8. However, substitution of SerP2 to GluP2 (peptide H2E) reversed T cell receptor (TCR) recognition; H-2Kbm8–H2E was recognized whereas H-2Kb–H2E was not. Insight into the structural basis of this discrimination was obtained by determining the crystal structures of all four MHC class I molecules in complex with bound peptide (pMHCs). Surprisingly, we find no concerted pMHC surface differences that can explain the differential TCR recognition. However, a correlation is apparent between the recognition data and the underlying peptide-binding groove chemistry of the B pocket, revealing that secondary anchor residues can profoundly affect TCR engagement through mechanisms distinct from the alteration of the resting state conformation of the pMHC surface.