tbuckley/cabot-search huggingface dataset:
Karnofsky Memorial Lecture. Breaking the cure barrier.
Authors: J F Holland
Journal: Journal of Clinical Oncology (1983)

Breaking the cure barrier is a biologic and a conceptual problem that has already been accomplished for several tumors. It is helpful to consider neoplasms in mathematical terms as many-celled tumors (polycytomas: kilocytomas, megacytomas, gigacytomas, and teracytomas). A new chemotherapeutic taxonomy recognizes curable, subcurable, and precurable cancers each with definable characteristics. A simplified technique of recognizing early cures is described by calculating the probability that an interruption in an exponential failure slope occurred by chance. Examples of cures of acute myelocytic leukemia, of superior chemotherapy for Hodgkin's disease in young adults, and of superior adjuvant chemotherapy for breast cancer are given. The interaction of surgery with chemotherapy is illustrated in pure form in acute myelocytic leukemia and in ovarian cancer. Curative chemotherapy is closer at hand than is generally believed. Nomograms for cure prediction are presented as inducements to contemplate curative approaches to cancer therapy.
The anti-IgE antibody omalizumab improves asthma-related quality of life in patients with allergic asthma
Authors: R. Buhl, G. Hanf, M. Solèr, G. Bensch, J. Wolfe, F. Everhard, K. Champain, H. Fox, J. Thirlwell
Journal: European Respiratory Journal (2002)

The aim of the present study was to determine the effect of treatment with omalizumab, an anti-immunoglobulin E antibody, on asthma-related quality of life (AQoL) in patients with moderate-to-severe allergic asthma. A total of 546 patients with allergic asthma were randomised to double-blind subcutaneous treatment with either placebo or omalizumab for 52 weeks. A constant beclomethasone dipropionate dose was maintained during the first 16 weeks (steroid-stable phase). This was followed by a 12-week steroid-reduction phase. The core study was followed by a 24-week double-blind extension phase. AQoL was evaluated at baseline and at the end of the steroid-stable (week 16), steroid-reduction (week 28) and extension phases (week 52) using the Juniper Asthma Quality of Life Questionnaire (AQLQ). Baseline AQLQ scores were comparable for the two treatment groups. Relative to placebo, omalizumab-treated patients demonstrated statistically significant improvements from baseline across all four AQLQ domains, as well as overall AQoL score, at weeks 16 (except environmental exposure), 28 and 52. Patients on omalizumab were also more likely to achieve clinically significant improvements in AQoL during the course of the study. Overall, almost 70% of patients and investigators rated treatment with omalizumab as “excellent/good”, compared with ∼40% of placebo recipients. Clinical studies show that omalizumab enhances disease control whilst reducing corticosteroid consumption in patients with allergic asthma. The results of the present study show that these changes are paralleled by improvements in asthma-related quality of life that are meaningful to such patients.
<i>C-MYC</i> Alterations and Association With Patient Outcome in Early-Stage HER2-Positive Breast Cancer From the North Central Cancer Treatment Group N9831 Adjuvant Trastuzumab Trial
Authors: Edith A. Perez, Robert B. Jenkins, Amylou C. Dueck, Anne E. Wiktor, Patrick P. Bedroske, S. Keith Anderson, Rhett P. Ketterling, William R. Sukov, Kazunori Kanehira, Beiyun Chen, Xochiquetzal J. Geiger, Cathy A. Andorfer, Ann E. McCullough, Nancy E. Davidson, Silvana Martino, George W. Sledge, Peter A. Kaufman, Leila A. Kutteh, Julie R. Gralow, Lyndsay N. Harris, James N. Ingle, Wilma L. Lingle, Monica M. Reinholz
Journal: Journal of Clinical Oncology (2011)

Findings from the human epidermal growth factor receptor 2 (HER2) -positive National Surgical Adjuvant Breast and Bowel Project (NSABP) B31 trial suggested that MYC/HER2 coamplification (> 5.0 copies/nucleus) was associated with additional benefit from adjuvant trastuzumab in patients with early-stage breast cancer. To further explore this relationship, we investigated associations between MYC amplification and disease-free survival (DFS) in a similar adjuvant trastuzumab HER2-positive breast cancer trial-North Central Cancer Treatment Group (NCCTG) N9831.This analysis included 799 patients randomly assigned to receive chemotherapy alone or with concurrent trastuzumab on N9831. Fluorescence in situ hybridization (FISH) was performed by using a dual-probe mixture for MYC and centromere 8 (MYC:CEP8) on tissue microarrays. MYC amplification was prespecified as MYC:CEP8 ratio > 2.2 or average MYC copies/nucleus > 5.0. Exploratory variables included polysomy 8.In comparing DFS (median follow-up, 4.0 years) between treatments, patients with MYC:CEP8 ratio ≤ 2.2 (n = 618; 77%) and > 2.2 (n = 181; 23%) had hazard ratios (HRs) of 0.46 (P < .001) and 0.67 (P = .33), respectively (interaction P = .38). Patients with MYC copies/nucleus ≤ 5.0 (n = 534; 67%) and > 5.0 (n = 265; 33%) had HRs of 0.52 (P = .002) and 0.48 (P = .02), respectively (interaction P = .94). Patients with MYC:CEP8 ratio < 1.3 with normal chromosome 8 copy number (n = 141; 18%) and ≥ 1.3 or < 1.3 with polysomy 8 (n = 658; 82%) had HRs of 0.66 (P = .28) and 0.44 (P < .001), respectively (interaction P = .23). Patients with MYC copies/nucleus < 2.5 (n = 130; 16%) and ≥ 2.5 (n = 669; 84%) had HRs of 1.07 (P = .87) and 0.42 (P < .001), respectively (interaction P = .05).We did not confirm the B31 association between MYC amplification and additional trastuzumab benefit. Exploratory analyses revealed potential associations between alternative MYC/chromosome 8 copy number alterations and differential benefit of adjuvant trastuzumab.
Abuse-Deterrent Formulations of Prescription Opioids
Authors: Richard C. Dart, S. Geoff Severtson, Jody L. Green
Journal: JAMA Psychiatry (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 Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast 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 Psychiatry journal
Deterioration in quality of life (QoL) in patients with malignant ascites: results from a phase II/III study comparing paracentesis plus catumaxomab with paracentesis alone
Authors: P. Wimberger, H. Gilet, A.-K. Gonschior, M.M. Heiss, M. Moehler, G. Oskay-Oezcelik, S.-E. Al-Batran, B. Schmalfeldt, A. Schmittel, E. Schulze, S.L. Parsons
Journal: Annals of Oncology (2012)
Resting macrophages produce distinct metabolites from exogenous arachidonic acid
Authors: WA Scott, NA Pawlowski, M Andreach, ZA Cohn
Journal: The Journal of Experimental Medicine (1982)

Resident mouse peritoneal macrophages rapidly metabolize free arachidonic acid (20:4) in the absence of a discernible trigger. After a 20-min incubation in serumless medium, one-third of the fatty acid was found esterified in cell phospholipid and two-thirds was metabolized to oxygenated products which were recovered in the culture medium. The 20:4 oxygenated metabolites were identified by reverse-phase high performance liquid chromatography as hydroxyeicosatetraenoic acids (HETEs) and 6-keto prostaglandin F(1a) (6-ketoPGF(1a)), the stable form of prostacyclin, together with prostaglandin E(2) (PGE(2)) in proportions of 67:24:9. Inhibitor studies using indomethacin, nordihydroguaiaretic acid, and 5,8,11,14-eicosatetraenoic acid confirmed these metabolites to be lipoxygenase and cyclo-oxygenase products. The proportion of products differs considerably from those generated from phospholipid 20:4 in response to a phagocytic stimulus (HETEs:6-ketoPGF(1a):PGE(2):leukotriene C, 15:25:40: 15-20). Cornyebacterium parvum-elicited macrophages incorporated a higher percentage (70 percent) of exogenously supplied 20:4 and converted less than 20 percent of the fatty acid to oxygenated metabolites. Cyclo-oxygenase products (PGE(2), PGF(2a), TXB(2), and 6-ketoPGF(1a)) represented the major 20:4 metabolites (74 percent) synthesized by these activated macrophages. Esterification of 20:4 into cell phospholipids appeared not to be an initial obligatory step for synthesis of 20:4 oxygenated products by this route. To the contrary, incorporation of 20:4 into cell lipids and metabolism via the cyclo-oxygenase and lipoxygenase pathways represent distinct metabolic fates of exogenously supplied 20:4. These observations establish that resting macrophages contain high levels of cyclo-oxygenase and lipoxygenase activity and suggest macrophages can synthesize lipid mediators of inflammation in the absence of an inflammatory stimulus.
Depression, antidepressants, and accidents
Authors: J G. Edwards
Journal: BMJ (1995)

Pharmacological concerns need epidemiological elucidation

Patients with depressive disorders could be more liable to accidents than others for several reasons. These include impaired attention and concentration (often due to preoccupation with morbid or worrying thoughts); anxiety, which usually accompanies depression; irritability; agitation or retardation; fatigue after sleepless nights; and weakness due to insufficient food intake. In addition, depressed patients may take risks with little regard to the consequences, make suicidal gestures or attempts that go wrong, and take alcohol or other substances that impair functioning to relieve distress. In keeping with these considerations are the reductions in performance in tests of cognitive and psychomotor function in depressed patients.1

If depression causes or contributes to accidents in these ways then therisk of accidents might be expected to fall as the disorder improves in response to treatment with antidepressant drugs (or other treatment). On the other hand, the unwanted effects of antidepressants may adversely affect cognitive and psychomotor function (especially in those with pre-existing cerebral impairment), thereby increasing the risk of accidents. This is particularly the case in patients who do not respond to treatment and thus are impaired by both the depression and the drug. Drug induced effects may be clinically obvious, with, for example, somnolence due to oversedation; mild effects may be evident only on formal psychometric testing. In tests of higher central nervous system functions the older tricyclic antidepressants, such …
S-1 plus oxaliplatin versus capecitabine plus oxaliplatin for first-line treatment of patients with metastatic colorectal cancer: a randomised, non-inferiority phase 3 trial
Authors: Yong Sang Hong, Young Suk Park, Ho Yeong Lim, Jeeyun Lee, Tae Won Kim, Kyu-pyo Kim, Sun Young Kim, Ji Yeon Baek, Jee Hyun Kim, Keun-Wook Lee, Ik-Joo Chung, Sang-Hee Cho, Kyung Hee Lee, Sang Joon Shin, Hye Jin Kang, Dong Bok Shin, Sook Jung Jo, Jae Won Lee
Journal: The Lancet Oncology (2012)
Interleukin-10 secretion from CD14+ peripheral blood mononuclear cells is downregulated in patients with acne vulgaris
Authors: F. Caillon, M. O’Connell, E.A. Eady, G.R. Jenkins, J.H. Cove, A.M. Layton, A.P. Mountford
Journal: British Journal of Dermatology (2009)

Journal Article Interleukin‐10 secretion from CD14+ peripheral blood mononuclear cells is downregulated in patients with acne vulgaris Get access F. Caillon, F. Caillon Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, U.K.Department of Dermatology, Harrogate District Hospital, Harrogate HG2 7SX, U.K. Search for other works by this author on: Oxford Academic Google Scholar M. O'Connell, M. O'Connell Department of Dermatology, Harrogate District Hospital, Harrogate HG2 7SX, U.K. Search for other works by this author on: Oxford Academic Google Scholar E.A. Eady, E.A. Eady Department of Dermatology, Harrogate District Hospital, Harrogate HG2 7SX, U.K. Search for other works by this author on: Oxford Academic Google Scholar G.R. Jenkins, G.R. Jenkins Centre for Immunology and Infection, Department of Biology and Hull York Medical School, University of York, York YO10 5YW, U.K. Search for other works by this author on: Oxford Academic Google Scholar J.H. Cove, J.H. Cove Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, U.K. Search for other works by this author on: Oxford Academic Google Scholar A.M. Layton, A.M. Layton Department of Dermatology, Harrogate District Hospital, Harrogate HG2 7SX, U.K. Search for other works by this author on: Oxford Academic Google Scholar A.P. Mountford A.P. Mountford Centre for Immunology and Infection, Department of Biology and Hull York Medical School, University of York, York YO10 5YW, U.K. Adrian Mountford. E‐mail: apm10@york.ac.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 162, Issue 2, 1 February 2010, Pages 296–303, https://doi.org/10.1111/j.1365-2133.2009.09420.x Published: 01 February 2010
Xenobiotic Metabolomics: Major Impact on the Metabolome
Authors: Caroline H. Johnson, Andrew D. Patterson, Jeffrey R. Idle, Frank J. Gonzalez
Journal: The Annual Review of Pharmacology and Toxicology (2011)

Xenobiotics are encountered by humans on a daily basis and include drugs, environmental pollutants, cosmetics, and even components of the diet. These chemicals undergo metabolism and detoxication to produce numerous metabolites, some of which have the potential to cause unintended effects such as toxicity. They can also block the action of enzymes or receptors used for endogenous metabolism or affect the efficacy and/or bioavailability of a coadministered drug. Therefore, it is essential to determine the full metabolic effects that these chemicals have on the body. Metabolomics, the comprehensive analysis of small molecules in a biofluid, can reveal biologically relevant perturbations that result from xenobiotic exposure. This review discusses the impact that genetic, environmental, and gut microflora variation has on the metabolome, and how these variables may interact, positively and negatively, with xenobiotic metabolism.
Clinical trials and tribulations: the MASCOT study
Authors: W. Lenney, S. Perry, D. Price
Journal: Thorax (2011)

Following the 1994 Lancet paper showing benefits of long-acting β-agonists (LABAs) in adults with asthma,1 British Paediatric Respiratory Society surveys have consistently recommended undertaking similar studies appropriately designed for children. Adult outcome measures should not be extrapolated into childhood, which explains why early studies indicated LABAs may be less helpful in children.2 With the advent of the Medicines for Children Research Network (MCRN) in 2004, the Health Technology Assessment (HTA) put out a call for children's medicines studies in 2005. The Management of Asthma in School Children On Therapy (MASCOT) study was funded in January 2006 pending Pharma approval to supply the medicines (fluticasone, fluticasone–salmeterol combination treatment and montelukast) as National Institute for Health Research funding does not include excess treatment costs. This task took 12 months including lengthy discussions with Merck, Sharp and Dome (MSD) about methodology and statistics. The protocol required 900 children to use inhaled corticosteroids (ICS) for a 4 week open run-in followed by 48 weeks (double blind, double dummy) taking ICS, ICS plus LABA or ICS plus montelukast. The primary outcome measure was the exacerbation rate. The HTA funded MASCOT research costs. MSD and GlaxoSmithKline (GSK) agreed to supply medication. There was a delay in appointing a trial coordinator to oversee the 13 sites which had readily agreed to participate. The lengthy task of writing the protocol to EU standards (in addition to the original protocol designed for HTA application) was new and baffling to many of us, as was the preparation and submission of the Clinical Trials Authorisation.
Endothelin. Key to coronary vasospasm?
Authors: T F Lüscher
Journal: Circulation (1991)

In 1959, Prinzmetal and colleagues described a new form of chest pain that developed at rest and very often occurred in the early morning hours.12The pain was associated with ST segment elevations in the electrocardiogram and relieved by nitroglycerin.They named the syndrome "variant angina" and suggested that it was caused by a spasm of a major epicardial coronary artery.Subsequently, coronary spasm has been docu- mented angiographically in patients with variant an- gina.3-7In addition, coronary vasomotion has been recognized as an important factor in the pathogenesis of most ischemic coronary syndromes.8'9Although the phenomenon has been well characterized clini- cally and angiographically, the cause of coronary spasm remains enigmatic.Moreover, it even appears uncertain whether all increases in coronary vascular tone occurring in acute ischemic syndromes can be explained by a single factor or represent a heteroge- nous entity ranging from normal coronary vasomo- tion in a narrowed vascular segment to "true spasm" (i.e., variant angina) with total or near-total occlusion of an angiographically normal or mildly atheroscle- rotic coronary artery.8See page 476 In patients with variant angina, vasospasm is a localized phenomenon that repeatedly affects the same coronary vascular segment either spontaneously or after provocation.Thus, a local dysfunction of the blood vessel wall at the site of spasm must be involved.Accordingly, alterations of local neurogenic control, vascular smooth muscle, the endothelium, or blood cells have been implicated.For years, research interest has focused on a local hyperresponsiveness of adrenergic nerves.Adrener- gic nerves are unlikely to play a primary role, how- ever, as phenylephrine and norepinephrine fail to precipitate and neither phentolamine nor prazosin
Pyrogenic reactions in patients receiving conventional, high-efficiency, or high-flux hemodialysis treatments with bicarbonate dialysate containing high concentrations of bacteria and endotoxin.
Authors: S M Gordon, C W Oettinger, L A Bland, J C Oliver, M J Arduino, S M Aguero, S K McAllister, M S Favero, W R Jarvis
Journal: Journal of the American Society of Nephrology (1992)

High-efficiency (HE) and high-flux (HF) hemodialysis are becoming increasingly popular methods for treating patients with chronic renal failure because they reduce the time required for dialysis treatment. HF and HE dialyzers require bicarbonate dialysate, often prepared from concentrates that can support bacterial growth with endotoxin production. There is a concern that endotoxins or bacteria may cross or interact at the membranes of these dialyzers, triggering the release of endogenous pyrogens (cytokines) by peripheral blood mononuclear cells to cause pyrogenic reactions (PR). To determine the incidence of PR and to examine the association between PR and levels of bacteria and endotoxin in dialysate, a cohort of patients receiving conventional, HE, or HF hemodialysis with bicarbonate dialysate and reprocessed dialyzers at three dialysis centers during a 12-month period was studied prospectively. All dialyzers underwent a test of membrane integrity before use. A total of 19 PR were identified among 18 patients in 26,877 hemodialysis treatments (0.7 PR/1,000 treatments). There was no significant difference in PR rates by treatment modality: conventional, 0.5 per 1,000 (7 PR/13,123 treatments) versus HE, 0.9 per 1,000 (9 PR/11,345) versus HF, 1.2 per 1,000 (3 PR/2,409) (P = 0.21; chi 2 test). Throughout the study period, bacterial counts for dialysate at each center significantly exceeded the Association for the Advancement of Medical Instrumentation's (AAMI) microbiologic standards for dialysate of less than 2,000 CFU/mL (mean, 19,000 CFU/mL), but water used in the reuse of dialyzers tested less than 200 CFU/mL.(ABSTRACT TRUNCATED AT 250 WORDS)
CKD Classification
Authors: T. Alp Ikizler
Journal: Journal of the American Society of Nephrology (2009)

The number of patients with ESRD is increasing worldwide. Despite recent advances in our understanding of the uremic state and improvements in the science and technology of renal replacement therapy, the morbidity and mortality of these patients is unacceptably high: More than 20% per year. Moreover, the health care cost of treating ESRD exceeds $17 billion annually in the United States alone.1

These observations led the nephrology community a few years ago to recognize chronic kidney disease (CKD) as an important public health problem while emphasizing the need for timely treatment for prevention of ESRD. Among a large number of initiatives aimed at increasing early awareness of CKD, the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) clinical practice guidelines for classification and staging of CKD receives most attention and acceptance.2 In addition to a working definition, KDOQI proposes a classification system based on severity determined by level of kidney function, calculated from the estimated GFR (eGFR), irrespective of the cause of kidney disease.

The KDOQI CKD definition and classification are widely accepted in clinical practice and influential in epidemiologic studies worldwide. Nevertheless, the classification is the subject of increasing scrutiny by investigators,3 regulators, and even members of the original KDOQI workgroup.4 A controversial aspect of KDOQI is the high prevalence of CKD imposed by the classification system itself. Use of KDOQI leads to prevalence estimates of combined stages 1 and 2 CKD ranging from 2.9 to 7.0% in the general population.5 In other studies, stage 3 CKD prevalence …