tbuckley/cabot-search huggingface dataset:
Serum markers associated with clinical improvement in patients with ankylosing spondylitis treated with golimumab
Authors: Carrie Wagner, Sudha Visvanathan, Jürgen Braun, Désirée van der Heijde, Atul Deodhar, Benjamin Hsu, Michael Mack, Michael Elashoff, Robert D Inman
Journal: Annals of the Rheumatic Diseases (2011)

Objective Identify serum biomarkers modulated by golimumab treatment and associated with clinical response in patients with ankylosing spondylitis (AS). Methods Sera were collected at weeks 0, 4 and 14 from 100 patients with active AS in the GO–RAISE study. Patients were randomly assigned subcutaneous injections of placebo, golimumab 50 mg, or golimumab 100 mg every 4 weeks. Samples were tested for select inflammatory, bone and cartilage markers, and protein profiling was also performed. Results Golimumab treatment resulted in significant decreases in several serum proteins at weeks 4 and 14 compared with placebo. Patients who achieved clinical response at week 14, as assessed by a ≥20% improvement in the Assessment in SpondyloArthitis international Society response criteria (ASAS 20), demonstrated a distinct biomarker profile with lower levels of acute phase reactants and inflammatory biomarkers compared with patients who did not. Notably, combinations of two or three biomarkers assessed at baseline were predictive of various clinical outcomes (ASAS 20, Bath ankylosing spondylitis disease activity index 50 or Bath ankylosing spondylitis functional index) using a logistic regression analysis, and the overall predictive values for these combined biomarkers were greater than observed for C-reactive protein (CRP) alone. Conclusion Golimumab modulated acute phase reactants and inflammatory markers in patients with active AS. Specific combinations of biomarkers at baseline demonstrated a stronger prediction for clinical efficacy than CRP alone. These data provide insights into the mechanism of golimumab on inflammatory processes driving AS pathology, and may have utility in managing the treatment of patients with AS.
Development of the 21-Gene Assay and Its Application in Clinical Practice and Clinical Trials
Authors: Joseph A. Sparano, Soonmyung Paik
Journal: Journal of Clinical Oncology (2008)

Several multigene markers that predict relapse more accurately than classical clinicopathologic features have been developed. The 21-gene assay was developed specifically for patients with estrogen receptor (ER)-positive breast cancer, and has been shown to predict distant recurrence more accurately that classical clinicopathologic features in patients with ER-positive breast cancer and negative axillary nodes treated with adjuvant tamoxifen; validation studies in this population led to its approval as a diagnostic test. In a similar population, it also may be used to assess the benefit of adding chemotherapy to hormonal therapy. Other validation studies indicate that it also predicts the risk of distant and local recurrence in other populations with ER-positive disease, including node-negative patients receiving no adjuvant therapy and patients with positive axillary nodes treated with doxorubicin-containing chemotherapy. The Trial Assigning Individualized Options for Treatment (TAILORx) is multicenter trial that integrates the 21-gene assay into the clinical decision-making process and is designed to refine the utility of the assay in clinical practice and to provide a resource for evaluating additional molecular markers as they are developed in the future.
Hospital contact for mental disorders in survivors of childhood cancer and their siblings in Denmark: a population-based cohort study
Authors: Lasse Wegener Lund, Jeanette F Winther, Susanne O Dalton, Luise Cederkvist, Pia Jeppesen, Isabelle Deltour, Marie Hargreave, Susanne K Kjær, Allan Jensen, Catherine Rechnitzer, Klaus K Andersen, Kjeld Schmiegelow, Christoffer Johansen
Journal: The Lancet Oncology (2013)
Pharmacokinetic Investigation of Imatinib Using Accelerator Mass Spectrometry in Patients with Chronic Myeloid Leukemia
Authors: Alan V. Boddy, Julieann Sludden, Melanie J. Griffin, Colin Garner, John Kendrick, Pritesh Mistry, Catherine Dutreix, David R. Newell, Stephen G. O'Brien
Journal: Clinical Cancer Research (2007)

Abstract Purpose: To investigate the potential use of accelerator mass spectrometry (AMS) in the study of the clinical pharmacology of imatinib. Experimental Design: Six patients who were receiving imatinib (400 mg/d) as part of their ongoing treatment for chronic myeloid leukemia (CML) received a dose containing a trace quantity (13.6 kBq) of 14C-imatinib. Blood samples were collected from patients before and at various times up to 72 h after administration of the test dose and were processed to provide samples of plasma and peripheral blood lymphocytes (PBL). Samples were analyzed by AMS, with chromatographic separation of parent compound from metabolites. In addition, plasma samples were analyzed by liquid chromatography/mass spectrometry (LCMS). Results: Analysis of the AMS data indicated that imatinib was rapidly absorbed and could be detected in plasma up to 72 h after administration. Imatinib was also detectable in PBL at 24 h after administration of the 14C-labeled dose. Comparison of plasma concentrations determined by AMS with those derived by LCMS analysis gave similar average estimates of area under plasma concentration time curve (26 ± 3 versus 27 ± 11 μg/mL·h), but with some variation within each individual. Conclusions: Using this technique, data were obtained in a small number of patients on the pharmacokinetics of a single dose of imatinib in the context of chronic dosing, which could shed light on possible pharmacologic causes of resistance to imatinib in CML.
Plasma renin activity and the renal response to nitric oxide synthesis inhibition.
Authors: D H Sigmon, O A Carretero, W H Beierwaltes
Journal: Journal of the American Society of Nephrology (1992)

Inhibition of systemic endothelium-derived relaxing factor (EDRF) synthesis with L-Nw-nitroarginine (L-NAME) results in decreased RBF, which can be reversed by acute blockade of angiotensin II (AII). Because AII is particularly elevated in the renal circulation, it was hypothesized that the degree of renal vasoconstriction produced by L-NAME in Inactin-anesthetized rats is related to PRA. To test this, PRA was chronically increased or suppressed by the manipulation of dietary sodium (eating 0.03% sodium chow or deoxycorticosterone acetate plus drinking 1% NaCl, respectively). After 10 days, rats were anesthetized for determination of blood pressure (BP) and RBF before and after L-NAME (10 mg/kg body wt). In rats with high PRA (61.6 +/- 10.4 ng of angiotensin I [Al]/mL/h; N = 8), L-NAME increased BP by 29 +/- 2 mm Hg (from 110 +/- 4 to 139 +/- 5 mm Hg; P < 0.001), decreased RBF by 27% (from 7.9 +/- 0.3 to 5.8 +/- 0.3 mL/min/g kidney wt; P < 0.001), and increased renal vascular resistance (RVR) by 67% (from 14.5 +/- 0.9 to 24.2 +/- 1.1 resistance units [RU]; P < 0.001). When rats with high PRA (N = 8) were treated with 10 mg/kg body wt of DuP 753, on AII receptor antagonist, L-NAME similarly increased BP by 30 +/- 5 mm Hg (from 81 +/- 3 to 111 +/- 5; P < 0.001) but RBF did not change and RVR increased by only 31% (from 10.9 +/- 0.8 to 13.3 +/- 0.7 RU; P < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)
EURAMOS-1, an international randomised study for osteosarcoma: results from pre-randomisation treatment
Authors: J.S. Whelan, S.S. Bielack, N. Marina, S. Smeland, G. Jovic, J.M. Hook, M. Krailo, J. Anninga, T. Butterfass-Bahloul, T. Böhling, G. Calaminus, M. Capra, C. Deffenbaugh, C. Dhooge, M. Eriksson, A.M. Flanagan, H. Gelderblom, A. Goorin, R. Gorlick, G. Gosheger, R.J. Grimer, K.S. Hall, K. Helmke, P.C.W. Hogendoorn, G. Jundt, L. Kager, T. Kuehne, C.C. Lau, G.D. Letson, J. Meyer, P.A. Meyers, C. Morris, H. Mottl, H. Nadel, R. Nagarajan, R.L. Randall, P. Schomberg, R. Schwarz, L.A. Teot, M.R. Sydes, M. Bernstein, James Pickering, Nicola Joffe, Matthias Kevric, Benjamin Sorg, Doojduen Villaluna, Caroline Wang, Martha Perisoglou, Leonardo Trani, Jenny Potratz, Dorothe Carrle, Miriam Wilhelm, Katja Zils, Carmen Teske
Journal: Annals of Oncology (2014)

Four international study groups undertook a large study in resectable osteosarcoma, which included two randomised controlled trials, to determine the effect on survival of changing post-operative chemotherapy based on histological response.Patients with resectable osteosarcoma aged ≤40 years were treated with the MAP regimen, comprising pre-operatively of two 5-week cycles of cisplatin 120 mg/m(2), doxorubicin 75 mg/m(2), methotrexate 12 g/m(2) × 2 (MAP) and post-operatively two further cycles of MAP and two cycles of just MA. Patients were randomised after surgery. Those with ≥10% viable tumour in the resected specimen received MAP or MAP with ifosfamide and etoposide. Those with <10% viable tumour were allocated to MAP or MAP followed by pegylated interferon. Longitudinal evaluation of quality of life was undertaken.Recruitment was completed to the largest osteosarcoma study to date in 75 months. Commencing March 2005, 2260 patients were registered from 326 centres across 17 countries. About 1334 of 2260 registered patients (59%) were randomised. Pre-operative chemotherapy was completed according to protocol in 94%. Grade 3-4 neutropenia affected 83% of cycles and 59% were complicated by infection. There were three (0.13%) deaths related to pre-operative chemotherapy. At definitive surgery, 50% of patients had at least 90% necrosis in the resected specimen.New models of collaboration are required to successfully conduct trials to improve outcomes of patients with rare cancers; EURAMOS-1 demonstrates achievability. Considerable regulatory, financial and operational challenges must be overcome to develop similar studies in the future. The trial is registered as NCT00134030 and ISRCTN 67613327.
The Gardner hypothesis Found wanting
Authors: A J M Slovak, C Kalman, N F Davies, K Pilling, J T Hodgson, J Osman, E Varney, B J Furness, D H Spodick
Journal: BMJ (1994)

EDITOR, - In 1990 Gardner et al identified an association between paternal preconceptional irradiation and childhood leukaemia and nonHodgkin's lymphoma in a sub population of workers at sellafield living in west Cumbria.1 The Gardner hypothesis asserted that this association might be casual. In her editorial Hazel Inskip cites a series of studies that have been conducted to test the hypothesis.2 Perhaps the most telling of these is the recently published work at Parker et al, which tested the Gardner theory in the whole of the population from which it was derived.3 This study, along with the others described by inskip, have failed to support the hypothesis of paternal preconceptional irradiation, as inskip acknowledges.

Also mentioned is the possibility that paternal preconceptional irradiation might be a marker for some other occupational exposure. Although these other occupational factors should more properly be seen as confounders of the original study, some people have raised them to the status of surrogate Gardner hypothesis. Now these two have been tested by the Health and Safety executive's recent study and found not to support a Gardner-type theory.4 We work as chief medical officers in the nuclear industry, and our first duty is to keep employees fully informed of the risks …
Acute Renal Failure After Acetaminophen Ingestion
Authors: R. Whit Curry
Journal: JAMA (1982)

Acute renal failure in the absence of severe hepatocellular damage developed in a young woman after ingestion of approximately 30 g of acetaminophen during a 36-hour period. Animal studies suggest that the nephrotoxic effect is due to a toxic oxidative metabolite of acetaminophen that arylates renal macromolecules. This case illustrates the need for detailed drug histories regarding over-the-counter medications. Acetaminophen ingestion should be considered in the differential diagnosis of acute renal failure. (<i>JAMA</i>1982;247:1012-1014)
Willingness to pay and time trade-off: useful utility indicators for the assessment of quality of life and patient satisfaction in patients with port wine stains
Authors: R. Schiffner, S. Brunnberg, U. Hohenleutner, W. Stolz, M. Landthaler
Journal: British Journal of Dermatology (2002)

For cost utility analyses in health economic research it is necessary to assess quality of life for content validation. Previously, both quality of life questionnaires and utility indicators such as willingness to pay and time trade-off have been used successfully in patients with chronic skin diseases, such as psoriasis vulgaris or atopic eczema.For the first time to assess willingness to pay and time trade-off in patients with port wine stains, and to study possible correlations between these indicators, patient income, quality of life questionnaires and subjective or objective outcome measures.The results of a survey on 36 patients with facial lesions who had completed laser treatment were used for assessments. The 'Chronic Skin Disease Questionnaire' (CSDQ) and the 'Short Form-36 Health Survey' (SF-36) were used as quality of life questionnaires. Special questions were used as a basis for calculating the utility indicators, willingness to pay and time trade-off.Completed questionnaires were sent back by 25 patients (69%). Willingness to pay and time trade-off were used as instruments for the assessment of quality of life [questions answered by 23 (92% of respondents)]; patients were willing to pay 11.8% of their monthly income and would offer a mean value of 1.2 h per day for an imaginary therapy leading to complete cure of the skin problem. Statistical correlation analyses were not performed because this pilot study included only a small number of patients. Frequency distributions show no apparent correlation between willingness to pay and patients' profession (used as a surrogate for income). Possible correlations were seen between willingness to pay, time trade-off, the scales 'anxiety/avoidance' and 'helplessness' of the CSDQ as well as 'social function' of SF-36 and subjective or objective efficacy. Twenty-nine patients (80%) were willing to pay for the treatment, a surrogate measure for patients' satisfaction with treatment modality. Overall, patients would pay an average of 16.0 euros per single treatment and 192.0 euros for the whole course of treatments. In contrast with patients who evaluated treatment modality as excellent or very good (willingness to pay for single treatment, euro 22.0; for whole treatment, 270.0 euros), patients who judged treatment good (8.0 euros, 145.0 euros), moderate or bad (12.0 euros, 146 .0 euros) were willing to pay markedly less.(i) The questions for willingness to pay and time trade-off were understood by most patients and produced meaningful answers. (ii) There were apparent correlations between the utility indicators, subjective or objective outcome and the scales of the quality of life questionnaires. (iii) The results show that these indicators have a high potential for use in this dermatological condition, especially as a basis for health economic evaluations.
Antiretroviral Therapies in Women after Single-Dose Nevirapine Exposure
Authors: S. Lockman, M.D. Hughes, J. McIntyre, Y. Zheng, T. Chipato, F. Conradie, F. Sawe, A. Asmelash, M.C. Hosseinipour, L. Mohapi, E. Stringer, R. Mngqibisa, A. Siika, D. Atwine, J. Hakim, D. Shaffer, C. Kanyama, K. Wools-Kaloustian, R.A. Salata, E. Hogg, B. Alston-Smith, A. Walawander, E. Purcelle-Smith, S. Eshleman, J. Rooney, S. Rahim, J.W. Mellors, R.T. Schooley, J.S. Currier
Journal: New England Journal of Medicine (2010)

Peripartum administration of single-dose nevirapine reduces mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) but selects for nevirapine-resistant virus.In seven African countries, women infected with HIV-1 whose CD4+ T-cell counts were below 200 per cubic millimeter and who either had or had not taken single-dose nevirapine at least 6 months before enrollment were randomly assigned to receive antiretroviral therapy with tenofovir–emtricitabine plus nevirapine or tenofovir-emtricitabine plus lopinavir boosted by a low dose of ritonavir. The primary end point was the time to confirmed virologic failure or death.A total of 241 women who had been exposed to single-dose nevirapine began the study treatments (121 received nevirapine and 120 received ritonavir-boosted lopinavir). Significantly more women in the nevirapine group reached the primary end point than in the ritonavir-boosted lopinavir group (26% vs. 8%) (adjusted P=0.001). Virologic failure occurred in 37 (28 in the nevirapine group and 9 in the ritonavir-boosted lopinavir group), and 5 died without prior virologic failure (4 in the nevirapine group and 1 in the ritonavir-boosted lopinavir group). The group differences appeared to decrease as the interval between single-dose nevirapine exposure and the start of antiretroviral therapy increased. Retrospective bulk sequencing of baseline plasma samples showed nevirapine resistance in 33 of 239 women tested (14%). Among 500 women without prior exposure to single-dose nevirapine, 34 of 249 in the nevirapine group (14%) and 36 of 251 in the ritonavir-boosted lopinavir group (14%) had virologic failure or died.In women with prior exposure to peripartum single-dose nevirapine (but not in those without prior exposure), ritonavir-boosted lopinavir plus tenofovir–emtricitabine was superior to nevirapine plus tenofovir–emtricitabine for initial antiretroviral therapy. (Funded by the National Institute of Allergy and Infectious Diseases and the National Research Center; ClinicalTrials.gov number, NCT00089505.).
Assessment of stroke volumeindex with three different bioimpedance algorithms: lack of agreement compared to thermodilution
Authors: Eric E. C. de Waal, Maurits K. Konings, Cor J. Kalkman, Wolfgang F. Buhre
Journal: Intensive Care Medicine (2008)

The accuracy of bioimpedance stroke volumeindex (SVI) is questionable as studies report inconsistent results. It remains unclear whether the algorithms alone are responsible for these findings. We analyzed the raw impedance data with three algorithms and compared bioimpedance SVI to transpulmonary thermodilution (SVITD). Prospective observational clinical study in a university hospital. Twenty adult patients scheduled for coronary artery bypass grafting (CABG). SVITD and bioimpedance parameters were simultaneously obtained before surgery (t 1), after bypass (t 2), after sternal closure (t 3), at the intensive care unit (t 4), at normothermia (t 5), after extubation (t 6) and before discharge (t 7). Bioimpedance data were analyzed off-line using cylinder (Kubicek: SVIK; Wang: SVIW) and truncated cone based algorithms (Sramek–Bernstein: SVISB). Bias and precision between the SVITD and SVIK, SVISB, and SVIW was 1.0 ± 10.8, 9.8 ± 11.4, and −15.7 ± 8.2 ml/m2 respectively, while the mean error was abundantly above 30%. Analysis of data per time moment resulted in a mean error above 30%, except for SVIW at t 2 (28%). Estimation of SVI by cylinder or truncated cone based algorithms is not reliable for clinical decision making in patients undergoing CABG surgery. A more robust approach for estimating bioimpedance based SVI may exclude inconsistencies in the underlying algorithms in existing thoracic bioimpedance cardiography devices.
Molecular Mechanisms of Developmental Neuronal Death
Authors: E M Johnson, T L Deckwerth
Journal: Annual Review of Neuroscience (1993)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Lessons in Environmental Health in the Twentieth Century
Authors: Michael Gochfeld, Bernard D. Goldstein
Journal: Annual Review of Public Health (1999)

▪ Abstract Environmental health has evolved rapidly in recent decades, drawing largely on new analytic technologies, advanced data acquisition and modeling, mechanistic studies in toxicology, and the conceptual framework of risk assessment. The latter combines toxicologic and epidemiologic data with improved techniques for quantifying exposure, producing estimates of risks from environmental hazards or conditions to selected target populations. The public and governments have become increasingly concerned with environmental health and quality. The major lessons have been (a) environmental-health scientists must participate in policy debates; (b) environmental health problems are exceedingly complex and require interdisciplinary research; and (c) environmental health is a global issue. The globalization of commerce, the untested impact of international trade agreements, increased migration, and especially increased population, have profound impact on the quality as well as availability of air, water, land, and food. Global atmospheric transport of pollutants and the effect on atmosphere and climate are two examples of globalization of environmental health.
Antimetastatic and Antitumor Activities of Interleukin 10 in a Murine Model of Breast Cancer
Authors: N. Kundu, T. L. Beaty, M. J. Jackson, A. M. Fulton
Journal: JNCI Journal of the National Cancer Institute (1996)

Background:Interleukin 10 (IL-10) is a potent immunoregulatory cytokine. It inhibits some cell functions, including T-helper (Th1) cell activity (i.e., interleukin 2 and interferon gamma production), and stimulates other functions such as natural killer (NK) activity. In mice, IL-10 suppresses tumorigenicity in a xenograft system using a nonmetastasizing hamster cell line.
Low prevalence of rheumatoid arthritis in black-Caribbeans compared with whites in inner city Manchester.
Authors: A J MacGregor, L K Riste, J M Hazes, A J Silman
Journal: Annals of the Rheumatic Diseases (1994)

OBJECTIVE--To compare the prevalence of rheumatoid arthritis (RA) in Black-Caribbeans and Whites living in the same urban area. METHODS--Cases of inflammatory joint disease were ascertained initially from a postal screening survey of 1851 Black and 1829 age and sex-matched non-Blacks identified from general practice age-sex registers of seven general practices in the Moss Side and Hulme districts of Manchester. The ethnicity of respondents was confirmed using data from a postal screening questionnaire. Those reporting joint swelling or a history of arthritis were reviewed by a rheumatologist at surgeries held in each practice. The clinical records of the questionnaire non-responders and questionnaire-positive non-attenders at surgery were reviewed. RESULTS--In an adjusted denominator population of 1046 Black-Caribbeans and 997 Whites, the cumulative prevalence of RA was 2.9/1000 in Black-Caribbeans and 8/1000 in Whites, representing a prevalence in Black-Caribbeans of 0.36 times that found in Whites (95% confidence interval 0.1-1.3). CONCLUSIONS--Rheumatoid arthritis occurs less commonly in Black-Caribbeans than in Whites. The findings are consistent with published studies showing a low RA prevalence in rural African Black populations.