tbuckley/cabot-search huggingface dataset:
Treatment of newly diagnosed acute promyelocytic leukemia (APL): a comparison of French-Belgian-Swiss and PETHEMA results
Authors: Lionel Adès, Miguel A. Sanz, Sylvie Chevret, Pau Montesinos, Patrice Chevallier, Emmanuel Raffoux, Edo Vellenga, Agnès Guerci, Arnaud Pigneux, Francoise Huguet, Consuelo Rayon, Anne Marie Stoppa, Javier de la Serna, Jean-Yves Cahn, Sandrine Meyer-Monard, Thomas Pabst, Xavier Thomas, Stéphane de Botton, Ricardo Parody, Juan Bergua, Thierry Lamy, Anne Vekhoff, Silvia Negri, Norbert Ifrah, Hervé Dombret, Augustin Ferrant, Dominique Bron, Laurent Degos, Pierre Fenaux
Journal: Blood (2007)
A phase I/II study of bortezomib and capecitabine in patients with metastatic breast cancer previously treated with taxanes and/or anthracyclines
Authors: P. Schmid, D. Kühnhardt, P. Kiewe, S. Lehenbauer-Dehm, W. Schippinger, R. Greil, W. Lange, J. Preiss, N. Niederle, P. Brossart, W. Freier, S. Kümmel, H. Van de Velde, A. Regierer, K. Possinger
Journal: Annals of Oncology (2008)
Pulmonary Infiltrates, Eosinophilia, and Cardiomyopathy Following Corticosteroid Withdrawal in Patients With Asthma Receiving Zafirlukast
Authors: M E Wechsler, E Garpestad, S R Flier, O Kocher, D A Weiland, A J Polito, M M Klinek, T D Bigby, G A Wong, R A Helmers, J M Drazen
Journal: JAMA (1998)

Context.—Zafirlukast is a potent leukotriene antagonist that recently was approved for the treatment of asthma. As use of this drug increases, adverse events that occur at low frequency or in populations not studied in premarketing clinical trials may become evident.Objective.—To describe a clinical syndrome associated with zafirlukast therapy.Design.—Case series.Patients.—Eight adults (7 women and 1 man) with steroid-dependent asthma who received zafirlukast.Main Outcome Measures.—Development of a clinical syndrome characterized by pulmonary infiltrates, cardiomyopathy, and eosinophilia following the withdrawal of corticosteroid treatment.Results.—The clinical syndrome developed while patients were receiving zafirlukast from 3 days to 4 months and from 3 days to 3 months after corticosteroid withdrawal. All 8 patients developed leukocytosis (range, 14.5-27.6×109/L) with eosinophilia (range, 0.19-0.71). Six patients had fever (temperature >38.5°C), 7 had muscle pain, 6 had sinusitis, and 6 had biopsy evidence of eosinophilic tissue infiltration. The clinical syndrome improved with discontinuation of zafirlukast treatment and reinitiation of corticosteroid treatment or addition of cyclophosphamide treatment.Comment.—Development of pulmonary infiltrates, cardiomyopathy, and eosinophilia may have occurred independent of zafirlukast use or may have resulted from an allergic response to this medication. We suspect that these patients may have had a primary eosinophilic infiltrative disorder that had been clinically recognized as asthma, was quelled by steroid treatment, and was unmasked following corticosteroid withdrawal facilitated by zafirlukast.
Adenosine Uptake by Canine Heart
Authors: Ray A. OLSSON, Jerry A. SNOW, Mary K. GENTRY, G. Peter FRICK
Journal: Circulation Research (1972)

The rate of myocardial adenosine uptake was studied in anesthetized openchest dogs to assess the importance of the process in the regulation of extracellular fluid concentrations of this coronary vasodilator. 8- 14 C-adenosine solutions were infused into the left coronary artery at rates that yielded concentrations in coronary artery plasma of 0.4-13.3 µM. The adenosine uptake rate was calculated as the product of the adenosine infusion rate and the extraction fraction of radioactivity assumed to be adenosine. Uptake appeared to follow Michaelis-Menten kinetics over the range of plasma adenosine concentrations tested, and the apparent values of K m and V max were 11.6 ± 1.4 (SE) µM and 4.9 ± 0.5 (SE) nmoles/g left ventricle min -1 , respectively. The K m and the tissue activity of dog heart adenosine deaminase were 43 µM and 1.2 µmoles/g left ventricle min -1 , respectively, and those of adenosine kinase were 0.4 µM and 23 nmoles/g left ventricle min -1 , values sufficiently different from the parameters of uptake to suggest that the limiting step in uptake is permeation into the cell. Uptake was inhibited by 8-13 µM 6-( p -nitrobenzylthio) guanoside, an adenosine analogue that inhibits the facilitated diffusion of a variety of nucleosides in erythrocytes, and by dipyridamole, a compound that inhibits nucleoside uptake in erythrocytes, platelets, and tissue culture cells. Uptake was not inhibited by cardiotoxic doses of ouabain. These findings are evidence against uptake by simple diffusion but are consistent with uptake mediated by a carrier. The rate of cellular adenosine uptake from the extracellular space of the heart appears to be rapid enough to be important in the regulation of myocardial levels of this coronary vasodilator metabolite.
IMMEDIATE FATAL CORONARY THROMBOSIS FOLLOWING ELECTRIC CONVULSIVE THERAPY
Authors: GEORGE C. SISLER, J. C. WILT
Journal: American Journal of Psychiatry (1953)

l. A review has been made of the pertinent literature on immediate deaths following ECT. 2. Two cases of acute fatal coronary thrombosis following treatment are reported. Possible mechanisms and prophylactic measures are discussed.
Expression of the neurogenic basic helix-loop-helix transcription factor NEUROG1 identifies a subgroup of medulloblastomas not expressing ATOH1
Authors: Ettore Salsano, Laura Croci, Emanuela Maderna, Linda Lupo, Bianca Pollo, Maria Teresa Giordana, G. Giacomo Consalez, Gaetano Finocchiaro
Journal: Neuro-Oncology (2007)

To gain insight into the lineage of origin of medulloblastomas, the mRNA expression of NEUROG1, a gene encoding a proneural transcription factor transiently detected during nervous system development, was investigated in 27 human medulloblastomas characterized for mRNA expression of ATOH1, a marker of cerebellar granule precursors and corresponding medulloblastomas. Expression of Ngn1, the mouse homolog of NEUROG1, was also analyzed in the mouse cerebellar primordium. In addition, we studied mRNA expression of GLI1 as a marker of the SHH pathway activation, and nuclear β-catenin staining, β-catenin mutations, and mRNA expression of MYC as indicators of the WNT pathway status. In 15 cases, we also examined expression of OTX2, a transcription factor recently indicated as a positive marker of medulloblastomas originating from cerebellar granule precursors. The mRNA expression of NEUROG1 and Ngn1 was selectively found in medulloblastomas not expressing ATOH1 and in progenitors of the cerebellar ventricular zone, respectively. GLI1 transcript was expressed in medulloblastomas with ATOH1 transcript, whereas high levels of MYC transcript were unrelated to NEUROG1 or ATOH1 expression. No clear association between MYC overexpression and nuclear β-catenin staining was found. Finally, OTX2 mRNA was expressed in all medulloblastomas with NEUROG1 transcript, but also in a subset of these malignancies with ATOH1 transcript. These observations may help to define the lineage of origin of medulloblastomas, and support a role for ATOH1 and NEUROG1 in the classification of these malignancies.
Cyclooxygenase-2 in Human and Experimental Ischemic Proliferative Retinopathy
Authors: F. Sennlaub, F. Valamanesh, A. Vazquez-Tello, A.M. El-Asrar, D. Checchin, S. Brault, F. Gobeil, M.H. Beauchamp, B. Mwaikambo, Y. Courtois, K. Geboes, D.R. Varma, P. Lachapelle, H. Ong, F. Behar-Cohen, S. Chemtob
Journal: Circulation (2003)

Background— Intravitreal neovascular diseases, as in ischemic retinopathies, are a major cause of blindness. Because inflammatory mechanisms influence vitreal neovascularization and cyclooxygenase (COX)–2 promotes tumor angiogenesis, we investigated the role of COX-2 in ischemic proliferative retinopathy. Methods and Results— We describe here that COX-2 is induced in retinal astrocytes in human diabetic retinopathy, in the murine and rat model of ischemic proliferative retinopathy in vivo, and in hypoxic astrocytes in vitro. Specific COX-2 but not COX-1 inhibitors prevented intravitreal neovascularization, whereas prostaglandin E 2 , mainly via its prostaglandin E receptor 3 (EP 3 ), exacerbated neovascularization. COX-2 inhibition induced an upregulation of thrombospondin-1 and its CD36 receptor, consistent with the observed antiangiogenic effects of COX-2 inhibition; EP 3 stimulation reversed effects of COX-2 inhibitors on thrombospondin-1 and CD36. Conclusion— These findings point to an important role for COX-2 in ischemic proliferative retinopathy, as in diabetes.
Dual Targeting of HER2-Positive Cancer with Trastuzumab Emtansine and Pertuzumab: Critical Role for Neuregulin Blockade in Antitumor Response to Combination Therapy
Authors: Gail D. Lewis Phillips, Carter T. Fields, Guangmin Li, Donald Dowbenko, Gabriele Schaefer, Kathy Miller, Fabrice Andre, Howard A. Burris, Kathy S. Albain, Nadia Harbeck, Veronique Dieras, Diana Crivellari, Liang Fang, Ellie Guardino, Steven R. Olsen, Lisa M. Crocker, Mark X. Sliwkowski
Journal: Clinical Cancer Research (2013)

Targeting HER2 with multiple HER2-directed therapies represents a promising area of treatment for HER2-positive cancers. We investigated combining the HER2-directed antibody-drug conjugate trastuzumab emtansine (T-DM1) with the HER2 dimerization inhibitor pertuzumab (Perjeta).Drug combination studies with T-DM1 and pertuzumab were performed on cultured tumor cells and in mouse xenograft models of HER2-amplified cancer. In patients with HER2-positive locally advanced or metastatic breast cancer (mBC), T-DM1 was dose-escalated with a fixed standard pertuzumab dose in a 3+3 phase Ib/II study design.Treatment of HER2-overexpressing tumor cells in vitro with T-DM1 plus pertuzumab resulted in synergistic inhibition of cell proliferation and induction of apoptotic cell death. The presence of the HER3 ligand, heregulin (NRG-1β), reduced the cytotoxic activity of T-DM1 in a subset of breast cancer lines; this effect was reversed by the addition of pertuzumab. Results from mouse xenograft models showed enhanced antitumor efficacy with T-DM1 and pertuzumab resulting from the unique antitumor activities of each agent. In patients with mBC previously treated with trastuzumab, lapatinib, and chemotherapy, T-DM1 could be dosed at the maximum tolerated dose (MTD; 3.6 mg/kg every 3 weeks) with standard dose pertuzumab. Adverse events were mostly grade 1 and 2, with indications of clinical activity.Dual targeting of HER2 with the combination of T-DM1 and pertuzumab in cell culture and mouse xenograft models resulted in enhanced antitumor activity. In patients, this combination showed an encouraging safety and tolerability profile with preliminary evidence of efficacy.
A biochemical and morphologic study of very low density lipoproteins in carbohydrate-induced hypertriglyceridemia
Authors: Neil B. Ruderman, Albert L. Jones, Ronald M. Krauss, Eleazar Shafrir
Journal: Journal of Clinical Investigation (1971)

On a high carbohydrate, fat-free diet, control and hypertriglyceridemic subject had a three-fold increase in d < 1.006, very low density lipoprotein (VLDL) triglyceride, and somewhat lesser increases in VLDL cholesterol and protein. Cholesterol and protein in 1.006 < d < 1.21 lipoprotein decreased in a reciprocal fashion, suggesting that these components might have been utilized in VLDL production. Electron microscope studies demonstrated a significant increase in the size of lipoprotein particles of the VLDL class and, in three of four subjects, an apparent increase in particle number. The change in particle size correlated with an increase in the triglyceride/protein ratio of the d < 1.006 lipoprotein. Hypertriglyceridemic individuals differed from the control subjects in that they had greater absolute increases in VLDL triglyceride, cholesterol, and protein, and greater decreases in 1.006 < d < 1.21 cholesterol and protein. In addition, they had larger VLDL particles with a higher triglyceride/protein ratio, both before the study and at the peak of the carbohydrate effect. The data suggest that the increase in plasma triglycerides induced by a high carbohydrate diet is usually due to the appearance in plasma of both greater numbers of VLDL particles and larger particles that are relatively richer in triglyceride content than those isolated during the basal state.
AN ECOLOGICAL APPROACH TO CREATING ACTIVE LIVING COMMUNITIES
Authors: James F. Sallis, Robert B. Cervero, William Ascher, Karla A. Henderson, M. Katherine Kraft, Jacqueline Kerr
Journal: Annual Review of Public Health (2005)

▪ Abstract The thesis of this article is that multilevel interventions based on ecological models and targeting individuals, social environments, physical environments, and policies must be implemented to achieve population change in physical activity. A model is proposed that identifies potential environmental and policy influences on four domains of active living: recreation, transport, occupation, and household. Multilevel research and interventions require multiple disciplines to combine concepts and methods to create new transdisciplinary approaches. The contributions being made by a broad range of disciplines are summarized. Research to date supports a conclusion that there are multiple levels of influence on physical activity, and the active living domains are associated with different environmental variables. Continued research is needed to provide detailed findings that can inform improved designs of communities, transportation systems, and recreation facilities. Collaborations with policy researchers may improve the likelihood of translating research findings into changes in environments, policies, and practices.
Decline in Lung Function in Lymphangioleiomyomatosis
Authors: SIMON R. JOHNSON, ANNE E. TATTERSFIELD
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

The progression of lymphangioleiomyomatosis, a rare lung disease in women, is thought to be influenced by hormonal factors. We studied the rate of decline in FEV1 and carbon monoxide transfer factor (Tl CO) in a national cohort of patients with lymphangioleiomyomatosis in the United Kingdom and its relation to two factors that might influence the disease, menopausal status and progesterone treatment. We used retrospective data from hospital notes, and of the 50 patients identified 43 had suitable lung function data spanning at least 3 mo. Mean (SD) annual decline in FEV1 was 118 (142) ml for all patients, and these figures changed little when only data spanning at least 2 and 3 yr were analyzed. There was considerable variation in the rate of decline between subjects, however, and although it tended to be less among postmenopausal women and those receiving progesterone, patient numbers were smaller and the findings were not significant. There was a significant reduction in decline in Tl CO in premenopausal patients receiving progesterone and in both FEV1 and Tl CO after starting progesterone in six patients who had data before and after starting treatment. This study documents the rapid decline in lung function in lymphangioleiomyomatosis, confirms the wide variation between patients, and provides some support for the suggestion that disease progression may be reduced by progesterone. The data provide a basis for designing prospective studies of treatment for lymphangioleiomyomatosis.
Vinblastine, bleomycin, and methotrexate chemotherapy plus extended-field radiotherapy in early, favorably presenting, clinically staged Hodgkin's patients: the Gruppo Italiano per lo Studio dei Linfomi Experience.
Authors: P G Gobbi, C Pieresca, A Frassoldati, M Carotenuto, N Di Renzo, A La Sala, R Berté, P Avanzini, M Federico, V Silingardi, E Ascari
Journal: Journal of Clinical Oncology (1996)

PURPOSE To ascertain whether vinblastine, bleomycin, and methotrexate (VBM) (CT) combined with extended-field radiotherapy (EF RT) is effective enough to spare laparotomy in early, favorably presenting Hodgkin's disease (HD) patients. PATIENTS AND METHODS Fifty patients with clinical stage IA or IIA HD with favorable histology and no bulky masses entered a prospective multicenter study started in January 1988. The median follow-up time was 38 months. RESULTS All patients achieved a complete remission (CR). Five relapsed after 3 to 40 months and underwent successful salvage therapy. The actuarial remission rate was 0.89% at 3 years and 0.82% at 5 years. Two patients died in CR: one of severe pulmonary toxicity, the other of a second neoplasia (adenocarcinoma of the lung), 2 and 43 months after the end of therapy, respectively. The hematologic toxicity recorded during VBM CT was mild on the whole. Major toxicity was represented by pulmonary side effects and neurologic symptoms. Multiple regression analysis demonstrated that pulmonary toxicity was significantly related only to the amount of RT delivered to the mediastinum and not to the relative dose of bleomycin, to the dose-intensities of the three drugs in the regimen, or to patient age or sex. The same statistical technique showed that the only clinical factor related to grade of neurotoxicity was vinblastine dosage. CONCLUSION VBM CT combined with EF RT is an effective treatment for early, clinically staged, favorable HD patients. However, the toxicity of this combination suggests that certain modifications should be evaluated.
Highly Specific Prediction of Antineoplastic Drug Resistance With an In Vitro Assay Using Suprapharmacologic Drug Exposures
Authors: D H Kern, L M Weisenthal
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Highly Specific Prediction of Antineoplastic Drug Resistance With an In Vitro Assay Using Suprapharmacologic Drug Exposures Get access David H. Kern, David H. Kern * Oncotech Inc.Irvine, CA *Correspondence to : David H. Kern, Ph.D., Oncotech, Inc., 1791 Kaiser Ave., Irvine, CA 92714. Search for other works by this author on: Oxford Academic PubMed Google Scholar Larry M. Weisenthal Larry M. Weisenthal Oncotech Inc.Irvine, CA Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 7, 4 April 1990, Pages 582–588, https://doi.org/10.1093/jnci/82.7.582 Published: 04 April 1990 Article history Received: 07 November 1989 Revision received: 18 December 1989 Accepted: 26 December 1989 Published: 04 April 1990
Computational Modeling to Predict Effect of Treatment Schedule on Drug Delivery to Prostate in Humans
Authors: Leijun Hu, Jessie L-S. Au, M. Guillaume Wientjes
Journal: Clinical Cancer Research (2007)

Abstract Purpose: To evaluate a computational approach that incorporates experimental data in preclinical models to depict doxorubicin human tissue pharmacokinetics. Experimental Design: Beagle dogs were given 2 mg/kg doxorubicin as i.v. bolus, 4-h infusion, or 96-h infusion. Concentrations in plasma, prostate (target tissue), heart (toxicity), and major tissues for disposition were determined and modeled. Model parameters were obtained after the bolus injection with model validation based on the 4-h and 96-h infusion data. Clinical pharmacokinetic data and scale-up gave doxorubicin profiles in human prostate and heart. Results: In agreement with in vitro results, tissues were best modeled with two compartments, one rapidly and one slowly equilibrating. The developed tissue distribution model predicted concentrations for all three administration regimens well, with an average deviation of 34% (median, 29%). Interspecies scale-up to humans showed that the change from a bolus injection to a slow, 96-h infusion (a) had different effects on the drug partition and accumulation in heart and prostate, and (b) lowered the peak concentration in the plasma by ∼100-fold but had relatively little effect on maximal heart concentration (∼33% lower). The simulated drug exposure in a human prostate was above the exposure required to inhibit tumor proliferation but was 30 to 50 times below that needed for cell death. Conclusion: The present study shows a computation-based paradigm for translating in vitro and in vivo preclinical data and to estimate and compare the drug delivery and pharmacokinetics in target tissues after different treatment schedules.
S82 Multi-centre prospective comparison of the BTS and ACCP guidelines to determine size in primary spontaneous pneumothorax
Authors: M Nikolic, L Lok, K Mattishent, S Barth, B Yung, N Cummings, L Shulgina, D Wade, M Shittu, Y Vali, K Chong, A Wilkinson, T Mikolasch, S Brij, S Jenkins, A Kamath, M Pasteur, J Wason, SJ Marciniak
Journal: Thorax (2013)

<h3>Introduction and Objectives</h3> Attempts to develop standardised guidelines in the management of primary spontaneous pneumothorax (PSP) have been severely hampered by a lack of high quality clinical research. The American College of Chest Physicians (ACCP) and BTS guidelines are based on non-analytical studies and expert opinion. Remarkably, no consensus regarding the definition of PSP severity exists, with the ACCP and BTS each using different arbitrary measurements: hilar size &gt; 2cm (BTS) versus apical size &gt;3cm (ACCP). The objective of this study is to define the critical size of PSP. <h3>Methods</h3> A multi-centre prospective comparison of 168 consecutive patients presenting with PSP was performed in 13 NHS hospitals in the East of England over a period of 15 months. We compared the ability of the BTS and ACCP definitions to predict the eventual need for intercostal chest drain (ICD) insertion. Since current BTS guidelines state that pleural aspiration should be attempted prior to drainage in non-compromised PSP patients, we reasoned that ICD insertion was a valid endpoint. Using a logistic regression model that included hospital, age, hilar size, apical size and the hilar-apical interaction, we generated receiver operating characteristic (ROC) curves reflecting the probability of either measure correctly predicting the eventual need for ICD. <h3>Results</h3> One hundred and sixteen of 168 patients for whom data were collected had been treated according to BTS guidelines. Of these, 39 eventually required ICD insertion. The correlation between hilar and apical distances was high (0.7). The logistic regression showed that hilar distance was statistically significant (p &lt; 0.001), but apical distance and the interaction were not. The sensitivity and specificity from using BTS guidelines were 0.667 (95% CI 0.510–0.794) and 0.805 (0.703–0.878) respectively, whereas the same values using the ACCP guidelines were 0.948 (0.831–0.986) and 0.351 (0.253–0.462). <h3>Conclusion</h3> Guidelines based on hilar distance, such as the BTS's, are likely to be more informative in predicting the eventual need for ICD. However, the two distances are highly correlated. This study, for the first time, provides an evidence-based clinically relevant definition of PSP requiring ICD that will guide treatment and serve as the foundation for subsequent trials.
Mycobacterium vaccae (SRL172) immunotherapy as an adjunct to standard antituberculosis treatment in HIV-infected adults with pulmonary tuberculosis: a randomised placebo-controlled trial
Authors: Alwyn Mwinga, Andrew Nunn, Bagrey Ngwira, Chifumbe Chintu, David Warndorff, Paul Fine, Janet Darbyshire, Alimuddin Zumla
Journal: The Lancet (2002)
Risk of hepatitis B reactivation and the role of novel agents and stem-cell transplantation in multiple myeloma patients with hepatitis B virus (HBV) infection
Authors: D.H.T. Mya, S.T. Han, Y.C. Linn, W.Y.K. Hwang, Y.T. Goh, D.C.L. Tan
Journal: Annals of Oncology (2011)