tbuckley/cabot-search huggingface dataset:
Abrogation of tumor necrosis alpha (TNF-alpha) pathway by anti-TNF therapy in hematological malignancies
Authors: J. Ramanarayanan, S. Pahuja, A. N. Elefante, F. J. Hernandez-Ilizaliturri
Journal: Journal of Clinical Oncology (2009)

7093 Background: Tumor necrosis factor-alpha (TNF-alpha) enhances tumor growth and mediates cancer-related inflammatory symptoms by inducing secretion of cytokines. Anti-TNF approaches have been evaluated in pilot studies for cancer treatment and for alleviation of cancer related cachexia, fatigue, and other constitutional symptoms with conflicting results. While the incidence of malignancies with TNF alpha inhibitors (infliximab, adalimumab, etanercept) are not significantly higher than the untreated control population, their role in cancer treatment itself is unclear. We explored the activity and tolerance of TNF-alpha inhibitors in various hematological malignancies. Methods: We reviewed the English literature by conducting systematic MEDLINE using the terms TNF-, infliximab, adalimumab, etanercept, cancer therapy, hematologic malignancies, myelodysplastic syndrome (MDS), multiple myeloma (MM), myeloproliferative disease (MPD), chronic lymphocytic leukemia (CLL), and lymphoma from January 2001 to August 2008. We also performed a complete literature search of American Society of Hematology (ASH) and American Society of Clinical Oncology (ASCO) published abstracts. Studies were analyzed for observed activity of TNF alpha inhibitors and also for reported safety. Results: Overall 11 phase I and II studies (n = 237; CLL n = 44, MM n = 10, MDS n = 109, MPD n = 51, HCL n = 3, TCL 13, FL 7) that involved anti-TNF- therapy in hematological malignancies were identified. As a single agent, etanercept did not yield significant responses. In conjunction with ATG or azacitidine in low-/intermediate-risk MDS, TNF inhibitors resulted in improvement in cytopenia. Improvement in constitutional symptoms were noted in at least 50% of patients with myelofibrosis(MF)/Ph- MPD. No significant clinical benefit was seen among lymphoproliferative disorders, but treatment was well tolerated. Conclusions: Existing data suggests that anti-TNF therapy by itself does not induce a therapeutic response in hematologic malignancies. Combination strategy with TNF inhibitors has to be evaluated further to determine any anti-tumor activity and their role to alleviate constitutional symptoms particularly in MF/MPD. No significant financial relationships to disclose.
Ongoing right ventricular hemodynamics in heart failure
Authors: Philip B Adamson, Anthony Magalski, Frieder Braunschweig, Michael Böhm, Dwight Reynolds, David Steinhaus, Allyson Luby, Cecilia Linde, Lars Ryden, Bodo Cremers, Teri Takle, Tom Bennett
Journal: Journal of the American College of Cardiology (2003)
Tuberculosis after renal transplantation
Authors: Ventsislava Pencheva, Ognian Georgiev, Daniela Petrova
Journal: European Respiratory Journal (2011)

Background:  Tuberculosis (TB) is one of the leading causes of morbidity and mortality in renal transplant recipients. Due to the chronic immunosuppression the diagnosis is difficult.   Aim:  The aim of our prospective study is to determine the frequency and outcome of TB after renal transplantation.   Material and methods:  For the period of 31 months were examined 52 patients after renal transplantation with pulmonary complaints. To diagnose the patients were used different noninvasive and invasive methods for diagnosis.   Results:  In 5 cases (9.61%) were proved active tuberculosis. The mean age of these patients was 45 years (range 34– 55 years) and mean time from transplantation to diagnosis was 94 months (range 2 –180months). The pulmonary infiltrative form was the most common form (60%), 1 patient was with specific pleuritis (20%) and disseminated TB occurred in 1 patient (20%).  The diagnosis was proved bacteriology on respiratory specimen cultures in 4 cases (80%) and histology in 1 case. The immunological tests for tuberculosis were positive in all 5 patients. In 3 patients (60%) there was co-infection with cytomegalovirus. The 3 patients (60%) were successfully treated with four-drug combination therapy. 1 of the patient loose the graft and 1 patient died.   Conclusions:  TB is one of the most common infections among renal transplant recipients. Early diagnosis by using immunology tests and invasive methods, treatment of CMV-infection and effective therapy can improve graft survival and reduce the morbidity and mortality from this condition.
A single agent, phase I pharmacodynamic study of nimotuzumab (TheraCIM-h-R3) in patients with advanced refractory solid tumors
Authors: A. M. Brade, J. Magalhaes, L. Siu, A. Oza, S. Lovell, M. de Borja, G. Pond, I. Sherman, D. Hedley, E. Chen
Journal: Journal of Clinical Oncology (2007)

14030 Background: Nimotuzumab (N) is a humanized mAb against the EGFR extracellular ligand binding domain. Although well tolerated when combined with radiotherapy in previous studies and lacking usual toxicities of EGFR-targeting agents, the pharmacodynamics (PD) of N has not been elucidated. This phase I study was designed to evaluate the safety, tolerability and PD of N. Methods: Eligibility criteria included advanced solid tumors refractory to standard therapy and ECOG PS = 0 - 2. IV N was administered weekly x 6 and then every other week (6 weeks = 1 treatment cycle). Tumor, skin and liver biopsies obtained pre- and 2 and 7 weeks post-treatment were evaluated using computer-based, whole mount assessment of immunohistochemical staining. Results: Accrual was completed 21/09/06, 17 patients (11m/6f, median age 63, 13 colorectal cancer, ECOG 0:1:2 = 6:10:1, prior therapy 1:2:3+ = 2:6:9) were registered and 16 patients were treated on 4 dose levels (100, 200, 400 and 800 mg) for a total of 43 treatment cycles (1 patient deemed ineligible after registration did not receive study therapy). Treatment was well tolerated. One dose-limiting toxicity was observed (dose level 1 - grade 3 fatigue possibly attributable to N) . Skin toxicity was mild (Gr 1/2 in 7/1 patients). Confirmed stable disease was seen in 6 patients, a confirmed partial response in 1 patient with prolonged progression-free status observed in 3 patients for 5.8, 14.1 and 18.7 months (the latter two remain on study). Baseline and week 2 biopsies of tumor/skin/liver were evaluable in 12/13/7 pts. Week 7 tumor/skin/liver biopsies in initially responding or stable patients were evaluable in 6/8/6 pts. Post treatment (week 2), EGFR staining decreased in 8/12 matched tumor [mean ratio (post/pre): 0.79 range: (0.37, 1.91)], 8/13 skin [0.96 (0.40, 1.31)] and 5/7 liver [0.88 (0.62, 1.17)] biopsies. No significant relationship was detected between pre/post-treatment EGFR expression with either response or toxicity. Evaluation of downstream targets of EGFR (in tumor, skin and liver) is ongoing and will be presented. Conclusions: Overall nimotuzumab was well tolerated and exhibits mild skin toxicity. Prolonged progression free-survival was observed in 3/16 of these heavily pre-treated patients. No significant financial relationships to disclose.
Abstract 17680: A Comparison of Primary Care, Home-Based Telemonitoring, Telemonitoring with Video, or Specialist Directed Heart Failure Clinic Care for Patients with High Risk Heart Failure
Authors: Jonathan G Howlett, David Marr, Krisan Palmer, Blair J O'Neill, Miroslaw Rajda
Journal: Circulation (2011)

Introduction: Most studies of telephone-based care for heart failure (HF) patients have not integrated primary care providers at the initial point of care. Further, the addition of video assessment to telemonitoring has not been studied. We aimed to evaluate, in heart failure outpatients, the safety and feasibility of a telephone-based monitoring system with involvement of primary care providers compared to the gold-standard heart failure clinic model. Methods: Patients with a heart failure and at least one hospitalization within the previous six months were randomized in a 1:1:1 fashion to either usual care in a nurse-managed heart failure clinic with cardiologist backup (UC), or a daily telemonitoring system, with standard phone (TM) or video (TV) capability. The latter two groups additionally underwent biweekly scripted telephone (TM) or videophone (TV) calls. Protocol-based interventions with involvement of primary care provider were utilized. The primary outcome was the composite total mortality and hospitalization at 12 months follow up. Results: There were 122 patients (44 to UC, 38 to TM and 40 to TV), with 100% follow up. The median age was 67 years, 35% were female, mean EF was 46% and median NT-pro-BNP was 2211 pg/ml. The primary endpoint of occurred in 40 (or 33%) of patients and was not different between the three groups (UC 14, TM 12, and TV 14 events respectively, p= 0.81). Additionally, no difference in death (UC 4, TM 2, TV 4, p= 0.65) or total hospitalitzations were seen (UC 20, TM 17, TV 21, p= 0.75). Conclusions: A home telemonitoring strategy with primary care provider involvement appears to be a safe and feasible alternative to care in a specialist led heart failure clinic for patients with ambulatory heart failure. The addition of video capability is unlikely to provide a major impact. Further, properly powered studies are justified in order to establish the relative benefits of this strategy as a routine treatment modality for heart failure.
Abstract 19933: Factors Contributing to Door-In/Door-Out Delays Among ST Elevation Myocardial Infarction (STEMI) Patients Undergoing Rural Inter-hospital Transfer for Primary Coronary Intervention
Authors: Anushree Agarwal, Frank Aguirre, Amanda Pfeiffer, Raed Al-Dallow, Charles Lucore, Steve Markwell, Kim Justice, Pam Shadowens
Journal: Circulation (2010)
FURTHER OBSERVATIONS ON THE HEART IN MYXEDEMA
Authors: J. Lerman, R. J. Clark, J. H. Means
Journal: Annals of Internal Medicine (1934)

Article1 July 1934FURTHER OBSERVATIONS ON THE HEART IN MYXEDEMAJ. LERMAN, M.D., R. J. CLARK, M.D., J. H. MEANS, M.D., F.A.C.P.J. LERMAN, M.D., R. J. CLARK, M.D., J. H. MEANS, M.D., F.A.C.P.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-8-1-82 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn a previous paper1 we presented data dealing with changes in the size of the heart, in the blood pressure and in the electrocardiograms resulting from thyroid medication in myxedema patients. The most striking finding was a shrinkage in the transverse diameter of the heart of from 1 to 7 cm. in 20 of the 30 patients observed. Since then 18 additional patients have been studied. Forty-seven teleroentgenograms were obtained and measured. The method of study and the precautions taken were the same as those previously described.RESULTSTable 1 summarizes the changes in the size of the heart and...Bibliography1. LERMANCLARKMEANS JRJJH: Heart in myxedema; electrocardiograms and roentgen-ray measurements before and after therapy, ANN. INT. MED., 1933, vi, 1251-1271. LinkGoogle Scholar2. HALLOCK P: The heart in myxedema, with a report of two cases, Am. Heart Jr., 1933, iv, 196. CrossrefGoogle Scholar3. OHLERABRAMSON WRJ: The heart in myxedema, Arch. Int. Med., 1934, liii, 165-187. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Boston, Massachusetts*Received for publication April 16, 1934.From the Thyroid Clinic and Metabolism Laboratory of the Massachusetts General Hospital. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byPERICARDIAL EFFUSION IN HYPOTHYROIDISMHerz und Kreislauf bei Störungen der SchilddrüsenfunktionKrankheiten der SchilddrüseInnere SekretionAngina pectoris and myocardial infarction as complications of myxedemaMYXŒDEMA HEART DISEASE TREATMENT AND RADIOGRAPHIC CHANGESMorbus Basedowi (Graves' Disease)1 1 July 1934Volume 8, Issue 1Page: 82-84KeywordsBlood pressureElectrocardiographyHeartHospitalsResearch laboratoriesThyroid ePublished: 1 December 2008 Issue Published: 1 July 1934 PDF downloadLoading ...
Chemical proteomics and characterization of [1,3,6]-trisubstituted-pyrazolo[3,4-d]-pyrimidin-4-ones: A novel class of selective CDK/CRK inhibitors
Authors: Maureen Caligiuri, Frank Becker, Krishna Murthi, Nick Bockovich, Andy Machl, Gabriele Zybarth, Arthur Kluge, Nikolai Kley
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

1543 

[1,3,6]-trisubstituted-pyrazolo[3,4-d]-pyrimidin-4-ones constitute a novel class of potent inhibitors of cyclin dependent kinases (CDKs) [1, 2]. Here, we describe the application of three-hybrid proteome scanning methodologies to the characterization of the target spectrum and biological activities of select compounds of this chemical class. These compounds were found to exhibit a remarkable selectivity for a subset of CDKs and CDK-related kinases (CRKs). The CDK/CRK target spectra varied significantly among various analogs, indicating that the [1,3,6]-trisubstituted-pyrazolo[3,4-d]-pyrimidin-4-one chemical scaffold provides a unique platform for the design and optimization of compounds with potentially diverse therapeutic applications, including compounds with potent apoptosis-inducing anticancer activities. 1. Markwalder, J.A et al. (2004). Synthesis and biological evaluation of 1-aryl-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4-one inhibitors of cyclin-dependent kinases. J Med Chem 47 , 5894-5911. 2. Caligiuri, M et al. (2005). A Proteome-Wide CDK/CRK-Specific Kinase Inhibitor Promotes Tumor Cell Death in the Absence of Cell Cycle Progression. Chem Biol 12 , 1103-1115.
Chronic Mucous Colitis
Authors: Milton A. Bridges
Journal: Annals of Internal Medicine (1929)

Article1 July 1929Chronic Mucous ColitisMILTON A. BRIDGES, B.S., M.D., F.A.C.P.MILTON A. BRIDGES, B.S., M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-3-1-40 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptWe fully realize when it comes to discussing a subject with the above title, that we are stepping into a severely controversial field, a field, the very definition and classification of which is open to desperate competitive argument and general lack of decision. No one condition in medicine is more confusing than the conflicting descriptions of diseases of the colon.During the past decade, great scientific interest has been exhibited in the study of the gastro-intestinal tract, with great stress laid upon that portion proximal to the colon. In spite of this thoroughness of investigation of the upper tract, the... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: MILTON A. BRIDGES, B.S., M.D., F.A.C.P.Affiliations: New York*Read before the Spanish-American Medical Society, January 29, 1929, at the New York Academy of Medicine. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 July 1929Volume 3, Issue 1 Page: 40-46 Keywords Colon Gastroenterology and hepatology Irritable bowel syndrome ePublished: 1 December 2008 Issue Published: 1 July 1929 PDF downloadLoading ...
A Fatality Following the Intravenous Use of Ammonium Ortho-Iodoxy Benzoate
Authors: Bernard A. Manace
Journal: Annals of Internal Medicine (1928)

Article1 April 1928A Fatality Following the Intravenous Use of Ammonium Ortho-Iodoxy BenzoateBERNARD A. MANACE, M.B. (TOR.)BERNARD A. MANACE, M.B. (TOR.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-1-10-825 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAmmonium ortho-iodoxy benzoate has been introduced recently by Young and Youmans' (1) for the treatment of arthritis, and these authors have reported favorable results in patients presenting the chronic infectious and hypertrophic forms of the disease. It is closely related in chemical structure to the salicylates and has been extensively investigated in order to determine its physiological action. Since its introduction in the therapy of arthritis, a little over three years ago, Smith (2) has investigated the use of the drug in the treatment of arthritis and emphasizes the similarity of its action to that of the salicylaes. Although he...Bibliography(1) YOUNGYOUMANS AGJB: Journal A. M. A., 87, 746 (1926.) CrossrefGoogle Scholar(2) SMITH M;Boston M. and S. J., 196, 305 (1927.) CrossrefGoogle Scholar(3) TRAUBA NC; Journal A. M. A., 89, 1124 (1927.) CrossrefGoogle Scholar(4) COTTRELL JE; Am. Journal Med. Sc., 174, 623 (1927.) Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Ann Arbor, Michigan*From the Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan). PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited by2-Iodoxybenzoesäure - ein einfaches Oxidationsmittel mit einer Vielfalt an Anwendungsmöglichkeiten2-Iodoxybenzoic Acid-A Simple Oxidant with a Dazzling Array of Potential Applications 1 April 1928Volume 1, Issue 10Page: 825-827KeywordsArthritisDrug therapyInfectious diseasesSalicylates ePublished: 1 December 2008 Issue Published: 1 April 1928 PDF downloadLoading ...
Abstract 4494: Attenuation of TNF-{alpha} Elevation and Ventricular Aneurysm by Postconditioning-60 Second in Patients with Acute Myocardial Infarction
Authors: Xiangmin Lin, Li Zhang, Lefeng Wang, Zhiyong Zhang, Guang Li, Wenmin Zhao, Lin Zhang
Journal: Circulation (2008)

Background We have reported that postconditioning (Postcon) reduces infarct size in patients with acute myocardial infarction. This study tested the hypothesis that Postcon 60 second (Postcon-60s) ...
Noninvasive imaging in acute coronary disease. A clinical perspective.
Authors: Gersh Bj
Journal: Circulation (1991)

Numerous highly complex and sensitive noninvasive imaging techniques have enhanced the care of patients with acute myocardial infarction. Optimum use requires specific objectives to be defined in advance, including a review of the potential impact of the test on subsequent decisions. An additional issue that is subject to scrutiny in the current climate of cost containment relates to the incremental value of a specific examination. The imaging modality to be used will partially depend on other issues, including accessibility, cost, and interindividual or institutional expertise with a particular technique. Major applications in noninvasive imaging in the acute coronary syndromes include the following: (1) diagnosis, including identification of associated diseases and contraindications for acute reperfusion; (2) evaluation and management of complications ; (3) determination of prognosis (both early and late); (4) estimation of myocardial viability; (5) assessment of therapeutic efficacy; (6) investigational approaches, including 99mTc-sestamibi tomographic imaging, ultrafast cine computed tomographic scanning, and nuclear magnetic resonance imaging. Previous studies in the prethrombolytic era have documented the powerful impact of radionuclide stress testing on prognosis, but this needs to be reevaluated in the light of the changing current population undergoing stress testing. Preliminary data imply that the prognostic accuracy of stress testingmore » after thrombolytic therapy is diminished. Moreover, the role of the open infarct-related artery in traditional estimates of prognosis requires further study. Noninvasive imaging has multiple applications in the diagnosis and management of patients with acute coronary disease, but the decision to use a specific technology in a particular circumstance mandates good clinical judgment and selectivity. 82 references.« less
Abstract 629 Secreted Frizzled Related Protein 2 Protects Cells from Apoptosis by Blocking the Effect of Canonical Wnt3a
Authors: Zhongyan Zhang, Arjun Deb, Alok Pachori, Wei He, Jian Guo, Zhiping Zhang, Richard E Pratt, Victor J Dzau
Journal: Circulation (2007)

We have demonstrated that mesenchymal stem cells (MSCs) overexpressing the survival gene Akt can confer paracrine protection to ischemic myocytes both in vivo and in vitro through the release of secreted frizzled related protein 2 (Sfrp2). However, the mechanisms mediating these effects of Sfrp2 have not been fully elucidated. In this study, we test the hypothesis that Sfrp2 exerts anti-apoptotic effect by antagonizing pro-apoptotic properties of specific Wnt ligands. To explore this possibility, we studied rat cardiomyoblasts subjected to hypoxia reoxygenation (HR) injury. We examined the effect of Wnt3a and Sfrp2 on HR-induced apoptosis. We choose to study Wnt3a because its expression is up-regulated in response to hypoxia. Wnt3a (3nM) significantly increased cellular caspase activities (35% increase, p&lt;0.05, n=3) and TUNEL staining (38% increase) in response to HR. Sfrp2 attenuated significantly Wnt3a-induced caspase activities in a concentration dependent fashion (0nM, 8.50±0.47; 3nM, 7.28±1.03; 30nM, 7.45±0.49; 300nM, 5.65±0.35), achieving 36% inhibition at a concentration of 300nM. Using a solid phase binding assay, our data demonstrates that Sfrp2 physically binds to Wnt3a. In addition, we observed that 600nM Sfrp2 inhibits 47% of the beta-catenin / TCF transcriptional activities induced by Wnt3a(0.55±0.07 vs 1.03±0.04). Impressively, Dickkopf-1, a protein that binds to the Wnt coreceptor LRP, significantly inhibited the Wnt3a-activated caspase and transcriptional activities by 31% and 77% respectively (caspase activities: 8.62±0.05 vs12.54±0.49; transcriptional activities: 0.41±0.03 vs 1.77±0.01) Similarly, siRNA against beta-catenin inhibited the Wnt3a-activated caspase activities by 59% (6.44±0.92 vs 15.71±0.67). Consistent with this, significantly fewer TUNEL positive cells were observed in siRNA transfected cells than in control cells (43% decrease). Together, our data provide strong evidence to support the notion that Wnt3a is a canonical Wnt with pro-apoptotic action whose cellular activity is prevented by, at least in part, Sfrp2 through direct binding of these molecules. These results can explain the in vivo protective effect of Sfrp2 and highlight its therapeutic potential for the ischemic heart.
Complete Hematologic Response to Sunitinib in an Eosinophilia-Associated Chronic Myeloproliferative Disorder with an ETV6-FLT3 Fusion Gene.
Authors: Christoph Walz, Michael Ritter, Claudia Haferlach, Susanne Schnittger, Christoph Schulte, Torsten Haferlach, Georgia Metzgeroth, Rüdiger Hehlmann, Andreas Hochhaus, Nicholas C.P. Cross, Andreas Reiter
Journal: Blood (2007)
Abstract 20: NT-proBNP Elevations in Adult Respiratory Distress Syndrome Strongly Predict Morbidity and Mortality: An Analysis from the Molecular Epidemiology of ARDS Study.
Authors: James Januzzi, Ednan Bajwa, Michelle Gong, B. T Thompson, David Christiani
Journal: Circulation (2007)

Introduction: Patients with ARDS suffer from a syndrome of marked cardiopulmonary derangement, including right ventricular strain and noncardiogenic pulmonary edema. We hypothesized that N-terminal...
High-Dose Cytarabine Monotherapy Versus Intermediate Or High-Dose Cytarabine In Combination With Other Agents As Second-Line Salvage Therapy In Patients With Acute Myeloid Leukemia Who Did Not Respond To Initial Induction Therapy
Authors: Thu Oanh T Dang, Patrick Hilden, Sean M. Devlin, Raajit K. Rampal, Ross L. Levine, Ellin Berman, Virginia M. Klimek, Nelly G. Adel, Martin S. Tallman
Journal: Blood (2013)