tbuckley/cabot-search huggingface dataset:
Abstract 5582: NY-ESO-1-specific T-cells in melanoma patients with good clinical outcome after vaccination using mRNA as the immunogen
Authors: Henning Zelba, Benjamin Weide, Claus Garbe, Graham P. Pawelec, Evelyna Derhovanessian
Journal: Cancer Research (2010)

Abstract Although success in active cancer immunotherapy is often disappointing, vaccination against cancer- associated antigens has become an important tool in cancer management, resulting in an increasing list of possible antigen targets. However, previous studies have shown that vaccination against certain antigens results in a better clinical outcome than others. This indicates the importance of immune monitoring by helping to choose the antigens with the highest potential for success. In order to address this issue, we have analysed CD4+ and CD8+ T-cell responses against four common melanoma-associated antigens, namely NY-ESO-1, Melan-A, MAGE-A3 and Survivin, in melanoma patients undergoing immunotherapy. Blood samples from 5 long-term survivors after treatment with anti-CTLA-4 antibody as well as 12 patients vaccinated with mRNA encoding these four antigens were tested in this study. Antigen-specific T-cell responses were detected using peptide mixtures spanning the whole sequence of the antigen after one round of in vitro sensitization. Intracellular production of six different cytokines (IFN-γ, TNF, IL-2, IL-4, IL-10 and IL-17) was measured in CD4+ and CD8+ T-cells by 14 colour multiparameter flow cytometry, allowing simultaneous analysis of the phenotype and effector functions (TH1, TH2, TH17) on a single-cell basis. NY-ESO-1-specific CD4+ and/or CD8+ T-cell responses were detected in 4/5 long-term (up to 3 years and continuing) survivors receiving anti-CTLA-4 treatment, whereas responses against the remaining three antigens were either absent or present at lower frequencies. In the mRNA vaccination trial, NY-ESO-1-specific responses were detected in the only stage IV patient with &amp;gt;25% shrinkage in the size of the metastasis and two stage IV patients, who have remained tumor-free for 21 and 12 months since start of the vaccination. NY-ESO-1-specific immune responses were present in only 1/9 patients who progressed or died during this period. In all 6 patients with clinical benefit, the NY-ESO-1-specific T-cells produced high levels of IFNγ and TNF. Our data suggest that NY-ESO-1 might be a promising target antigen in melanoma patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5582.
Treatment of Out-of-Hospital Cardiac Arrests with Rapid Defibrillation by Emergency Medical Technicians
Authors: Mickey S. Eisenberg, Michael K. Copass, Alfred P. Hallstrom, Barbara Blake, Lawrence Bergner, Floyd A. Short, Leonard A. Cobb
Journal: New England Journal of Medicine (1980)

The survival rate for patients with out-of-hospital cardiac arrest is low in communities where emergency service is provided solely by emergency medical technicians. We trained such technicians in a suburban community of 79,000 to recognize and treat out-of-hospital ventricular fibrillation with up to three defibrillatory shocks without the use of medications or special airway protection. Outcomes from cardiac arrest due to underlying heart disease were determined during two periods: two years with standard care by emergency medical technicians and one year with defibrillator-trained technicians. During the period with standard care, four of 100 patients with cardiac arrest were resuscitated and discharged alive from the hospital, as compared with 10 of 54 patients during the period with defibrillator-trained technicians (P less than 0.01). In 12 of 38 patients with ventricular fibrillation, a stable perfusing cardiac rhythm followed defibrillatory shocks given by defibrillator technicians. The enhanced survival after cardiac arrest is encouraging, and further trials of defibrillation by emergency medical technicians are warranted.
On Diabetic Osteopathy: A Radiographic Study of 21 Patients
Authors: Fried W Whitehouse, Malcolm Weckstein
Journal: Diabetes Care (1978)

Twenty-one diabetic patients with anesthetic peripheral neuropathy who never suffered a foot infection or local ulceration had roentgenograms of both feet to seek whether osseous changes characteristic of diabetic osteopathy were present. We found nine patients with vascular calcification (all 21 patients had palpable pedal pulses); four patients with ancient fractures; one patient with two phalangeal erosions; and two patients with equivocal osseous cystic lesions. No patient had findings typical of diabetic osteopathy. From this study, plus experience with other diabetic patients who had infected, ulcerated feet, we conclude that diabetic osteopathy represents healing or healed lesions of local osteomyelitis.
Mismatch Between lodine-123 IMP and Technetium-99m HM-PAO Brain Perfusion Imaging in a Patient with Meningioma
Authors: HIROAKI HOSHI, SEISHI JINNOUCHI, KATSUSHI WATANABE, SHINICHI NAKANO, KAZUO KINSHITA
Journal: Clinical Nuclear Medicine (1987)

The discrepancy between three methods for cerebral perfusion imagings in the case of a man with meningioma is presented. Imaging with N-isopropyl-P-[l-123] iodoamphetamine (IMP) showed no activity in the tumor. Imaging with Tc-99m hexamethylpropyleneamine oxime (HM-PAO) and the local cerebral blood flow (LCBF) image with Xe-133 inhalation showed high tumor activity. IMP is a more accurate method for imaging the brain tissue blood flow.
Dual Inhibition of Bcl-2 and Bcl-xL Strikingly Enhances PI3K Inhibition-Induced Apoptosis in Human Myeloid Leukemia Cells through a GSK3- and Bim-Dependent Mechanism
Authors: Mohamed Rahmani, Mandy Mayo Aust, Elisa Attkisson, David C. Williams, Andrea Ferreira-Gonzalez, Steven Grant
Journal: Cancer Research (2012)

Abstract Effects of concomitant inhibition of the PI3K/AKT/mTOR pathway and Bcl-2/Bcl-xL (BCL2L1) were examined in human myeloid leukemia cells. Tetracycline-inducible Bcl-2 and Bcl-xL dual knockdown sharply increased PI3K/AKT/mTOR inhibitor lethality. Conversely, inducible knockdown or dominant-negative AKT increased, whereas constitutively active AKT reduced lethality of the Bcl-2/Bcl-xL inhibitor ABT-737. Furthermore, PI3K/mTOR inhibitors (e.g., BEZ235 and PI-103) synergistically increased ABT-737–mediated cell death in multiple leukemia cell lines and reduced colony formation in leukemic, but not normal, CD34+ cells. Notably, increased lethality was observed in four of six primary acute myelogenous leukemia (AML) specimens. Responding, but not nonresponding, samples exhibited basal AKT phosphorylation. PI3K/mTOR inhibitors markedly downregulated Mcl-1 but increased Bim binding to Bcl-2/Bcl-xL; the latter effect was abrogated by ABT-737. Combined treatment also markedly diminished Bax/Bak binding to Mcl-1, Bcl-2, or Bcl-xL. Bax, Bak, or Bim (BCL2L11) knockdown or Mcl-1 overexpression significantly diminished regimen-induced apoptosis. Interestingly, pharmacologic inhibition or short hairpin RNA knockdown of GSK3α/β significantly attenuated Mcl-1 downregulation and decreased apoptosis. In a systemic AML xenograft model, dual tetracycline-inducible knockdown of Bcl-2/Bcl-xL sharply increased BEZ235 antileukemic effects. In a subcutaneous xenograft model, BEZ235 and ABT-737 coadministration significantly diminished tumor growth, downregulated Mcl-1, activated caspases, and prolonged survival. Together, these findings suggest that antileukemic synergism between PI3K/AKT/mTOR inhibitors and BH3 mimetics involves multiple mechanisms, including Mcl-1 downregulation, release of Bim from Bcl-2/Bcl-xL as well as Bak and Bax from Mcl-1/Bcl-2/Bcl-xL, and GSK3α/β, culminating in Bax/Bak activation and apoptosis. They also argue that combining PI3K/AKT/mTOR inhibitors with BH3 mimetics warrants attention in AML, particularly in the setting of basal AKT activation and/or addiction. Cancer Res; 73(4); 1340–51. ©2012 AACR.
Secondhand Smoke Exposure and Coronary Artery Calcification among Nonsmoking Participants of a Population-Based Cohort
Authors: Frank Peinemann, Susanne Moebus, Nico Dragano, Stefan Möhlenkamp, Nils Lehmann, Hajo Zeeb, Raimund Erbel, Karl-Heinz Jöckel, Barbara Hoffmann
Journal: Environmental Health Perspectives (2011)

Secondhand smoke (SHS) consists of fine particulate matter, carcinogens, and various toxins that affect large parts of the population. SHS increases the risk for acute cardiovascular events and may contribute to the development of atherosclerosis.We investigated the association of SHS with coronary artery calcification (CAC).In this cross-sectional analysis, we used baseline data (2000-2003) from 1,766 never-smokers without clinically manifested coronary heart disease, 45-75 years of age, from the Heinz Nixdorf Recall Study, an ongoing, prospective, population-based cohort study in Germany. Self-reported frequent SHS at home, at work, and in other places was assessed by questionnaire. CAC scores were derived based on electron-beam computed tomography. We conducted multiple linear regression analysis using exposure to SHS as the explanatory variable and ln(CAC+1) as the response variable. We conducted logistic regression to estimate the odds ratio (OR) for presence of any CAC.Frequent exposure to SHS was reported by 21.5% of participants. After adjustment for age, sex, and socioeconomic status, CAC + 1 was 21.1% [95% confidence interval (CI): -5.5%, 55.2%] higher in exposed than in unexposed participants. After adjusting for other cardiovascular risk factors, the association was attenuated (15.4%; 95% CI: -9.6%, 47.2%). SHS exposure was also associated with a CAC score > 0 (fully adjusted OR = 1.38; 95% CI: 1.03, 1.84).Self-reported frequent exposure to SHS was associated with subclinical coronary atherosclerosis in our cross-sectional study population. Considering the widespread exposure and the clinical relevance of coronary atherosclerosis, this result, if confirmed, is of public health importance.
ERBB2/HER2-SPECIFIC NATURAL KILLER CELLS FOR ADOPTIVE IMMUNOTHERAPY OF GLIOBLASTOMA
Authors: J. P. Steinbach, C. Zhang, M. Burger, L. Jennewein, K. Schonfeld, S. Genssler, C. Sahm, C. Brendel, S. Naundorf, M. Odendahl, U. Kohl, P. Nowakowska, E. Seifried, H. Bonig, T. Tonn, M. Grez, M. Mittelbronn, W. S. Wels
Journal: Neuro-Oncology (2014)

BACKGROUND: While EGFRvIII appears a logical target for immunotherapy, only a subpopulation of tumor cells express EGFRvIII and immune escape has been demonstrated. ErbB2 is overexpressed in a substantial proportion of glioblastomas and has been successfully utilized in immunotherapies. Natural killer (NK) cells are the first line of defense against viral infections and malignant cells. The continuously growing cytotoxic cell line NK-92 holds promise for cancer immunotherapy. Safety of infusion of high doses of NK-92 was established in previous phase I clinical trials utilizing irradiated cells to prevent permanent engraftment. METHODS: To provide NK-92 cells with pre-determined tumor-cell specificity, we generated a lentiviral second generation chimeric antigen receptor (CAR) construct (5.28.z) employing the ErbB2 (HER2)-specific scFv(FRP5) antibody fragment for target cell recognition, and human CD28-CD3 ζ as a composite signaling moiety. An ErbB2-specific single cell clone (NK-92/5.28.z) was isolated, which showed high and selective cytotoxicity towards ErbB2-expressing tumor cells of various origins in vitro. We evaluated the cytotoxicity of NK-93/5.28.z cells against a panel of glioblastoma cell lines and primary glioblastoma cultures with different levels of Erb2 expression in vitro and in vivo. RESULTS: To provide NK-92 cells with pre-determined tumor-cell specificity, we generated a lentiviral second generation chimeric antigen receptor (CAR) construct (5.28.z) employing the ErbB2 (HER2)-specific scFv(FRP5) antibody fragment for target cell recognition, and human CD28-CD3 ζ as a composite signaling moiety. An ErbB2-specific single cell clone (NK-92/5.28.z) was isolated, which showed high and selective cytotoxicity towards ErbB2-expressing tumor cells of various origins in vitro. We evaluated the cytotoxicity of NK-93/5.28.z cells against a panel of glioblastoma cell lines and primary glioblastoma cultures with different levels of Erb2 expression in vitro and in vivo. CONCLUSIONS: Adoptive immunotherapy with application of ErbB2-specific NK-92/5.28.z cells may be a promising new immunotherapy approach for ErB2 positive glioblastoma. A phase I trial for glioblastoma patients with local injections of NK-92/5.28.z cells is in preparation. SECONDARY CATEGORY: Preclinical Experimental Therapeutics.
Transient rebound of HCV RNA levels among HIV/HCV-coinfected patients early after starting highly active antiretroviral therapy (HAART)
Authors: R. Rosa, A. Sanchez-Quijano, M. Leal, R. Torronteras, M.A. Abad, J.A. Pineda, E. Alpanes, J. Macias, J. Delgado, E. Lissen
Journal: Journal of Hepatology (2001)
Gradual Dosage of Flu Vaccine
Authors: Arthur F. Greenwald
Journal: JAMA (1967)

To the Editor:—  Many patients react to polyvalent influenza virus vaccine with fever, malaise, and other symptoms. I have been able to prevent these reactions simply by not giving the full 1-cc injection usually recommended. I start with a 0.25-cc dose. One or two weeks later, I give 0.5 to 0.75 cc, depending on individual patient factors. Two weeks later this dosage is repeated until a total of at least 1.75 cc has been given. I have seen no significant adverse symptoms from this schedule and find it fully protective.
Androgenic Alopecia is Associated with Increased Arterial Stiffness in Asymptomatic Young Adults
Authors: Mustafa Tarık Ağaç, Levent Korkmaz, Mustafa Cetin, Turhan Turan, Ali Rıza Akyüz, Hakan Erkan, Bülent Vatan, Ramazan Akdemir, Şükrü Çelik
Journal: Journal of the American College of Cardiology (2013)
Clinical experience, complications, and survival in 70 patients with the automatic implantable cardioverter/defibrillator.
Authors: D S Echt, K Armstrong, P Schmidt, P E Oyer, E B Stinson, R A Winkle
Journal: Circulation (1985)

Seventy patients received the automatic implantable defibrillator, five original devices and 72 modified second-generation devices using only bipolar rate sensing and delivering an R wave synchronous cardioverting/defibrillating shock, for either ventricular tachycardia or fibrillation. The primary clinical arrhythmia was sustained ventricular tachycardia in 32 patients, ventricular fibrillation in 20 patients, and both ventricular tachycardia and fibrillation in 18 patients. Before implantation of the device the patients had survived 3.1 +/- 2.3 arrhythmic episodes, including 1.9 +/- 1.7 cardiac arrest, and had received 4.0 +/- 2.1 antiarrhythmic drugs without improvement. Sixty-eight patients ultimately received devices. After a follow-up period of 8.9 +/- 7.7 months (range 1 to 33), 37 patients received a total of 463 discharges. Inability to determine the precise reason for most discharges and the unpleasant nature of the discharges were the major clinical problems encountered. Complications included postoperative death (one patient), lead problems (six patients), inadequate energy requiring explanation (two patients), and pocket infection (one patient. Life-table analysis revealed 6 and 12 month cardiovascular survival of 95.0% and 89.9% and sudden death survival of 98.2%. In our experience, survival with the automatic implantable cardioverter/defibrillator exceeds that with other forms of therapy.
Pancreatic rupture during childbirth treated successfully by endoscopic drainage
Authors: J. Khan, J. Ylinen, M. Victorzon
Journal: Endoscopy (2012)

A 22-year-old woman was referred to our hospital for intensifying epigastric pain, 3 days after giving birth. The last stage of labor had been assisted by manual compression of the uterus, during which the patient had a painful, tearing sensation in the upper abdomen. Initial laboratory findings were as follows: hemoglobin 91 g/L, white blood cell count 21500 /µL, and amylase 567 IU/L. Abdominal computed tomography (CT) revealed near-total rupture of the pancreas ([Fig. 1]).
Tc-99m HMPAO SPECT Brain Imaging of Gilles de la Tourette??s Syndrome
Authors: KARL G. SIEG, DIANE BUCKINGHAM, GARY R. GAFFNEY, DAVID F. PRESTON, KENT G. SIEG
Journal: Clinical Nuclear Medicine (1993)

SIEG, KARL G. M. D.; BUCKINGHAM, DIANE M. D.; PRESTON, DAVID F. M. D.; SIEG, KENT G. PH. D. Author Information
A serum factor that suppresses the cytotoxic function of cytokine-stimulated human eosinophils.
Authors: D S Silberstein, M S Minkoff, A A Creasey, J R David
Journal: The Journal of Experimental Medicine (1990)

A human subject (NR) was identified whose eosinophils and neutrophils failed to respond to TNF in vitro in 29 of 33 experiments, using several biological assays. There was a response rate to TNF of 100% among 37 control subjects whose leukocytes were tested in parallel. NR serum contained an activity that inhibited the cytotoxic function of TNF- and GM-CSF-stimulated normal human eosinophils. A similar activity was detected in 4 of 122 control sera and in sera of two subjects with hypereosinophilia. This activity (ECI) had an apparent molecular weight of 80,000-100,000 and was sensitive to heating at 80 degrees C or to trypsin treatment. HPLC sizing chromatography increased the titer of ECI by a factor of 50 to 2,000 in experiments using NR serum or other sera with detectable inhibitory activity. In seven experiments using sera with no inhibitory activity, HPLC generated ECI of the same apparent molecular weight. The effect of HPLC on ECI activity required the separation of serum components and did not result from exposure to HPLC system components or other sample processing methods. This suggests that ECI in serum can be stabilized in an inactive or partially active form and that HPLC removes the stabilizing component. ECI suppressed TNF-stimulated eosinophil cytotoxic function when added to cultures up to 4 h after exposure of eosinophils to cytokine. However, ECI did not protect L929 cells from the toxic effects of TNF. Thus, ECI did not act by preventing the initial interaction of TNF with eosinophils or by interfering with the binding of TNF to its receptor on L929 cells. The results suggest that ECI is a component of a feedback mechanism that suppresses functions of cytokine-activated eosinophils in inflammation.
A&amp;E department: a missed opportunity for diagnosis of TB?
Authors: A Smith
Journal: Thorax (2006)

<h3>Background</h3> Home accidents are a leading cause of death and injury in the UK. Falls among older people lead to over 4 million hospital bed days each year. Almost 1 million children require emergency care following home accidents. Partnership working is vital to address this key public health issue. <h3>Description</h3> The Safer Homes Programme provided a package of consultancy, training and intervention across 30 local authority areas with higher than average hospital admission rates for accidents. The programme helped partners, who included local authorities, home improvement agencies, charities, Fire Services and NHS, to develop strategic plans and business cases. It trained local practitioners to plan, implement and evaluate community interventions including home safety checks, falls and burns interventions and advice to vulnerable families. <h3>Results</h3> Over 740 staff received the home safety training. The community interventions and advice given to families reached over 166,000 people. An independent evaluation by ICF International found increased home safety awareness among staff; improved partnership working and the development of clear injury prevention strategies. Training increased confidence of staff to raise awareness among client families. Families demonstrated practical safety improvements and behaviour change. One area reported a 12% drop in hospital admissions due to falls. <h3>Conclusions</h3> The programme raised the profile of accident prevention among local partners at a crucial time of change as well as making homes safer within their local communities. Learning about effective strategic development and local delivery of interventions has been shared between partners and more widely to improve practice.
Response to Letter Regarding Article, “Influence of Nonfatal Hospitalization for Heart Failure on Subsequent Mortality in Patients With Chronic Heart Failure”
Authors: Scott D. Solomon, Marc A. Pfeffer, Stuart Pocock, Joanna Marro, John J.V. McMurray, Christopher B. Granger, Salim Yusuf, Karl Swedberg, James B. Young, Eric Michelson
Journal: Circulation (2008)
The Choroid Plexus — Two-Way Traffic?
Authors: Philip R. Dodge, Marvin A. Fishman
Journal: New England Journal of Medicine (1970)

The concept that the choroid plexus might participate in the absorption of cerebrospinal fluid is not a new one. Frederick Foley,1 in 1921, postulated the resorption of cerebrospinal fluid by the choroid plexus under certain conditions, and George Hassin,2 in 1924, also espoused an absorptive rather than a secretory role for the plexus. However, since substantive data were lacking, this theory, which ran counter to prevailing thought, was not accepted. With the advent of new technics, including that of ventriculocisternal perfusion, together with the availability of isotope tracers, a new era in the study of cerebrospinal-fluid physiology began. It soon . . .
American Foreign Medical Graduates
Authors: Fred Rosner
Journal: JAMA (1979)

The performance during graduate medical education of Americans who have studied medicine abroad and who have taken a year of intense and closely supervised clinical clerkships (fifth pathway program) was assessed. Only 14% of such house officers were given inadequate or below-average ratings in overall clinical performance by residency program directors. Ninety percent or more received average, good, very good, or excellent evaluations in their ability to take medical histories and perform physical examinations, in their response to instruction, in behavior and interpersonal relationships, and in appearance and emotional stability. Seventy percent were said to be as good as or better than house staff in general. Carefully selected and properly motivated Americans who have studied medicine in a foreign country can become good physicians following a well-organized, comprehensive, closely supervised year of clinical clerkship education. (<i>JAMA</i>241:714-716, 1979)
Herbal Remedies in the United States: Potential Adverse Interactions With Anticancer Agents
Authors: Alex Sparreboom, Michael C. Cox, Milin R. Acharya, William D. Figg
Journal: Journal of Clinical Oncology (2004)

Purpose Interest in the use of herbal products has grown dramatically in the Western world. Recent estimates suggest an overall prevalence for herbal preparation use of 13% to 63% among cancer patients. With the narrow therapeutic range associated with most anticancer drugs, there is an increasing need for understanding possible adverse drug interactions in medical oncology. Methods In this article, a literature overview is provided of known or suspected interactions of the 15 best-selling herbs in the United States with conventional allopathic therapies for cancer. Results Herbs with the potential to significantly modulate the activity of drug-metabolizing enzymes (notably cytochrome P450 isozymes) and/or the drug transporter P-glycoprotein include garlic (Allium sativum), ginkgo (Ginkgo biloba), echinacea (Echinacea purpurea), ginseng (Panax ginseng), St John's wort (Hypericum perforatum), and kava (Piper methysticum). All of these products participate in potential pharmacokinetic interactions with anticancer drugs. Conclusion It is suggested that health care professionals and consumers should be aware of the potential for adverse interactions with these herbs, question their patients on their use of them, especially among patients whose disease is not responding to treatments as expected, and urge patients to avoid herbs that could confound their cancer care.