tbuckley/cabot-search huggingface dataset:
Avoidance of Immune Response Prolongs Expression of Genes Delivered to the Adult Rat Myocardium by Replication-Defective Adenovirus
Authors: Manuel J. Quin˜ones, Jonathan Leor, Robert A. Kloner, Masamichi Ito, Michael Patterson, Werner F. Witke, Larry Kedes
Journal: Circulation (1996)

Background Gene delivery is a rapidly expanding field with potential applications to every human organ system. Recently, adenoviruses have been used as efficient vectors for in vivo gene transfer into the myocardium. These methods, however, have shown a sharp decline of gene expression after 1 week. To test the hypothesis that an immune-effector mechanism is involved in this decline, we compared the results after injection of adenovirus-5 carrying the β-galactosidase gene (Adβ-gal) into the left ventricular myocardium of athymic nude rats (NDRs) versus immunocompetent Sprague-Dawley rats (SDRs). Methods and Results Adβ-gal (5.0×10 9 PFU/mL) was injected into the left ventricle of NDRs (n=16) and SDRs (n=22). Hearts were harvested, embedded in paraffin, and sectioned and stained for β-gal activity, hematoxylin and eosin and picrosirius red at 4, 21, 35, 85, and 120 days. Representative samples were immunostained with antibodies directed at inflammatory markers. β-gal activity was quantified by digital planimetry and expressed as area of staining (%±SEM). Peak β-gal activity was highest at 4 days, with NDRs displaying significantly greater staining (83±3.0% versus 54±8.0%; P =.03). SDRs sustained a rapid drop in activity, such that at 35 (1±0.19%) and 85 (1±0.4%) days, only occasional cells stained positive and by 120 days (0.3±0.0%), activity had been extinguished. NDRs continued to show transgene expression at all time periods (35 and 85 days, 25±7.1% and 7.4±2.7%, respectively) and was still readily detected at 120 days. An inflammatory response was limited in NDRs compared with SDRs, in which there was intense mononuclear cell infiltration, with collagen deposition and scar formation. Immunostaining identified the majority of these inflammatory cells as not being of lymphocyte lineage, although small numbers of lymphocytes and phagocytic and activated plasma cells were identified. Conclusions Our data suggest that immune-effector mechanisms can severely affect the expression of genes delivered by adenovirus. The present model provides efficient gene expression for at least 120 days without significant inflammatory reaction.
Abstract LB-55: The European Cancer Patient Coalition speaks with a <i>single</i> voice for <i>all</i> cancer patients
Authors: Ingrid Kossler
Journal: Cancer Research (2012)

Abstract Established in 2003, The European Cancer Patient Coalition is the voice of the European cancer patient community, uniquely representing the interests of all cancer patient groups from the major to the rarer cancers. ECPC is an independent, non-profit “umbrella” organization based in Brussels close to the European institutions, governed by an elected Board of seven members most of whom must be cancer patients, survivors or carers. ECPC maintains close links with EU institutions (Commission, Parliament, Council, and European Medicines Agency). ECPC monitors political development at EU level, identifies those which could impact the field of oncology, informs its member societies and supports European health issues. Priority Areas- • Influence EU policy that has an impact on the prevention, detection and treatment of cancer. • Reach out to national level to support ECPC members in their capacity building efforts on the national level • Build strategic partnerships with key cancer stakeholders to create mutual benefit One of ECPC's key priorities is to make cancer a priority for action on the European health policy agenda. With its policy activities, ECPC aims to effect change in legislative or regulatory policies to help optimize cancer prevention, detection, treatment and care throughout Europe. The policies also need to ensure that gaps within and between Member States are identified and eradicated, and that best practice is shared. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-55. doi:1538-7445.AM2012-LB-55
Phase I Study of Bryostatin 1 and Gemcitabine
Authors: Basil F. El-Rayes, Shirish Gadgeel, Anthony F. Shields, Stephanie Manza, Patricia Lorusso, Philip A. Philip
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Bryostatin 1 is a macrocyclic lactone with protein kinase C inhibitory activity. Gemcitabine is a nucleotide analogue with a broad spectrum of anticancer activity. Bryostatin 1 enhanced the activity of antitumor agents including gemcitabine in preclinical models. The primary objective of this phase I study was to determine the recommended doses for phase II trials of bryostatin 1 and gemcitabine. Experimental Design: Eligible patients had histologic or cytologic diagnosis of nonhematologic cancer refractory to conventional treatment; life expectancy of &amp;gt;3 months; normal renal, hepatic, and bone marrow function; and a Southwest Oncology Group performance status of 0 to 2. Gemcitabine was administered i.v. over 30 minutes and was followed by bryostatin 1 by i.v. infusion over 24 hours on days 1, 8, and 15 of a 28-day cycle. Bryostatin 1 (μg/m2) and gemcitabine (mg/m2) doses were escalated as follows: 25/600, 25/800, 25/1,000, 30/1,000, 35/1,000, and 45/1,000, respectively. Results: Thirty-six patients (mean age, 57 years; male/female 15:21) were treated. The median number of treatment cycles per patient was 3 (range, 0-24). Four patients developed dose limiting toxicities: myalgia, 2; myelosuppression, 1; and elevation of serum alanine aminotransferase levels, 1. Ten grade 3 toxicities were observed (anemia, 2; neutropenia, 5; thrombocytopenia, 3). No treatment-related death was seen. The recommended doses for phase II trials for bryostatin 1 and gemcitabine were 35 μg/m2 and 1,000 mg/m2, respectively. Two heavily pretreated patients with breast and colon cancer experienced partial responses lasting 22 and 8 months, respectively. Eight patients had stable disease. Conclusion: The combination of bryostatin 1 and gemcitabine seemed to be well tolerated with limited grade 3 toxicity. The recommended dose of bryostatin 1 in combination with full doses of gemcitabine was 35 μg/m2.
Clinical presentation and time course in hypersensitivity reactions to β‐lactams
Authors: P. J. Bousquet, V. Kvedariene, H.‐B. Co‐Minh, P. Martins, M. Rongier, B. Arnoux, P. Demoly
Journal: Allergy (2007)

Background: β‐lactam hypersensitivity reactions are classified as immediate or nonimmediate. Diagnosis is usually based upon skin tests and provocation challenges. Objective: The time course of the reactions in proven β‐lactam hypersensitivities was studied and then correlated with the symptoms to determine the relationship between the clinical presentations and the time course. Method: All of the patients who consulted between 1996 and 2004 for a suspected β‐lactam hypersensitivity reaction were studied. Two hundred and ten patients with a proven hypersensitivity reaction diagnosed according to the European Network on Drug Allergy were included in the present study. Results: Of the patients, 36.7% had urticaria as a single symptom, 19.1% anaphylaxis without shock, 17.6% anaphylactic shock and 19.1% maculopapular exanthema. Anaphylactic shock and anaphylaxis mostly occurred within 1 h after drug administration. Exanthema mainly occurred after 24 h. Urticaria as a single symptom occurred at any time. A firm diagnosis was determined using immediate‐reading skin prick (10.0%) and intradermal tests (38.1%), late‐reading skin tests (19.1%) or provocation tests (32.9%). Conclusion and clinical implication: Depending on the time course of the reaction, three clinical groups were identified: anaphylaxis and anaphylactic shock (immediate reaction); maculopapular exanthema (late reaction) as well as urticaria (immediate and late reaction).
Practice Guideline for Pulmonary Hypertension in Sickle Cell: Direct Evidence Needed before Universal Adoption
Authors: Kathryn L. Hassell, Araba Afenyi-Annan, Samir K. Ballas, George R. Buchanan, James R. Eckman, Lanetta Jordan, Sophie Lanzkron, Richard Lottenberg, Russell Ware
Journal: American Journal of Respiratory and Critical Care Medicine (2014)
ON WHOSE SIDE ARE SIDE-EFFECTS?
Authors: Walter Modell
Journal: JAMA (1961)

With increasing frequency in my current reading, especially on drugs and their application, I encounter the term<i>side-effects</i>; sometimes as the heading of a section in papers in which there is no further discussion of other undesirable effects, sometimes as a subheading under toxic effects, most often in simple summary statements such as, "Toxic effects were rare; side-effects were common." Side-effects seem to cause more anguish to me than to their victims or to the authors of papers I read, yet I do not believe I am unduly sensitive. I am disturbed because I am not certain what the term really means in each case. Side-effects seem so innocent that in most papers there is a tendency to do nothing about them beyond counting. Sometimes "undesirable" side-effects are enumerated as if to imply that there might also be some "desirable" side-effects. But then I also read about "serious side-effects." Occasionally
31 CD4+CD25HIFOXP3+ T-REGS AND LIVER TRANSPLANTATION FOR END-STAGE HCV-RELATED LIVER DISEASE: A ROLE IN HCV RECURRENCE?
Authors: S. Ferri, G. Lanzoni, C. Lalanne, M.C. Morelli, M. Bassi, P. Muratori, S. Berardi, M.R. Tarné, A. Gianstefani, M. Cescon, G. Ballardini, A.D. Pinna, M. Lenzi, L. Muratori
Journal: Journal of Hepatology (2011)
Defining the Optimal Activated Clotting Time During Percutaneous Coronary Intervention
Authors: Derek P. Chew, Deepak L. Bhatt, A. Michael Lincoff, David J. Moliterno, Sorin J. Brener, Katherine E. Wolski, Eric J. Topol
Journal: Circulation (2001)

Background —Unfractionated heparin has been the primary anticoagulant therapy for percutaneous coronary intervention for &gt;20 years. Despite the availability of rapid “point of care” testing, little clinical data defining the optimal level of anticoagulation are available. Furthermore, recent reports have advocated the use of low-dose heparin regimens in the absence of large-scale, well-conducted studies to support this practice. Methods and Results —We pooled the data from 6 randomized, controlled trials of novel adjunctive antithrombotic regimens for percutaneous coronary interventions in which unfractionated heparin constituted the control arm. Patients were divided into 25-s intervals of activated clotting times (ACTs), from &lt;275 s to &gt;476 s. In a total of 5216 patients, the incidence of death, myocardial infarction, or any revascularization and major or minor bleeding at 7 days were calculated for each group and compared. An ACT in the range of 350 to 375 s provided the lowest composite ischemic event rate of 6.6%, or a 34% relative risk reduction in 7-day ischemic events compared with rates observed between 171 and 295 s by quartile analysis ( P =0.001). Conclusions —Contrary to recent reports, the optimal suppression of ischemic events with unfractionated heparin therapy in patients undergoing percutaneous coronary intervention demands treatment to ACT levels that are substantially higher than currently appreciated. These data define a goal for heparin dosing within coronary interventions and establish a benchmark of optimal unfractionated heparin therapy against which future trials of novel antithrombotic regimens in percutaneous interventions can be compared.
Action of Human Plasma on the Isolated Frog Heart
Authors: STEPHEN HAJDU, EDWARD LEONARD, ROBERT P. AKERS
Journal: Circulation Research (1957)

Plasma samples from certain patients affect the staircase phenomenon of the frog heart. Comparison of 3 groups of subjects, normal controls, patients without essential hypertension, and patients with severe essential hypertension shows that plasmas from the last group generally abolish the staircase, whereas plasmas of the other 2 groups exhibit little or no such activity.
Inactivated Poliovirus Vaccine and Vaccine-Associated Paralytic Poliomyelitis-Reply
Authors: Roland W. Sutter
Journal: JAMA (1997)

<h3>In Reply.</h3> —Two recent reviews<sup>1,2</sup>have updated our understanding of the epidemiology of VAPP in the United States and the relative proportions of recipient, contact, and immunologically abnormal cases. These data as well as a review of immunologically abnormal VAPP cases were considered by the Delphi panel.<sup>3</sup>With respect to immunologically abnormal VAPP cases, the panel noted the following: (1) 95% of such patients were associated with B-cell disorders, and IPV administration would not be expected to induce an effective immune response in these individuals; (2) the median age at onset of paralytic disease among recipients was 11.2 months; and (3) with the exception of 1 contact case, VAPP was the precipitating event that led to the diagnosis of immunodeficiency. In addition, few cases of agammaglobulinemia (the most severe form of B-cell disorders) are diagnosed in the first year of life. In one study the mean age at diagnosis of
Visceral Leishmaniasis in Southern Sudan
Authors: Sergio de A. Nishioka
Journal: Annals of Internal Medicine (1997)

Letters15 February 1997Visceral Leishmaniasis in Southern SudanSergio de A. Nishioka, MD, MScSergio de A. Nishioka, MD, MScUniversidade Federal de Uberlandia, Uberlandia, BrazilSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-126-4-199702150-00018 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Seaman and colleagues [1] recently found that increasing age, long duration of illness, decreasing hemoglobin level, and decreasing body mass index were independently associated with death from (or with) visceral leishmaniasis in adults in Sudan. The large sample size in their study makes it unlikely that random error had any effect on the risk ratio estimates, but measurement errors resulting from the limited resources that were available to the investigators may have affected the validity of the results. Age was particularly likely to be systematically overestimated in patients whose disease was more severe and had lasted longer ...References1. Seaman J, Mercer AJ, Sondorp HE, Herwaldt BL. Epidemic visceral leishmaniasis in southern Sudan: treatment of severely debilitated patients under wartime conditions and with limited resources. Ann Intern Med. 1996; 124:664-72. Google Scholar2. Neva F, Sacks D. Leishmaniasis. In: Warren KS, Mahmoud AA, eds. Tropical and Geographical Medicine. New York: McGraw-Hill; 1990:296-308. Google Scholar Author, Article, and Disclosure InformationAffiliations: Universidade Federal de Uberlandia, Uberlandia, Brazil PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byImportation of visceral leishmaniasis in returning Romanian workers from Spain 15 February 1997Volume 126, Issue 4Page: 332KeywordsAnemiaBody mass indexDeath ratesHemoglobinLeishmaniasisMalnutritionMedical risk factorsNeutropeniaPneumoniaRisk ratio ePublished: 15 August 2000 Issue Published: 15 February 1997 Copyright & PermissionsCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Acquired Immunodeficiency Syndrome in Saudi Arabia
Authors: Harb A. Harfi
Journal: JAMA (1986)

Two Saudi Arabian patients, one adult and one child, developed acquired immunodeficiency syndrome (AIDS) 2 1/2 and 3 1/2 years after blood transfusion. Both patients received blood imported from the United States in 1981. These are the first cases reported in Saudi Arabia. Since an undetermined number of Saudi patients have received blood imported from the United States, an outbreak of AIDS in Saudi Arabia might prove to be a serious problem in the near future. Measures such as limiting the importation of blood products from countries with a high incidence of AIDS and screening for human T-cell lymphotropic virus type III should be taken to stop the spread of this fatal disease.
Limiting dilution comparison of the repertoires of high and low responder MHC-restricted T cells.
Authors: M Kojima, K B Cease, G K Buckenmeyer, J A Berzofsky
Journal: The Journal of Experimental Medicine (1988)

To approach the mechanism that determines Ir gene-controlled high or low responsiveness to whole proteins, such as sperm whale myoglobin (SWMb), we compared the repertoires of high and low responder haplotype-restricted T cells for different myoglobin epitopes by limiting dilution frequency analysis. Poisson analysis was performed using long-term limiting dilution cell lines of (B10.BR [low] X B10.D2[high])F1 T cells maintained on high or low responder APCs. The cell lines were tested with SWMb peptides and fragments for T cell repertoire fine specificities and Ia restrictions. The frequency of SWMb-specific F1 T cells responsive on B10.BR (H-2k) APCs was 2.5-3.6-fold lower than on B10.D2 (H-2d) APCs. Strikingly, all of the H-2k-restricted T cells used I-Ek as a restriction element, whereas both I-Ad- and I-Ed-restricted T cells were found among the H-2d-restricted lines. The I-Ad-restricted T cells were dominant, and the majority was specific for the synthetic peptide 102-118. T cells specific for peptide 132-146, dominant in association with I-Ed, were less frequent. However, no detectable H-2k-restricted T cells were specific for either of these peptides, but instead they were specific for fragment 1-55 or peptide 59-80. Fragment 1-55 also stimulated a similar number of H-2d-restricted T cells. Therefore, the low response of F1 T cells on H-2k-presenting cells may be due to the failure to see myoglobin plus I-Ak, in particular the immunodominant site around Glu 109, in contrast to the dominant response of high responder mice (both H-2d and H-2s) focused on the I-A molecule and the site around residue Glu 109. The I-E- low responder B10 strain also failed to respond to peptide 102-118, supporting the idea that the low responder status results from a limited repertoire lacking response to 102-118 plus I-A. In those strains that respond to the immunodominant site 102-118, the frequency of T cells in the repertoire specific for this site was always considerably greater than that for other sites. These results suggest that there is an important difference between immunodominant epitopes and minor epitopes and that Ir gene-controlled low responsiveness to a natural whole protein may be due primarily to the failure to respond to a single immunodominant site, even though a number of other epitopes can be recognized.
Cost-Effectiveness of Screening for Pre-Diabetes Among Overweight and Obese U.S. Adults
Authors: Jaro Wex Wechowski
Journal: Diabetes Care (2008)

I read with great interest the article by Hoerger et al. regarding cost-effectiveness of screening for pre-diabetes in the U.S. setting (1). The results reported by the authors have potentially global implications and should be viewed in the context of similar analyses conducted elsewhere.

The cost-effectiveness ratio obtained in the study is in broad agreement with recent findings for the U.K. (2). The U.K. analysis was based on a pre-diabetes screening module linked to a validated diabetes model (3). The value of the incremental cost-effectiveness ratio (ICER) was determined as £23,717 for patients with both impaired glucose tolerance and impaired fasting glucose treated with intensive …
Tuberculin Delayed Hypersensitivity in Myocardial Infarction
Authors: EVANGELOS K. PANAYOTOPOULOS
Journal: Annals of Internal Medicine (1973)

Letters1 August 1973Tuberculin Delayed Hypersensitivity in Myocardial InfarctionEVANGELOS K. PANAYOTOPOULOS, M.D.EVANGELOS K. PANAYOTOPOULOS, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-79-2-276_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Although atherosclerotic coronary heart disease (ACHD) has been classified among the degenerative diseases, some recent data are consistent with the concept that humoral immune factors are involved in the atherosclerotic process (1, 2).During the last 4 years, most of my patients with atherosclerotic heart disease also had a positive history of serositis, signs of bronchitis, and a family history of proved or suspected tuberculosis.I tested for tuberculin delayed (cell-mediated) hypersensitivity in 34 patients with documented myocardial infarction.Old tuberculin of the Greek Institute of Pasteur was used intradermally (Mantoux skin test), in a dilution of...References1. HEINEFRIEDMANMANDELL WHM: Antibodies to cardiac tissue in ischemic heart disease. Am J Cardiol 17:798-803, 1966 CrossrefGoogle Scholar2. HOLLANDERKRAMSCHMCCOMBS WDH: Identification of immunoglobulin A, G and B1A globulin in the human atherosclerotic plaque. Circulation 42(suppl 3):16, 1970 Google Scholar3. Symposium: Morbidity, prevention and treatment of tuberculosis. Present status. Iatriki Epitheorisis Enoplon Dynameon 5:109-120, 1971 Google Scholar4. KAPLANFRENGLEY MJ: Autoimmunity to the heart in cardiac disease. Am J Cardiol 24:459-473, 1969 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: EVANGELOS K. PANAYOTOPOULOS, M.D. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byPositive tuberculin skin tests in nursing home residents in Southern Taiwan 1 August 1973Volume 79, Issue 2Page: 276-277KeywordsBronchitisCardiovascular therapyCoronary heart diseaseHypersensitivityMyocardial infarctionSkin testsTuberculin ePublished: 1 December 2008 Issue Published: 1 August 1973 PDF downloadLoading ...
Polymyalgia rheumatica/giant cell arteritis in a Cambridge general practice.
Authors: V Kyle, B Silverman, A Silman, H King, N Oswald, B Reiss, B Hazleman
Journal: BMJ (1985)

The aim of this study was to establish the incidence and prevalence of polymyalgia rheumatica/giant cell arteritis in general practice. Patients with this disorder, whether previously diagnosed or not, were ascertained by using a questionnaire administered by interview, and all received full clinical and laboratory assessment. A total of 579 patients aged 65 and over was seen, and 19 (33/1000) had been diagnosed or developed symptoms within the previous eight years. Thus the calculated annual incidence in those aged 65 and over was about 4/1000. The figures from this first large scale study of polymyalgia rheumatica/giant cell arteritis in general practice are much higher than those from studies carried out in hospital. The questionnaire was effective in both identifying known cases of polymyalgia rheumatica/giant cell arteritis and detecting new cases. As this is a treatable disorder, it is important that doctors become aware of how common it is in elderly people.