tbuckley/cabot-search huggingface dataset:
Effect of preconditioning ischemia on reperfusion arrhythmias after coronary artery occlusion and reperfusion in the rat.
Authors: J M Hagar, S L Hale, R A Kloner
Journal: Circulation Research (1991)

Severe arrhythmias occur predictably on reperfusion after 5 minutes of coronary occlusion in the rat. There is little data available on whether ischemic preconditioning (PC) of hearts can reduce the incidence of such arrhythmias. The effect of PC (three cycles of 2 minutes of coronary occlusion and 5 minutes of reperfusion) on development of arrhythmias after a subsequent 5-minute coronary artery occlusion and reperfusion was studied. Rats (n = 16 each group) underwent 5-minute occlusion and reperfusion alone or preceded by PC; arrhythmias were monitored during ischemia and for 10 minutes of reperfusion, and biopsies were taken for creatine phosphate and adenosine triphosphate in ischemic and nonischemic zones of the left ventricle. PC reduced the incidence of ventricular tachycardia (VT) during occlusion (81% control versus 13% PC, p less than 0.001). On subsequent reperfusion, ventricular fibrillation (VF) developed in zero PC animals versus 13 (81%) of controls (p less than 0.001), and irreversible VF in zero of PC versus seven (44%) of controls (p = 0.007). VT occurred in four (25%) of PC versus all (100%) of controls (p less than 0.001). PC reduced mean duration of VT plus VF from 320 +/- 54 to 5 +/- 1 seconds (p less than 0.001) and delayed arrhythmia onset from 8 +/- 2 to 85 +/- 35 seconds after reperfusion. There was no difference in creatine phosphate levels in the ischemic zone at the end of reperfusion in PC animals compared with controls without irreversible VF (16.2 +/- 4.1 versus 15.5 +/- 3.9 nmol/mg protein, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)
The Consult Guys - Is That Hemoglobin High Enough?
Authors: Geno J. Merli, Howard H. Weitz
Journal: Annals of Internal Medicine (2014)

Web Exclusives19 August 2014The Consult Guys - Is That Hemoglobin High Enough?FREEGeno J. Merli, MD and Howard H. Weitz, MDGeno J. Merli, MDSearch for more papers by this author and Howard H. Weitz, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G14-3008 SectionsSupplemental MaterialAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The Consult Guys bring a new perspective to the art and science of medicine with lively discussion and analysis of real-world cases and situations.For more videos from and information on The Consult Guys, visit www.annals.org/ConsultGuys. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Disclosures: Geno J. Merli, MD, reports the following: Research grants/contracts: Bristol-Myers Squibb, Bayer, sanofi-aventis; Consultancies: Bristol-Myers Squibb, Bayer, sanofi-aventis. Howard H. Weitz, MD, reports that he has no financial relationships or interests to disclose. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 19 August 2014Volume 161, Issue 4Page: CG8KeywordsConflicts of interestHemoglobinResearch grantsResearch reporting guidelines ePublished: 19 August 2014 Issue Published: 19 August 2014 CopyrightCopyright © 2014 by American College of Physicians. All Rights Reserved.Loading ...
Higher Frequency of Diploidy in Young-Onset Microsatellite-Stable Colorectal Cancer
Authors: Lisa A. Boardman, Ruth A. Johnson, Gloria M. Petersen, Ann L. Oberg, Brian F. Kabat, Joshua P. Slusser, Liang Wang, Bruce W. Morlan, Amy J. French, Thomas C. Smyrk, Noralane M. Lindor, Stephen N. Thibodeau
Journal: Clinical Cancer Research (2007)

Colorectal carcinoma (CRC) can be divided into two nonoverlapping groups: those that are chromosomally unstable but microsatellite stable (MSS CIN+) and those that are chromosomally stable but microsatellite unstable (MSI CIN-). However, a third group with neither chromosome nor microsatellite instability (MSS CIN-) makes a substantial contribution to the total CRC burden. The clinicopathologic features of MSS CIN- CRC are not well delineated. We assessed the relationship between age and chromosomal instability (CIN) status as measured by ploidy and allelic imbalance in a series of MSS tumors.We studied a prospectively collected series of CRC patients at Mayo Clinic Rochester. A total of 84 samples of MSS CRC in patients <or=50 years old were identified between 1994 and 1997. A consecutive series of 90 MSS CRC in patients >or=65 years old served as a comparison group. CIN status was assessed using two techniques: ploidy analysis by flow cytometry and small chromosome changes as measured by genomewide fractional allelic imbalance.CRC in the young-onset group was more likely to involve the rectum and to be high stage. MSS tumors in the young-onset group were more often diploid (46%) than those in older patients (26%; P = 0.006). This difference was maintained in the subset of MSS CRC that were high stage (42% versus 18%; P = 0.02) and in rectal cancers (50% versus 23%; P = 0.04).A greater proportion of young patients with MSS CRC has diploid tumors than patients who develop MSS CRC over age 65.
A Critical Appraisal of the Efficacy of Continuing Medical Education
Authors: R. Brian Haynes
Journal: JAMA (1984)

To determine the efficacy of continuing medical education (CME), we collected 248 original articles describing studies of CME interventions. These articles were reviewed for applicability and scientific credibility by applying preset methodological criteria. Thirteen percent of articles described randomized trials, but only 7% of all articles and 20% of randomized trials assessed the impact of CME on patient outcomes. Seven articles met all our criteria and were reviewed in detail. These studies provide convincing evidence that CME can improve physician behaviors. However, only three of these methodologically sound studies assessed patient outcomes and only one demonstrated any improvement in outcomes. (<i>JAMA</i>1984;251:61-64)
Rituximab versus Azathioprine for Maintenance in ANCA-Associated Vasculitis
Authors: Loïc Guillevin, Christian Pagnoux, Alexandre Karras, Chahera Khouatra, Olivier Aumaître, Pascal Cohen, François Maurier, Olivier Decaux, Jacques Ninet, Pierre Gobert, Thomas Quémeneur, Claire Blanchard-Delaunay, Pascal Godmer, Xavier Puéchal, Pierre-Louis Carron, Pierre-Yves Hatron, Nicolas Limal, Mohamed Hamidou, Maize Ducret, Eric Daugas, Thomas Papo, Bernard Bonnotte, Alfred Mahr, Philippe Ravaud, Luc Mouthon
Journal: New England Journal of Medicine (2014)

The combination of cyclophosphamide and glucocorticoids leads to remission in most patients with antineutrophil cytoplasm antibody (ANCA)–associated vasculitides. However, even when patients receive maintenance treatment with azathioprine or methotrexate, the relapse rate remains high. Rituximab may help to maintain remission.
Cancer Stem Cells in Squamous Cell Carcinoma Switch between Two Distinct Phenotypes That Are Preferentially Migratory or Proliferative
Authors: Adrian Biddle, Xiao Liang, Luke Gammon, Bilal Fazil, Lisa J. Harper, Helena Emich, Daniela Elena Costea, Ian C. Mackenzie
Journal: Cancer Research (2011)

Abstract Epithelial-to-mesenchymal transition (EMT) is an important driver of tumor invasion and metastasis, which causes many cancer deaths. Cancer stem cells (CSC) that maintain and initiate tumors have also been implicated in invasion and metastasis, but whether EMT is an important contributor to CSC function is unclear. In this study, we investigated whether a population of CSCs that have undergone EMT (EMT CSCs) exists in squamous cell carcinoma (SCC). We also determined whether a separate population of CSCs that retain epithelial characteristics (non-EMT CSCs) is also present. Our studies revealed that self-renewing CSCs in SCC include two biologically-distinct phenotypes. One phenotype, termed CD44highESAhigh, was proliferative and retained epithelial characteristics (non-EMT CSCs), whereas the other phenotype, termed CD44highESAlow, was migratory and had mesenchymal traits characteristic of EMT CSCs. We found that non-EMT and EMT CSCs could switch their epithelial or mesenchymal traits to reconstitute the cellular heterogeneity which was characteristic of CSCs. However, the ability of EMT CSCs to switch to non-EMT character was restricted to cells that were also ALDH1+, implying that only ALDH1+ EMT cells had the ability to seed a new epithelial tumor. Taken together, our findings highlight the identification of two distinct CSC phenotypes and suggest a need to define therapeutic targets that can eradicate both of these variants to achieve effective SCC treatment. Cancer Res; 71(15); 5317–26. ©2011 AACR.
Emergence of immunoglobulin variants following treatment of a B cell leukemia with an immunotoxin composed of antiidiotypic antibody and saporin.
Authors: M J Glennie, H M McBride, F Stirpe, P E Thorpe, A T Worth, G T Stevenson
Journal: The Journal of Experimental Medicine (1987)

The potency and specificity of immunotoxins consisting of monoclonal antiidiotype conjugated to the ribosome-inactivating protein, saporin, have been evaluated in the treatment of guinea pig L2C B lymphocytic leukemia. The immunotoxins were therapeutically much more effective than their parent antibodies. Their specificity reflected that of their antiidiotype component. Although the leukemia emerged eventually in most animals treated with these conjugates, most of the cells showed altered Ig expression, which rendered them resistant to the therapy. Commonly, the emerging cells had lost mu heavy chain production, leaving them negative for intracellular, surface, and secreted IgM, but still positive for lambda light chain production. In addition, a minor group of L2C variants was identified in a protocol designed to detect mutants at very low frequency: here the cells were exposed in vitro to immunotoxin and, while still viable as judged by dye-exclusion, inoculated in large numbers into animals. In tumor that emerged under these circumstances, the majority of cells were again immunoglobulin-negative; however a minority exhibited IgM with an altered idiotype (Idiotope-loss variants), rendering them unreactive with immunotoxin. Immunotherapy with unmodified anti-Id antibody alone does not reveal these variants, and we suggest it is the increased selective force exerted by the highly potent immunotoxins that allow these minor nonreactive populations to emerge.
Outcome of BRCA1- compared with BRCA2-associated ovarian cancer: a nationwide study in the Netherlands
Authors: P.M.L.H. Vencken, W. Reitsma, M. Kriege, M.J.E. Mourits, G.H. de Bock, J.A. de Hullu, A.M. van Altena, K.N. Gaarenstroom, H.F.A. Vasen, M.A. Adank, M.K. Schmidt, M. van Beurden, R.P. Zweemer, F. Rijcken, B.F.M. Slangen, C.W. Burger, C. Seynaeve
Journal: Annals of Oncology (2013)
Relative prevalence and risk factors of HTLV-I and HTLV-II infection in US blood donors
Authors: H.H. Lee, P. Swanson, J.D. Rosenblatt, I.S.Y. Chen, W.C. Sherwood, D.E. Smith, G.E. Tegtmeier, L.P. Fernando, C.T. Fang, M. Osame, S.H. Kleinman
Journal: The Lancet (1991)
Asthma in the elderly: Clinical findings
Authors: Hanene Smadhi, Leila Elfekih, Othmen Neffeti, Hela Hassen, Ines Akrout Akrout, Dorra Greb, Tawaddod Khmis, Hajer Benabdelghaffar, Souraya Fenniche, Mohamed Lamine Megdiche
Journal: European Respiratory Journal (2013)

Introduction:  Asthma is a common disease throughout the world. Its prevalence had net increased in recent years. Often known as a disease of childhood and adolescence, asthma can occur at late age and make a challenge of its positive diagnosis and its therapeutic management.  Aim: The aim of our work is to clarify the clinical, diagnostic and therapeutic difficulties of late asthma.  Methods: This is a retrospective study including 50 patients during the period from January 1995 until January 2012 and in whom the diagnosis of asthma with a late start has been selected.  Results: The mean age in our study was 58 years (range 42-86). 70% of patients were female. 11 patients (22%) were smokers and 20 women were postmenopausal. Oldness of asthma was at an average of 6 years with a range from 1 to 24 years. Symptoms were dominated by attacks of breathlessness, wheezing and spasmodic dry cough. The allergological bilan revealed allergy in 25 cases. Factors associated with late asthma were gastroesophageal reflux (26 patients), menopause (20 cases) and infectious sinusitis (10 patients). Inhaled corticosteroid treatment was prescribed in 49 patients, associated in 40 cases with a long duration action bronchodilator. Evolution was favorable with treatment in 18 cases with a control of all parameters, 22 patients were partially controlled, 8 patients were not controlled and 2 patients were lost to view.  Conclusion: Although it was believed that asthma is predominantly a childhood disease, asthma in the elderly is not a rare disorder. Moreover, it is frequently underdiagnosed or misdiagnosed due to atypical presentation, age-related reduction of dyspnea perception, and associated comorbidities.
Identification of Protein Kinase C Isoforms in Rat Mesenteric Small Arteries and Their Possible Role in Agonist-Induced Contraction
Authors: Vasken Ohanian, Jacqueline Ohanian, Linda Shaw, Sylvia Scarth, Peter J. Parker, Anthony M. Heagerty
Journal: Circulation Research (1996)

Abstract We have identified immunologically the protein kinase C (PKC) isoforms present in rat mesenteric small arteries, defined their distribution between particulate and soluble fractions, and studied their involvement in phorbol ester–induced contraction. Our analysis revealed the presence of the Ca 2+ -dependent PKCs (α and γ), Ca 2+ -independent PKCs (δ and ε), and the atypical isoform (ζ). PKCβ could not be detected, whereas PKCγ is likely to be of neural origin. All isoforms exhibited different distributions: PKCα, PKCε, and PKCζ were found in both particulate and soluble fractions. In contrast, PKCδ was mainly in the particulate fraction, and PKCγ was in the soluble fraction. Phorbol esters, which activate PKC and cause smooth muscle contraction, downregulated only the α and δ isoforms. This was associated with a parallel loss of contractile response to phorbol ester. The force developed to submaximal concentrations of noradrenaline was decreased after phorbol dibutyrate pretreatment, although the sensitivity and maximal response were unchanged. Phorbol ester pretreatment did not affect the contractile response to vasopressin. The sensitivity to non–receptor-mediated contraction, caused by K + in the presence of prazosin, was slightly reduced by 4α- and 4β-phorbol ester pretreatment. Maximal tension in response to this agonist was not affected. We conclude that PKCα and/or PKCδ is necessary for phorbol ester–mediated contraction but is not essential for noradrenaline-, vasopressin-, or K + -induced contraction, demonstrating differences in the mechanisms involved in the contractile response between these agents.
Lenalidomide Plus Prednisone Results in Durable Clinical, Histopathologic, and Molecular Responses in Patients With Myelofibrosis
Authors: Alfonso Quintás-Cardama, Hagop M. Kantarjian, Taghi Manshouri, Deborah Thomas, Jorge Cortes, Farhad Ravandi, Guillermo Garcia-Manero, Alessandra Ferrajoli, Carlos Bueso-Ramos, Srdan Verstovsek
Journal: Journal of Clinical Oncology (2009)

To investigate the safety and efficacy of the combination of lenalidomide and prednisone in patients with myelofibrosis (MF).Forty patients with MF were treated. Therapy consisted of lenalidomide 10 mg/d (5 mg/d if baseline platelet count < 100 x 10(9)/L) on days 1 through 21 of a 28-day cycle for six cycles, in combination with prednisone 30 mg/d orally during cycle 1, 15 mg/d during cycle 2, and 15 mg/d every other day during cycle 3. Lenalidomide therapy was continued indefinitely in patients exhibiting clinical benefit.The median follow-up was 22 months (range, 6 to 27). Responses were recorded in 12 patients (30%) and are ongoing in 10 (25%). The median time to response was 12 weeks (range, 2 to 32). According to the International Working Group for Myelofibrosis Research and Treatment consensus criteria, three patients (7.5%) had partial response and nine patients (22.5%) had clinical improvement durable for a median of 18 months (range, 3.5 to 24+). Overall response rates were 30% for anemia and 42% for splenomegaly. Moreover, 10 of 11 assessable responders who started therapy with reticulin fibrosis grade 4 experienced reductions to at least a score of 2. All eight JAK2(V617F)-positive responders experienced a reduction of the baseline mutant allele burden, which was greater than 50% in four, including one of whom the mutation became undetectable. Grade 3 to 4 hematologic adverse events included neutropenia (58%), anemia (42%), and thrombocytopenia (13%).The combination of lenalidomide and prednisone induces durable clinical, molecular, and pathologic responses in MF.
Progression of Retinopathy in Insulin-Treated Type 2 Diabetic Patients
Authors: Marianne Henricsson, Kerstin Berntorp, Per Fernlund, Göran Sundkvist
Journal: Diabetes Care (2002)

OBJECTIVE—To study the progression of retinopathy 3 years after initiation of insulin therapy. RESEARCH DESIGN AND METHODS—In a prospective, observational case-control study, 42 type 2 diabetic patients were examined at baseline and 1, 3, 6, 12, 24, and 36 months after change to insulin therapy. Retinopathy was graded based on fundus photographs using the Wisconsin scale; HbA1c and IGF-1 were measured. RESULTS—During the observation period of 3 years, 26 patients progressed in the retinopathy scale; 11 patients progressed at least three levels. After 3 years of insulin therapy, HbA1c and IGF-1 were significantly lower than at baseline. Progression of retinopathy greater than or equal to three levels was related to high IGF-1 levels. CONCLUSIONS—A relationship was found between high IGF-1 levels at 3 years and progression of retinopathy in type 2 diabetic patients.
Cough, chest pain and haemoptysis in a young nurse
Authors: AF Mobeireek
Journal: European Respiratory Journal (1996)

Case reportA 26 year old female nurse, of East African origin, presented with a 4 month history of intermittent cough, left-sided chest pain in the upper region, and mild haemoptysis for 2 days prior to admission.She gave a history of low grade intermittent fever and night sweats, and weight loss of about 3 kg over the previous 4 months, but denied anorexia.She had a long-standing history of intermittent breathlessness, cough, wheeze, runny nose and sneezing related to smells dating back to childhood.She was diagnosed to have mild asthma and allergic rhinitis, and responded to treatment with inhaled salbutamol and intranasal steroid sprays.She was, otherwise in excellent health, and was never admitted to hospital.She admitted possible contact with tuberculous patients 1 year earlier, when she was training as a student nurse at a chest hospital.She was a nonsmoker.Her family history was unremarkable.
Supraoptimal Peptide–Major Histocompatibility Complex Causes a Decrease in Bcl-2 Levels and Allows Tumor Necrosis Factor α Receptor II–mediated Apoptosis of Cytotoxic T Lymphocytes
Authors: Martha A. Alexander-Miller, Michael A. Derby, Apurva Sarin, Pierre A. Henkart, Jay A. Berzofsky
Journal: The Journal of Experimental Medicine (1998)

Cytotoxic T lymphocytes (CTLs) are primary mediators of viral clearance, but high viral burden can result in deletion of antigen-specific CTLs. We previously reported a potential mechanism for this deletion: tumor necrosis factor (TNF)-alpha-mediated apoptosis resulting from stimulation with supraoptimal peptide-major histocompatibility complex. Here, we show that although death is mediated by TNF-alpha and its receptor (TNF-RII), surprisingly neither the antigen dose dependence of TNF-alpha production nor that of TNF-RII expression can account for the dose dependence of apoptosis. Rather, a previously unrecognized effect of supraoptimal antigen in markedly decreasing levels of the antiapoptotic protein Bc1-2 was discovered and is likely to account for the gain in susceptibility or competence to sustain the death signal through TNF-RII. This decrease requires a signal through the TCR, not just through TNF-RII. Although death mediated by TNF-RII is not as widely studied as that mediated by TNF-RI, we show here that it is also dependent on proteolytic cleavage by caspases and triggered by a brief initial encounter with antigen. These results suggest that determinant density can regulate the immune response by altering the sensitivity of CTLs to the apoptotic effects of TNF-alpha by decreasing Bc1-2 levels.
Normalisation of CD4 counts in patients with HIV-1 infection and maximum virological suppression who are taking combination antiretroviral therapy: an observational cohort study
Authors: A Mocroft, AN Phillips, J Gatell, B Ledergerber, M Fisher, N Clumeck, M Losso, A Lazzarin, G Fatkenheuer, JD Lundgren
Journal: The Lancet (2007)
Type of Alcohol Consumed and Mortality from All Causes, Coronary Heart Disease, and Cancer
Authors: Morten Grønbæk
Journal: Annals of Internal Medicine (2000)

Background: Although the J-shaped relation between alcohol intake and mortality has been reproduced in many large cohort studies, the question of whether the effects of beer, wine, and spirits differ remains controversial. Objective: To examine the relation between intake of different types of alcohol and death from all causes, coronary heart disease, and cancer. Design: Pooled cohort studies in which intake of beer, wine, and spirits; smoking status; educational level; physical activity; and body mass index were assessed at baseline. Setting: Copenhagen, Denmark. Participants: 13 064 men and 11 459 women 20 to 98 years of age. Measurements: Number of deaths and time to death from all causes, coronary heart disease, and cancer during follow-up. Results: During 257 859 person-years of follow-up, 4833 participants died. J-shaped relations were found between total alcohol intake and mortality at various levels of wine intake. Compared with nondrinkers, light drinkers who avoided wine had a relative risk for death from all causes of 0.90 (95% CI, 0.82 to 0.99) and those who drank wine had a relative risk of 0.66 (CI, 0.55 to 0.77). Heavy drinkers who avoided wine were at higher risk for death from all causes than were heavy drinkers who included wine in their alcohol intake. Wine drinkers had significantly lower mortality from both coronary heart disease and cancer than did non–wine drinkers (P = 0.007 and P = 0.004, respectively). Conclusion: Wine intake may have a beneficial effect on all-cause mortality that is additive to that of alcohol. This effect may be attributable to a reduction in death from both coronary heart disease and cancer.