tbuckley/cabot-search huggingface dataset:
Quality of Life After PCI vs CABG Among Patients With Diabetes and Multivessel Coronary Artery Disease
Authors: Mouin S. Abdallah
Journal: JAMA (2013)

The FREEDOM trial demonstrated that among patients with diabetes mellitus and multivessel coronary artery disease, coronary artery bypass graft (CABG) surgery resulted in lower rates of death and myocardial infarction but a higher risk of stroke when compared with percutaneous coronary intervention (PCI) using drug-eluting stents. Whether there are treatment differences in health status, as assessed from the patient's perspective, is unknown.To compare the relative effects of CABG vs PCI using drug-eluting stents on health status among patients with diabetes mellitus and multivessel coronary artery disease.Between 2005 and 2010, 1900 patients from 18 countries with diabetes mellitus and multivessel coronary artery disease were randomized to undergo either CABG surgery (n = 947) or PCI (n = 953) as an initial treatment strategy. Of these, a total of 1880 patients had baseline health status assessed (935 CABG, 945 PCI) and comprised the primary analytic sample.Initial revascularization with CABG surgery or PCI.Health status was assessed using the angina frequency, physical limitations, and quality-of-life domains of the Seattle Angina Questionnaire at baseline, at 1, 6, and 12 months, and annually thereafter. For each scale, scores range from 0 to 100 with higher scores representing better health. The effect of CABG surgery vs PCI was evaluated using longitudinal mixed-effect models.At baseline, mean (SD) scores for the angina frequency, physical limitations, and quality-of-life subscales of the Seattle Angina Questionnaire were 70.9 (25.1), 67.3 (24.4), and 47.8 (25.0) for the CABG group and 71.4 (24.7), 69.9 (23.2), and 49.2 (25.7) for the PCI group, respectively. At 2-year follow-up, mean (SD) scores were 96.0 (11.9), 87.8 (18.7), and 82.2 (18.9) after CABG and 94.7 (14.3), 86.0 (19.3), and 80.4 (19.6) after PCI, with significantly greater benefit of CABG on each domain (mean treatment benefit, 1.3 [95% CI, 0.3-2.2], 4.4 [95% CI, 2.7-6.1], and 2.2 [95% CI, 0.7-3.8] points, respectively; P < .01 for each comparison). Beyond 2 years, the 2 revascularization strategies provided generally similar patient-reported outcomes.For patients with diabetes and multivessel CAD, CABG surgery provided slightly better intermediate-term health status and quality of life than PCI using drug-eluting stents. The magnitude of benefit was small, without consistent differences beyond 2 years, in part due to the higher rate of repeat revascularization with PCI.clinicaltrials.gov Identifier: NCT00086450.
Predictors of Response to Cardiac Resynchronization Therapy in the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT)
Authors: Ilan Goldenberg, Arthur J. Moss, W. Jackson Hall, Elyse Foster, Jeffrey J. Goldberger, Peter Santucci, Timothy Shinn, Scott Solomon, Jonathan S. Steinberg, David Wilber, Alon Barsheshet, Scott McNitt, Wojciech Zareba, Helmut Klein
Journal: Circulation (2011)

Background— We hypothesized that combined assessment of factors that are associated with favorable reverse remodeling after cardiac resynchronization-defibrillator therapy (CRT-D) can be used to predict clinical response to the device. Methods and Results— The study population comprised 1761 patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT). Best-subset regression analysis was performed to identify factors associated with echocardiographic response (defined as percent reduction in left ventricular end-diastolic volume 1 year after CRT-D implantation) and to create a response score. Cox proportional hazards regression analysis was used to evaluate the CRT-D versus defibrillator-only reduction in the risk of heart failure or death by the response score. Seven factors were identified as associated with echocardiographic response to CRT-D and made up the response score (female sex, nonischemic origin, left bundle-branch block, QRS ≥150 milliseconds, prior hospitalization for heart failure, left ventricular end-diastolic volume ≥125 mL/m 2 , and left atrial volume &lt;40 mL/m 2 ). Multivariate analysis showed a 13% ( P &lt;0.001) increase in the clinical benefit of CRT-D per 1-point increment in the response score (range, 0–14) and a significant direct correlation between risk reduction associated with CRT-D and response score quartiles: Patients in the first quartile did not derive a significant reduction in the risk of heart failure or death with CRT-D (hazard ratio=0.87; P =0.52); patients in the second and third quartiles derived 33% ( P =0.04) and 36% ( P =0.03) risk reductions, respectively; and patients in the upper quartile experienced a 69% ( P &lt;0.001) risk reduction ( P for trend=0.005). Conclusion— Combined assessment of factors associated with reverse remodeling can be used for improved selection of patients for cardiac resynchronization therapy. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00180271.
Autophagy deficiency leads to protection from obesity and insulin resistance by inducing Fgf21 as a mitokine
Authors: Kook Hwan Kim, Yeon Taek Jeong, Hyunhee Oh, Seong Hun Kim, Jae Min Cho, Yo-Na Kim, Su Sung Kim, Do Hoon Kim, Kyu Yeon Hur, Hyoung Kyu Kim, TaeHee Ko, Jin Han, Hong Lim Kim, Jin Kim, Sung Hoon Back, Masaaki Komatsu, Hsiuchen Chen, David C Chan, Morichika Konishi, Nobuyuki Itoh, Cheol Soo Choi, Myung-Shik Lee
Journal: Nature Medicine (2012)
Malaria Prophylaxis Among American Travelers
Authors: Donald Catino
Journal: JAMA (1982)

<h3>To the Editor.—</h3> Between 1979 and 1980, there was a 32% increase in civilian imported malaria in the United States.<sup>1</sup>Our previous studies showed that only 20% of travelers were properly warned about malaria risks and that only 15% took prophylaxis.<sup>2,3</sup>The responsibility for the dissemination of such health information has not been defined, and the weak links in the chain of information have not been pinpointed. For this reason, we decided to repeat our survey in 1981 on a different group of high-risk travelers to determine whether they were any better informed or protected. The eastern portion of Peru is a part of the Amazon jungle and is endemic for chloroquine-sensitive malaria year-round; therefore, malaria prophylaxis is indicated. In March 1981, 49 persons traveling to Iquitos on the Amazon river in eastern Peru were interviewed. The 49 travelers interviewed had a median age of 42 years; there
Preferential utilization of specific immunoglobulin heavy chain diversity and joining segments in adult human peripheral blood B lymphocytes.
Authors: M Yamada, R Wasserman, B A Reichard, S Shane, A J Caton, G Rovera
Journal: The Journal of Experimental Medicine (1991)

We have examined at the molecular level the CDR3 and adjacent regions in peripheral blood B lymphocytes of normal individuals. A total of 111 sequences (12-28 sequences from six individuals) were obtained after cloning of the polymerase chain reaction-amplified segments into plasmids or phage. The average length of the VDJ joining was 109 nucleotides, with a range from 79 to 151. Approximately 75% of the sequences were in frame when translated into amino acids. Among the JH segments, JH4 was found most frequently (in 52.5% of the sequences), and JH1 and JH2 segments the least frequently (approximately 1% of the clones). A polymorphic JH6 gene with a one-codon deletion accompanied by a base change was present in two of six patients. Preferential breakpoints were found for JH2, JH3, JH4, and JH5, although the breakpoints of JH6 were distributed more heterogenously. In approximately 90% of the cases, significant homology of the D regions with published D sequences was found. Preferential usage of a particular coding frame was observed in in-frame sequences utilizing DA, D21/9, and DM1 segments. However, in general, all coding frames of germline D genes were used to generate CDR3s. Eight sequences that have a DN1-like D sequence with two base changes at the same positions were identified, suggesting the likely existence of a new germ line D gene belonging to the DN families. Using probes specific for a particular CDR3, the frequency of a specific B cell clone in the peripheral blood of normal individuals was estimated to be at most as high as 1/20,000.
Antibodies to acetaldehyde-protein adducts: Epiphenomenon or pathogenic mechanism?
Authors: Richard B. Jennett, Dean J. Tuma, Michael F. Sorrell
Journal: Hepatology (1987)

Immunization of mice with acetaldehyde conjugated to human plasma proteins resulted in the production of polyclonal antibodies that reacted with erythrocyte protein-acetaldehyde conjugates, but not with control erythrocyte proteins. Such antibodies recognized erythrocyte protein-acetaldehyde conjugates prepared with 20-100 μM acetaldehyde, concentrations that exist in the blood of alcoholics. The antibodies also recognized acetaldehyde condensation products with synthetic poly-(L-lysine). Immunization with keyhole limpet hemocyanin-acetaldehyde conjugates resulted in antibodies against both plasma protein-acetaldehyde and erythrocyte protein-acetaldehyde conjugates, which did not cross-react with the respective unmodified carrier proteins. Immunization with human erythrocyte protein-acetaldehyde condensates led to the production of antibodies against both the protein moiety as well as the condensate. Monoclonal antibodies with affinities 50 times greater for the condensate than for the carrier protein were produced by hybridization of spleen cells from the immunized mice. Chronic alcohol administration to mice for 45-50 days led to the generation of antibodies that reacted against protein-acetaldehyde conjugates, suggesting that such adducts are formed in vivo and can act as neoantigens. Antibodies against acetaldehyde adducts should be of value in the identification of alcohol consumption and in the study of the biology of the adducts in relation to organ pathology.
Magnesium Sulfate for Preeclampsia
Authors: Michael F. Greene
Journal: New England Journal of Medicine (2003)

For centuries, practitioners of midwifery have feared the occurrence of convulsions during pregnancy because they carried a particularly grave prognosis for both mother and fetus. In 17th-century Paris, eclampsia was associated with a 50 percent maternal mortality rate. The seizures of eclampsia were distinguished from other types of seizures largely by the absence of a history of seizures before pregnancy. In 1776, Thomas Young of Edinburgh, Scotland, said, "If the woman has had these fits before, there is less danger to be apprehended from them." John Burns in Glasgow, Scotland, wrote in 1832 that "there is nothing either more difficult, . . .
Lymphomas of mucosal‐associated lymphoid tissue in common variable immunodeficiency
Authors: C. Cunningham‐Rundles, Dennis L. Cooper, Thomas P. Duffy, James Strauchen
Journal: American Journal of Hematology (2002)

Abstract Common variable immunodeficiency (CVID) is a primary immunodeficiency disease characterized by low serum immunoglobulins IgG, IgA, and usually IgM. The central immune deficiency is impaired secretion of immunoglobulins and lack of antibody production; however, T cell dysfunction and a variety of inflammatory complications suggest global immune dysregulation. A number of reports have documented the association of primary immunodeficiency diseases with the development of non‐Hodgkin's lymphoma (NHL). In CVID, the risk has been estimated to lie between 1.4% and 7%. As for NHL arising in other immunodeficiency states, the lymphomas in CVID are extranodal and are usually B cell in type. Of 22 B cell lymphomas that have appeared over a period of 25 years in a cohort of subjects with CVID, five lymphomas, appearing in more recently studied subjects, that arose in mucosal sites would be classified as mucosa‐associated lymphoid tissue (MALT) lymphomas. MALT lymphomas are low‐grade B cell lymphomas that result from a proliferation of neoplastic marginal‐zone related cells of lymphoid tissue and tend to occur in organs that have acquired lymphoid tissue due to long‐term infectious or autoimmune stimulation. Lymphomas of this kind have not been described in patients with congenital immunodeficiency, although chronic mucosal antigen stimulation is an integral part of these immune deficiency states. Am. J. Hematol. 69:171–178, 2002. © 2002 Wiley‐Liss, Inc.
Hospital Outcome of Moderate to Severe Pericardial Effusion Complicating ST-Elevation Acute Myocardial Infarction
Authors: Jaume Figueras, José A. Barrabés, Vicens Serra, Josefa Cortadellas, Rosa-Maria Lidón, Alvaro Carrizo, David Garcia-Dorado
Journal: Circulation (2010)

Hospital prognosis of moderate to severe pericardial effusion (MPE; ≥10 mm) in ST-elevation myocardial infarction is largely unknown.Data from 446 ST-elevation myocardial infarction patients, 228 with MPE-88 with cardiac tamponade (CT) and electromechanical dissociation (EMD), 44 with CT without EMD (w/oEMD), and 96 without initial CT-and 218 with small PE (5 to 9 mm), were compared. Patients with MPE without initial CT were also compared with 96 patients without PE. CT patients showed larger PE (P<0.001) than those without initial CT; 85% of those with CT+EMD and 86% with CTw/oEMD were treated with pericardiocentesis and 10% and 21% were treated with a surgical repair, respectively. Among MPE patients, 30-day mortality was 43% and was higher in those with CT+EMD (operated, 89%; and nonoperated, 85%) than in those with CTw/oEMD (22% and 11%, respectively; P<0.001) and those without initial CT (17%; P<0.001). It was also higher than in patients with small PE (10%; P<0.001) or those without PE (6%; P=0.001). Death was attributable to cardiac rupture in 83% of patients with CT+EMD, 7% with CTw/oEMD, and 8% with MPE without initial CT and occurred late (≥7 days) in 14%, 67%, and 100%, respectively.MPE carries an increased mortality that is highest in patients with CT+EMD. In those with CTw/oEMD, however, mortality is considerably low after pericardiocentesis, and subsequent management may be individualized because a conservative approach is often successful. Importantly, MPE patients without initial CT are not free from late rupture and deserve further investigation.
Water movement across rat bile duct units is transcellular and channel-mediated
Authors: Emanuela Cova, Ai-Yu Gong, Raul A. Marinelli, Nicholas F. LaRusso
Journal: Hepatology (2001)

In recent studies using freshly isolated rat cholangiocytes, we established that water crosses the cholangiocyte membrane by a channel-mediated mechanism involving aquaporins, a family of water-channel proteins. Our goal was to address the importance of channel-mediated water transport in ductal bile formation by employing a physiologic experimental model, the enclosed, polarized rat intrahepatic bile duct unit (IBDU). Expansion and reduction of luminal areas as a reflection of water movement into and out of IBDUs prepared from livers of normal rats were measured by quantitative computer-assisted image analysis. When enclosed IBDUs were exposed to inward or outward osmotic gradients, their luminal area rapidly increased (approximately 25%) or decreased (approximately 20%) reflecting net water secretion or absorption, respectively. These effects were specifically inhibited by 2 water channel blockers, DMSO and HgCl2. In both instances, beta-mercaptoethanol reversed the inhibitory effects. In the absence of an osmotic gradient, choleretic agents (secretin and forskolin) and a cholestatic hormone (somatostatin) induced a significant increase or decrease of IBDU luminal area by 21% and 22%, respectively. These effects were also inhibited by DMSO and reversed by beta-mercaptoethanol. Under our experimental conditions, DMSO did not interfere with either forskolin-induced cAMP synthesis or the generation of osmotic driving forces via the apical chloride-bicarbonate exchanger. Protamine, an inhibitor of the paracellular pathway, had no effect on hypotonic or forskolin-induced water secretion in IBDUs. These results in a physiologically relevant model of ductal bile formation provide additional support for the concept that osmotically driven and agonist-stimulated water movement into (secretion) and out of (absorption) the biliary ductal lumen is transcellular and water channel-mediated.
Breakthroughs and wars
Authors: G. Dunea
Journal: BMJ (1997)

It is difficult to argue with the proposition that the greatest advances affecting medicine in the past two decades have been in computer technology and molecular biology. Where once we retyped manuscripts endlessly and communicated by slow mail we now fax, email, scan, select, save, and surf on the Web. In molecular medicine there is likewise no end to new techniques, promises of new treatments, and newly discovered genes for a variety of diseases.

Success on other fronts has been more modest, especially in the war against cancer, declared by President Nixon with great fanfare 25 years …
The Protective Mechanism of Antioxidants in Cadmium-Induced Ototoxicity <i>in Vitro</i> and <i>in Vivo</i>
Authors: Su-Jin Kim, Hyun-Ja Jeong, Noh-Yil Myung, Min-chol Kim, Jeong-Han Lee, Hong-seob So, Rae-Kil Park, Hyung-Min Kim, Jae-Young Um, Seung-Heon Hong
Journal: Environmental Health Perspectives (2008)

Several heavy metals have been shown to have toxic effects on the peripheral and central auditory system. Cadmium (Cd2+) is an environmental contaminant showing a variety of adverse effects. Given the current rate of release into the environment, the amount of Cd2+ present in the human body and the incidence of Cd2+-related diseases are expected to increase.The overall aim of this study was to gain further insights into the mechanism of Cd2+-induced ototoxicity.Cell viability, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), cytochrome c (cyt c), phosphorylated extracellular signal-regulated protein kinase (p-ERK), caspases, morphologic change, and functional changes in HEI-OC1 cells, rat cochlear explants, and mouse cochlea after Cd2+ exposure were measured by flow cytometry, immunohistochemical staining, Western blot analysis, and auditory brainstem response (ABR) recording. Mechanisms underlying Cd2+ototoxicity were studied using inhibitors of different signaling pathways, caspases, and antioxidants.Cd2+ exposure caused cell death, ROS generation, MMP loss, cyt c release, activation of caspases, ERK activation, apoptosis, and finally auditory threshold shift. Cd2+ toxicity interfered with inhibitors of cellular signaling pathways, such as ERK and c-jun N-terminal kinase, and with caspase inhibitors, especially inhibitors of caspase-9 and caspase-3. The antioxidants N-acetyl-l-cysteine and ebselen showed a significant protective effect on the Cd2+ toxicity.Cd2+ is ototoxic with a complex underlying mechanism. However, ROS generation may be the cause of the toxicity, and application of antioxidants can prevent the toxic effect.
Tetanus and inhalation of a foreign body.
Authors: W G Notcutt, D Ashley
Journal: BMJ (1977)

but in both the bone age is often advanced and in Beckwith's syndrome the large size is associated with exomphalos or umbilical hernia, hypoglycaemia, and pronounced visceromegaly.This patient did not have these clinical features but appeared to have a new kind of diencephalic syndrome.I thank Drs A Carmichael, I Fletcher, and J Winter for clinical help and Drs P Rayner and N Barnes for advice.Thyrotrophin and growth hormone levels were measured in the
Ankylosing Spondylitis and Chronic Inflammatory Diseases of the Intestines
Authors: J. A. McBride, M. J. King, A. G. Baikie, G. P. Crean, W. Sircus
Journal: BMJ (1963)

ANKYLOSING SPONDYLITISCBARnH abnormality of connective-tissue metabolism or a dis- ordered immune mechanism involving connective tissue may underlie both conditions.The factors which determine whether a predisposed individual develops ankylosing spondylitis, Crohn's disease, or ulcerative colitis, or these diseases in association, are quite unknown; as are the factors which determine the order in which the associated diseases may appear. SummaryThe association of ankylosing spondylitis with ulcerative colitis and Crohn's disease is described.Of 870 patients with ankylosing spondylitis, 16 were found to have ulcera- tive colitis and four to have Crohn's disease.Four cases of ankylosing spondylitis were found among 170 patients with ulcerative colitis or Crohn's disease.The limitations of the methods of study make it likely that the real coinci- dence of ankylosing spondylitis with chronic inflammatory intestinal disease is even higher.Attention is drawn to the relatively higher incidence of intestinal disease in females with ankylosing spondylitis.The occurrence of ankylosing spondylitis and intestinal disease in different members of the same family is described and discussed.
Childhood allergic rhinitis predicts asthma incidence and persistence to middle age: A longitudinal study
Authors: John A. Burgess, E. Haydn Walters, Graham B. Byrnes, Melanie C. Matheson, Mark A. Jenkins, Cathryn L. Wharton, David P. Johns, Michael J. Abramson, John L. Hopper, Shyamali C. Dharmage
Journal: Journal of Allergy and Clinical Immunology (2007)
Identification of a Small Molecule Inhibitor of the Human DNA Repair Enzyme Polynucleotide Kinase/Phosphatase
Authors: Gary K. Freschauf, Feridoun Karimi-Busheri, Agnieszka Ulaczyk-Lesanko, Todd R. Mereniuk, Ashley Ahrens, Jonathan M. Koshy, Aghdass Rasouli-Nia, Phuwadet Pasarj, Charles F.B. Holmes, Frauke Rininsland, Dennis G. Hall, Michael Weinfeld
Journal: Cancer Research (2009)

Abstract Human polynucleotide kinase/phosphatase (hPNKP) is a 57.1-kDa enzyme that phosphorylates DNA 5′-termini and dephosphorylates DNA 3′-termini. hPNKP is involved in both single- and double-strand break repair, and cells depleted of hPNKP show a marked sensitivity to ionizing radiation. Therefore, small molecule inhibitors of hPNKP should potentially increase the sensitivity of human tumors to γ-radiation. To identify small molecule inhibitors of hPNKP, we modified a novel fluorescence-based assay to measure the phosphatase activity of the protein, and screened a diverse library of over 200 polysubstituted piperidines. We identified five compounds that significantly inhibited hPNKP phosphatase activity. Further analysis revealed that one of these compounds, 2-(1-hydroxyundecyl)-1-(4-nitrophenylamino)-6-phenyl-6,7a-dihydro-1H-pyrrolo[3,4-b]pyridine-5,7(2H,4aH)-dione (A12B4C3), was the most effective, with an IC50 of 0.06 μmol/L. When tested for its specificity, A12B4C3 displayed no inhibition of two well-known eukaryotic protein phosphatases, calcineurin and protein phosphatase-1, or APTX, another human DNA 3′-phosphatase, and only limited inhibition of the related PNKP from Schizosaccharomyces pombe. At a nontoxic dose (1 μmol/L), A12B4C3 enhanced the radiosensitivity of human A549 lung carcinoma and MDA-MB-231 breast adenocarcinoma cells by a factor of two, which was almost identical to the increased sensitivity resulting from shRNA-mediated depletion of hPNKP. Importantly, A12B4C3 failed to increase the radiosensitivity of the hPNKP-depleted cells, implicating hPNKP as the principal cellular target of A12B4C3 responsible for increasing the response to radiation. A12B4C3 is thus a useful reagent for probing hPNKP cellular function and will serve as the lead compound for further development of PNKP-targeting drugs. [Cancer Res 2009;69(19):7739–46]