tbuckley/cabot-search huggingface dataset:
Abstract 12162: Risk of Hemorrhagic Stroke and Gastrointestinal Bleeding After Hospitalization for a Serious Acute Coronary Event
Authors: María E Sáez, Antonio González-Pérez, Saga Johansson, Anders Himmelmann, Luis A García Rodríguez
Journal: Circulation (2014)

Introduction:  Bleeding events have been associated with the use of antiplatelet agents. This study estimated the incidence of bleeding events in patients previously hospitalized for an acute coronary event and determined the risks of bleeding associated with the use of acetylsalicylic acid (ASA) and/or clopidogrel.   Methods:  The Health Improvement Network (a UK primary care database) was used to identify patients aged 50-84 years, hospitalized for a myocardial infarction, coronary artery revascularization or unstable angina during 2000-2007 and who were alive 30 days after the event (N=27,707). Patients were followed up from their start date (30 days after their coronary event or revascularization) until they reached an endpoint (hemorrhagic stroke [HS], upper or lower gastrointestinal bleeding [UGIB/LGIB]), death or end of study [30 June 2011]) or an exclusion criterion. The incidence of bleeding events was calculated. Adjusted relative risks of bleeding associated with the use of ASA and/or clopidogrel were estimated in a nested case-control analysis.   Results:  The incidence rates of HS, UGIB and LGIB were 5.0, 11.9 and 25.5 events per 10,000 person years, respectively. HS was strongly associated with a history of HS (odds ratio [OR]: 15.82; 95% confidence interval [CI]: 3.59-69.75]). UGIB was associated with a history of complicated peptic ulcer disease (OR: 3.40; 95% CI: 1.65-6.98). Overall, current use of ASA was associated with a significantly reduced risk of HS compared with non-use of ASA (OR: 0.47; 95% CI: 0.26-0.85) but was not shown to affect the risk of UGIB and LGIB significantly. Current use of clopidogrel significantly increased the risk of UGIB (OR: 1.84; 95% CI: 1.18-2.88) and LGIB (OR: 1.77; 95% CI: 1.31-2.40) but not HS compared with non-use of clopidogrel. Use of dual antiplatelet therapy (ASA and clopidogrel) was associated with a non-significant increase in the risk of UGIB (OR: 1.99; 95% CI: 0.98-4.01) and LGIB (OR: 1.55; 95% CI: 0.95-2.52).   Conclusions:  Use of clopidogrel significantly increased the risk of UGIB and LGIB in patients previously hospitalized for an acute coronary event. Use of ASA was not shown to increase the risk of HS, UGIB or LGIB significantly.
Methodological Issues in Trials of Acupuncture
Authors: Erica Frank
Journal: JAMA (2001)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Safety and tolerability of immunotherapy using various updosing schedules of a new SCIT product with an optimised allergen/aluminium hydroxide ratio
Authors: K. Jung
Journal: Allergy (2011)

Allergen extracts for subcutaneous specific immunotherapy (SCIT) may be adsorbed to aluminium hydroxide for adjuvant effect and to delay allergen discharge. A product with an optimised allergen-to-aluminium hydroxide ratio enables a lower allergen dose and shorter introduction phase. The new therapeutic product Avanz (ALK, Denmark) has an optimised allergen-to-aluminium hydroxide ratio. A multicentre, randomised, phase II clinical trial evaluated the immunological effects and tolerability of two different five-step updosing schedules for Avanz in 400 patients with grass pollen-induced rhinoconjunctivitis with or without asthma, randomised into two groups. Group 1 were administered weekly, and group 2 were administered every 3 to 4 days. After updosing, patients received two maintenance injections after 2 and 4 weeks. In the updosing phase, local and systemic reactions were significantly more frequent in group 2 than group 1. In the maintenance phase, adverse reactions were less common in both groups. No generalised reactions with hypotension or fatal reactions occurred. An increase in allergen-specific immunoglobulin G(4) (IgG(4) ) and IgE antibodies was established one week after the last injection. Avanz is a SCIT product with an optimised allergen-to-aluminium hydroxide ratio that enables a shorter updosing phase. We established an improved safety profile with weekly updosing compared with 3-4-day intervals. Clinical trials are needed to confirm clinical efficacy.
Myocardial Insulin-Like Growth Factor-I Gene Expression During Recovery From Heart Failure After Combined Left Ventricular Assist Device and Clenbuterol Therapy
Authors: Paul J. R. Barton, Leanne E. Felkin, Emma J. Birks, Martin E. Cullen, Nicholas R. Banner, Suzanne Grindle, Jennifer L. Hall, Leslie W. Miller, Magdi H. Yacoub
Journal: Circulation (2005)

Patients who undergo mechanical support with a left ventricular assist device (LVAD) exhibit reverse remodeling and in some cases recover from heart failure. We have developed a combination therapy using LVAD support combined with pharmacological therapy to maximize reverse remodeling, followed by the beta2 adrenergic agonist clenbuterol. We recently found that clenbuterol induces insulin-like growth factor I (IGF-I) in cardiac myocytes in vitro. The purpose of this study is to examine IGF-I expression in recovery patients after combination therapy.Myocardial mRNA levels were determined by real-time quantitative polymerase chain reaction in 12 recovery patients (at LVAD implantation, explantation, and 1 year after explantation). IGF-I mRNA was elevated at the time of LVAD explantation relative to donors, with 2 groups distinguishable: Those with low IGF-I mRNA at implantation who showed significant increase during recovery and those with high IGF-I mRNA at implantation who remained high. Levels returned to normal by 1 year after explantation. Microarray analysis of implantation and explantation samples of recovery patients further revealed elevated IGF-II and IGF binding proteins IGFBP4 and IGFBP6. IGF-I levels correlated with stromal cell-derived factor mRNA measured both in LVAD patients and in a wider cohort of heart failure patients.The data suggest involvement of elevated myocardial IGF-I mRNA in recovery. IGF-I may act to limit atrophy and apoptosis during reverse remodeling and to promote repair and regeneration in concert with stromal cell derived factor.
Abstract 13426: Percent Time With a Supratherapeutic Inr in Atrial Fibrillation Patients Using an Antiplatelet Agent is Associated With Long-term Risk of Dementia
Authors: Thomas J Bunch, Heidi T May, Tami L Bair, Victoria Jacobs, Brian G Crandall, J P Weiss, Jeffrey S Osborn, Charles Mallendar, John D Day, Jeffrey L Anderson, Jeffrey L Olson, Katie Johanning, Yenh Long Long, Scott M Stevens, Scott C Woller
Journal: Circulation (2014)

Background: Patients with atrial fibrillation (AF) are at higher risk of developing all forms of dementia. The mechanisms behind the association of AF and dementia are unknown. One possibility is that exposure to chronic microbleeds results in repetitive cerebral injury that is manifest by cognitive decline. We hypothesize that AF patients receiving antiplatelet therapy will display higher rates of dementia if coupled with a higher percentage of time exposed to over-anticoagulation. Methods: Chronically anticoagulated patients receiving warfarin (target INR 2-3) for AF and managed by the Intermountain Healthcare Clinical Pharmacist Anticoagulation Service (CPAS) with no history of dementia or stroke/TIA and receiving antiplatelet therapy were included. The primary outcome was the presence of dementia defined by neurology determined ICD-9 codes. Percent time with an INR above 3.0 was determined. Multivariable Cox hazard regression was utilized to determine dementia incidence by percentage categories of supratherapeutic INR. Results: A total of 1031 patients were studied. Of these, the categories of the mean percent time with an INR &gt;3.0 were 25% (n=240). Patients with a higher percent of time with supratherapeutic INRs were more likely to have valvular heart disease, renal failure (Cr&gt;2.0), a higher percent of CHADS 3-6 scores, and a prior bleed. Dementia was diagnosed in 2.7% of patients with supratherapeutic INR levels 25%, p=0.05. Those with a supratherapeutic INR &gt;25% of the time were at an increased dementia risk throughout follow-up. After multivariate adjustment, those with levels &gt;25% had significantly higher rates of dementia compared to those with levels &lt;10% (HR 2.40, p=0.04). Discussion: In AF patients receiving antiplatelet and anticoagulant therapies, the percent of time exposed to over anticoagulation increases risk of dementia. These data support the possibility of chronic cerebral injury from microbleeds as a mechanism that underlies the association of AF and dementia.
Abstract 18326: Heart Rate-independent Qt Variability in Congenital Long Qt Syndrome
Authors: Srikanth Seethala, Prabhpreet Singh, Vladimir Shusterman, Kristina H Haugaa, Jan Nemec
Journal: Circulation (2014)

Introduction: Heart rate is a major factor affecting QT interval duration. In normal ambulatory subjects, modeling QT interval as a linear function of preceding RR intervals weighted with an exponential function with 60 s time-constant reproduces gradual QT accommodation and provides a better fit than any function of instantaneous RR interval. QT accommodation in LQTS is not well understood. Methods: Digitized Holter recordings (24 hrs) from 63 genotyped LQTS patients (47 LQT1, 13 LQT2, 2 JLN, 1 unknown) were analyzed. LQTS-related symptoms (syncope, ventricular tachycardia, cardiac arrest, or appropriate device shock) were present in 21 patients. RR and QT intervals were automatically determined with custom software; all data were manually edited. QT was modeled as a linear function of preceding RR interval, or of the RR intervals in preceding 180 s weighted with a 30 s or 60 s time-constant exponential function. QTc was determined for each patient from the 60 s time-constant model. Results: The 60 s tim...
ABC of oxygen: Diving and oxygen
Authors: P. Wilmshurst
Journal: BMJ (1998)

All organisms require oxygen for metabolism, but the oxygen in water is unavailable to mammals. Divers (and diving mammals such as whales and seals) are entirely dependent on the oxygen carried in the air in their lungs or their gas supply. Divers also have a paradoxical problem with oxygen. At higher partial pressures oxygen causes acute toxicity leading to convulsions. To understand the diver's narrow knife edge between fatal hypoxia and fatal hyperoxia we need to recall some of the physical properties of gases.



A dive to 30 m for 20 minutes puts the scuba diver at risk of nitrogen narcosis and decompression illness. The elephant seal can dive to 1 km for 1 hour without risk of either condition



At sea level atmospheric pressure is 1 bar absolute (1 standard atmosphere =101 kPa=1.013 bars). The weight of the atmosphere exerts a pressure which will support a column of water 10 m high; 10 m under water the pressure on a diver is 200 kPa. The volume of gas in an early diving bell full of air at sea level is halved at 10 m according to Boyle's law; at 20 m pressure is 300 kPa absolute and the gas is compressed into one third the volume.

The pressure on a diver increases by 100 kPa for every 10 m he or she descends

Dry air is composed of roughly 21% oxygen, 78% nitrogen, and 1% other gases. According to Dalton's law the partial pressure of oxygen at any depth will be 21% of the total pressure exerted by the air and the partial pressure of nitrogen will be 78% of total pressure.



Effect of depth on partial pressures of nitrogen and oxygen



Gases dissolve in the liquid with which they are in contact. Nitrogen is fat soluble and at …
Deregulation of PERK in the autoimmune disease pemphigus vulgaris occurs via IgG-independent mechanisms
Authors: A. Lanza, M. Lanza, R. Santoro, V. Soro, S.S. Prime, N. Cirillo
Journal: British Journal of Dermatology (2010)

Serum and IgG isolated from patients with the autoimmune blistering disease pemphigus vulgaris (PV) trigger complex intracellular pathways in keratinocytes, including alterations of the cell cycle and metabolism, which ultimately lead to cell-cell detachment (acantholysis). We have shown previously that one of the earliest pathogenic events in PV is the activation of protein kinases, including the PKR-like endoplasmic reticulum (ER) kinase PERK.In the present study we investigated in more detail the role of PERK in the pathogenesis of PV.PERK levels were assessed by Western blotting and in-cell enzyme-linked immunosorbent assay, and PERK expression was silenced by siRNA technology. The effects of PV sera/IgG on keratinocyte cultures were investigated by flow cytometry, MTT and adhesion assays.We show that PERK is activated in keratinocytes exposed to PV serum, as demonstrated by an increase in phosphorylated PERK levels and phosphorylation of eIF2α. Decreased expression of PERK by siRNA reduced the effects of PV serum on the cell cycle and keratinocyte viability, two key events in PV pathophysiology. As impairment of metabolic activity in PV is partially due to non-IgG serum factors, we then investigated the activation of PERK in keratinocytes incubated with whole PV serum, purified PV IgG and IgG-depleted PV serum. The data demonstrated that PV sera depleted of IgG, but not PV IgG, triggered PERK phosphorylation and this correlated with a marked reduction of metabolic activity in keratinocytes exposed to IgG-free serum. Knockdown of PERK by siRNA abrogated the changes in the cell cycle and apoptosis induced by IgG-depleted PV serum. Finally, the reduction of metabolic activity observed in keratinocytes exposed to IgG-depleted PV serum was almost absent in PERK-deficient cells.Taken together, the results demonstrate that activation of PERK participates in the reduction of metabolic activity and cell viability seen in PV and that this phenomenon depends on non-IgG factors. PERK activation may represent a novel signalling mechanism linking ER stress and acantholysis in PV.
ABC of allergies: Allergy in general practice
Authors: S. Cross, S. Buck, J. Hubbard
Journal: BMJ (1998)

<h3>Abstract</h3> CRISPR-associated transposons (CASTs) exist in different groups of bacteria, including certain cyanobacteria, which contain type V-K CAST systems. These systems contain genes encoding Tn7-like transposase subunits and a divergent number of cargo genes. How the activity of these systems is controlled <i>in situ</i> has remained largely unknown but possibly regulatory genes within these elements are prime candidates. Deletion of the respective regulator gene <i>alr3614</i> in the cyanobacterium <i>Anabaena (Nostoc)</i> sp. PCC 7120 led to the overexpression of CRISPR tracrRNA, precursor crRNAs and mRNAs encoding the Cas12k effector protein (<i>all3613</i>) and Tn7-like transposase subunits. Upon complementation, these same genes were repressed again. DNase I footprinting and electrophoretic mobility shift assays verified the direct interaction between Alr3614 and the promoter of <i>cas12k</i> and identified a widely conserved binding motif. Structural analysis of Alr3614 at 1.5 Å resolution revealed that it belongs to the MerR-type transcription factor family but with distinct dimerization and effector-binding domains. This protein assembles into a homodimer interacting with DNA through its N-terminal winged helix-turn-helix (wHTH) domain and binds an effector molecule through a C-terminal α-helical domain lacking a conserved cysteine. These results identify Alr3614 as a transcriptional repressor of the CAST system in <i>Anabaena</i> sp. PCC 7120. We suggest naming this family of repressors CvkR for Cas V-K repressors, which are at the core of a widely conserved regulatory mechanism that controls type V-K CAST systems.
Visuo-cognitive disambiguation of occluded shapes
Authors: Rob van Lier
Journal: Behavioral and Brain Sciences (2001)

Pessoa et al. (1998a) underexposed the broad and rich variety of stimuli in the amodal completion domain. The disambiguation of occluded shapes depends on very specific figural properties. Elaborations on such disambiguations of rich and complex stimuli, tied up with a visuo-cognitive origin of amodal completion, further position Pessoa et al.'s considerations on neural filling-in and the personal-subpersonal distinction.
846. In Vivo and In Vitro Cell Targeting with Library-Selected Protease-Activatable Replication-Competent Retroviruses
Authors: Klaus Cichutek, Richard M. Schneider, Astrid Schwantes, Yuansheng Sun, Christian J. Buchholz, Irene Hartl, S.J. Russell
Journal: Molecular Therapy (2005)

Top of pageAbstract
Viruses conditionally replicating in cancer cells form an attractive novel class of anti-tumoural agents. To engineer such viruses we couple infectivity with proteolytic activity of the target cell by modifying the envelope (Env) protein of murine leukemia virus (MLV) with blocking domains that prevent cell entry unless they are cleaved off by tumor-associated proteases like the matrix metalloproteases (MMP).

Here we show that MLV variants selectively spreading through MMP-positive cells can be evolved from virus libraries, in which a standard MMP-2 substrate peptide connecting the blocking domain CD40L with the Env protein was diversified. Passaging the virus library on a human fibrosarcoma cell line resulted in the selection of about 10 virus clones of which the two most frequent ones were reconstituted as molecular virus clones and characterized. While the origin of the activating protease for the AKGLYK linker peptide encompassing virus remained elusive, the PSGLYQ linker peptide encompassing virus was cleaved by MMP-2 in vitro and could be inhibited by a broad-range MMP inhibitor. Yet, both linker peptides conferred a remarkable advantage in the spreading through MMP-positive tumor cell lines.

The in vivo spreading behavior of these viruses was monitored in SCID mice transplanted with HT1080 tumor cells. In a first experimental setting we applied mixtures of HT1080 cells infected with the selected viruses or the parental virus, respectively, and uninfected HT1080 cells. The AKGLYK linker peptide encompassing virus was able to spread through the complete tumor mass within two weeks when 0.2% infected cells were injected. The parental virus, in contrast, reverted to wildtype virus within the same period by deletion of the blocking domain, which is most likely enhanced by its low spreading efficiency. Similar results were obtained when the selected viruses were injected intratumorally into established HT1080 tumor tissue. Moreover, initial biodistribution data indicate, that the selected viruses, in contrast to the wildtype virus, show a clear preference for tumour tissue. Thus, the growth advantage of MMP-activatable viruses engineered by directed evolution observed in vitro was confirmed in vivo in mouse tumor models.

The data suggest that retroviral protease substrate libraries form a potent tool for the engineering of viruses conditionally replicating in a given cancer cell type.
Anemia and Neutropenia Caused by Copper Deficiency
Authors: William M. Dunlap, G. Watson James, David M. Hume
Journal: Annals of Internal Medicine (1974)

Two patients with copper deficiency had extensive bowel surgery and received long-term parenteral hyperalimentation. One was neutropenic and anemic, with dimorphous erythrocytes. Marrow examination showed a predominance of early granulocytes and cytoplasmic vacuolization of erythroid and myeloid elements. Erythroid development was megaloblastoid and diminished, with increased sideroblasts. These abnormalities disappeared after oral copper therapy, reappeared when therapy was withdrawn, and again disappeared with intravenous copper therapy. The other patient, not as severely hypocupremic, was neutropenic but not anemic. Her marrow showed normoblastic erythropoiesis with cytoplasmic vacuolization of erythroid and myeloid precursors and a predominance of early granulocytes. The neutropenia was corrected with oral copper. Possible mechanisms causing the anemia and neutropenia are discussed. The duodenum seems to be a site of copper absorption. Copper supplementation is needed for patients receiving long-term parenteral hyperalimentation.
<i>Bird’s Nest and Ferns</i>
Authors: Jeanette M. Smith
Journal: JAMA (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal