tbuckley/cabot-search huggingface dataset:
On Gene Patenting
Authors: Bernadine Healy
Journal: New England Journal of Medicine (1992)

Certain breakthroughs — such as the discoveries of electricity, the atom, and DNA — transcend their time by redefining our world. But the exact nature of the transformation is never known with certainty at the outset. This has been the case with the biologic revolution, and in particular with the ability it has conferred to define, recombine, and express at will the genes of virtually all living organisms. The discovery of a gene traditionally starts from a known protein with a defined biologic function or an inherited characteristic and works back to the cloning of the gene. This process has . . .
Effect of Mitral Commissurotomy on Coexisting Aortic-Valve Lesions
Authors: Joseph F. Uricchio, William Likoff
Journal: New England Journal of Medicine (1957)

THE ideal response to mitral commissurotomy includes a normal blood flow into the left ventricle without the need for an elevated pressure in the left atrium and the return of cardiac output to normal levels even under the stress of exercise.The manner in which the heart responds to the surgical correction of mitral-valve obstruction when aortic-valve lesions are uncorrected has rarely been brought to serious question. The present communication records 3 cases in which mitral commissurotomy was succeeded by unmistakable evidence of an exaggeration in the severity of co-existing aortic-valve defects. The devolutionary patterns of these patients, their clinical . . .
Defective Superoxide Production by Granulocytes from Patients with Chronic Granulomatous Disease
Authors: John T. Curnutte, Dana M. Whitten, Bernard M. Babior
Journal: New England Journal of Medicine (1974)

Superoxide-dependent cytochrome c reduction was used to measure Superoxide production by granulocytes from two patients with chronic granulomatous disease, from children of similar age with infectious and noninfectious diseases unrelated to defects in granulocyte metabolism, and from normal adults. Superoxide production by granulocytes from normal adults was 12.4 ± 4.9 (± S.D.) nmoles per 3 x 106 cells per 30 minutes for resting cells, and 29.7 ± 2.8 nmoles for cells incubated with bacteria (stimulated cells). Values of 10.9 ± 1.5 and 26.1 ± 3.1 nmoles for resting and stimulated granulocytes obtained from children 11 to 18 months of age were not significantly different from corresponding values in adult granulocytes. Superoxide production by cells from two patients with chronic granulomatous disease was greatly reduced (0.3 and 0.2 for resting cells, and 0.9 and 0.9 for stimulated cells), but normal production was obtained with cells from both parents of one of these patients and from the mother of the second patient. (N Engl J Med 290:593–597, 1974)
Abstract 18272: The Increasing Proportion of Acute Myocardial Infarction Represented by the Uninsured: a Growing Financial Burden in the United States
Authors: Bethany Doran, Yu Guo, Jinfeng Xu, Sripal Bangalore
Journal: Circulation (2014)

Introduction: Under the provisions of the Affordable Care Act, insurance coverage will markedly increase with the Congressional Budgetary Office estimating the number of insured to increase by approximately 13 million in 2014 and 25 million in 2016. However, approximately 31 million non-elderly US citizens are expected to remain without health insurance in 2016. Acute myocardial infarction (AMI) remains a source of significant morbidity and mortality, as well as cost to society. No prior studies have examined temporal rates of uninsured among patients presenting with an AMI using a nationally representative database. Hypothesis: We tested the hypothesis that the proportion of uninsured individuals with AMI and cost of uninsured to society will vary by year. Methods: We used the Nationwide Inpatient Sample (NIS), which contains estimates from approximately 8 million hospital visits and information related to number of discharges, aggregate charges, and principal diagnoses of all patients discharged in the US. We calculated the percentage of acute myocardial infarction by insurance status, and the sum of all charges of hospital stays in the US adjusted for inflation. Results: The cost to society due to acute myocardial infarction in the uninsured increased substantially from 1997 to 2012, with total cost in 1997 of $852,596,272 and $3,446,893,954 in 2012 after adjustment for inflation. In addition, although rates of AMI decreased in the general population (from 268.6/100,000 individuals in 1997 to 193.8/100,000 individuals in 2012), the proportion of individuals with AMI who were uninsured increased (from 3.83% in 1997 to 7.37% in 2012). Conclusions: The proportion of those experiencing AMI who are uninsured is rising, as is cost to society. It remains to be seen what the effects of expanding health insurance will have on the rate of AMI as well as proportion of AMI represented by the uninsured.
Is Primary Care Practice Sustainable?
Authors: Edward Volpintesta
Journal: Annals of Internal Medicine (2016)

Letters19 April 2016Is Primary Care Practice Sustainable?Edward Volpintesta, MDEdward Volpintesta, MDFrom Bethel, Connecticut.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L15-0591 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:In her essay on the sustainability of primary care practice, Montecalvo (1) described the very real challenges and difficulties facing primary care physicians today.Her rendering of the nonmedical chores (I prefer to call them “drudgery chores”) of primary care truthfully describes why most primary care physicians are dissatisfied and demoralized and are either burned out or close to it. Her solution is simple—pay primary care physicians for the distracting and time-consuming tasks demanded of them so that they can reduce their patient load and thus make it more manageable. The results will be that the numerous ...Reference1. Montecalvo MA. Is primary care practice sustainable? From the secretary's desk. Ann Intern Med. 2015;163:394-5. [PMID: 26322699]. doi:10.7326/M15-0339 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Bethel, Connecticut.Disclosures: Author has disclosed no conflicts of interest. Form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterest Forms.do?msNum=L16-0591. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoIs Primary Care Practice Sustainable? From the Secretary's Desk Marisa A. Montecalvo Is Primary Care Practice Sustainable? Marisa A. Montecalvo Metrics 19 April 2016Volume 164, Issue 8Page: 570KeywordsConflicts of interestDisclosureForecastingPrimary care physicians ePublished: 19 April 2016 Issue Published: 19 April 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Platelet Function in Recipients of Platelets from Donors Ingesting Aspirin
Authors: Marie J. Stuart, Scott Murphy, Frank A. Oski, Audrey E. Evans, Milton H. Donaldson, Frank H. Gardner
Journal: New England Journal of Medicine (1972)

The effect of fresh platelet transfusions from donors ingesting aspirin was evaluated in a group of thrombocytopenic recipients. Prolonged bleeding times were corrected to normal in recipients of platelets from donors who had taken aspirin 36 hours before donation, but not in those receiving platelets from donors who had taken aspirin within 12 hours of donation. In healthy volunteers, the abnormalities induced by aspirin ingestion on the bleeding time and epinephrine-induced platelet aggregation disappeared by 72 hours after ingestion. Analysis of the data indicates that when approximately 20 per cent of the circulating platelets have not been exposed to aspirin, the hemostatic function of the platelet pool is maintained. Thus, widespread use of aspirin should not present a serious problem in the selection of platelet donors.
BRD4 Connects Enhancer Remodeling to Senescence Immune Surveillance
Authors: Nilgun Tasdemir, Ana Banito, Jae-Seok Roe, Direna Alonso-Curbelo, Matthew Camiolo, Darjus F. Tschaharganeh, Chun-Hao Huang, Ozlem Aksoy, Jessica E. Bolden, Chi-Chao Chen, Myles Fennell, Vishal Thapar, Agustin Chicas, Christopher R. Vakoc, Scott W. Lowe
Journal: Cancer Discovery (2016)

Oncogene-induced senescence is a potent barrier to tumorigenesis that limits cellular expansion following certain oncogenic events. Senescent cells display a repressive chromatin configuration thought to stably silence proliferation-promoting genes while simultaneously activating an unusual form of immune surveillance involving a secretory program referred to as the senescence-associated secretory phenotype (SASP). Here, we demonstrate that senescence also involves a global remodeling of the enhancer landscape with recruitment of the chromatin reader BRD4 to newly activated super-enhancers adjacent to key SASP genes. Transcriptional profiling and functional studies indicate that BRD4 is required for the SASP and downstream paracrine signaling. Consequently, BRD4 inhibition disrupts immune cell-mediated targeting and elimination of premalignant senescent cells in vitro and in vivo Our results identify a critical role for BRD4-bound super-enhancers in senescence immune surveillance and in the proper execution of a tumor-suppressive program.This study reveals how cells undergoing oncogene-induced senescence acquire a distinctive enhancer landscape that includes formation of super-enhancers adjacent to immune-modulatory genes required for paracrine immune activation. This process links BRD4 and super-enhancers to a tumor-suppressive immune surveillance program that can be disrupted by small molecule inhibitors of the bromo and extra terminal domain family of proteins. Cancer Discov; 6(6); 612-29. ©2016 AACR.See related commentary by Vizioli and Adams, p. 576This article is highlighted in the In This Issue feature, p. 561.
Infection with a Babesia-Like Organism in Northern California
Authors: David H. Persing, Barbara L. Herwaldt, Carol Glaser, Robert S. Lane, John W. Thomford, Dane Mathiesen, Peter J. Krause, Douglas F. Phillip, Patricia A. Conrad
Journal: New England Journal of Medicine (1995)

Human babesiosis is a tick-transmitted zoonosis associated with two protozoa of the family Piroplasmorida: Babesia microti (in the United States) and B. divergens (in Europe). Recently, infection with an unusual babesia-like piroplasm (designated WA1) was described in a patient from Washington State. We studied four patients in California who were identified as being infected with a similar protozoal parasite. All four patients had undergone splenectomy, two because of trauma and two for other medical reasons. Two of the patients had complicated courses, and one died.
Evaluation Of Bcma As a Therapeutic Target In Multiple Myeloma Using An Antibody-Drug Conjugate
Authors: Kwee L Yong, Fiona M Germaschewski, Manuel Rodriguez-Justo, Danton Bounds, Lydia Lee, Patrick A Mayes, Katherine Sully, Laura M Seestaller-Wehr, William E Fieles, James R Tunstead, Lee McCahon, Jennifer Paterson, Gaelle Herledan, Jenny L Craigen
Journal: Blood (2013)
P1000 : Prevalence and predictors of transient elastography-defined non-alcoholic fatty liver disease with and without significant liver fibrosis among asymptomatic subjects undergoing a medical health check-up
Authors: None H.W.Lee, S.U. Kim, B.K. Kim, J.Y. Park, D.Y. Kim, S.H. Ahn, K.J. Song, K.-H. Han
Journal: Journal of Hepatology (2015)
The Treatment of Subacute Bacterial Endocarditis with Penicillin in Peanut Oil and Beeswax
Authors: Arthur J. Geiger, Jessamine R. Goerner
Journal: New England Journal of Medicine (1946)

THE apparent curability of subacute bacterial endocarditis with penicillin has been unequivocally established within the last two years.1 The essentials of successful therapeusis consist of treatment with massive daily doses of penicillin for a month or longer, the actual amount given daily depending on the resistance of the infecting organism to penicillin and on the serum penicillin concentrations attained. Supplementation of the penicillin with heparin, as first advocated by Loewe and his associates,2 has proved unnecessary in our experience3 as well as that of others,1 and the dispensability of this costly and usually troublesome adjuvant has gratifyingly simplified the therapeutic . . .
Wallerian Degeneration of the Pyramidal Tract
Authors: J A Dol, E S Louwerse
Journal: New England Journal of Medicine (1994)

Figure 1. Wallerian Degeneration of the Pyramidal Tract. Coronal views of the brain of a 41-year-old man with the acquired immunodeficiency syndrome and right-sided spastic hemiplegia, aphasia, and hemianopia were obtained by magnetic resonance imaging (MRI) eight months after the patient had an intracerebral hemorrhage. The consecutive T2 weighted coronal MRI slices show the old hematoma as an irregular lesion, which is hypointense because of hemosiderin deposition; dilatation of the left lateral ventricle is also evident. In addition, a long band of increased signal intensity traces the anatomical course of the pyramidal tract from the lesion in the internal . . .
OC-072 Does endoscopic duodenal-jejunal exclusion improve non-alcoholic fatty liver disease (nafld) in patients with diabesity?
Authors: P Sen Gupta, RS Bajwa, AA Roy, D Butler, J Ashmore, SI Lee, L Murray, B McGowan, RS Drummond, B Hayee, SA Amiel, RE Ryder
Journal: Gut (2015)

<h3>Introduction</h3> The rapidly increasing global prevalence of NAFLD paralleling the diabesity pandemic demands that new effective therapies are identified. The aim of this study was to investigate the impact of an endoscopic duodenal-jejunal liner (DJL) (endobarrier) with or without glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy on NAFLD. <h3>Method</h3> Adults with type 2 diabetes and obesity despite GLP-1RA therapy (HbA1c ≥7.5%, BMI ≥35 kg/m<sup>2</sup>) were randomised to (1) DJL+GLP1RA (liraglutide 1.2 mg daily) therapy; (2) DJL alone; (3) escalated dose liraglutide (1.8 mg daily). Descriptive statistics were performed (%frequency, mean ±SD, median (IQR)). Changes in weight, HbA1c (paired t-test) and non-invasive composite scores (NAFLD fibrosis score (NFS) and AST to platelet ratio index (APRI) score) were calculated over 3 months within groups (Wilcoxon test). A sub-group underwent magnetic resonance imaging (MRI) to evaluate hepatic fat fraction over 4 months of DJL implant (paired t-test). Hepatic fat fraction (HFF) was calculated by comparing the in-phase/ out-of-phase signal by 3 blinded independent assessors using 3 regions of interest in the liver. <h3>Results</h3> Of 40 patients (age 51.2 ± 10.0 years, 40.0% male, 60.0% Caucasian, baseline BMI 41.4 ± 4.9 kg/m<sup>2</sup>, HbA1c 78 ± 16 mmol/mol (9.3 ± 1.4%)), baseline ALT was 27 (17.8–41.0) IU/l, AST 21 (17.8–41.5) IU/l, ƔGT 35 (22.0–71.5) IU/l and 82.5% had a NFS regarded as at intermediate (65.0%) or high risk (17.5%) for fibrosis. Over 3 months, there was a reduction in weight by 7.3 ± 4.0 kg and in HbA1c by 14.5 ± 15.3 mmol/mol (1.3 ± 1.4%), P &lt; 0.0001. NFS reduced by 0.36 (–0.1 to 1.0), n = 15, P = 0.04; 0.7 (0.2 to 1.6), n = 14, P = 0.003; 0.2 (–0.1 to 0.8), n = 11, P = 0.14 in groups 1, 2 and 3 respectively. APRI fell by 0.08 (0.04 to 0.14), P = 0.02 but was not significantly altered in groups 1 or 3. Of 5 patients undergoing MRI, baseline HFF fell from 16.2 ± 10.4% to 3.5 ± 5.6% at 4 months post-DJL (% reduction of 82.1 ± 24.4%, P = 0.028). <h3>Conclusion</h3> There was a high prevalence of NAFLD in this group of patients with diabesity. Despite previous suboptimal response to GLP1RA therapy there was improvement in NFS and APRI scores in those treated with DJL+GLP1RA and DJL alone, the latter group demonstrating a superior response. Implantation of DJL was effective at reducing HFF. These data suggest duodenal exclusion may be an effective future therapy for NAFLD. <h3>Disclosure of interest</h3> None Declared.
SAT0570 Joint Damage is Not Associated with Smoking Status in Patients with Psoriatic Arthritis
Authors: H. Maldonado-Ficco, D. Gladman
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> The association between smoking and radiographic progression has been established in axial spondyloarthritides and rheumatoid arthritis (RA) but this association has not been established in psoriatic arthritis (PsA). <h3>Objectives</h3> The aim of this study was to determine the effects of cigarette smoking on clinical joint damage in patients with psoriatic arthritis. <h3>Methods</h3> From 1306 PsA patients followed prospectively between 1978 and 2014 as part of an observational cohort, a total of 1107 that started treatment after the first visit was included in the current study. We defined clinical damage as limitation of movement of more than 20% of the range that is not related to a joint effusion, the presence of flexion contractures, fused or flail joints, or evidence of surgery in a particular joint. We used clinical damage as it is assessed at each protocol visit and we have previously demonstrated that clinical joint damage in linked to radiological joint damage. We evaluated the smoking status at the baseline visit up until the first development of clinical joint damage. Smoking status was defined as "non-smoker", "past smoker" and "current smoker". Time to development of joint damage was assessed using a Cox Regression Analysis to determine the factors predictive of clinical damage, including age, sex, dactylitis and smoking status, joint counts, treatment and HLA B*27 status. <h3>Results</h3> Among the 1107 patients, 55.6% were males, with a mean age of 46 years, duration of psoriasis 17.4 years and the duration of PsA 8.4 years at baseline. 55.6% of the patients were non-smokers, 24.4% were past-smokers and 12.4% were current smokers. 7.9% of the patient had clinical joint damage and 26% had dactylitis at baseline. Males, HLA-B*27 positivity, higher age at diagnosis of PsA, clinical damage at baseline, dactylitis and swollen joints were associated with a higher probability of developing clinically damaged joints whereas current and past-smokers at baseline were associated with a lower probability of developing clinically damaged joints compared to nonsmokers. <h3>Conclusions</h3> Unlike what occurs in RA and ankylosing spondylitis, the clinical damage in PsA was not associated with smoking status but was associated with disease-specific features. <h3>Disclosure of Interest</h3> None declared
T5 MicroRNA-140–5p Regulates Disease Phenotype in Experimental Pulmonary Arterial Hypertension via SMURF1
Authors: AMK Rothman, ND Arnold, JA Pickworth, J Iremonger, L Ciuclan, R Allen, S Guth-Gundel, M Southwood, NW Morrell, SE Francis, DJ Rowlands, A Lawrie
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> Clinical therapies for the treatment of pulmonary arterial hypertension (PAH) target vasoconstriction. However, the proliferative pulmonary vascular remodelling that drives disease persists contributing to significant patient morbidity and mortality. MicroRNA (miR) are short non-coding RNA that mediate post-transcriptional regulation of mRNA targets. We hypothesise that dysregulation of miR leads to de-repression of cellular targets central to disease pathogenesis. We sought to identify dysregulated circulating miR in patients with PAH, determine their phenotypic effect using <i>in vitro</i> and <i>in vivo</i> models and identify key mechanistic regulators that may represent novel therapeutic targets. <h3>Methods</h3> Two patient cohorts were used to identify and validate differential expression of miR in whole blood by microarray and single assay qPCR. Binding site and network analysis was used to identify key miR targets. Effect of miR on identified targets and disease phenotype was determined in pulmonary artery smooth muscle cells (PASMC) and in the monocrotaline (MCT) and Sugen5416 plus Hypoxia (SuHx) models of PAH. <h3>Results</h3> Expression of miR-140–5p was reduced in whole blood samples from patients with PAH and experimental models of PAH. Network and pathway analysis identified key regulators of TGFß and PDGF signalling as miR-140–5p targets. Transfection with miR-140–5p inhibitor resulted in increased proliferation and migration of PASMC and de-repression of key targets. Nebulised delivery of miR-140–5p mimic prevented the development of PAH in the MCT rat model and attenuated progression of established PAH in MCT and SuHx rat models. In experimental models levels of SMURF1 protein correlated inversely with miR-140–5p. Direct regulation of SMURF1 by miR-140–5p was demonstrated <i>in vitro</i> by 3’UTR luciferase activity. Both miR-140–5p mimic and SMURF1 siRNA increased BMP response element activity identifying SMURF1 as a key negative regulator of BMP signalling in PASMC. Genetic ablation of SMURF1 in C57BL6 mice conferred allele dependent protection from SuHx induced PAH. Finally, whole blood mRNA and pulmonary vascular immunoreactivity of SMURF1 was increased in patients with PAH. <h3>Conclusions</h3> These studies suggest that miR-140–5p and SMURF1 are key regulators of BMP signalling and disease pathology in PAH and highlight SMURF1 as a potential novel therapeutic target.
Cardiac Manifestation of Acute Lymphoblastic Leukemia
Authors: Rudolf A. Werner, Martina Rudelius, Annette Thurner, Takahiro Higuchi, Constantin Lapa
Journal: Clinical Nuclear Medicine (2016)

Here, we report on a 38-year-old man with unclear right heart failure. Imaging with cardiac MRI and combined PET/CT with F-FDG revealed a hypermetabolic mass extending from the right ventricle to the atrium. In addition, intense glucose utilization throughout the bone marrow was noted. Biopsies of both bone marrow and cardiac mass were performed and revealed precursor B-cell acute lymphoblastic leukemia with gross leukemic infiltration of the myopericardium, a rare manifestation of acute lymphoblastic leukemia at initial diagnosis.
Pregnancy Rate and Preservation of Cyclic Ovarian Function With Gonadotropin-Releasing Hormone Agonist Cotreatment During Chemotherapy
Authors: Zeev Blumenfeld
Journal: JAMA Oncology (2016)

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