tbuckley/cabot-search huggingface dataset:
Compound-Heterozygous Mutations in the Plasminogen Gene Predispose to the Development of Ligneous Conjunctivitis
Authors: Volker Schuster, Silvia Seidenspinner, Petra Zeitler, Cornelia Escher, Uwe Pleyer, Wolfgang Bernauer, E. Richard Stiehm, Sherwin Isenberg, Stefan Seregard, Thomas Olsson, Anne-Marie Mingers, Christian Schambeck, Hans Wolfgang Kreth
Journal: Blood (1999)
Junior doctors' pay: a wake-up call to the NHS
Authors: F. Moss
Journal: BMJ (2000)

Next week junior doctors in the United Kingdom will vote on whether to accept a pay deal that was painstakingly negotiated on their behalf.1 But this is no ordinary deal: a completely new framework for assessing payment has been worked out. It represents a fairer system of remuneration and will force hospitals to examine how they use junior doctors and, by implication, other healthcare professionals.

Under the proposed arrangements junior doctors will no longer suffer the ignominy of overtime paid at a fraction of the basic hourly rate.2 Instead posts will be banded to reflect the number and timing of extra hours, intensity of work, and antisocial nature of duty commitments. Junior doctors will receive a salary supplement linked to the banding of the post. So, doctors working in band 1c posts—the least onerous—will receive a supplement of 20% and …
Immunoglobulin M–Enriched Human Intravenous Immunoglobulin Prevents Complement Activation In Vitro and In Vivo in a Rat Model of Acute Inflammation
Authors: Robert Rieben, Anja Roos, Yvonne Muizert, Caroline Tinguely, Arnout F. Gerritsen, Mohamed R. Daha
Journal: Blood (1999)
A cynical consultation exercise?
Authors: Charles Medawar
Journal: BMJ (2008)

The dismal proposals to allow pharmaceutical companies to promote prescription drugs directly to consumers have been orchestrated by the European Commission’s Directorate General for Enterprise and Industry (DGEI).1

The DGEI’s main objective is to promote European trade and economic development, which presents grotesque conflicts of interest when it comes to shaping health policy. DGEI greatly overestimates the support …
A molecular diagnostic panel for thyroid cancer disease management.
Authors: Shih-Min Cheng, Kevin Qu, Adam Abdool, Anthony Sferruzza, Frederic Waldman, Richard E Reitz
Journal: Journal of Clinical Oncology (2012)

5510 Background: In 2009, the American Thyroid Association revised its guidelines for patients with thyroid nodules and differentiated thyroid cancers, recommending BRAF, RAS, RET/PTC, and PAX8-PPARγ molecular testing in patients with indeterminate fine-needle aspirate (FNA) cytology. Alterations in any of these markers in thyroid nodules are strongly associated with malignancy. We studied the prevalence of these alterations in thyroid FNA specimens in order to establish a strategy to improve disease management. Methods: DNA and RNA were extracted from thyroid FNA specimens (N=149) and tested for BRAF mutations using allele-specific PCR (V600E and K601E); for RAS (H-, K-, N-) mutations using pyrosequencing (codons 12, 13, and 61); and for RET/PTC1 and RET/PTC3 rearrangements and PAX8-PPARγ translocations using RT-PCR. Results: Overall, 90 (60.4%) of the specimens had alterations in ≥1 of the 4 molecular markers (Table). BRAF V600E mutations (54.4%) were the most prevalent mutations in papillary thyroid cancer (PTC); no K601E mutations were found. RAS mutations were found in PTC, follicular adenoma (FA), and follicular thyroid cancer (FTC) specimens; half of these mutations involved N-RAS Q61. RET/PTC rearrangements were detected in 3.5% of PTC specimens and were evenly distributed between the 2 major subtypes, RET/PTC1 and RET/PTC3. PAX8/PPARγ translocations were detected in 18.8% of FTC but not in FA, probably due to small sample size. Out of 7 indeterminate thyroid nodules, 2 had BRAF mutations and 2 had RAS mutations. The presence of the 4 markers was generally mutually exclusive; only 1 PTC specimen had concurrent RAS and RET/PTC1 alterations. Conclusions: The prevalence of BRAF, RAS, RET/PTC, and PAX8/PPARγ alterations in thyroid cancer specimens highlights the potential for targeted therapeutic strategies. The mutually exclusive pattern of alterations also suggests a hierarchical screening strategy for samples with limited availability. [Table: see text]
Abstract 6: A 15-Year Spectrum of Resuscitation Outcomes: A Story of Success or Failure?
Authors: Marwan S Abougergi, Shaker M Eid, Aiham Albaeni, Nisha Chandra-Strobos
Journal: Circulation (2013)

Background: Care strategies including automated defibrillators, improved emergency response systems, hypothermia and early revascularization have individually been shown to improve non-traumatic out-of-hospital cardiac arrest (OHCA) survival. We examined a national database to assess the cumulative impact of care change on outcomes in OHCA over a period of 15 years. Methods: We used the Nationwide Inpatient Sample, the largest nationally representative inpatient database, to calculate outcomes every 5 years from 1995 to 2010. Patients with an ICD-9 CM code for a principle diagnosis of cardiac arrest were included. Patients with any diagnosis of trauma were excluded. Admission rate was calculated using the July 1 population census estimate for each year. In-hospital mortality rate was adjusted for age, sex and Charlson comorbidity index taking year 2010 as a reference. All charges were adjusted for inflation using the consumer price index. Results: From 1995 to 2010, adjusted in-hospital mortality for OHCA has worsened. On subgroup analysis, mortality has improved when the coded presenting rhythm was Ventricular fibrillation (VF) and worsened when it was non-VF. The rate of poor neurologic outcome has increased with time. These changes have occurred despite the increasing use of hypothermia, coronary catheterization and stenting in all patients. Both the adjusted median hospitalization charges and the total OHCA economic burden have increased, especially after the year 2000. Conclusions: Comorbidity, age and gender adjusted in-hospital mortality from non-traumatic out-of-hospital cardiac arrest has increased over the past 15 years. Escalating resource utilization has yielded no improvement in survival for the majority of patients but has resulted in increased hospitalization costs, reaching a staggering annual economic burden of ~$1 billion in 2010. More in-depth review of care strategies is needed to improve survival and healthcare expenditure.
Abstract 17200: Alternate Statin Protocol: A Novel Nurse Practitioner Managed Approach for Treating Women with Previous Statin Intolerance
Authors: Margo Minissian, Kamlesh Kothawade, Frida Pena, Chrisandra Shufelt, Megha Agarwal, Puja K Mehta, JoAnn Eastwood, YuChing Yang, Noel Bairey Merz
Journal: Circulation (2010)

Background: HMG-CoA reductase inhibitors (statins) are efficacious in treating coronary artery disease (CAD). Adherence is problematic due to side effects which prevent high risk patients from receiving optimal benefit from statin therapy. Despite the prevalence of this problem, the tolerability and effectiveness of alternate dosing in statin therapy has not been evaluated clinically. The aim of this study was to evaluate the effectiveness of a nurse practitioner (NP) alternate statin dosing protocol to increase adherence, tolerance, and reduction of lipid levels.

Methods: At a tertiary chest pain center, we analyzed 15 women who tolerated alternate dosing who had prior statin intolerance, defined as the inability to tolerate daily dosing. An NP protocol was used for initiation and maintenance of alternate dosing. Women with prior statin intolerance were placed on atorvastatin, pravastatin, rosuvastatin or simvastatin for the reduction of total cholesterol (TC) and low-density lipoprotein (LDL-C). Patients were initially started on twice weekly statin dosing on Mondays and Thursdays for 4 weeks then titrated up one day per week as tolerated. Fasting baseline and follow-up lipid levels were obtained by chart review. Wilcoxon signed rank test was performed on the data.

Results: We evaluated 15 female patients with a mean age of 62 ± 14 years and a BMI of 26 ± 5. Overall, 60% had CAD, 60% had hypertension, 7% had diabetes, and 47% had a history of smoking. Prior to initiating the alternate dosing NP protocol 93% were intolerant to 2 or more statins with myalgias. Utilizing the alternate dosing NP protocol, we observed a mean 32% reduction in LDL 84 ± 39 mg/dl compared to their prior highest LDL level 134 ± 49 mg/dl (p<0.001). We also observed a 20% statistically significant reduction of TC after initiation of the alternate dosing NP protocol (p<0.0001).

Conclusions: In a group of women who tolerated alternate dosing, utilizing an NP alternate dosing protocol increases tolerability and is effective in reducing TC and LDL-C levels. Further studies are warranted in larger populations in an effort to increase adherence in women who are labeled statin intolerant.
Abstract 17597: Deletion of Fibroblast Activation Protein (FAP) Attenuates Atherosclerotic Lesion Development via Changes in the Accumulation of Fibrillar Collagen and in Inflammatory Cell Recruitment
Authors: James Monslow, Rebecca Evans, Leslie Todd, Rajrupar Majumdar, Elizabeth Hawthorne, Richard Assoian, Ellen Pure
Journal: Circulation (2013)

Atherosclerosis and the formation of vascular lesions is a highly integrated process involving the endothelium, vascular smooth muscle cells (VSMCs), inflammatory cell recruitment and lipid metabol...
Pregnancy and Medication
Authors: Tracy Hampton
Journal: JAMA (2004)

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
Finding the Proper Context for the MATRIX Trial
Authors: Peter B. Berger
Journal: New England Journal of Medicine (2015)

Despite the widespread use of percutaneous coronary intervention (PCI) in patients with an acute coronary syndrome, questions persist about the best method for preventing thrombotic complications while limiting the risk of bleeding during and after such procedures. The results of the multicenter MATRIX (Minimizing Adverse Hemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) trial, as now described by Valgimigli et al.1 in the Journal, provide some new and important data.The large, ambitious MATRIX trial enrolled 7213 patients at 78 European centers and was designed to address three hotly debated issues.1 First, are there differences in . . .
Abstract 1372: Sirt3 Promotes Survival of Cardiac Myocytes under oxidative stress and Upregulates Mitochondrial Genes Through Nuclear Respiratory Factor
Authors: Ibrahim Odewale, Ralph Alcendor, Junichi Sadoshima
Journal: Circulation (2008)

Silent information regulator 1 (Sirt1), the prototype member of the sirtuin family, has been implicated in longevity and stress resistance. Sirt3, another member of the sirtuin family, is localized primarily in mitochondria and involved in metabolism in both white and brown adipose tissues. However, the cardiac role of Sirt3 is not well understood. Here, we examined the cellular function of Sirt3 in cardiac myocytes. Western blot analysis revealed that Sirt3 is highly expressed in cardiac myocytes, at the level comparable to Sirt3 in white and brown adipose tissues. Although Sirt1 in the heart was upregulated in response to glucose deprivation, high-fat diet, or pressure overload, expression of Sirt3 was unchanged in these conditions. Expression of Sirt3 was increased two-fold, however, after H 2 O 2 (100 μ M) treatment in primary cardiac myocytes and two-fold by aging (18 vs 3 months) in the heart. Sirt3 is localized primarily in the mitochondria in myocytes under normal conditions, but it translocates into the nucleus when cells are treated with H 2 O 2 . Adenovirus-mediated overexpression of Sirt3 significantly reduced myocyte cell death in serum free media or in the presence of H 2 O 2 as determined by cytoplasmic accumulation of mono- and oligonucleosomes (p&lt;0.05), suggesting that Sirt3 protects myocytes from apoptosis under oxidative stress. Furthermore, Sirt3 increased expression of NRF1, a transcriptional modulator of metabolic genes and mitochondrial DNA transcription, by 2.5-fold. There was a 3.4-fold increase in Glut4 expression as well as a 4-fold increase in COX IV. On the other hand, Sirt1 failed to upregulate NRF1. Sirt3 neither interacted with PGC-1 α nor stimulated PGC-1 α -mediated transcription. Thus, although both Sirt1 and Sirt3 exert their function by regulating metabolic genes, their mechanism of action is different. In summary, cardiac myocytes abundantly express Sirt3 in mitochondria. Sirt3 is upregulated by oxidative stress and translocates into the nucleus, where Sirt3 regulates expression of mitochondrial genes, such as Glut4 and COX IV, through upregulation of NRF1 and plays a protective role against oxidative stress in cardiac myocytes.
Ig V Gene Mutation Status and CD38 Expression As Novel Prognostic Indicators in Chronic Lymphocytic Leukemia
Authors: Rajendra N. Damle, Tarun Wasil, Franco Fais, Fabio Ghiotto, Angelo Valetto, Steven L. Allen, Aby Buchbinder, Daniel Budman, Klaus Dittmar, Jonathan Kolitz, Stuart M. Lichtman, Philip Schulman, Vincent P. Vinciguerra, Kanti R. Rai, Manlio Ferrarini, Nicholas Chiorazzi
Journal: Blood (1999)
Late Cardiac Death in Patients Undergoing Transcatheter Aortic Valve Replacement
Authors: Marina Urena, John G. Webb, Helene Eltchaninoff, Antonio J. Muñoz-García, Claire Bouleti, Corrado Tamburino, Luis Nombela-Franco, Fabian Nietlispach, Cesar Moris, Marc Ruel, Antonio E. Dager, Vicenç Serra, Asim N. Cheema, Ignacio J. Amat-Santos, Fabio Sandoli de Brito, Pedro Alves Lemos, Alexandre Abizaid, Rogério Sarmento-Leite, Henrique B. Ribeiro, Eric Dumont, Marco Barbanti, Eric Durand, Juan H. Alonso Briales, Dominique Himbert, Alec Vahanian, Sebastien Immè, Eulogio Garcia, Francesco Maisano, Raquel del Valle, Luis Miguel Benitez, Bruno García del Blanco, Hipólito Gutiérrez, Marco Antonio Perin, Dimytri Siqueira, Guilherme Bernardi, François Philippon, Josep Rodés-Cabau
Journal: Journal of the American College of Cardiology (2015)
Abstract P053: Chocolate Consumption is Associated with a Lower Risk of Diabetes Melitus in the Physicians’ Health Study
Authors: Chisa Matsumoto, Howard D Sesso, J. Michael Gaziano, Luc Djousse
Journal: Circulation (2013)

Background: Previous studies have reported beneficial effects of cocoa or chocolate on insulin resistance, oxidative stress, and inflammation. However, it is unclear whether chocolate consumption i...
Abstract 16710: Induced Pluripotent Stem Cell-Derived Endothelial Cells From Diet-Induced Obesity Mice Exhibit Decreased Vascular Function in a Murine Model of Hindlimb Ischemia
Authors: Nicholas M Mordwinkin, Mingxia Gu, Nigel G Kooreman, Shijun Hu, Jared M Churko, Sebastian Diecke, Paul W Burridge, Chunjiang He, Jaechol Lee, Joseph D Gold, Joseph C Wu
Journal: Circulation (2013)
Duration of Androgen Suppression in Prostate Cancer
Authors: Kas R Badiozamani
Journal: New England Journal of Medicine (2009)

To the Editor: In the trial conducted by Bolla et al. (June 11 issue), 1 more than 70% of the patients had clinical T3 disease, and the median level of prostate-specific antigen (PSA) in patients who underwent randomization was 18.8 ng per milliliter, with a range of up to 159.2. Furthermore, about 20% of the patients presented with Gleason scores of 5 or less, suggesting that these tumors were downgraded as compared with current trends in diagnosis. 2 Since bone scans were not mandated as part of the study, a clinically significant number of patients were likely to have had metastatic disease at presentation. The study, therefore, has limited applicability for most patients whose disease is diagnosed with the use of PSA screening. For patients with an intermediate risk of disease as defined by D’Amico et al., 3 short-term androgen suppression should not be considered inferior to long-term treatment.
Abstract 1316: Preclinical Atherosclerosis in Primary Antiphospholipid Syndrome: The Impact of Oxidative Properties of High Density Lipopoprotein
Authors: Marietta Charakida, Julian Halcox, Joanna Batuca, Ann Donald, Shirish Sangle, Jose Delgado Alves, David Cruz, Charles Mackworth-Young, Graham Hughes, John Deanfield
Journal: Circulation (2007)

Background: Antiphospholipid syndrome (APS) is characterised by increased thrombogenicity and/or pregnancy morbidity in the presence of raised levels of antiphospholipid antibodies (aPL). Increased oxidative properties of high density lipoprotein (HDL)(decreased activity of paraoxonase (PON)) is associated with increased risk for atherosclerosis and has been described in APS. The impact of PON on atherosclerotic disease progression in APS is unclear. We therefore examined the effect of PON on intima media thickness (IMT), and pulse wave velocity (PWV) in patients with positive aPL. Methods: We studied 77 women with positive aPL (aPL) aged 46.6±1.2 yrs (mean±SE) and a control group of 77 women aged 47.5±1.2 yrs matched for traditional cardiovascular risk factors. High resolution ultrasound was used to determine carotid IMT. Arterial stiffness was assessed non-invasively by carotid-radial PWV. PON activity was assessed by measuring p-nitrophenol formation and activity expressed as nmoles p-nitrophenol/ml serum/minute. Results: APL patients had significantly increased IMT and PWV compared to controls (0.75±0.02mm vs 0.65±0.01mm, p&lt;0.001 and 9.14±0.18 m/s vs 8.56±0.21m/s, p&lt;0.05 respectively). PON activity was significantly reduced in aPL compared to controls (91.5[64.3, 05.1]mmol/ml/min, median[IQR] vs 103.1[80.4, 111.5] mmol/ml/min, p&lt;0.006). Although PON activity was not associated with vascular measures in controls, an inverse association was noted in aPL patients (r=−0.26 [cIMT] and r=−0.23 [PWV], both p&lt;0.05). In multivariate analysis, accounting for cardiovascular risk factors, PON activity (β=−0.42, p&lt;0.001), age (β=0.33, p&lt;0.001) and systolic blood pressure (β=0.24, p&lt;0.05) were independent determinants of cIMT while PON activity (β=−0.32, p&lt;0.01) and systolic blood pressure (β=0.28, p&lt;0.05) remained the only independent predictors of PWV in aPL positive patients. Conclusions: APS is associated with increased arterial stiffness and carotid intimal thickening. Paraoxonase activity is inversely associated with IMT and PWV in ApL positve patients. These findings indicate that oxidative stress may play an important role in the development of atherosclerosis in patients with primary antiphospholipid syndrome.
Prevention of graft rejection following bone marrow transplantation
Authors: RP Gale, W Ho, S Feig, R Champlin, A Tesler, E Arenson, S Ladish, L Young, D Winston, R Sparkes, J Fitchen, M Territo, G Sarna, L Wong, Y Paik, Y Bryson, D Golde, J Fahey, M Cline
Journal: Blood (1981)
Heated Fats and Allied Compounds as Carcinogens: A Critical Review of Experimental Results&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: E. Arffmann
Journal: JNCI Journal of the National Cancer Institute (1960)

A critical review of the literature shows no valid experimental evidence that heated fats are carcinogenic on oral administration, and chemical studies have failed to demonstrate known carcinogens in heated fats. From general experience on experimental carcinogenesis in the alimentary tract, it is concluded that feeding experiments on rodents are inadequate for the demonstration of carcinogenic components in human food. Experimental evidence on heated fats as carcinogens after subcutaneous and cutaneous application is critically reviewed, together with results obtained by similar procedures with cholesterol and other unheated lipides. The results are variable and inconclusive. Subcutaneous application is discussed, and it is concluded that this method is not suitable to disclose dietary carcinogens. Thus experimental methods available at present are invalid as evidence on the possible carcinogenicity of heated fats.
Abstract 471: Paradigm Shift to Epigenetic Memory for the Pathological Understanding of Chronic Heart Failure
Authors: Yoshihiro Asano, Seiji Takashima, Yulin Liao, Masafumi Kitakaze
Journal: Circulation (2008)

Background- Epigenetic modification becomes a popular regulatory mechanism of gene expression in development or tumor progression. However its role in cardiovascular diseases has not been elucidated. Since reactivation of cardiac fetal gene expression in chronic heart failure (CHF) is more remarkable than that expected by the increased transcriptional factors, the concept of epigenetic modification may be required for the explanation of such a phenomenon. We tested this idea. Methods- To test the epigenetic potency in cardiomyocytes, we focused on the expression of both BNP and ANP genes. As epigenetic markers, nucleic chromatin structure by electron microscopy and the entire-regional histone modifications were evaluated using our newly developed in vivo chromatin immunoprecipitation (ChIP) assay. Results- In the developmental stage of hearts, we observed a parallel movement of fetal gene expression and epigenetic markers. On the other hand, in the short time stimuli of GPCR agonists in murine cardiomyocytes, fetal gene expression was controlled only by the amount of transcription factors, Gata4 and Nkx2.5, but epigenetic maker was not altered. In contrast, in in vivo murine model of CHF both Gata4 and Nkx2.5 depressed despite elevated expression of both BNP and ANP. Nucleic chromatin structure in failing cardiomyocytes was changed to less condensed forms and increased accumulation of both histone H3K9-acetylation and H3K4-trimethylation was observed across these gene loci. Also in human failing heart, similar changes of nucleic chromatin structure were observed as that in murine CHF model and interestingly these changes was reversed when the heart function was recovered along with proper treatment. Conclusions- We for the first time clarified that both BNP and ANP reactivation mechanisms in chronic heart failure link to the alteration of histone modification by the in vivo ChIP method. Different from acute stimuli, this change was coincided with nucleic chromatin structure and was explicable of paradoxical depression of transcription factors, suggesting epigenetic potency. Epigenetic mechanism may play a pivotal role in the nuclear memory-mediating failing myocardium, raising the hope for a novel pathological understanding for human CHF.
Small noncleaved cell lymphoma and leukemia in adults. A retrospective study of 65 adults treated with the LMB pediatric protocols
Authors: C Soussain, C Patte, M Ostronoff, A Delmer, F Rigal-Huguet, N Cambier, PY Leprise, S Francois, P Cony-Makhoul, JL Harousseau
Journal: Blood (1995)