tbuckley/cabot-search huggingface dataset:
The Concept of Axial Spondyloarthritis: Joint Statement of the Spondyloarthritis Research and Treatment Network and the Assessment of SpondyloArthritis international Society in Response to the US Food and Drug Administration's Comments and Concerns
Authors: Atul Deodhar, John D. Reveille, Filip van den Bosch, Jürgen Braun, Ruben Burgos‐Vargas, Liron Caplan, Daniel O. Clegg, Robert A. Colbert, Lianne S. Gensler, Désirée van der Heijde, Irene E. van der Horst‐Bruinsma, Robert D. Inman, Walter P. Maksymowych, Philip J. Mease, Siba Raychaudhuri, Andreas Reimold, Martin Rudwaleit, Joachim Sieper, Michael H. Weisman, Robert B. M. Landewé
Journal: Arthritis & Rheumatology (2014)
Abstract 19105: Basis for Biochemical Discordance Between Activated Partial Thromboplastin Time and Anti-factor Xa in Patients with Continuous Flow Left Ventricular Assist Device on Unfractionated Heparin Infusion
Authors: Hirad Yarmohammadi, Amy J Feng, Chadi M Alraies, Thenappan Thenappan, Monica Colvin, Ranjit John, Peter Eckman, Marc Pritzker, Sirtaz Adatya
Journal: Circulation (2014)

Introduction: Unfractionated Heparin (UFH) has been the mainstay of therapy for bridging and treatment of suspected device thrombosis/hemolysis in Continuous Flow Left Ventricular Assist Device (CF-LVAD), however the optimal monitoring test has not been prospectively evaluated. We previously reported that that Activated Partial Thromboplastin Time (aPTT) and anti-Xa levels measured simultaneously are frequently discordant in these patients. Hypothesis: Warfarin administration and hemolysis might be the biochemical basis for discordance between aPTT and anti-Xa in patients with CF-LVAD requiring UFH. Methods: A prospective observational study consisting of 38 patients with HeartMateII, consecutively admitted for UFH therapy with simultaneous measurements of aPTT and anti-factor Xa levels. Patients were stratified based on requirement of UFH for either sub-therapeutic INR or suspected device thrombosis. Patients were grouped according to whether the paired values fell within or outside the concordant therapeutic range, when discordant thromboelastography and factor analysis were performed. Results: Anti-Xa and aPTT were concordant 41.9% of the time in those getting treated for sub-therapeutic INR and only 18.8% in the group that getting treated for hemolysis/ device thrombosis. Data pairs with a supratherapeutic aPTT values were most likely to be associated with an INR ≥1.5, (p&lt;0.001) (figure). On logistic regression analysis, high LDH was found to be a significant predictor of discordance (95% CI: 1.47-3.84). There was no consistent relationship between thromboelastography and factor analysis in the incidence of discordance. Conclusions: The relationship between aPTT and anti-factor Xa is not consistent in patients with CF-LVAD and the most common pattern was a supra-therapeutic aPTT relative to anti-factor Xa . Elevated LDH which is the sign for hemolysis and warfarin administration might contribute to an increased incidence of discordance.
Pitfalls in the diagnosis of heparin-Induced thrombocytopenia: A 6-year experience from a reference laboratory
Authors: Ishac Nazi, Donald M. Arnold, Jane C. Moore, James W. Smith, Nikola Ivetic, Peter Horsewood, Theodore E. Warkentin, John G. Kelton
Journal: American Journal of Hematology (2015)

Heparin-induced thrombocytopenia (HIT) is caused by platelet-activating antibodies against complexes of platelet factor 4 (PF4) and heparin. The diagnosis of HIT is contingent on accurate and timely laboratory testing. Recently, alternative anticoagulants for the treatment of HIT have been introduced along with algorithms for better HIT diagnosis. However, the increased reliance on immunoassays for the diagnosis of HIT may have harmful consequences due to the high rate of false positive results. To compare trends and implications of current HIT testing approaches, we analyzed results over a six-year period from the McMaster University Platelet Immunology Reference Laboratory. From 2008 to 2013, 8,546 samples were investigated for HIT using both an in-house IgG-specific anti-PF4/heparin enzyme immunoassay (EIA) and the serotonin-release assay (SRA). Of 8,546 samples tested, 13.4% were true-positives (positive in both assays); 65.6% were true-negatives (negative in both assays); 20.9% were presumed false positive for HIT (EIA-positive/SRA-negative); and 0.2% were EIA-negative/SRA-positive. The frequency of EIA-positive/SRA-negative results increased over time (from 12.9% in 2008 to 22.9% in 2013). We found that the number of SRA-negative samples was reduced from referring centers that used an immunoassay as an initial screen; however, 41% of those samples tested negative in the immunoassay and in the SRA at the reference laboratory. The suspicion of HIT continues at a high rate and the agreement between the EIA and SRA test results remains problematic.
Loss of caspase-8 in hepatocytes accelerates the onset of liver regeneration in mice through premature nuclear factor kappa B activation
Authors: Julia Freimuth, Jörg-Martin Bangen, Daniela Lambertz, Wei Hu, Yulia Alexandrowna Nevzorova, Roland Sonntag, Nikolaus Gassler, Dieter Riethmacher, Christian Trautwein, Christian Liedtke
Journal: Hepatology (2013)

The cytokine tumor necrosis factor alpha (TNF-α; TNF) plays a critical role early in liver regeneration following partial hepatectomy (PH). TNF stimulates at least three different pathways leading to nuclear factor kappa B (NF-κB) activation, apoptosis signaling by way of caspase-8 (Casp8), and activation of cJun N-terminal kinases (JNK). The present study aimed to better define the role of Casp8 during liver regeneration. We performed PH in mice lacking Casp8 specifically in hepatocytes (Casp8(Δhepa) ) and determined their liver regeneration capacity by measuring liver mass restoration and kinetics of cell cycle progression. Casp8(Δhepa) mice showed an accelerated onset of DNA synthesis after PH, delayed hepatocyte mitosis, but overall normal liver mass restoration. Analysis of immediate TNF-dependent signaling pathways revealed that loss of Casp8 prevents proteolytic cleavage of the receptor-interacting protein 1 (RIP1) in hepatocytes and subsequently triggers premature activation of NF-κB and JNK/cJun related signals. In order to define the role of NF-κB in this setting we blocked NF-κB activation in Casp8(Δhepa) mice by concomitant inactivation of the NF-κB essential modulator (NEMO) in hepatocytes. Lack of NEMO largely reverted aberrant DNA synthesis in Casp8(Δhepa) mice but resulted in incomplete termination of the regeneration process and hepatomegaly.Casp8 comprises a nonapoptotic function during liver regeneration by balancing RIP1, NF-κB, and JNK activation. While loss of Casp8 triggers NF-κB activation and thus improves liver regeneration, combined loss of Casp8 and NEMO impairs a controlled regenerative response and drives hepatomegaly.
Changes in gene expression of cholesterol metabolism pathways in mouse models of haemochromatosis
Authors: R. Graham, R.D. Delima, D. Johnstone, E.A. Milward, J.K. Olynyk, D. Trinder
Journal: American Journal of Hematology (2013)

Introduction: The liver is central to the metabolism of both iron and cholesterol. Cholesterol is synthesised and further metabolised to bile acids in the liver and the liver plays an important role in regulation of iron metabolism. It is also the organ in which excess iron is stored. Clinically, links have been noted between lipid and iron metabolism, with approximately one - third of patients with non - alcoholic fatty liver disease exhibiting altered iron parameters. On a molecular level, we have previously reported that wild - type mice fed iron - deficient, normal or iron - loaded diets exhibited increased hepatic cholesterol and  increased hepatic gene expression of enzymes in the cholesterol biosynthesis pathway with increasing hepatic iron burden. In the genetic disorder, haemochromatosis, the liver can become overloaded with iron; however, clinical studies have suggested that lipid metabolism may not be perturbed in haemochromatosis.  

Methods and Materials: We investigated hepatic cholesterol metabolis m in three mouse models of hereditary haemochromatosis: Hfe - / - , Tfr2 Y245X single mutant and Hfe - / - x Tfr2 Y245X double mutant animals as well as wild - type controls.  Mice were fed normal mouse chow and sacrificed at 10 weeks of age. Hepatic gene expression, total cholesterol and non – haem iron were measured. Liver non - haem iron was similar in Hfe - / - and Tfr2 Y245X mice (16.6±0.8 and 17±1 μmol Fe /g liver,  respectively) and significantly higher in the double mutant animals (22.4±0.7 μmol Fe /g liver ; P<0.004) than  either of the single  mutant mice.

Results: Only one group of genes increased significantly with increasing hepatic iron: those involved in cholesterol transport.  Gene expression of apolipoproteins A4, C1, C2, C3 and E increased significantly with increasing hepatic iron as did expression of VLDL receptor. In contrast to our findings in wild - type mice, gene expression of cholesterol biosynthetic enzymes did not increase significantly with liver iron burden and there were no differences in hepatic cholesterol between the groups of mutant mice. We also measured expression of genes involved in cholesterol regulation, which similarly, did not increase with increasing hepatic iron. Approximately 50% of cholesterol synthesised in the liver is directed to bile acid synthesis; however, gene expression of bile acid pathway enzymes did not change with respect to hepatic iron burden. Conclusion: These results suggest that iron - associated cholesterol regulation may be ameliorated by the genetic changes which occur in haemochromatosis.
Rapid diagnostic testing of methicillin-resistant Staphylococcus aureus carriage at different anatomical sites: costs and benefits of less extensive screening regimens
Authors: M.W.M. Wassenberg, J.A.J.W Kluytmans, R.W. Bosboom, A.G.M. Buiting, E.P.M. van Elzakker, W.J.G. Melchers, S.F.T. Thijsen, A. Troelstra, C.M.J.E Vandenbroucke-Grauls, C.E. Visser, A. Voss, P.F.G. Wolffs, M.W.H. Wulf, A.A. van Zwet, G.A. de Wit, M.J.M. Bonten
Journal: Clinical Microbiology and Infection (2011)
Medical Oncology: Basic Principles and Clinical Management of Cancer.
Authors: Laurens P. White
Journal: Annals of Internal Medicine (1988)

This is a 1,576 page textbook.It may be a little bit more medical oncology than most people want to read.For medical oncologists, much of the field is fast moving enough that any text is somewhat outdated when it is published.A very broad spectrum of collaborators of very high quality, however, have made most of the material in this book worth reading.For nononcologists, nonspecialists, there is in-depth consideration of most of the aspects of medical oncology and most of the basic concepts that underlie our current
795. Highly Purified, In Vitro Constructed SV40 Vectors for In Vivo Gene Delivery
Authors: Santanu Mukherjee, Michal Bronstein, Mahmoud Abd-El-Latif, Orly Ben-nun-Shaul, Ariella Oppenheim
Journal: Molecular Therapy (2004)

Viral vectors are highly efficient in gene delivery to a wide spectrum of target tissues, but their propagation in tissue culture cells carries the risk of undesired recombinants and mutant vectors and is costly. Non viral vectors are based on DNA that is faithfully replicated in appropriate E. coli strains. However their target spectrum is limited. In vitro constructed SV40 vectors combine efficient gene delivery of viral vectors with safety and flexibility of non viral vectors. The procedure is amenable to high scale biotechnological production and may be performed under stringent quality control, as appropriate for medical use. We have previously reported the production of vectors by mixing pre-assembled SV40 virus-like particles, produced as recombinant proteins in insect cells, with plasmid DNA prepared in E. coli. The vector was shown to be efficient in ex vivo gene delivery to hematopoietic cells, dendritic cells, cardiomyocytes, endothelial cells, stem cells and other cell types. It can accommodate large plasmids (17–18 kb), and does not require viral DNA elements. However, vector production was inefficient, and it was difficult to reach the quantities and titers required for efficacy and toxicity assessment in animal models.
The compensatory mechanisms of loaded and unloaded breathing in exercising men
Authors: Marina Segizbaeva
Journal: European Respiratory Journal (2011)

To characterize the ventilatory responses to the resistive loading or unloading, we studied the effect of breathing 79% helium – 21% oxygen (He-O2), 79% argon – 21% oxygen (Ar-O2) and 79% SF6 – 21% oxygen (SF6-O2) on the volume-time parameters, PETCO2, mouth pressure (PmI), work of breathing (WI), central inspiratory activity (dP/dtI) and electromyographic activity of parasternal muscles in 10 normal subjects at rest and during 3 min steady-state exercise. There were no significant changes in tidal volume (VT), breathing frequency (f), inspiratory (TI) and expiratory (TE) durations, minute ventilation (VE) and PETCO2 when air was replaced by He-O2 or SF6-O2 at rest. VE and PETCO2 were not significantly different after replacement of air by He-O2 or SF6-O2 during exercise. However inhalation of He-O2 decreased in VT and increased in f, whereas inhalation of SF6-O2 led to opposite effects compared with air during exercise. Both at rest and exercise, PmI, WI, dP/dtI and EMGps were significantly less during He-O2 breathing and higher during SF6-O2 breathing from the first respiratory cycle after room air was replaced by He-O2 or SF6-O2. Ar-O2 breathing did not affect on time-volume parameters both at rest and during exercise compared with air. The increase in PmI, WI, dP/dtI was observed at Ar-O2 inhalation during exercise relatively to air. We conclude that internal resistive loading or unloading breathing changes the neuromuscular output required to maintain constant ventilation. The mechanisms of load or unload compensation seem to be mediated by afferent impulsation from lung and respiratory muscle receptors as well as due to segmentary level reflexes and properties of the muscle fiber itself.
Changes in exhaled breath condensate pH following specific inhalation challenge in patients with occupational asthma to persulfate salts
Authors: Xavier Muñoz, Sara Sánchez-Vidaurre, Meritxell Espuga, María-Dolores Untoria, Ferran Morell, María-Jesús Cruz
Journal: European Respiratory Journal (2011)

Introduction: Exposure to persulfate salts in hairdressing professionals is one of the most common causes of occupational asthma (OA) in our setting. pH measurement in exhaled breath condensate (EBC) has proven to be a useful, noninvasive method for monitoring pulmonary inflammation. This study investigates possible changes in EBC pH in patients with OA to persulfate salts following specific inhalation challenge (SIC) testing.

Material and methods: The study population included 13 patients with OA caused by exposure to persulfate salts, diagnosed by a positive SIC (Group 1) and 25 patients exposed to persulfates, but with a negative SIC (Group 2). EBC samples were collected before and after SIC was performed. pH was determined in all samples following degasification with helium.

Result: The mean (SD) EBC pH values before and after SIC were 7.65 (0.63) and 7.32 (0.85), respectively, in Group 1, and 7.73 (0.68) and 7.88 (0.66) in Group 2. There were no significant differences in the pH values between the 2 groups. However, when a decrease in EBC pH greater than 0.4 units following SIC was established as significant, 6 patients in Group 1 (43%) and only 1 patient in Group 2 (4%) exceeded this value.

Conclusions: Persulfate salts can induce an inflammatory response in patients with OA. A larger percentage of SIC-positive patients showed a significant EBC pH decrease following the test. This fact could contribute to improving the diagnostic yield of SBC.

This study was funded by grants from the Spanish Ministry of Health (FIS PI050100) and SEPAR.
Medicare coverage of genetic testing
Authors: Jeffrey Roche
Journal: Clinical Cancer Research (2008)

PL08-02   The process leading to a national coverage determination for Medicare at the Center for Medicare and Medicaid Services (CMS) is outlined. In particular, the use of reasonable and necessary criteria for Medicare coverage (as required by the Social Security Act) is explained. Specifically, coverage for molecular and genomic testing at the local Medicare contractor level is distinguished from national coverage decisions in terms of process and scope. Examples of coverage decision thinking are provided. Some of the preferred features of evidence to support a coverage determination are explained. The overarching principle of any Medicare coverage determination-- to enhance health outcomes for Medicare beneficiaries-- is illustrated by an example in progress at CMS. References for obtaining further information about the coverage determination process at CMS are provided.
Gene Therapy Trials Show Clinical Efficacy
Authors: J Stephenson
Journal: JAMA (2000)

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
Abstract P214: Patient and Physician Factors Influence Decision-Making in Hypercholesterolemia
Authors: Michel Krempf, Ross J Simpson, Dena R Ramey, Philippe Brudi, Hilde Giezek, Raymond Lee, Michel Farnier
Journal: Circulation (2015)

Objectives: Little is known about how patient factors influence physicians’ treatment decision-making in hypercholesterolemia. We surveyed physicians’ treatment recommendations in high-risk patients with LDL-C not controlled on statin monotherapy. Methods: Physicians completed a questionnaire pre-randomization for each patient in a double-blind trial (NCT01154036) assessing LDL-C goal attainment rates with different treatment strategies. Patients had LDL-C ≥100 mg/dL after 5 weeks’ atorvastatin 10 mg/day and before randomization. Physicians were asked about treatment recommendations for three scenarios: (1) LDL-C near goal (100-105 mg/dL), (2) LDL-C far from goal (120 mg/dL), then (3) known baseline LDL-C of enrolled patients on atorvastatin 10 mg/day. Factors considered in their choice were specified. Physicians had been informed of projected LDL-C reductions for each treatment strategy in the trial. Regression analysis identified prognostic factors associated with each scenario, and projected LDL-C values for physicians’ treatment choices were compared to actual LDL-C values achieved in the trial. Results: Physicians at 296 sites completed questionnaires for 1535 patients. The most common treatment strategies for all three scenarios were: 1) not to change therapy, 2) double atorvastatin dose, 3) add ezetimibe, 4) double atorvastatin dose and add ezetimibe. Doubling atorvastatin dose was the most common treatment recommendation in all scenarios (43-52% of patients). ‘No change in therapy’ was recommended in 6.5% of patients when LDL-C was assumed far from goal. Treatment recommendations were more aggressive if actual LDL-C was known or considered far from goal. When compared with the ‘no change in therapy’ recommendation, CV risk factors and desire to achieve a more aggressive LDL-C goal were generally considered in decision-making for each treatment choice, regardless of LDL-C scenario. Patients randomized to a more aggressive regimen than recommended by physicians had larger reductions in LDL-C: the actual reduction in LDL-C in patients randomized to ‘add ezetimibe’ was -20.8% versus a projected reduction of -10.0% when physicians recommended ‘doubling atorvastatin dose’. Conclusions: This study provides insight into physicians’ perspectives on clinical management of hypercholesterolemia and highlights a gap in knowledge translation from guidelines to clinical practice. Targeting lower LDL-C and CV risk were key drivers in clinical decision-making but, generally, physicians were more conservative in their treatment choice than guidelines recommend, which may result in poorer LDL-C reduction. When compared with actual outcomes, projected LDL-C control was better if physicians used more comprehensive strategies rather than simply doubling the statin dose.
An Ethical Debate: Commentary: A flexible approach--but not too flexible
Authors: F N Bamford
Journal: BMJ (1996)

An Ethical DebateChild protection: medical responsibilites If a doctor has reason for believing that a child is being physically or sexually abused, not only is it permissible for the doctor to disclose information to a third party but it is a duty of the doctor to do so.Working Together, 19881
Ten e-pistles for the e-fficient trimillennial physician
Authors: D Isaacs, D Fitzgerald
Journal: JAMA (2000)

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