tbuckley/cabot-search huggingface dataset:
Abstract 14860: Young Women with Stable CHD are More Likely to Develop Myocardial Ischemia with Mental Stress Than Men of Similar Age
Authors: Viola Vaccarino, Pratik M Pimple, Ernest V Garcia, Jonathon Nye, Ibhar Al Mheid, Kobina Wilmot, Ronnie Ramadan, Amit J Shah, Paolo Raggi, Fabio Esteves, Michael Kutner, Qi Long, J D Bremner, Arshed A Quyyumi
Journal: Circulation (2014)

Introduction: Emerging data suggest that young women with coronary heart disease (CHD) are disproportionally vulnerable to the adverse cardiovascular effects of emotional stress. We assessed myocardial ischemia induced by a standardized mental stress protocol to address this question. Hypothesis: Young women (≤55 years) with stable CHD are more likely than men of similar age to develop ischemia with a mental stress test, but not ischemia with a standard exercise or pharmacological stress test. Methods: We studied 534 patients with stable CHD who underwent 99mTc[[Unable to Display Character: ‐]]sestamibi myocardial perfusion imaging at rest and with both mental (speech task) and physical (exercise or pharmacological) stress testing. A summed total severity score was computed to quantify hypoperfusion size and severity at rest and under both stress conditions with observer-independent software. The difference between stress and rest provided a quantitative measure of total ischemic perfusion deficit (...
Making Treatment Choices From “Dark Places”: A Role for Ethics Consultation
Authors: Gail Leslie, Ellen M. Robinson, Mary Zwirner, John J. Purcell, Cornelia Cremens
Journal: The American Journal of Bioethics (2015)

This case is a most appropriate consult to the ethics committee at our institution. While the right to withhold and withdraw life-sustaining treatment (LST) has been clearly established in American...
Mutations in the CCN gene family member WISP3 cause progressive pseudorheumatoid dysplasia
Authors: Jennifer R. Hurvitz, Wafaa M. Suwairi, Wim Van Hul, Hatem El-Shanti, Andrea Superti-Furga, Jean Roudier, Daniel Holderbaum, Richard M. Pauli, J. Kenneth Herd, Els Van Hul, Hossien Rezai-Delui, Eric Legius, Martine Le Merrer, Jamil Al-Alami, Sultan A. Bahabri, Matthew L. Warman
Journal: Nature Genetics (1999)
325. Identification of Mechanistically Distinct Repression Domains at Endogenous Genes Using Engineered Zinc Finger Proteins
Authors: Siyuan Tan, Lei Zhang, H. Steven Zhang, Xaohong Zhong, Yann Jouvenot, Andrew W. Snowden, Andrew R. McNamara, Casey C. Case, Carl O. Pabo, Philip D. Gregory
Journal: Molecular Therapy (2004)
Abstract IA19: Response and resistance PD-1 pathway blockade
Authors: Suzanne L. Topalian
Journal: Cancer Research (2015)

Abstract Melanoma is a genetically complex cancer harboring a multitude of somatic mutations for potential targeting by the immune system. However, melanoma cells can co-opt normal immune tolerance mechanisms to evade elimination. The immunoglobulin-like molecule PD-L1 (B7-H1), expressed by many melanomas in situ, creates a protective shield against immune attack. PD-L1 is a ligand for the programmed death-1 (PD-1) receptor expressed on activated T and B cells, and it delivers an inhibitory signal to suppress antitumor immunity. Blocking the PD-1:PD-L1 interaction can rejuvenate anti-melanoma immunity and mediate tumor regression. Multicenter clinical trials of blocking antibodies against PD-1 (nivolumab, pembrolizumab) or PD-L1 (BMS-936559, MPDL3280A, MEDI4736) have been undertaken. In an early phase trial of biweekly nivolumab administration, durable objective tumor regressions and disease stabilization were observed among 31% and 7%, respectively, of 107 patients with advanced treatment-refractory melanoma. Median overall survival in this trial was 17 months. Partial tumor regressions that are durable and persist after drug discontinuation suggest that PD-1 blockade can reset the balance between the immune system and melanoma. In some patients, “mixed” tumor regressions or initial disease progression followed by regression suggest that tumor lesions separated anatomically or chronologically may be immunologically heterogeneous. Durable objective tumor regressions reported in clinical trials of various antibodies blocking the PD-1 and PD-L1 immune checkpoints validate the importance of targeting this pathway in melanoma therapy. Ongoing investigations into pharmacodynamics and potential biomarkers of response are designed to reveal the basis for immunological heterogeneity among different patients, and among diverse tumor sites in individual patients, to enable the optimal clinical development of these drugs. Supported by research grants from Bristol-Myers Squibb, the National Institutes of Health, Stand Up 2 Cancer, the Barney Family Foundation, the Laverna Hahn Charitable Trust, Moving for Melanoma of Delaware, and the Melanoma Research Alliance. Citation Format: Suzanne L. Topalian. Response and resistance PD-1 pathway blockade. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Melanoma: From Biology to Therapy; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(14 Suppl):Abstract nr IA19.
Features of pregnancy duration & outcomes in asthmatic pregnants due to their smoking status
Authors: Olga Lavrova, Olga Sukhovskaia, Anna Piskynova, Maria Petrova, Elena Shapovalova
Journal: European Respiratory Journal (2012)

Prevalence. Asthma is the most common respiratory disease in pregnant. Combined influence of asthma and smoking on pregnancy duration as well as newborn9s health appears not to be completely studied.  The goal of the study was to investigate influence of intensity and severity of smoking in asthmatic patients to variety of pregnancy complications and newborn health status.  Materials and methods: 643 pregnants with asthma and their kids were studied.  Results: 50,9% of studied females never smoked, 49,1% smoke before or during pregnancy. Among latter females 19,3% stopped smoking before pregnancy (1 group), 54,1%– interrupted smoking while pregnancy(2 group) but 26,6% continued smoking while pregnancy (3 group). Risk of abortion or premature delivery was more frequent in pregnants with more than 10 years smoking experience in comparison with less than 9 years smoking experience 77,8% versus 43,2% (p  Conclusions: Asthmatic patients are to stop smoking before pregnancy onset in order to decrease pregnancy complications and to increase newborn health status.
Survival in the Prostate Cancer Prevention Trial
Authors: Swaroop Revannasiddaiah, Sridhar P Susheela
Journal: New England Journal of Medicine (2013)

In their article on long-term survival in the Prostate Cancer Prevention Trial (PCPT), Thompson et al. (Aug.15 issue) comment on the aggressiveness of high-grade disease (which they defined as a tumor having a Gleason score of 7 to 10).These authors have always argued that the increase in high-grade disease in men receiving finasteride was an artifact.If this were true, men with high-grade disease who are treated with finasteride should have a better survival rate than men in the placebo group.However, the survival rates in these groups were virtually the same.This finding indicates that the increase in highgrade disease is not an artifact but is real.The Food and Drug Administration rejected the use of finasteride for the prevention of prostate cancer on the basis of a related increase in the most aggressive, potentially lethal form of high-grade disease (Gleason score, 8 to 10), excluding the less aggressive pattern of disease (Gleason score of 7). ,In another recent report, the PCPT investigators stated that tumors with a Gleason score of 8 to 10 may cause "a small increase in prostate cancer mortality."In the study published in the Journal, which defined a high-grade tumor as one having a Gleason score of 7 to 10, there is no report on prevalence or mortality for cancers with Gleason scores of 8 to 10.What are they?
Abstract 14644: Impact of Time to Return of Spontaneous Circulation on Neuro-protective Effect of Target Temperature Management at 33 and 36 Degrees in Comatose Survivors of Out of Hospital Cardiac Arrest
Authors: Jesper Kjaergaard, Matilde Winther-Jensen, Niklas Nielsen, Anders åneman, Wise P Matt, Jørn Wetterslev, Michael Wanscher, Stammet Pascal, Thomas Pellis, Michael Kuiper, Jan Hovdenes, Janneke Horn, Yvan Gasche, Hans Friberg, David Erlinge, Tobias Cronberg, Christian Hassager
Journal: Circulation (2014)

Introduction: Prolonged time to Return of Spontaneous Circulation (ttROSC) after Out of Hospital Cardiac Arrest (OHCA) has consistently been associated with adverse outcome by a plausible direct relation to severity of anoxic injury. Hypothesis: Target temperature management (TTM) is assumed effective against anoxic brain injury and we hypothesized that TTM at 33 degrees would be more beneficial with prolonged time to ROSC compared to 36 degrees. Methods: In a post hoc analysis of the TTM trial, which showed no overall benefit of targeting 33 °C over 36 in 939 patients (NEJM 2013), we investigated the relation of time to ROSC and mortality and neurological outcome as assessed by the Cerebral Performance Category (CPC) and Modified Ranking Scale (mRS) after 180 days. Results: Prolonged ttROSC was significantly and independently associated with increased mortality, p&lt;0.001 (figure), with Hazard Ratio (HR) of 1.02 (95% CI 1.01-1.02, p&lt;0.001) per minute increase and level of TTM did not modify this association, p interaction =0.85. In survivors prolonged ttROSC was associated with increased odds of surviving with an unfavorable neurological outcome for CPC (p=0.008 for CPC 3-4) and a similar trend, albeit not statistically significant was observed for mRS (p=0.17, mRS 4-5). Odds for unfavorable neurological outcome (CPC&gt;2, mRS&gt;3) was not modified by levels of TTM overall. Conclusion: Time to ROSC remains a significant prognostic factor in comatose patients resuscitated from OHCA with regards to risk of death and risk of adverse neurological outcome in survivors. TTM at 33 degrees offers no advantage over targeting 36 degrees with regards to mortality or neurological outcome in patients with prolonged time to ROSC. Figure: Mortality rates stratified by quartiles of tome to ROSC and by TTM level. Differences tested by log rank test in between TTM in strata
Anaphylaxis in patients with mastocytosis: a study on history, clinical features and risk factors in 120 patients
Authors: K. Brockow, C. Jofer, H. Behrendt, J. Ring
Journal: Allergy (2008)

Excessive mast cell mediator release may lead to anaphylaxis in patients with mastocytosis. However, the incidence, clinical features and trigger factors have not yet been analyzed.To identify risk factors for anaphylaxis in mastocytosis, we determined cumulative incidence, severity, clinical characteristics, and trigger factors for anaphylaxis in 120 consecutive patients (53 male; 67 female, median age and range 24 years, 1 month to 73 years), and correlated these with disease severity of mastocytosis, skin involvement, basal total serum tryptase, and diaminooxidase concentrations.The cumulative incidence of anaphylaxis in patients with mastocytosis was higher in adults (49%; P < 0.01) compared with that in children (9%). Only children with extensive skin involvement had experienced anaphylaxis. In adults, anaphylaxis was correlated to the absence of urticaria pigmentosa lesions (P < 0.03). Reactions occurred more frequently in adults with systemic (56%) when compared with cutaneous mastocytosis (13%; P < 0.02). In adults, 48% of reactions were severe, and 38% resulted in unconsciousness. Major perceived trigger factors for adults were hymenoptera stings (19%), foods (16%), and medication (9%); however, in 26% of reactions, only a combination of different triggers preceded anaphylaxis. Trigger factors remained unidentified in 67% of reactions in children compared with 13% in adults. Patients with anaphylaxis had higher basal tryptase values (60.2 +/- 55 ng/ml, P < 0.0001) in comparison with those without (21.2 +/- 33 ng/ml), but not diaminooxidase levels.Adult patients and children with extensive skin disease with mastocytosis have an increased risk to develop severe anaphylaxis; thus, an emergency set of medication including epinephrine is recommended.
The human hair follicle immune system: cellular composition and immune privilege
Authors: T. Christoph, S. Müller-Röver, H. Audring, D.J. Tobin, B. Hermes, G. Cotsarelis, R. Rückert, R. Paus
Journal: British Journal of Dermatology (2000)

The immunology of the hair follicle, its relationship with the 'skin immune system' and its role in hair diseases remain biologically intriguing and clinically important. In this study, we analysed the immunoreactivity patterns of 15 immunodermatological markers to determine the cellular composition and immune privilege of the human hair follicle immune system in anagen VI (growth phase). The most prominent cells located in or around the hair follicle were Langerhans cells, CD4+ or CD8+ T cells, macrophages and mast cells, whereas B cells, natural killer cells and γδ T cells were found very rarely. Langerhans cells (CD1a+, major histocompatibility complex, MHC class II+), and T cells (CD4+ or CD8+) were predominantly distributed in the distal hair follicle epithelium, whereas macrophages (CD68+, MHC class II+) and mast cells (Giemsa+) were located in the perifollicular connective tissue sheath. Transmission electron microscopy confirmed low numbers of immune cells in the proximal hair follicle epithelium, and very few macrophages and Langerhans cells were seen in the dermal papilla. Melanophages were observed in the connective tissue sheath and dermal papilla. MHC class I (HLA‐A, ‐B, ‐C) and β2‐microglobulin immunoreactivity was found on most skin cells, but was substantially reduced on isthmus keratinocytes and virtually absent in the proximal hair follicle epithelium. Apart from the absence of Fas ligand immunoreactivity, the sharply reduced numbers of T cells and Langerhans cells, and the virtual absence of MHC class I expression all suggest that the anagen proximal hair follicle constitutes an area of immune privilege within the hair follicle immune system, whose collapse may be crucial for the pathogenesis of alopecia areata.
Abstract 19734: Advantages of the Cardiac Isochrone Positioning System for Localization of PVCs to the Endocardium, Epicardium, and Mid-myocardium from a 12 lead ECG
Authors: Jeffrey P Gordon, Michael Laks, Noel G Boyle, Peter M van Dam
Journal: Circulation (2014)

Introduction: PVC localization from a 12 lead ECG is an imperfect deduction prone to inaccuracy. The cardiac isochrone positioning system (CIPS) is a non-invasive cardiac imaging method to localize the PVC origin quantitatively to the ventricles using a 12 lead ECG coupled with anatomical imaging data from MRI/CT. The purpose of this study is to: 1) Demonstrate and clarify the limitations of using only the 12 lead ECG to localize a PVC, and 2) Show the advantages of CIPS to localize a PVC, including to the mid-myocardium. Methods: 9 subjects had successful PVC ablation in the endo- , epi, or mid-myocardium. To demonstrate the limitations of localizing PVCs using only a 12 lead ECG, 8 blinded physicians were asked both to localize the PVC origin to a specific myocardial area using polar map representations of the LV and RV and to specify the PVC as endo- or epicardial in origin. CIPS was used to localize the same PVCs using the MRI derived models and the same 12 lead ECG. Results: All 8 blinded reviewers located the PVCs to the correct location with an accuracy of 27%. A qualification of the PVC to an endo- or epicardial surface could not be reliably determined. In contrast, CIPS located the PVCs with an accuracy of 86%. CIPS also successfully localized all 9 PVCs to endo-, epi-, or mid-myocardium. Conclusions: Our results confirm the limited capability of using only a 12 lead ECG to localize a PVC origin. Currently, there are no criteria to differentiate the location of the PVC specifically to the mid-myocardium. Coupling the 12 lead ECG and anatomical data, CIPS is able to reliably determine PVC origin. As demonstrated here, it also has the ability to successfully localize PVCs to an epi-, endo-, or mid-myocardial site. CIPS is a promising new technology that could be used to quickly and accurately ascertain an exact PVC location, translating into a direct clinical benefit for patients undergoing ablation.
Hematology: A Pathophysiological Approach.
Authors: Bernard M. Babior, Thomas P. Stossel
Journal: Annals of Internal Medicine (1984)

An Overview of the Blood RED BLOOD CELLS and THEIR DISEASES: Red Blood Cell Diseases: Red Cell Production, Red Cell Indices, And Reticulocyte Count. Hemoglobin and Oxygen Transport: Disorders of Oxygen Binding. Heme Formation: The Supply of Iron, Iron Deficiency and Iron Excess. Heme Formation: Biosynthesis of the Tetrapyrrole, Porphyrias and Sideroblastic Anemias. DNA Replication and Hematopoiesis: Megaloblastic Anemias. Hypoproliferative Anemia. Hemolytic Anemias: Extravascular Destruction of Red Cells. Hemolytic Anemias: Intravascular Destruction of Red Cells. Hemoglobin Biosynthesis: Thalassemia and Hemoglobin E. Sickle Cell Amemiaand Related Hemoglobinpathies. Polycythemia COAGULATION: The Clotting Cascade and Its Regulation: Congenital and Acquired Clotting Factor Disorders. Platelets. Disseminated Intravascular Coagulation and Thrombotic Thrombocytopenic Purpura. Antithrombotic Therapy: Anticoagulants, Antiplatelet Drugs, And Fibronolytic Agents WHITE BLOOD CELLS and THEIR DISEASES: Immunoproteins and Immunoprotein Disorders. Phagocytes and Nonneoplastic Phagocytes Diseases. Lymphoid Cells and Immune Reactions Associated with Defence and Disease. Immunodeficiency and Autoimmunity Caused By Defects in the Lymphoid System. Pathophysiology of Blood Cell Replication, Neoplasia, And Therapy of Hematological Malignancies. Stem Cell Disorders. Acute Myelogenous Leukemias. Lymphoid Neopasms: Overview. Acute Lympocytic Leukemia. Chronic Lymphocytic Leukemias. Hodgkin's Lymphoma. Non-Hodgkin's Lymphomas. Plasma Cell Neoplasms. Immune Destruction of Blood Cells. Blood Transfusion Therapy. Bone Marrow Transplantation Index
Science commentary: Renal function and how to assess it
Authors: A. Berger
Journal: BMJ (2000)

The gold standard test for assessing renal function is the glomerular filtration rate.1 Measuring this rate is a laborious process but is most useful for assessing renal function in patients whose serum creatinine concentration is at the upper limit of normal or in patients who develop early renal impairment secondary to treatment with non-steroidal anti-inflammatory drugs, lithium, or angiotensin converting enzyme inhibitors. The normal range is 80-120 ml/min.

A useful and practical surrogate …
Abstract 778: Antioxidants decrease the apoptotic effect of 5-Fu in colon cancer by regulating Src-dependent caspase-7 phosphorylation
Authors: Yang Fu, Ge Yang, Feng Zhu, Cong Peng, Wei Li, Haitao Li, Hong-Gyum Kim, Ann M. Bode, Ziming Dong, Zigang Dong
Journal: Cancer Research (2014)

Abstract Although the rate of development of drug resistance remains very high, 5-Fu is still the most common chemotherapeutic drug used for the treatment of colon cancer. A better understanding of the mechanism of why cancers develop resistance to 5-Fu could improve its therapeutic effect. Sometimes antioxidants are used simultaneously with 5-Fu treatment. However, a recent clinical trial showed no advantage or even a harmful effect of combining antioxidants with 5-Fu compared to administration of 5-Fu alone. The mechanism explaining this phenomenon is still poorly understood. In this study, we show that 5-Fu can induce reactive oxygen species-dependent Src activation in colon cancer cells. Mouse embryonic fibroblasts that are deficient in Src showed a clear resistance to 5-Fu, and knocking down Src protein expression in colon cancer cells also decreased 5-Fu-induced apoptosis. We found that Src could interact with and phosphorylate caspase-7 at multiple tyrosine sites. Functionally, the tyrosine phosphorylation of caspase-7 increases its activity, thereby enhancing cellular apoptosis. When using 5-Fu and antioxidants together, Src activation was blocked, resulting in decreased 5-Fu-induced apoptosis. Our results provide a novel explanation as to why 5-Fu is not effective in combination with some antioxidants in colon cancer patients, which is important for clinical chemotherapy. Keywords: antioxidant; 5-Fu; Src; caspase-7; colon cancer; apoptosis Citation Format: Yang Fu, Ge Yang, Feng Zhu, Cong Peng, Wei Li, Haitao Li, Hong-Gyum Kim, Ann M. Bode, Ziming Dong, Zigang Dong. Antioxidants decrease the apoptotic effect of 5-Fu in colon cancer by regulating Src-dependent caspase-7 phosphorylation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 778. doi:10.1158/1538-7445.AM2014-778
Varenicline for Smoking Reduction Prior to Cessation
Authors: R. Brooks Robey, Clay A. Block, Daniel J. O’Rourke
Journal: JAMA (2015)

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Abstract 3710: Dose-Dependent Effects of N-3-Polyunsaturated Fatty Acids on Left Ventricular Function, Endothelial Dysfunction, and Interleukin-6 in Patients With Severe Chronic Heart Failure of Non-Ischemic Origin
Authors: Deddo Moertl, Alexandra Hammer, Rudolf Berger
Journal: Circulation (2009)

Objectives The GISSI-HF trial demonstrated that 1g of n-3 polyunsaturated fatty acids (n-3 PUFA) provides a small survival advantage in patients with chronic heart failure (CHF). However, for trigl...