tbuckley/cabot-search huggingface dataset:
Hydroxyurea treatment decreases glomerular hyperfiltration in children with sickle cell anemia
Authors: Banu Aygun, Nicole A. Mortier, Matthew P. Smeltzer, Barry L. Shulkin, Jane S. Hankins, Russell E. Ware
Journal: American Journal of Hematology (2012)

Glomerular hyperfiltration and microalbuminuria/proteinuria are early manifestations of sickle nephropathy. The effects of hydroxyurea therapy on these renal manifestations of sickle cell anemia (SCA) are not well defined. Our objective was to investigate the effects of hydroxyurea on glomerular filtration rate (GFR) measured by 99m Tc‐DTPA clearance, and on microalbuminuria/proteinuria in children with SCA. Hydroxyurea study of long‐term effects (HUSTLE) is a prospective study (NCT00305175) with the goal of describing the long‐term cellular, molecular, and clinical effects of hydroxyurea therapy in SCA. Glomerular filtration rate, urine microalbumin, and serum cystatin C were measured before initiating hydroxyurea therapy and then repeated after 3 years. Baseline and Year 3 values for HUSTLE subjects were compared using the Wilcoxon Signed Rank test. Associations between continuous variables were evaluated using Spearman correlation coefficient. Twenty‐three children with SCA (median age 7.5 years, range, 2.5–14.0 years) received hydroxyurea at maximum tolerated dose (MTD, 24.4 ± 4.5 mg/kg/day, range, 15.3–30.6 mg/kg/day). After 3 years of treatment, GFR measured by 99m Tc‐DTPA decreased significantly from 167 ± 46 mL/min/1.73 m 2 to 145 ± 27 mL/min/1.73 m 2 ( P = 0.016). This decrease in GFR was significantly associated with increase in fetal hemoglobin ( P = 0.042) and decrease in lactate dehydrogenase levels ( P = 0.035). Urine microalbumin and cystatin C levels did not change significantly. Hydroxyurea at MTD is associated with a decrease in hyperfiltration in young children with SCA. Am. J. Hematol., 88:116–119, 2013. © 2012 Wiley Periodicals, Inc.
The role of B lymphocyte stimulator (BLyS) in systemic lupus erythematosus
Authors: Michael P. Cancro, David P. D’Cruz, Munther A. Khamashta
Journal: Journal of Clinical Investigation (2009)

SLE, a chronic, multisystem autoimmune disorder with a broad range of symptoms, involves defective B cell selection and elimination of self-reactive B cells. B lymphocyte stimulator (BLyS), a soluble ligand of the TNF cytokine family, is a prominent factor in B cell differentiation, homeostasis, and selection. BLyS levels affect survival signals and selective apoptosis of autoantibody-producing B cells. High levels of BLyS may relax B cell selection and contribute to autoantibody production, exacerbating the SLE disease state. This review discusses the mechanism of BLyS action on B cells, its role in SLE, and specific targeting of BLyS in the treatment of SLE.
The Anesthesiologist in Patient Care
Authors: Kenneth M. Janis
Journal: JAMA (1970)

<h3>To the Editor.—</h3> The statement by Brown et al (<b>211</b>:76, 1970) that "paradoxically, the physician groups most in favor of change were those least responsible for the care of dying patients—anesthesiologists" is not only an oversimplification but a wrong impression of what actually occurs in intensive care units and in the care of the dying. In many transplant centers anesthesiologists are key members of teams acting to certify donor suitability and are often charged with great responsibility in determination of the actual moment of death. The anesthesiologist is rapidly becoming the bearer of the responsibility for the institution and management of resuscitative procedures and the judge of their success or failure. An anesthesiologist is often the first one to answer a "Code 99" call and by nature of his training is frequently the most qualified of the personnel available. To say that anesthesiologists are "... specialists not giving traditional kinds
1055. High Levels of Human Factor IX Expression in Hemophilia B Mice after Adult Stem Cell-Based Gene Therapy Combined with Non- Myeloablative Conditioning
Authors: Alex H. Chang, Leszek Lisowski, Michel Sadelain
Journal: Molecular Therapy (2006)

Various cell types have been targeted for expression of clotting factors in experimental models of hemophilia, with muscle and hepatocyte-directed gene transfer advancing to clinical trials. Hematopoietic stem cells (HSCs) are attractive alternative targets because of their self-renewing properties, their ability to generate blood cells over extended periods of time, and their ease of manipulation ex vivo. However, several hurdles must be overcome to make this approach safe and practical. These include the need to express sufficient amount of therapeutic gene products and minimize the risk of insertional mutagenesis and the toxicity of host conditioning to facilitate HSC engraftment. We have previously developed an erythoid cell-specific platform for long-term and systemic therapeutic protein delivery in vivo using an erythroid- specific lentiviral vector. We demonstrated in an immune competent C57BL/6 hemophilia B mouse model, that therapeutic levels of human factor IX (hFIX) can be expressed at low average vector copy (VC) number (250-350 ng/mL with under 0.5 VC per cell). In this study, we examined the level of erythroid-specific protein delivery obtained after engraftment following minimal conditioning, eventually in the presence of in vivo methylguanine methyltransferase (MGMT)-mediated drug resistance. Low to moderate levels of hFIX expression were achieved in control, lethally irradiated mice (average 100-200 ng/ml), 4-weeks post-transplantation. In non-myeloablated recipients conditioned with 400 cGy or Busulfan (20 mg/kg, given twice at 48 h and 24 h before engraftment), the levels of hFIX expression were ranged from negligible to low (0-20 ng/ml and 0 – 100 ng/ml, respectively). Four weeks after the first round of BG/BCNU (30 mg/kg and 5 mg/kg, respectively), a wide range of hFIX expression levels were achieved, reaching in some mice levels equivalent to 20% of physiological levels in humans. We are currently monitoring long-term hFIX expression, as well as the average VC number in blood cells and CFUs. Further rounds of drug selection are also in progress. In conclusion, our data suggest that it is possible to express high levels of a secreted protein from HSC-derived erythroid cells engrafted under minimal conditioning. The combined features of reduced intensity conditioning, reduced insertional mutagenesis due to low vector copy number requirement and erythroid-specific transgene expression, as well as long-term protein expression at therapeutic levels, increase the potential applicability of adult stem cell-based gene therapy in non-lethal disorders such as hemophilia.
Tetralogy of Fallot
Authors: MALCOM C. MCCORD, JACK VAN ELK, S. GILBERT BLOUNT
Journal: Circulation (1957)

The considerable body of clinical and physiologic data in patients with the tetralogy of Fallot that has been accumulated over the past 15 years now indicates that the original concept of the lesion as a single, fairly narrowly limited entity is no longer valid. The tetralogy can now be demonstrated to occupy a broad spectrum in the field of congenital cardiac anomalies, representing widely varying forms. While the entity has been termed a tetralogy, only 2 features, namely the pulmonary stenosis and the ventricular septal defect, are essential in the determination of the clinical and physiologic pattern that patients with this defect portray.
Is all learning innovation?
Authors: Luke Rendell, William Hoppitt, Jeremy Kendal
Journal: Behavioral and Brain Sciences (2007)

Abstract Research on animal innovation is an underdeveloped field, and for this reason we welcome the efforts Ramsey and colleagues have made to stimulate its study in wild populations. However, we feel that in attempting to find an operational definition the authors have overstretched the idea of what we should consider innovation in some areas and over-restricted it in others.
SI Units in Medicine: An Introduction to the International System of Units With Conversion Tables and Normal Ranges
Authors: Rudolph H. de Jong
Journal: JAMA (1978)

The World Health Organization, at its 30th assembly in 1977, recommended adoption of the International System of Units of Measurement (SI) by the medical community throughout the world. While our European colleagues already have behind them several years of this modern version of the metric system and British medical journals introduced SI this year, American journals are just now awakening to WHO's call. American readers will profit from the Continental experience collected in this handy reference manual—a translation-revision of the 1976 German text, with normal laboratory values adjusted for norms reported in English-language texts. The color band arrangement is extremely useful for quickly getting used to unfamiliar numbers and units: green band covers the range of normal values, and the surrounding yellow bands bracket the extreme limits of normal. Values printed against the white background outside of these colored bands are considered beyond normal limits. For quick reference, tables of
Recurrent renal calculi.
Authors: W Brumfitt, I Rosenstein, J M Hamilton-Miller
Journal: BMJ (1981)

East.-9 Fifthly, far from having no side effects as stated by Dr Haworth, mepacrine in doses of 100 mg/day is well known to cause in a proportion of persons mental disturbances, aplastic anaemia, and derma- toses.I " Finally, not one but six of the seven signatories have recent experience of practising medicine in the tropics.This brings us to the substance of our recommendations.In areas of chloroquine resistance our first recommendation would be Fansidar, but there is need for an alternative during pregnancy and for those sensitive to sulphonamides.In our view the risks from malaria are greater than the risks from twice-weekly Maloprim.Nevertheless, it is only fair to state that whereas our recommendations were made in conformity with those of a committee at the London School of Hygiene and Tropical Medicine, that committee decided at a subsequent meeting on 14 January to err on the side of caution and to recommend a once-weekly dose of Maloprim for those who need to take it.The subject needs further study.However, on the basis of our own and other people's experience we believe that the recommendations were the best available in the light of current knowledge.
Engraftment capacity of mesenchymal cells following hematopoietic stem cell transplantation in patients receiving reduced-intensity conditioning regimen
Authors: A Poloni, P Leoni, L Buscemi, F Balducci, R Pasquini, M C Masia, N Viola, E Costantino, G Discepoli, P Corradini, A Tagliabracci, A Olivieri
Journal: Leukemia (2005)
Abstract 757: Identification and characterization of small molecule activators of BRCA1 expression
Authors: Lisa M. Harlan-Williams, Jeffrey A. Overton, Shane R. Stecklein, Wenjia Wang, Roy A. Jensen
Journal: Cancer Research (2010)

Abstract Breast cancer susceptibility gene 1 (BRCA1) has been intensely investigated in normal and cancerous cells and mutations in the BRCA1 gene have been found to account for half of the hereditary breast cancer cases. Although the role of BRCA1 in sporadic breast cancer is still uncertain, 30-40% of such cases show downregulation of BRCA1 expression. Because BRCA1 is a tumor suppressor gene, decreased expression of BRCA1 accelerates growth of mammary tumor cells, while increased expression leads to growth arrest and apoptosis. Furthermore, overexpression of BRCA1 in the murine mammary gland provides protection against mutagen-induced mammary neoplasia. In 2009, the American Cancer Society estimates that 254,650 new cases of invasive and in situ breast cancer will be diagnosed among women. Based on estimates of BRCA1 dysfunction in sporadic breast cancers, over 80,000 newly diagnosed malignancies would have decreased BRCA1 expression. Therefore, a novel prevention or therapeutic strategy targeting BRCA1 could have significant impact on incidence and/or survival. We developed an MCF-7 breast cancer cell line containing stably integrated copies of a BRCA1 promoter-driven firefly luciferase reporter plasmid and screened over 100,000 compounds for their ability to increase BRCA1-firefly luciferase expression. Six hundred and sixty two compounds (hits) increased BRCA1-firefly luciferase activity greater than 2 standard deviations above the control, DMSO. Secondary dose-response BRCA1-firefly luciferase assays confirmed 27 of the top 32 hits as true active compounds. Potency and efficacy of the active compounds were characterized quantitatively as effective concentration (EC50) and area under the curve (AUC), respectively. Cell viability assays determined that the active compounds had little cytotoxic effects. Non-cytotoxic compounds that increased BRCA1-firefly luciferase activity in a dose-dependent manner with a potency (EC50) and efficacy (AUC) greater than or equal to that of genistein, the positive control, were selected to move forward as lead compounds. Thus far, several lead compounds have been identified. Western blot analysis indicates lead compound 17 increases endogenous BRCA1 expression. Furthermore, DNA foci formation assays indicate compound 17 enhances the ability of BRCA1 to localize to sites of ionizing radiation-induced DNA damage. Because BRCA1 appears to play a role as a growth inhibitor and tumor suppressor in adult breast tissues, identification and characterization of a plausible active compound that enhances BRCA1 expression could potentially translate into a novel prevention or therapeutic option for patients afflicted with breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 757.
Liability Immunity for Physician Volunteers
Authors: Robert McCool
Journal: JAMA (1994)

<h3>To the Editor.</h3> —Many physicians who entered the medical profession with an idea of ministering to the underprivileged are frustrated. They think of volunteering as a means of restoring a balance to their lives, but are severely constrained by high malpractice costs. The state of Virginia set a precedent when it passed a state law in 1983 (amended in 1992 and 1994) that holds volunteers at free clinics throughout the state free of liability (Va Code ch 1, Title 54.1-1.06 §32.1-127.3). This law was essential in convincing physicians to volunteer.<sup>1</sup>Utah (§58-12-3.5.), North Carolina (GS 90-21.14, §1), Florida (§766.1115), Kentucky (Ky Rev Stat ch 42), and South Carolina (§33-55-210) also passed legislation granting liability immunity with various restrictions to physicians providing free care at eligible places. The intent is to protect the volunteer from frivolous and unwarranted lawsuits; all states mentioned allow for recovery when physicians act in a
A systematic review of mechanisms of change in mindfulness-based cognitive therapy in the treatment of recurrent major depressive disorder
Authors: Anne Maj van der Velden, Willem Kuyken, Ulla Wattar, Catherine Crane, Karen Johanne Pallesen, Jesper Dahlgaard, Lone Overby Fjorback, Jacob Piet
Journal: Clinical Psychology Review (2015)

The investigation of treatment mechanisms in randomized controlled trials has considerable clinical and theoretical relevance. Despite the empirical support for the effect of mindfulness-based cognitive therapy (MBCT) in the treatment of recurrent major depressive disorder (MDD), the specific mechanisms by which MBCT leads to therapeutic change remain unclear.
Frozen Pre-embryos
Authors: J. A. Kiernan
Journal: JAMA (1990)

7b the Editor.—  The article Frozen Pre-embryos 1 by the Board of Trustees of the American Medical Association contains the following statement: Because fertilized eggs are frozen before the embryonic stage of development, they are referred to as pre-embryos.  The early stages of development, including the formation of the blastocyst and inner cell mass, are described in textbooks of embryology, and there is no reason for using a special word for the early embryo. The only terms needed are oocyte (before fertilization), embryo (the period of morphogenesis occupying the first 8 weeks) and fetus (the period dominated by growth, from the ninth week until delivery). 2,3   The ridiculous term pre-embryo was introduced in Britain in 1986, when practitioners of in vitro fertilization were campaigning for legislation to permit research with early human embryos. 4 The intention was to pull the wool over the eyes of the general public, among whom
Fibroid Uterus Confounding the Correct Localization of Active Gastrointestinal Bleeding During Tc-99m RBC Scan
Authors: Andreia Roxana Gafton, Vicente Jose Caride
Journal: Clinical Nuclear Medicine (2006)

The unexpected visualization of the normal or pathologic uterus has been reported in the radionuclide imaging literature. Occasionally, this may create a diagnostic dilemma during interpretation of Tc-99m RBC scans, bone scans, or renal scans and additional imaging modalities are usually necessary to further define the abnormality. We report an interesting case of fibroid uterus identified as an intense, heterogeneous, and persistent vascular pelvic mass during a Tc-99m RBC scan in a patient with concomitant active lower gastrointestinal hemorrhage.
EXTRAPERITONEAL PELVIC CONDITIONS IN WOMEN
Authors: LEO BRADY
Journal: JAMA (1930)

It is not with the intention of presenting any new method of diagnosis or treatment that I have prepared this paper. It is rather to direct attention more forcibly to a group of conditions which, although not of frequent occurrence, are encountered sufficiently often to deserve more attention than is usually given them. Specifically, by reporting a few cases that I have had under my care I will stress the fact that any one doing abdominal surgery is apt to encounter an inflammatory condition or tumor which, on superficial examination, appears to be within the peritoneal cavity, whereas careful study will show it to be extraperitoneal. The general treatment and the surgical approach are different in extraperitoneal and intraperitoneal conditions, and failure to differentiate between these two groups of cases may result in serious consequences to the patient. On three occasions I have been asked to see patients who were
International Expert Committee Report on the Role of the A1C Assay in the Diagnosis of Diabetes
Authors: Eric S. Kilpatrick, Zachary T. Bloomgarden, Paul Z. Zimmet
Journal: Diabetes Care (2009)

Members of the International Expert Committee have recommended that diabetes should be diagnosed if A1C is ≤6.5%, without need to measure the plasma glucose concentration (1). We are concerned that practical limitations will lead to false positives and negatives with this approach.

A given A1C instrument may identify some but not other abnormal hemoglobins (http://www.ngsp.org/prog/index2.html). How, therefore, can we be sure whether a hemoglobinopathy is causing (or preventing) diagnosis? Before diagnosis, should we not also exclude iron deficiency anemia, which may increase A1C by 1–1.5%, as well as hemolytic anemia and renal failure or chronic infections, which also lower …
Escitalopram, Problem-Solving Therapy, and Poststroke Depression
Authors: Alice Rasmussen
Journal: JAMA (2008)

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Intramuscular Gene Transfer of Soluble Tumor Necrosis Factor-α Receptor 1 Activates Vascular Endothelial Growth Factor Receptor and Accelerates Angiogenesis in a Rat Model of Hindlimb Ischemia
Authors: Masahiro Sugano, Keiko Tsuchida, Naoki Makino
Journal: Circulation (2004)

In a pathological setting, tumor necrosis factor (TNF)-alpha inhibits the proliferative response of endothelial cells through inactivation of receptors for vascular endothelial growth factor (VEGF). Soluble TNF-alpha receptor 1 (sTNFR1) is an extracellular domain of TNFR1 and an antagonist to TNF-alpha. In the present study, we examined the effect of sTNFR1 expression plasmid on receptor for VEGF (KDR/flk-1) and angiogenesis in a rat model of hindlimb ischemia.The left femoral artery was exposed and excised to induce limb ischemia. A total of 400 microg of sTNFR1 or LacZ plasmid was injected into 3 different sites of the adductor muscle immediately after the induction of ischemia. TNF-alpha bioactivity in ischemic adductors increased in rats receiving LacZ plasmid compared with sham-operated rats. However, sTNFR1 plasmid significantly suppressed the increase in TNF-alpha bioactivity. KDR/flk-1 mRNA and tyrosine phosphorylation of KDR/flk-1 were significantly increased in the muscles injected with sTNFR1 plasmid compared with those injected with LacZ plasmid. VEGF increased both in muscles injected with sTNFR1 plasmid and in muscles injected with LacZ plasmid but did not differ significantly between them. At 21 days after the induction of ischemia, the sTNFR1 plasmid-transfected muscles showed significantly increased capillary density compared with LacZ plasmid-transfected muscles.In a rat model of hindlimb ischemia, VEGF increased but activation of KDR/flk-1 was suppressed, possibly by TNF-alpha, which might impair angiogenesis. Suppression of TNF-alpha with sTNFR1 plasmid upregulated KDR/flk-1 and accelerated angiogenesis. Local transfection of the sTNFR1 gene can be a new strategy for therapeutic angiogenesis in peripheral ischemic diseases.
A Unique Population of Ventral Tegmental Area Neurons Inhibits the Lateral Habenula to Promote Reward
Authors: Alice M. Stamatakis, Joshua H. Jennings, Randall L. Ung, Grace A. Blair, Richard J. Weinberg, Rachael L. Neve, Frederick Boyce, Joanna Mattis, Charu Ramakrishnan, Karl Deisseroth, Garret D. Stuber
Journal: Neuron (2013)