tbuckley/cabot-search huggingface dataset:
Research Ethics Boards: Reply from Trudo Lemmens and Carl Elliott
Authors: Trudo Lemmens, Carl Elliott
Journal: PLoS Medicine (2006)

Joal HillI read with interest the debate about for-profi t versus non-profi t institutional review boards (IRBs) [1], but was disappointed that no one addressed the ability (or inability) of for-profi t IRBs to review studies with the local context of research subjects in mind and then monitor what actually occurs during the consent process throughout the research trial.To my mind the "bigness" of for-profi t IRBs may be more of an impediment in protecting research subjects than their inherent confl ict of interest.Our IRB has reviewed consent forms approved by central/for-profi t IRBs that contained obvious errors such as schemas that did not match protocol narrative and use of eight point font in a study of geriatric subjects.Even when the initial review is outstanding, it seems a practical impossibility for a single IRB to provide meaningful monitoring of the actual consent process and implementation of the protocol at sites throughout the country.The greater "effi ciency" of for-profi t IRBs is only a meaningful benefi t if increased speed can be shown not to occur at the expense of careful review of consent forms, real understanding of the local research context, and a commitment to audit the informed consent process throughout the study for the protection of research subjects, including ongoing education and advice for researchers and their teams.This is not to say that all local IRBs perform this function as they should, but it does seem almost impossible for one IRB to perform local review and oversight for research sites around the nation in a way that really makes a difference for the men, women, and children who give of their time and their bodies so that society can benefi t.
miR-18b overexpression identifies mantle cell lymphoma patients with poor outcome and improves the MIPI-B prognosticator
Authors: Simon Husby, Ulrik Ralfkiaer, Christian Garde, Roza Zandi, Sara Ek, Arne Kolstad, Mats Jerkeman, Anna Laurell, Riikka Räty, Lone B. Pedersen, Anja Pedersen, Mats Ehinger, Christer Sundström, Marja-Liisa Karjalainen-Lindsberg, Jan Delabie, Erik Clasen-Linde, Peter Brown, Jack B. Cowland, Christopher T. Workman, Christian H. Geisler, Kirsten Grønbæk
Journal: Blood (2015)
Heart Failure and Neonatal Hypocalcaemia
Authors: O. Troughton, S. P. Singh
Journal: BMJ (1972)

Six infants had congestive heart failure for which no cause could be found apart from a low serum calcium. All except one recovered completely and had normal chest x-ray appearances and E.C.G.s on discharge from hospital. Necropsy on the infant who died shoed engorgement and dilation of the right side of the heart and a small ductus but no other abnormalities. It is suggested that hypocalcaemia should be considered as a possible cause of heart failure in infants, especially when oedema is prominent.
Hospitalization for Congestive Heart Failure
Authors: Mark Alexander
Journal: JAMA (1995)

<h3>Objective.</h3> —To determine whether the higher rate of hospitalization among African Americans for congestive heart failure (CHF) could be explained by racial differences in the prevalence of clinical risk factors for CHF. <h3>Design.</h3> —Retrospective cohort study. <h3>Setting.</h3> —A large health maintenance organization (HMO). <h3>Patients.</h3> —A sample of 64877 enrollees (27% African American and 73% white) of the Northern California Kaiser Permanente Medical Care Program who took at least one multiphasic health checkup (MHC) at or after the age of 40 years and were free of CHF at that time. <h3>Main Outcome Measures.</h3> —First hospitalization with a principal diagnosis of CHF. <h3>Results.</h3> —Among cohort members younger than 60 years at baseline MHC, the age-adjusted risk ratio (RR) (African American/white) for CHF hospitalization was 2.14 for men and 2.73 for women, while for persons 60 years of age and older at MHC, the age-adjusted RR was 1.48 for both sexes. Cox proportional hazards models were used to adjust for risk factors and length of follow-up. In persons aged 60 years and older, the race difference was explained by greater prevalence of hypertension and diabetes in African Americans (RR=1.12; 95% confidence interval [Cl], 0.94 to 1.34 after adjustment for hypertension and diabetes). In those younger than 60 years, findings differed by sex. For men, African-American race was no longer a significant predictor of CHF after adjusting for hypertension, diabetes, left ventricular hypertrophy on electrocardiogram, and body mass index (adjusted RR=1.16; 95% Cl, 0.86 to 1.56). However, among younger women, African Americans continued at increased risk despite adjustment for these variables as well as smoking, plasma cholesterol, renal function, alcohol use, and myocardial infarction (adjusted RR=1.49; 95% Cl, 1.00 to 2.21). <h3>Conclusions.</h3> —In this HMO population, the race differences in first hospitalization for CHF are largely explained by known clinical and behavioral risk factors, although in younger women these risk factors do not completely explain the excess risk among African Americans. These findings highlight the role of hypertension and diabetes in the development of CHF, particularly among African Americans. (<i>JAMA</i>. 1995;274:1037-1042)
Global health initiatives need to be better coordinated
Authors: Tessa Richards
Journal: BMJ (2008)

Managing aid has become a challenge for healthcare providers and policy makers in poor countries. Their task would be easier if there were better coordination and collaboration between the 100 or so different global health initiatives, delegates were told at a recent conference on global health held on 29 April at the Royal College of Physicians in London.

In a day devoted to discussing challenges in global health, from climate change to the rise in non-communicable disease, several speakers focused on the need for more concerted efforts.

Nick Banatvala, head of global health at the Department of Health, drew attention to the UK government’s new global health strategy, which will be launched later this year.

He emphasised that its evolution has been underpinned by a recognition of the need …
Abstract 970: Acquired sorafenib resistance is associated with enhanced invasive capability in A549 cells.
Authors: Qingyu S. Zhou, Diane Allen-Gipson
Journal: Cancer Research (2013)

Abstract Acquired tumor resistance to molecular targeted anti-cancer therapeutics poses a significant challenge in cancer therapy. Extensive studies have revealed diverse mechanisms that give rise to resistant phenotypes. The present study aims to identify phenotypic characteristics associated with acquired tumor resistance to sorafenib, a multi-targeted tyrosine kinase inhibitor, using both in vitro and in vivo sorafenib-resistant human lung cancer models. We established our in vitro sorafenib-resistant model using A549 human lung adenocarcinoma cells, which were continuously exposed to increasing concentrations of sorafenib (from 4 μM to 9 μM) over 10 months. Sorafenib-resistant A549 (A549R) cells gained the spindle-shaped morphology and exhibited an approximately 2-fold increase in the IC50 as compared with parental A549 cells [mean IC50 of 9.0 μM vs. 4.4 μM, p &amp;lt; 0.01 (N=6)]. Both Western blotting and immunocytochemical analysis revealed the loss of E-cadherin expression in A549R cells. Measurements of transendothelial electrical resistance (TEER; ohms) were conducted using Electric Cell Impendence Sensing (ECIS) in human umbilical vascular endothelial cell (HUVEC) monolayer co-cultured with A549 parental or A549R cells. A549R cells reduced HUVEC resistance and exhibited greater ability to invade HUVEC monolayer as compared with A549 parental cells. Our in vivo sorafenib-resistant tumor model was established by exposing A549 xenografts to once daily treatment with 40 mg/kg of sorafenib for 3 months. Complete tumor regression was observed in 5 out of 8 sorafenib-treated mice bearing A549 xenografts, while invasive tumor growth was seen in the other 3 animals. The resultant in vivo sorafenib-resistant A549 xenografts further provide evidence that the development of sorafenib resistance in A549 cells are associated with enhanced invasive and disseminative capabilities. The ongoing effort is focused on the characterization of in vivo sorafenib-resistant A549 xenografts in order to identify the important drivers of invasion and motility of human lung cancer cells with acquired resistance to sorafenib. Citation Format: Qingyu S. Zhou, Diane Allen-Gipson. Acquired sorafenib resistance is associated with enhanced invasive capability in A549 cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 970. doi:10.1158/1538-7445.AM2013-970
Scintillation Scanning of Kidneys
Authors: MARIA G. BUSE
Journal: Annals of Internal Medicine (1964)

ExcerptRecent interest in unilateral renal disease as a cause of hypertension has prompted the development of several diagnostic tests. The renogram was the first attempt to use radioisotopes to compare the function of the two kidneys. However, this test did not indicate the relative sizes of the kidneys nor did it permit the visualization of parenchymal lesions. In 1959 Denneberg and Hedenskog (1) used I131-labeled sodium diatrizoate (Hypaque®) and iodopyracet (Diodrast®) for scintillation scanning of the kidneys. In 1960 McAfee and Wagner (2) proposed the use of chlormerodrin (Neohydrin®) labeled with radiomercury (Hg203), because it was highly concentrated in the...
Microbial IgA Proteases
Authors: Howard L. Bleich, Emily S. Boro, Andrew G. Plaut
Journal: New England Journal of Medicine (1978)

ALTHOUGH human beings swallow, inhale and otherwise encounter thousands of strains of bacteria and viruses during their lives, few of these micro-organisms are pathogenic. The vast majority are expelled unchanged; many others gain a place in the "normal flora" of the skin and mucous membranes, and very few cause infection. Nearly all disease-producing micro-organisms gain their initial foothold on the skin, mucous membranes, teeth and other structures in direct contact with the external environment. Those unable to attach are swept away by fluid flow, propulsive organ motility or cell shedding. Those that stick have withstood these mechanical defenses, but they . . .
Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis
Authors: Hong Wang, Hong Liao, Mahendar Ochani, Marilou Justiniani, Xinchun Lin, Lihong Yang, Yousef Al-Abed, Haichao Wang, Christine Metz, Edmund J Miller, Kevin J Tracey, Luis Ulloa
Journal: Nature Medicine (2004)
Efficacy of the topical nasal steroid budesonide on improving sleep and daytime somnolence in patients with perennial allergic rhinitis
Authors: K. Hughes, C. Glass, M. Ripchinski, F. Gurevich, T. E. Weaver, E. Lehman, L. H. Fisher, T. J. Craig
Journal: Allergy (2003)

Background: Improving quality of life is considered to be a major endpoint and motivation for clinical intervention in patients with perennial allergic rhinitis (PAR). In addition to classical symptoms of congestion, pruritus, and rhinorrhea, patients will often complain of not being able to sleep well at night and of feeling fatigued during the day. Like sleep apnea, PAR has also been shown to cause sleep disturbance and consequently worsen daytime fatigue and somnolence. Hypothesis: It is proposed that by decreasing nasal obstruction due to allergic rhinitis by treating with the topical steroid budesonide, symptoms of daytime fatigue and somnolence can be improved. Methods: Twenty‐two subjects were enrolled in a double‐blind, placebo‐controlled, crossover study using Baalam's design. Patients were treated with either budesonide 128 μ g/day or placebo. Subjective data include the Epworth Sleepiness Scale, Functional Outcomes of Sleep Questionnaire, Rhino‐conjunctivitis Quality of Life Questionnaire, and a daily diary recording nasal symptoms, sleep problems, and daytime fatigue. Results: The results illustrated that the topical nasal corticosteroid significantly improved daytime fatigue ( P = 0.03), somnolence ( P = 0.02), and quality of sleep ( P = 0.05) compared to placebo in patients suffering from PAR. Summary: Budesonide is able to improve congestion, sleep, and daytime somnolence.
Uraemic Pericarditis With Cardiac Tamponade: A Report of Four Cases
Authors: H. S. Symons, O. M. Wrong
Journal: BMJ (1964)

Pericarditis is a common complication of renal failure.It is usually an aseptic inflammatory process with fibrin formation but little fluid.Many authorities-for instance, de Wardener (1961) and Wood (1961)-make no mention of pericardial effusion resulting from uraemic pericarditis.However, Fish- berg (1954) remarked that " exceptionally there is a considerable serous or haemorrhagic effusion," and Lowry and Boyd (1960), out of a total of 227 cases of uraemic pericarditis, recorded 58 with hydropericardium and 3 with massive haemopericardium.Cardiac tamponade in uraemic pericarditis was first reported in the literature in 1956, when Goodner and Brown recorded the deaths of two young males with chronic renal disease.Acute right heart failure with pulsus paradoxus preceded death in both cases, and at necropsy 800 and 850 ml. of blood-stained fluid were found in the pericardial cavities.Since then six further cases have been reported (Guild, Bray, and Merrill, 1957;Hutt and Holmes, 1961;Merikas, Samartzis, and Marketos, 1962 ;Rappaport, 1962).In four of these cases some prolongation of life was obtained by pericardial tap; one case improved spontaneously.The following four cases of cardiac tamponade from uraemic pericarditis were seen in the renal unit at Hammersmith Hospital during 1961-2.
Ronald Canney John (Jack) Douglas Davies Edward Mervyn Evans Colin McLaren Maddox Ernst Philipp Jacob Shapiro Eric Charles Till Leon J Warshaw Arthur Whitewright Stanley Fausst Yolles
Authors: R. E C Collins
Journal: BMJ (2001)

Before going up to Cambridge, he spent a year at Würzburg University in Germany studying anatomy, where he was reprimanded for his anti-Nazi views.During the second world war he served in the Royal Navy as surgeon lieutenant, escorting convoys in the north Atlantic on HMS Maplin, a converted merchant ship
A ROENTGEN-RAY PHENOMENON IN THE NORMAL AND PATHOLOGIC HILUM
Authors: FELIX BAUM
Journal: JAMA (1927)

One of the most difficult problems of the roentgenologist is the distinction between the normal and the pathologic hilum. The clinician, in search of the roentgen-ray diagnosis, only too frequently receives the valueless information that the hilum is enlarged, suspicious looking, hazy, dense, swollen, or that there is a diffuse infiltration of the hilum. In order to understand the pathology of the hilum, we must bear in mind, first, that it is composed of: (1) pulmonary arteries and veins; (2) bronchial tubes, and (3) lymph glands and lymph vessels. The normal bronchial tubes and the normal lymph glands are practically invisible in a roentgen-ray film. The shadow, therefore, which is called "the normal hilum shadow," is caused by the pulmonary artery. Figure 1 shows the topography of the arteries and the bronchi. This picture was published, first, by my teacher Narath in Heidelberg. It demonstrates clearly the branches of the
Lupus Erythematosus-like Syndrome with Selective Complete Deficiency of C1q
Authors: HIROSHI NISHINO
Journal: Annals of Internal Medicine (1981)

A 37-year-old Japanese man in previously good health was hospitalized because of swelling of the auricles and discoid erythema of the face. Clinical and laboratory findings satisfied the diagnostic criteria for systemic lupus erythematosus proposed by the American Rheumatism Association. However, serologic studies showed weakly positive antinuclear factor and absence of anti-DNA antibody and lupus erythematosus cells. A striking abnormality was the total absence of serum hemolytic complement activity (CH50). Further studies showed selective complete deficiency of C1q, a subunit of the first component of complement (C1). This is the first reported case of lupus erythematosus-like syndrome with selective complete deficiency of C1q.
LOX-1 as a natural IFN-α–mediated signal for apoptotic cell uptake and antigen presentation in dendritic cells
Authors: Stefania Parlato, Giulia Romagnoli, Francesca Spadaro, Irene Canini, Paolo Sirabella, Paola Borghi, Carlo Ramoni, Ilaria Filesi, Silvia Biocca, Lucia Gabriele, Filippo Belardelli
Journal: Blood (2009)
The effects of milrinone on conduction, reflection, and automaticity in canine Purkinje fibers.
Authors: J M Davidenko, C Antzelevitch
Journal: Circulation (1984)

Milrinone is a newly developed analogue of amrinone possessing potent positive inotropic action. Electrophysiologic actions of the drug have not been reported. In this study microelectrode techniques were used to assess the electrophysiologic effects of milrinone in canine false tendons homogeneously superfused with either normal or high-K Tyrode's solution and in Purkinje fibers mounted in a three-compartment chamber in which the central segment was depressed with an "ischemic" solution. Milrinone (0.2 to 20 micrograms/ml) caused no major changes in the action potential characteristics, refractoriness, or conduction velocity in fibers exposed to normal Tyrode's solution, but markedly improved conduction and abbreviated or eliminated postrepolarization refractoriness in the ischemic gap preparations. The drug also exerted important effects on reflected reentry generated in these preparations. Depending on the initial level of block, milrinone (1) suppressed the arrhythmia, (2) shifted its frequency dependence, or (3) created the conditions that allowed reflection to occur. Similar results were obtained in homogeneously depressed fibers. At similar concentrations, milrinone caused a relatively small enhancement of automaticity. Thus, in addition to its inotropic actions, milrinone produces important electrophysiologic effects. By restoring or improving conduction through areas of depressed conductivity, the drug may exert either antiarrhythmic or arrhythmogenic effects.
Periodontal Disease: The sixth complication of diabetes mellitus
Authors: Harald Löe
Journal: Diabetes Care (1993)

Periodontal disease is a chronic inflammatory condition characterized by destruction of the periodontal tissues and resulting in loss of connective tissue attachment, loss of alveolar bone, and the formation of pathological pockets around the diseased teeth. Some level of periodontal disease has been found in most populations studied and is responsible for a substantial portion of the tooth loss in adulthood.
274. Genetic Immunotherapy Targeted to Antigen Presenting Cells Using a CD40-Targeted Adenoviral Vector
Authors: Disha A. Mody, Larry Smart, Yoshinobu Odaka, Xiao L. Li, Cigdem E. Yilmaz, Alexander V. Pereboev, J. Michael Mathis
Journal: Molecular Therapy (2005)

Introduction: Antigen Presenting Cells (APCs) specialize in capturing foreign antigens, displaying them on their cell surface along with MHC molecules to the lymphocytes and providing activation signals for their differentiation and proliferation. The main cell types that serve as APCs are dendritic cells and macrophages. They can capture, process and present antigens in association with MHC class I and class II molecules to na|[iuml]|ve CD8+ (cytotoxic) and CD4+ (helper) T lymphocytes, respectively. Through this process, specific cytotoxic T lymphocytes for that antigen are activated and they can recognize a target cell and kill it. The goal of this study was to determine the transducion efficiency of APCs using a CD40-targeted adenoviral vector expressing a tumor antigen. A second goal was to characterize transduced APCs to determine if APCs are suitable for use in tumor immunotherapy.
Endothelin and cardiac arrhythmias: do endothelin antagonists have a therapeutic potential as antiarrhythmic drugs?
Authors: F Duru
Journal: Cardiovascular Research (2001)

Endothelin-1 (ET-1), the predominant isoform of the ET peptide family and a potent vasoconstrictor, has been shown to aggravate ischemia-induced ventricular arrhythmias. However, there is also evidence that ET-1 may have a direct arrhythmogenic action that is not solely attributable to myocardial ischemia. Proposed mechanisms for the arrhythmogenic effects of ET-1 are prolongation or increased dispersion of monophasic action potential duration, QT prolongation, development of early afterdepolarizations, acidosis, and augmentation of cellular injury. As for an ionic basis for the observed electrophysiologic effects, ET-induced Ca(2+) release from intracellular stores, generation of inositol triphosphate, inhibition of delayed rectifier K(+) current, and stimulation of the Na(+)/H(+) exchanger may be involved. Recently, some studies have shown that ET receptor antagonists, which promise to be powerful tools in cardiovascular medicine, may also demonstrate antiarrhythmic properties. This review describes the current state of knowledge on the interactions between the ET system and cardiac arrhythmias, and discusses the therapeutic potential of ET antagonists as antiarrhythmic drugs.
Drug Therapy in the Heart Transplant Recipient
Authors: JoAnn Lindenfeld, Geraldine G. Miller, Simon F. Shakar, Ronald Zolty, Brian D. Lowes, Eugene E. Wolfel, Luisa Mestroni, Robert L. Page, Jon Kobashigawa
Journal: Circulation (2004)

art I of this series describes the mechanisms and types of rejection and the intravenous immunosuppressive drugs commonly used for induction or antirejection therapy.In this article, we review the commonly used oral immunosuppressive drugs.Intravenous corticosteroid methylprednisolone is included in the discussion of corticosteroids.Table 1 gives trade names, pharmacology, necessary adjustments for renal or hepatic dysfunction, and dosing and general monitoring guidelines for drugs described in this section.Table 2 lists the major adverse effects of immunosuppressive drugs described in Parts I and II of this review and provides an estimate of their relative frequency. Corticosteroids (Steroids)Steroids, among the first immunosuppressive agents used in clinical transplantation, have remained an important component of induction, maintenance, and rejection regimens.
Melanoma, halothane, and liver necrosis
Authors: M. Johnstone
Journal: BMJ (1967)

CYP2C19 is an important enzyme for human drug metabolism, and it also participates in the metabolism of endogenous substrates, whereas the CYP2C18 enzyme is not expressed in human liver despite high mRNA expression. Mice transgenic for the human <i>CYP2C18</i> and <i>CYP2C19</i> genes were generated. Quantitative mRNA analysis showed CYP2C18 and CYP2C19 transcripts in liver, kidneys, and heart to be expressed in a sexually dimorphic manner, with male mice having 2- to 100-fold higher levels. Transcript levels in the small intestine were somewhat higher than liver but were similar in both sexes. Transgene mRNA expression was much lower in lung and brain and least in the heart. Immunoblotting using an antipeptide antiserum, reactive with human CYP2Cs and mouse CYP2C70, revealed increased immunoreactive protein in liver microsomes from heterozygous transgenic male mice and a concomitant increase in 5′-hydroxylation of <i>R</i>-omeprazole and <i>S</i>-mephenytoin intrinsic clearance, consistent with CYP2C19 overexpression. A CYP2C18-specific antiserum showed that this enzyme was not expressed in livers or kidneys from heterozygous transgenic mice, but the antiserum had high affinity for recombinant CYP2C18 expressed in COS-7 cells. It is concluded that 1) both the <i>CYP2C18</i> and <i>CYP2C19</i> genes are subject to sexually dimorphic regulation in murine liver, kidney, and heart; 2) the CYP2C18 protein is not expressed in murine liver or kidney despite high levels of the corresponding mRNA; and 3) this transgenic model may be suitable for studying sex-dependent regulation of the human <i>CYP2C</i> genes and possibly serve as an in vivo model for CYP2C19-dependent drug metabolism.