tbuckley/cabot-search huggingface dataset:
Management of Multiple Sclerosis
Authors: Richard A. Rudick, Jeffrey A. Cohen, Bianca Weinstock-Guttman, Revere P. Kinkel, Richard M. Ransohoff
Journal: New England Journal of Medicine (1997)

Multiple sclerosis is a common disease of the central nervous system affecting approximately 1 million young adults, mostly women, worldwide.1 It is characterized by episodic neurologic symptoms that are often followed by fixed neurologic deficits, increasing disability, and medical, socioeconomic, and physical decline over a period of 30 to 40 years.For most of the 20th century, multiple sclerosis was considered untreatable. In 1982, the Multiple Sclerosis Society of Canada and the National Multiple Sclerosis Society of the United States sponsored the first international workshop on therapeutic trials.2 This workshop served to usher in an era of activism and optimism . . .
KINETIC ENERGY EJECTION FRACTION: A BETTER MARKER OF CARDIAC FUNCTION IN THE SINGLE VENTRICLE CIRCULATION
Authors: James Wong, Radomir Chabiniok, Kuberan Pushparajah, Eva Sammut, Shane M. Tibby, David Celermajer, Daniel Giese, Tarique Hussain, Gerald Greil, Tobias Schaeffter, Reza Razavi
Journal: Journal of the American College of Cardiology (2015)
IMPACT OF EICOSAPENTAENOIC ACID ON PROGNOSIS IN PATIENTS WITH ISCHEMIC HEART DISEASE AND OPTIMALLY CONTROLLED LDL-CHOLESTEROL LEVEL
Authors: Ryotaro Yamada, Teruyoshi Kume, Yoji Neishi, Ai Kawamura, Koichiro Imai, Tomitaka Higa, Kenzo Fukuhara, Tomoko Tamada, Terumasa Koyama, Hiroshi Okamoto, Kiyoshi Yoshida, Hiroyuki Okura
Journal: Journal of the American College of Cardiology (2015)
NOVEL IN-HUMAN FOUR DIMENSIONAL WALL SHEAR STRESS CALCULATION OF A CORONARY BIORESORBABLE SCAFFOLD USING OPTICAL COHERENCE TOMOGRAPHY IMAGES AND BLOOD FLOW SIMULATIONS
Authors: Boyi Yang, Bill Gogas, Gaetano Esposito, Olivia Hung, Emad Rasoul Arzrumly, Marina Piccinelli, Spencer King, Don Giddens, Alessandro Veneziani, Habib Samady
Journal: Journal of the American College of Cardiology (2015)
Incontinentia pigmenti in a father and daughter
Authors: E. Rashidghamat, C.K. Hsu, A. Nanda, L. Liu, H. Al-Ajmi, J.A. McGrath
Journal: British Journal of Dermatology (2016)

Incontinentia pigmenti (IP) is a rare multi-system X-linked dominant genetic disorder caused by mutations in IKBKG, encoding inhibitor of nuclear factor kappa-B kinase subunit gamma (IKK-γ).Functionally, the encoded IKK-γ protein participates in nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) signalling to regulate inflammatory and immune responses and prevent
A9.7 Cholesterol crystals induce neutrophil extracellular traps formation
Authors: Ivica Jeremic, Christine Schorn, Luis Munoz, Tatjana Terzic, Georg Schett, Martin Herrmann
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> Besides phagocytosis as mechanism to combat pathogens, neutrophils are able to eject DNA decorated with microbicidal proteins (neutrophil extracellular traps-NETs), that can immobilize and kill microorganisms extracellularly. Procoagulative properties of NETs have already been shown, however, a role of NETs formation in atherosclerotic disease has not been described so far. The process of chromatin release is referred to as NETosis. The aim of this study was to assess if cholesterol crystals are able to induce NETosis <i>in vivo</i> and <i>in vitro</i>. <h3>Materials and Methods</h3> Polymorphonuclear cells-PMNs were isolated from blood obtained from healthy volunteers after informed consent. Isolated PMNs as well as whole blood were co/cultured with cholesterol crystals. After the treatment, cytospins were prepared and stained for DNA and neutrophil elastase. Extracelullar DNA was quantified by fluorometry. For <i>in vivo</i> experiments, cholesterol crystals were injected into murine air pouches. After 24h, air pouches were lavaged with PBS. After centrifugation cells were used for cytospins and supernatants for cytokines determination. Tophus-like aggregates were isolated and characterised by immune histochemistry and immunobloting. In addition, human autopsy specimens obtained from subject died of cardiac diseases were assessed for presence of NET markers. <h3>Results</h3> Cholesterol induced dose dependent NETosis in isolated PMNs as well as in whole blood samples. The maximal applied concentration of cholesterol crystals induced 236.5% higher DNA release when compared to control. Cholesterol crystal injected in air pouches induced tophus-like aggregates composed of aggregated NETs attached to the cholesterol crystals. These structures were highly positive for citrullinated histones, markers of NET formation. NET markers were also found in atherosclerotic blood vessels in zones surrounding necrotic core of atheromatous plaque, which is rich in cholesterol crystals <h3>Discussion</h3> This study showed for the first time ability of cholesterol crystals to induce NETosis <i>in vitro</i>, as well as <i>in vivo</i>. These data may explain prompt thrombus formation in atherosclerotic disease after rupture of fibrous cap of an atheromatous plaque containing huge amount of cholesterol crystals, which will be the subject of our future research.
Abstract LB-39: Development of a novel water-soluble prodrug of paclitaxel that is cleaved by prostate-specific antigen (PSA): <i>In vitro</i> and <i>in vivo</i> evaluation
Authors: Bakheet Elsadek, Ralph Graeser, Norbert Esser, Khalid Abu Ajaj, Tahia Saleem, Nagla El Melegy, Hafez Madkor, Felix Kratz
Journal: Cancer Research (2010)

Abstract In developed countries, prostate cancer is the second most frequently diagnosed cancer, and the third most common cause of death from cancer in men. Unfortunately, while accumulating clinical data have suggested that the taxanes may prolong the survival in a subset of men with prostate carcinoma, the dose and duration of administration of these drugs are limited by their significant systemic toxicities due to a lack of tumor selectivity. Besides prostate cancer, paclitaxel (Taxol®) is currently showing a promising antitumor activity against a variety of human tumors. In an attempt to improve both the water solubility and tumor targeting properties of paclitaxel, we set out to develop a water soluble paclitaxel prodrug that is activated specifically by prostate-specific antigen (PSA) which is solely expressed in prostate tissue and prostate carcinoma with high levels up to mg/g present in human prostate carcinoma. Using albumin as an efficient carrier for drug delivery, we describe a novel albumin-binding prodrug of paclitaxel, EMC-Arg-Ser-Ser-Tyr-Tyr-Ser-Leu-PABC-Paclitaxel [EMC: -maleimidocaproyl; PABC: p-aminobenzyloxycarbonyl] that was synthesized by reacting EMC-Arg-Ser-Ser-Tyr-Tyr-Ser-OH with H-Leu-PABC-Paclitaxel. This prodrug exhibited excellent water-solubility and was bound rapidly to the cysteine-34 position of endogenous and exogenous albumin. Moreover, incubation studies with PSA demonstrated that the albumin-bound form of the prodrug was cleaved rapidly at the P1-P‘1 scissile bond releasing the paclitaxel-dipeptide H-Ser-Leu-PABC-Paclitaxel. Above all, due to the incorporation of a PABC self-eliminating linker, this dipeptide was rapidly degraded to liberate paclitaxel as a final cleavage product within a few hours in prostate tumor tissue homogenates. Of note was that the albumin-bound form of the prodrug was approximately 4-fold more active in killing PSA-positive LNCaP cells than paclitaxel. In addition, orientating toxicity studies in mice showed that the maximum tolerated dose of the novel paclitaxel prodrug was twice that of conventional paclitaxel. Therefore, the in vivo efficacy of the prodrug (24 mg/kg paclitaxel equivalents) in comparison to free paclitaxel (12 mg/kg) is currently being evaluated in a mouse model of human prostate cancer using luciferase transduced LNCaP LN cells orthotopically implanted in SCID mice. 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 LB-39.
Latent introduction to the Netherlands of multiple antibiotic resistance including NDM-1 after hospitalisation in Egypt, August 2013
Authors: E Bathoorn, A W Friedrich, K Zhou, J P Arends, D M Borst, H Grundmann, J W Rossen
Journal: Eurosurveillance (2013)

We describe the introduction of various multi-drug resistant bacterial strains, including an NDM-1-producing Klebsiella pneumoniae, through a traveller returning from Egypt, where they had been admitted to a private hospital. All family members of the patient were colonised with one or more extended-spectrum beta-lactamase producing strains. These findings emphasise the importance of adherence to isolation precautions for returning patients and suggest the need for inclusion of Enterobacteriaceae in admission screening.
Oral Flecainide Acetate for the Treatment of Ventricular Arrhythmias
Authors: Jeffrey L. Anderson, James R. Stewart, Benjamin A. Perry, Daniel D. Van Hamersveld, Theresa A. Johnson, Gordon J. Conard, Shaw F. Chang, Donald C. Kvam, Bertram Pitt
Journal: New England Journal of Medicine (1981)

The antiarrhythmic efficacy and safety of oral flecainide acetate were assessed during a controlled, short-term dosage-maintenance study. Thirteen patients with chronic ventricular ectopy entered a placebo control period, and 11 with persistent, frequent (>600 per 12 hours) premature ventricular complexes (PVCs) advanced to drug therapy. Of 10 patients completing a trial of different doses, nine responded completely, with a mean PVC suppression of 98.3 per cent. Repetitive PVCs were eliminated. The mean effective dose was 189 mg per 12 hours, and the effective plasma concentration before administration of a dose averaged 635 ng per milliliter. One patient responded partially (68 per cent of PVCs suppressed). Flecainide continued to be effective and well tolerated at the end of a two-week outpatient trial in the nine complete responders, maintaining an average PVC suppression of 94.6 per cent. The PR and QRS intervals were mildly prolonged. The echocardiographic ejection fraction was unchanged during treatment. The elimination half-life was long — 18.8±3.8 hours. Flecainide thus appears to be a highly effective and well-tolerated antiarrhythmic agent with favorable pharmacokinetics. (N Engl J Med. 1981; 305:473–7.)
THU0145 Novel Peptide Biomarkers Detected by Mass Spectrometry Predict Arthritis in Seropositive Arthralgia Patients
Authors: T. V. Pham, L. A. van de Stadt, J. C. Knol, P. M. van de Ven, M. Boers, C. R. Jimenez, D. van Schaardenburg
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Persons with IgM-rheumatoid factor and/or anti-CCP in their blood (seropositive) are at increased risk for developing rheumatoid arthritis (RA). In our ongoing seropositive arthralgia cohort, this risk is 40% after 2 years if there is a high level of anti-CCP or anti-CCP and RF are both positive [Bos ARD 2010]. Other biomarkers may further improve the predictive value of these tests for developing RA. Serum mass spectrometry-based peptide profiles of different patient groups can be compared and correlated with clinical data to assist in diagnosis, monitoring and/or prediction. <h3>Objectives</h3> To identify peptides in patient plasma associated with risk for RA. <h3>Methods</h3> Out of 370 seropositive arthralgia patients (arthritis conversion rate of 35% after two years), we selected 40 patients who had developed arthritis during follow up (after a mean of 1 year, 90% RA according to the 2010 criteria) and 40 who had not developed arthritis. Their plasma had been stored at -20 degrees. Serum peptide profiling was carried out using automated magnetic C18 bead-assisted serum peptide capture coupled to matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS). The raw mass spectra were pre-processed with in-house bioinformatics software tools [Voortman, Proteome Science 2009]. Statistical analysis was conducted by using the Mann–Whitney <i>U</i> test with adjustment for multiple testing by the Benjamini-Hochberg method. Significance was defined as an adjusted <i>p</i>-value below 0.05. Logistic regression with forward selection was used to select from the peptides found in univariate analyses those that improved prediction of group membership over RF and anti-CCP. <h3>Results</h3> Five peptides were significantly elevated in patients who developed arthritis compared to those who did not (Figure 1). In four out of five peptides this association was independent of RF, anti-CCP or double positivity. One peptide was associated with anti-CCP status. In logistic regression two peptides were identified that, when added to RF and anti-CCP, significantly improved the predictive accuracy for RA (the Nagelkerke <i>R</i><sup>2</sup> increased from 30% to 60%, <i>p</i>-value for likelihood ratio test for model comparison &lt; 0.001). <h3>Image/graph</h3> <h3>Conclusions</h3> We found five peptides strongly related to arthritis development. This result was independent of the presence of (the combination of) RF and anti-CCP. A panel of two peptides, and RF and anti-CCP were found to be highly predictive of arthritis development. Validation in an independent cohort is necessary to verify the added value of these peptides in the prediction of RA. <h3>Disclosure of Interest</h3> None Declared
A8.08 The role of epigenetics in determining the clinical response to methotrexate for the treatment of rheumatoid arthritis
Authors: S Cregan, K Creevey, T McGarry, C Orr, DJ Veale, U Fearon, AG Wilson
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> Rheumatoid Arthritis (RA) is a chronic inflammatory autoimmune disease which leads to progressive joint destruction. RA is characterised by synovial hyperplasia and invasion of the synovium into the adjacent bone and cartilage. The precise aetiology of RA is not known, but both genetic and environmental influences play a role. Methotrexate (MTX) is the most commonly used disease modifying anti-rheumatic drug in the management of RA, however its mechanism of action remains poorly understood. In this study, we aim to identify the functional effects of MTX on primary RA synovial fibroblasts (RASFC) and to determine if the epigenetic signature of RASFC/CD14<sup>+</sup> monocytes can predict clinical response to MTX. <h3>Materials and methods</h3> Primary RASFC were isolated from synovial biopsies obtained from patients undergoing arthroscopic examination. RASFC were cultured in the presence or absence of MTX (10–100 μM). Cell migration, invasion, viability/proliferation, adhesion and pro-inflammatory cytokine expression were assessed by: wound repairs assays, transwell matrigel<sup>TM</sup> invasion chambers, MTT/ Crystal violet cell growth assay, xCELLigence Real Time Cell Analyser and ELISA respectively. In parallel, CD14<sup>+</sup> monocytes were isolated from peripheral blood mononuclear cells from RA patients both pre- and 12 weeks post-MTX therapy and global methylation was assessed. <h3>Results</h3> MTX (10 μM) inhibited RASFC repopulation of the wound margins in comparison to vehicle control where migration across the wound was clearly evident (n = 7, p = 0.03). In parallel, MTX (100 μM)significantly decreased RASFC invasion (n = 7, p = 0.01) and altered cytoskeletal dynamics through inhibition of lamellopodia and filopodia formation, which are indicative of cell movement. MTX had no inhibitory effect on the expression of IL-6, IL-8 and RANTES. Importantly, we determined that the effect of MTX on RASFC migration and invasion were independent of both cell viability (p = 0.37) and proliferation (p = 0.18). Finally preliminary results demonstrated altered DNA methylation in CD14<sup>+</sup> monocytes from RA patients (n = 11) at 3 months post MTX treatment. <h3>Conclusions</h3> MTX inhibits RASFC migration, invasion and cytoskeletal re-arrangement, mechanisms which are critically involved in the pathogenesis of RA. Further preliminary data suggests that the effect of MTX on pro-inflammatory mechanisms in RA, maybe be mediated through alterations in epigenome.
The Vital Capacity as a Measure of the Spontaneous Breathing Ability in Poliomyelitis
Authors: B. G. Ferris, A. Warren, C. A. Beals
Journal: New England Journal of Medicine (1955)

THERE has long been a need for a simple objective criterion to indicate when use of a respirator should be started during the acute illness of poliomyelitis and to guide the weaning of patients with respiratory-muscle paralysis from respirators. Some authors1 , 2 have used the vital capacity during the acute illness to indicate when patients should be placed in a respirator. They presented no objective data for the statement that patients should be placed in tank respirators when the vital capacity was 25 per cent of the predicted value. Affeldt3 measured the vital capacity at intervals during periods of unassisted breathing . . .
A Traumatic Experience
Authors: Patricia Thomas, Nancy Ryan Lowitt
Journal: New England Journal of Medicine (1995)

A 41-year-old woman collapsed at home and was taken to the hospital. In the emergency room, her blood pressure was 130/78 mm Hg, and her temperature was 36.5°C. No arrhythmia, murmur, or bruits were detected on cardiovascular examination. She was aphasic and had a left hemiparesis involving the face, arm, and leg.The case presented is of a young woman who was brought to the emergency room with a persistent neurologic deficit that is most consistent with stroke. I would like to know her history at this point, particularly whether she smoked or used medications, including oral contraceptives . . .
Sites of Abnormal Tracer Accumulation on a Radionuclide Cystogram
Authors: MANU M. BHATTATHIRY, JOHN H. MILLER
Journal: Clinical Nuclear Medicine (1996)

A 13-year-old girl with an 8-year history of paraplegia, neurogenic bladder, and ileocystoplasty (a surgical reconstruction of the bladder incorporating an isolated loop of the distal ileum as part of the bladder wall) was examined for vesicoureteral reflux with a radionuclide cystogram using Tc-99m pertechnetate. Abnormal tracer uptake was noted in the thyroid and stomach, which was likely due to the rapid absorption of tracer into the circulation after being absorbed from the ileal/colonic mucosa in the ileocystoplasty. The authors recommend that a nonabsorbable tracer such as Tc-99m SC be used when performing a radionuclide cystogram in patients with bladders reconstructed from the gastrointestinal tract.
Abstract 1864: Role of store-operated Ca2+ entry in proliferation and cell cycle in melanoma
Authors: Masanari Umemura, Erdene Baljinnyam, Mariana S. De Lorenzo, Stefan Feske, Lai-Hua Xie, Kousaku Iwatsubo
Journal: Cancer Research (2012)

Abstract Background: Melanoma has a poor prognosis due to its rapid progression and a high metastatic ability. Ca2+ homeostasis plays a pivotal role in proliferation in cancer cells, but little is known about the role of Ca2+ in melanoma. Store-operated calcium entry (SOCE) is defined as Ca2+ entry from extracellular space triggered when Ca2+ store in the endoplasmic reticulum (ER) is depleted. SOCE is regulated by coordination between Orai (ORAI calcium release-activated calcium modulator) in the plasma membrane, and STIM1 (stromal interaction molecule 1) in the ER. We examined the role of Ca2+ in melanoma cells especially focusing on SOCE. Method: Intracellular Ca2+ level was measured by using Fluo4-AM, a Ca2+-sensing fluorescent dye. Cell proliferation was measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Cells were stained with propidium iodide and cell cycle was assessed using flow cytometer. Protein phosphorylation microarray was performed by using a commercially available kit (Cancer Signaling Phospho-Antibody Array). Results: SOCE, as demonstrated by enhancement of Ca2+ entry from extracellular space after Ca2+ depletion in the ER, was observed in SK-MEL-2, C8161, SK-MEL-24, UACC257 (human) and B16 (mouse) melanoma cell lines, suggesting that the existence of SOCE is universal among melanoma cells. SOCE was attenuated by Pyr3, a pyrazole compound which is known to inhibit SOCE, as well as by EGTA that chelates extracellular Ca2+. Pyr3 inhibits cellular proliferation in SK-MEL-2 cells (IC50: 5.1uM) and C8161 cells (IC50: 2.1uM). Cell cycle was analyzed in C8161 cells, and the cell number in the G2 phase was increased by both Pyr3 and EGTA, indicating that SOCE plays a role in the transition of G2/S phase. Protein microarray data showed that Pyr3 reduces phosphorylation of signal transducers and activators of transcription 5 (STAT5) by 93%, suggesting that the JAK/STAT pathway may be involved in SOCE-induced alteration of cell cycle. Conclusion: Our results showed that inhibition of SOCE suppresses proliferation in melanoma, thus it could be a new strategy for melanoma therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1864. doi:1538-7445.AM2012-1864
Aminoglycoside Therapy of Gram-Negative Bacillary Meningitis
Authors: Allen B. Kaiser, Zell A. McGee
Journal: New England Journal of Medicine (1975)

The distribution of aminoglycosides in the cerebrospinal fluid (CSF) space was examined after intralumbar, intraventricular, and systemic administration during seven episodes of gram-negative bacillary meningitis. Six episodes were associated with culture proved ventriculitis. Parenteral therapy with gentamicin or tobramycin produced low concentrations of aminoglycoside (less than 1.0 mug/ml) in the lumbar, ventricular, and cisternal CSF. Administration of 5 to 10 mg of aminoglycoside into the lumbar intrathecal space resulted in 27-81 mug/ml in the lumbar CSF, but 0-2.1 mug/ml in the ventricular CSF. In contrast, aminoglycoside administered into the cerebral ventricles produced concentrations in the lumbar CSF of 11.5-27.5 mug/ml and ventricular CSF of 12.8-40 mug/ml. All six episodes treated via the ventricular route resulted in a bacteriologic cure. Intraventricular administration of aminoglycosides offers a reliable means of achieving high aminoglycoside concentrations throughout the subarachnoid space.