tbuckley/cabot-search huggingface dataset:
Abstract 1266: Glioma biomarker discovery by mass spectrometry
Authors: Lennard Dekker, Majid Kheirollahi, Guenther Stockhammer, Theo Luider, Peter Sillevis Smitt
Journal: Cancer Research (2012)

Abstract BACKGROUND Approximately 200.000 people are diagnosed with a primary brain tumor each year worldwide. The most common type of primary brain tumor (∼40%) are gliomas. Currently available prognostic markers require evaluation of tumor tissue, such as 1p and 19q choromosome co-deletion in oligodendroglial tumors, MGMT promoter methylation for glioblastomas (GBMs), and IDH mutations in several glioma subtypes. Serum biomarkers that correlate with tumor status have prognostic and predictive value and could significantly improve the care for glioma patients. In addition biomarkers could provide unique information related to longitudinal response to therapy. The only clinically validated serum marker of prognosis and disease status in high grade gliomas is serum YKL-40, a chitinase homolog also called human cartilage glycoprotein 39 or chitinase 3-like 1. DESIGN/METHODS For the discovery phase we used a set of 31 cerebrospinal fluid samples. This sample set included 5 CSF samples of patients with a GBM and 26 controls. These samples were digested by trypsin and subsequently measured by LCMS-Orbitrap. The acquired data were analyzed using a database search and a subsequent analyses of the spectral counts by Scaffold. The spectral counts for each individual identified protein are used as a semi quantitative measure for protein abundance. RESULTS / CONCLUSIONS From the total list of 771 identified proteins, candidate biomarker proteins were selected that showed a significant difference between the control and GBM (p&amp;lt;0.01) and were at least 3 fold higher in spectral count than in the control group. Abundant serum proteins were removed to avoid inclusion of proteins that relate to the disruption of the blood-CSF barrier. Eventually, a list of eleven proteins was obtained that included 14-3-3 protein gamma, 72 kDa type IV collagenase, Alpha-enolase, Chitinase-3-like protein 1 (YKL-40), Fetuin-B, Glial fibrillary acidic protein, Insulin-like growth factor II, Metalloproteinase inhibitor 1, Serum paraoxonase/arylesterase 1, SPARC, IGF binding protein 2 and Metalloproteinase inhibitor 2. Many of the identified candidate markers have been previously reported in literature in relation to glioma including the clinically validated serum marker for glioma YKL-40. We are now planning a validation of these markers in a set of serum samples of glioma patients. 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 1266. doi:1538-7445.AM2012-1266
Naloxone, Itch, Asthma, Urticaria, and Angioedema
Authors: Simon Smitz, Jean-Jacques Legros, Marc Le Maire
Journal: Annals of Internal Medicine (1982)

Letters and Corrections1 November 1982Naloxone, Itch, Asthma, Urticaria, and AngioedemaSIMON SMITZ, M.D., JEAN-JACQUES LEGROS, M.D., MARC LE MAIRE, PH.D.SIMON SMITZ, M.D.Search for more papers by this author, JEAN-JACQUES LEGROS, M.D.Search for more papers by this author, MARC LE MAIRE, PH.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-97-5-788_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: We write to report beneficial actions of naloxone in two patients.A 54-year-old woman with a 5-year history of generalised itch of unknown origin was given a naloxone infusion (1.6 mg/h during 4 hours). During the days after this infusion, the itch gradually disappeared. Her perception of painful stimuli was reduced and remained unmodified by the treatment.A 39-year-old woman had a 25-year history of asthma, chronic urticaria, and angioedema. No specific allergy had been shown. Because of frequent episodes of laryngeal obstruction, glucocorticosteroids were administered for more than 10 years. After a similar naloxone infusion, clinical...References1. BERNSTEINSWIFT JR. Relief of intractable pruritus with naloxone. Arch Dermatol. 1979;115:1366-7. CrossrefMedlineGoogle Scholar2. BERNSTEINGRINZI JR. Butorphanol-induced pruritus antagonized by naloxone. J Am Acad Dermatol. 1981;5:227-8. CrossrefMedlineGoogle Scholar3. SUMMERFIELD J. Naloxone modulates the perception of itch in man. Br J Clin Pharmacol. 1980;10:180-2. CrossrefMedlineGoogle Scholar4. LESLIEBELLAMYPYKE RDD. Asthma induced by enkephalin. Br Med J. 1980;1:16-8. CrossrefGoogle Scholar5. BAR-ORMARXGOOD DJJ. Naloxone, beta-endorphins and high-altitude pulmonary edema. Ann Intern Med. 1982;96:684-5. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByAntipruritic treatment with systemic μ-opioid receptor antagonists: A reviewAntipruritische Therapie mit dem oralen Opiatrezeptorantagonisten NaltrexonPruritusPharmacokinetic data on antituberculous and antileprotic agentsEfficacy and safety of nalmefene in patients with severe pruritus caused by chronic urticaria and atopic dermatitisThe effects of nalmefene, a potent oral opiate antagonist, on exercise-induced bronchospasmDermatologic therapy: December, 1982, through November, 1983 1 November 1982Volume 97, Issue 5Page: 788-789KeywordsAllergy and immunologyAsthmaPerceptionUrticaria Issue Published: 1 November 1982 PDF DownloadLoading ...
The Doctor as Patient Advocate
Authors: Douglas D. Lind
Journal: JAMA (1989)

<h3>To the Editor.—</h3> The Journalcontinues to challenge the status quo and stimulate professional introspection. I have just read the commentary by Dr Moore<sup>1</sup>entitled "The Need for a Patient Advocate." Never have I felt so offended by a colleague. As a senior medical resident, I have spent 7 challenging and rewarding years in an attempt to become a physician. What, may I ask, is any physician if not foremost a patient advocate? Am I naive? The profession of medicine is under siege on many fronts. I, too, share many of Dr Moore's concerns about the new conflicting roles that physicians are increasingly asked to play. It seems clear to me that only by the vigilant preservation of a patient advocacy role for<i>all</i>physicians will we ever weather the storm. When did we throw in the towel?
Mediators of Ca2(+)-dependent secretion.
Authors: A Chaudhry, R P Rubin
Journal: Environmental Health Perspectives (1990)

Ca2+, an obligatory mediator of the secretory process, acts in concert with other second messengers that further amplify or inhibit the secretory response. In this overview, we will consider the relative roles of diacylglycerol (DAG), arachidonic acid, and cyclic AMP (cAMP) in modulating Ca2(+)-dependent secretion in nonexcitable cells. DAG, a product of phospholipase C (PLC)-catalyzed breakdown of phosphoinositides, stimulates protein kinase C. Ca2+ ionophores and phorbol esters (or DAG analogues) elicit a synergistic secretory response in the exocrine pancreas and parotid gland. These findings suggest that the complete activation of secretion requires stimulation of both Ca2(+)-dependent and protein kinase C-dependent pathways. Hydrolysis of phospholipids can also lead to the liberation of arachidonic acid in secretory cells. Endogenously generated arachidonic acid inhibits polyphosphoinositide synthesis in exocrine pancreas, leading to inhibition of agonist-induced IP3 formation, Ca2(+)-mobilization and amylase secretion. By contrast, arachidonic acid and its metabolites stimulate PLC in the rabbit peritoneal neutrophil, causing Ca2(+)-mobilization and lysosomal enzyme secretion. Arachidonic acid can thus serve as a positive or negative feedback regulator of secretion induced by Ca2(+)-mobilizing agonists. Finally, in the parotid gland, stimulation of amylase secretion by norepinephrine, the physiological mediator, which stimulates both the alpha and beta adrenoceptors, requires the interaction of both Ca2+ and cAMP pathways to produce a full secretory response. These studies, taken together, indicate that phosphoinositide and cAMP-dependent pathways play coordinate roles in signal transduction, leading to the Ca2(+)-mediated secretion.
Simple Gastric Ulcer and Carcinoma
Authors: B. F. Swynnerton, S. C. Truelove
Journal: BMJ (1951)

Equipoise is widely regarded to be an essential prerequisite for the ethical conduct of a randomised controlled trial. There are some circumstances however, under which it is acceptable to conduct a randomised controlled trial (RCT) in the absence of equipoise. Limited access to the preferred intervention is one such circumstance. In this paper we present an example of a randomised trial in which access to the preferred intervention, preschool education, was severely limited by resource constraints. The ethical issues that arise when conducting randomised trials in health care are considered in the context of trials of social interventions. In health, education and social welfare, effective interventions are frequently limited due to budgetary constraints. Explicit acknowledgement of the need to ration interventions, and the use of random allocation to do this even in the absence of equipoise, would facilitate learning more about the effects of these interventions.
Birch and ragweed pollinosis north of Milan: a model to investigate the effects of exposure to “new” airborne allergens
Authors: R. Asero
Journal: Allergy (2002)

Background: The effects of sudden and massive exposure of the general population to novel airborne allergens are not known. This study aimed to investigate the clinical effects of two “new” allergens, ragweed and birch, in an area north of Milan during the last 15 years. Methods: We reviewed the records of 2571 monosensitized patients seen during the last 10 years in two allergy units north of Milan. Data included age at onset of allergic symptoms, and family history of allergic diseases. In this sample, 500 were allergic to grass, mite, birch, and ragweed; 293 to pellitory; 167 to mugwort; 100 to Alternaria ; and 11 to plantain. Results: Birch pollen‐allergic patients and ragweed pollen‐allergic patients showed a similar mean age at onset (35.3 years vs. 35.1 years; P = NS), but were significantly older than all other groups of patients ( P &lt; 0.001). Patients allergic to ragweed and birch pollen, 304 and 323 respectively, were &gt;30 years at the onset of allergic symptoms. A family history of allergic disorders among first degree relatives was far less frequent among patients allergic to birch pollen (29%) or ragweed pollen (27%) than among patients sensitive to all other airborne allergens, except those allergic to mugwort pollen ( P &lt; 0.001). In both ragweed and birch groups, a positive family history was significantly more common among subjects &lt; 30 years than in those &gt; 30 years at onset of respiratory allergy (81/196 (41%) vs . 54/304 (18%), P &lt; 0.001 for the ragweed group; 80/177 [45%] vs. 65/323 (20%), P &lt; 0.001 for the birch group). Conclusion: Exposure of the general population of this area to two new airborne allergens resulted in the onset of respiratory allergy in many older people who lacked any relevant predisposing factor. Although we cannot exclude the possibility that those who became allergic had been exposed to birch or ragweed pollen elsewhere, a more likely explanation is a specific susceptibility that remains viable until the subject encounters the “right” allergen.
WHY PERCENTAGE FEEDING FAILS.A PLEA FOR ITS MORE FREQUENT ADOPTION BY THE GENERAL PRACTITIONER.
Authors: H. LOWENBURG
Journal: JAMA (1907)

3.5 per cent, to 4.5 per cent., and other usual condi- tions were imposed.The milk is cooled and bottled within a few minutes after it is drawn, put in the crate, the top of which is filled with cracked ice, whence it is delivered to the consumers.Because of the nearness of the farm to the city, less than three miles, the night and morning milk is delivered, reaching the consumer not more than nineteen hours from the time the oldest of it was drawn the night before.This has not been accomplished with the aid of an agricultural college graduate, or even an up-to-date farmer, but simply by using the means at hand.Our farmer employed the same foreman she had before, guided, of course, by the commission and its experts.every phase of it and in a brief space of time it will dawn on him what a simple matter percentage feeding is after all.Of the many methods of home modification
Cardiac Arrest and Anaphylaxis With Anesthetic Agents-Reply
Authors: Richard L. Keenan
Journal: JAMA (1985)

<h3>In Reply.—</h3> We are grateful to Forand and colleagues for calling attention to what should be a "hot" topic among anesthesiologists for the next few years. We agree that routine monitoring of blood oxygenation would not have warned the anesthetist of trouble in all the cardiac arrests in our report. But it would have given a valuable early warning in an important subset, as Forand et al suggest. Their contention that "hypoxia would have been a late sign" is a mere quibble. Our experience is that a monitored fall in saturation to as low as 50% occurs well before bradycardia is observed, and serves as a timely and very dramatic warning of a misplaced endotracheal tube. End-tidal carbon dioxide monitoring might prove to be an even better monitor of general well-being than oximetry. Any interruption in breathing would be immediately obvious; low cardiac output states might also be detected. Mass
P26 Utility of the chest X-ray in the era of IGRA testing for latent TB prior to anti-TNF therapy
Authors: S Tsim, J Anwar, L McLure, G Roditi, MM Cotton
Journal: Thorax (2013)

<h3>Introduction</h3> Anti-TNF therapies are associated with increased risk of reactivation of latent <i>Mycobacterium tuberculosis</i> infection (LTBI). Screening for LTBI is recommended prior to commencing anti-TNF therapy. BTS guidelines for screening incorporate epidemiologic risk, clinical examination, Mantoux testing and chest radiography (CXR). Other guidelines recommend use of interferon gamma release assays (IGRAs). We audited the use of IGRA and CXR as part of screening for LTBI in patients who were being considered for immuno-suppresant therapy. <h3>Methods</h3> All IGRAs requested from Glasgow Royal Infirmary (GRI) over a 21 month period were retrospectively assessed for the following: patient history, test indication and result, CXR report and patient outcome. GRI serves the most deprived population in the UK. A single laboratory provides TB bacteriology for the whole of Glasgow, and is the sole provider of IGRA testing for LTBI utilising the ‘T-Spot.<i>TB</i>’. <h3>Results</h3> Between August 2010-May 2012, 354 T-Spot.<i>TB</i> tests were performed. Planned immuno-suppressant therapy was the indication in 70% (n = 248); etanercept was the most commonly proposed drug (32%, n = 78), followed by adaluminab (29%, n = 72), anti-TNF not otherwise specified (11%, n = 28) and infliximab (6%, n = 15). Of those for whom immunosupression was the indication, 80% (n = 199) of T-Spot.<i>TB</i> tests were negative, 17% (n = 41) indeterminate and 3% (n = 8) positive. A CXR was performed in all but 6% (n = 11). CXR findings and patient outcomes for patients with negative T-Spot.<i>TB</i> tests are summarised in table 1. All 16 abnormal CXRs were referred to a TB specialist for review and none had chemoprophylaxis commenced or any alterations in their management recommended. <h3>Conclusions</h3> With increasing use of IGRAs, new guidance on screening for LTBI prior to anti-TNF therapy is required. In our cohort of 248 patients, the majority had a negative T-spot test reflecting that despite high levels of deprivation TB prevalence in Glasgow is low. CXR did not alter patient management, TB chemoprophylaxis was not given in any case and there were no cases of LTBI reactivation or <i>de novo</i> TB within the follow-up period (11–32 months). We propose that if IGRA is negative, CXR is not required as part of screening for LTBI prior to anti-TNF therapy.
ERROR OF BASING SERUM DIAGNOSIS OF SYPHILIS ON THE KAHN REACTION ALONE
Authors: SIGMUND S. GREENBAUM
Journal: JAMA (1926)

It is so well known and generally recognized that the Wassermann test may at times yield a falsely negative reaction in syphilis that it is not my purpose here to discuss the subject except to state that improvements in technic have reduced their occurrence to a minimum, this being especially true of the Kolmer complement-fixation test. But the question of falsely positive reac  tions has been discussed at even greater length, so that the impression generally prevails that the occurrence of falsely positive Wassermann reactions is even more common than falsely negative reactions. This is certainly not true of the Kolmer complement-fixation test, as experience has shown conclusively its specificity for syphilis, as indicated by the recent review of Kilduffe.1The Kolmer test has been used in this clinic for about four years, and in no instance can falsely positive reactions be said to have occurred. But the Kolmer test
Prediction of Steroid Responsiveness in the Idiopathic Nephrotic Syndrome Using Urinary Retinol-binding Protein and Beta-2-Microglobulin
Authors: Ricardo Sesso, Alze P. Santos, Sonia K. Nishida, Michael J. Klag, Joao T. Carvalhaes, Horacio Ajzen, Oswaldo L. Ramos, Aparecido B. Pereira
Journal: Annals of Internal Medicine (1992)

▪ Objectives: To determine the prevalence of early proximal tubular dysfunction, measured by urinary excretion of retinol-binding protein (RBP) and beta-2-microglobulin (B2M), in patients with the idiopathic nephrotic syndrome and to investigate the value of these tests in predicting steroid responsiveness. ▪ Design: Before-after trial with 8-week treatment period. ▪ Setting: Tertiary referral center. ▪ Patients: Sequential sample of 37 patients with the idiopathic nephrotic syndrome caused by minimal change disease, focal segmental glomerulosclerosis, or mesangial proliferative glomerulonephritis. ▪ Intervention: All patients were treated with prednisone as one dose of 1 to 1.5 mg/kg body weight per day for 8 weeks. ▪ Measurements: Urinary RBP was measured by an immunoenzymometric assay and B2M, by an enzyme-linked immunosorbent assay. Remission of the nephrotic syndrome after steroid treatment was the main outcome variable. ▪ Results: Elevated levels of urinary RBP and B2M before treatment were detected in 65% and 75% of the patients, respectively. Median urinary RBP and B2M, before treatment, were significantly higher in the steroid-unresponsive group than in the responsive group (P < 0.01). In the steroid-responsive group, urinary RBP and B2M levels decreased significantly after remission (P < 0.01). In the steroid-unresponsive group, the likelihood ratios for urinary RBP greater than 4000 μg/g creatinine and for B2M greater than 3000 μg/g creatinine were 3.8 and 3.0, respectively. The probability was 100% that values of RBP of less than 1300 μg/g creatinine and B2M of less than 130 μg/g creatinine were from steroid-responsive patients. Multivariate analysis confirmed that higher urinary levels of RBP and B2M were associated with a lower likelihood of steroid responsiveness, independent of age and histologic diagnosis. ▪ Conclusions: Proximal tubular dysfunction is frequent in patients with the idiopathic nephrotic syndrome. Pretreatment urinary RBP and B2M levels may be helpful in identifying nephrotic patients who are more likely to be responsive to steroids.
Sleep Deprivation and Performance of Residents
Authors: Timothy B. McCall
Journal: JAMA (1989)

<h3>To the Editor.—</h3> In their article entitled "Sleep Deprivation and Resident Performance," Deaconson et al<sup>1</sup>state, "The strength of our study is its design." They could not be more wrong; the study's design is so flawed that their results and conclusions must be questioned. The subjects were surgical residents working every other night on call. The residents served as their own controls: the study compared them when sleep deprived—after a night on call—with when rested—after a night off. The authors assumed that residents who slept the previous night were rested, but this is hardly a safe assumption. The effects of acute sleep deprivation last far longer than 24 hours.<sup>2</sup>Many residents describe difficulty concentrating "the day after the day after" a night on call—precisely when the rested controls were tested. The authors fail to consider that the control group may also have been sleep deprived, both acutely, as
GW25-e4351 Sodium Tanshinone IIA Sulfate Reduces Elevated Serum High Sensitivity C-Reactive Protein in Patients with Coronary Heart Disease: a Prospective Randomized Open-label Blinded End Point Trial
Authors: Li Siming, Shang Qinghua, Chen Keji, Xu Hao
Journal: Journal of the American College of Cardiology (2014)
Microcylinders of endoplasmic reticulum in histiocytes in patients suffering from Degos' syndrome and dermatomyositis
Authors: L. OLMOS, N. HUNZIKER, P. LAUGIER
Journal: British Journal of Dermatology (1979)

Rare intracytoplasmic membranous inclusions derived from the endoplasmic reticulum were observed in the histiocytes of one case of Dego' syndrome and one case of dermatomyositis. Cross-section and longitudinal sections made it possible to establish a three-dimensional model in which both microcylinders and layers of rolled-up double membranes appear.
Clenbuterol Induces Hypertrophy of the Latissimus Dorsi Muscle and Heart in the Rat With Molecular and Phenotypic Changes
Authors: Mario Petrou, Dylan G. Wynne, Kenneth R. Boheler, Magdi H. Yacoub
Journal: Circulation (1995)

Background Skeletal muscle assistance of the circulation for patients in end-stage heart failure requires electrical training of the latissimus dorsi flap to produce fatigue resistance. This process of electrical transformation and the development of postmobilization atrophy results in a profound loss in peak power generated. The β 2 -adrenoceptor agonist clenbuterol was used to investigate its potential to selectively induce skeletal muscle hypertrophy, particularly the latissimus dorsi muscle (LDM), independent of adverse effects on cardiac muscle. Methods and Results Forty-one male Sprague-Dawley rats were divided into four groups and used in this study. Clenbuterol 2 μg · g body wt −1 · d −1 was administered subcutaneously for a period of either 5 weeks (group A) or 2 weeks (group A1). Groups B and B1 (controls) were injected with 0.5 mL normal saline once daily. At the end of the experimental period, all rats were weighed and terminally anesthetized for removal of the left LDM, left gastrocnemius-plantaris-soleus (GPS) muscles, and heart. The results showed that the increase in body weight did not differ significantly between the clenbuterol-treated and control groups ( P &gt;.5). The ratio of LDM to tibial length (hypertrophic index) for groups A and A1 was significantly greater than controls ( P &lt;.01), which represented a 20% to 29% increase. The hypertrophy was more pronounced for hindlimb skeletal muscle (21% to 35% for GPS), and the effects of this relatively high dose of clenbuterol on the heart were less marked (18% to 20% hypertrophy). RNA analyses indicate that ventricles of clenbuterol-treated rats express elevated levels of mRNA to atrial natriuretic factor without a concomitant increase in skeletal α-actin and β-myosin heavy chain, consistent with a “physiological” form of cardiac hypertrophy. Conclusions Clenbuterol induces significant hypertrophy of the LDM associated with specific changes in cardiac gene expression.