tbuckley/cabot-search huggingface dataset:
The future of onychomycosis therapy may involve a combination of approaches
Authors: R.J. Hay
Journal: British Journal of Dermatology (2008)

Onychomycosis is a fungal infection of the nail unit, most commonly caused by the anthropophilic dermatophyte fungi. It is generally accepted that this disease is increasing in prevalence despite the introduction of new and efficacious antifungal drugs. Several studies have documented health-related quality-of-life issues associated with onychomycosis and it is clear that patient treatment is both necessary and desirable. The aetiology and pathogenesis of onychomycosis is coming under increasing scrutiny and work in this field has grown substantially in recent years. This is reflected by the increased assurance with which clinicians can now prescribe treatment and be confident of improvement in a majority of their patients. However, a significant proportion of patients, perhaps as many as 25-40% of those encountered in clinical practice, are classified as treatment failures. Clinical indicators for poor prognosis include the development of residual foci of subungual fungal growth, onycholysis and severe disease. These observations have led to a resurgence of interest in combination treatments for use in patients at risk of failure/relapse. Several types of combination can be considered, including the use of oral or topical drugs and the concomitant use of surgical techniques, all of which have a place in the treatment of onychomycosis.
Smoke and Letters
Authors: Simon Chapman
Journal: JAMA (1994)

<h3>To the Editor.</h3> —We read with interest the Editorial by Dr Rennie<sup>1</sup>concerning letters to the editor written by individuals affiliated with the tobacco industry. Rennie did a good job in explaining the industry's apparent motives in submitting these letters and in describing how the industry uses such published letters. Rennie states that "the editor must strive to see every side presented, to let the reader assess how substantial the arguments really are." The problem with this position is that it ignores the role of the editor in assessing the quality of the arguments. In deciding whether to publish a letter to the editor, journal editors must judge the quality of the evidence and argument in the letter, just as they make judgments about the quality of research papers they receive. When Rennie "lean[s] over backwards to ensure that rational criticism is published," does he lean over so far
Effect of Sodium Phytate on the Hypercalciuria of Acute Quadriplegia Due to Poliomyelitis
Authors: P. Roy Vagelos, Philip H. Henneman
Journal: New England Journal of Medicine (1957)

DURING the 1955 Boston poliomyelitis epidemic attention was again called to the marked hypercalciuria that follows sudden immobilization and to the renal stones and other renal complications that may occur in patients with poliomyelitis. Since many more paraplegic and quadriplegic patients are now surviving for prolonged periods, these renal complications have become increasingly important. The current study was designed to determine the effect of sodium phytate on hypercalciuria in acute quadriplegia due to poliomyelitis.Albright and Reifenstein1 have emphasized the fact that the normal stimulus to osteoblastic activity is stress and strain. Immobilization inhibits osteoblastic activity while bone resorption continues . . .
Simultaneous manifestation of chronic lymphocytic leukemia (CLL) and hairy cell leukemia (HCL)
Authors: Lubomir Sokol, Steven J. Agosti
Journal: American Journal of Hematology (2004)

Abstract We report a unique case of 83‐year‐old Caucasian male with the initial simultaneous manifestation of chronic lymphocytic leukemia (CLL) and hairy cell leukemia (HCL). The patient presented with absolute lymphocytosis in the blood, asymptomatic generalized lymphadenopathy, and mild splenomegaly. The diagnosis of CLL was suggested from the blood film, but subsequent flow cytometric (FC) analysis on peripheral blood mononuclear cells (PBMNC) revealed two distinct abnormal clones of mature B cells. A small subpopulation (7%) of lymphoid cells expressed CD20, CD11c, FMC‐7, CD103, CD25, and kappa surface light chain, consistent with HCL. The larger subpopulation (75%) of lymphoid cells expressed CD19, CD20, CD23, CD5, and lambda light chain, consistent with CLL. The expression of different immunoglobulin light chains on the circulating CLL (lambda) and HCL (kappa) cells suggested two, independent, malignant B‐cell clones. Interestingly, FC analysis of bone marrow (BM) cells done 6 months later revealed bright lambda light chain expression on the HCL cells. Despite administration of several different courses of chemotherapy, the HCL subpopulation was not eliminated from the BM but remained stable between 7% and 10% of total BM lymphoid cells. The CLL, responsible for most of clinical symptoms in our patient, responded to combination chemotherapy with fludarabine and cytoxan, and later to monotherapy with rituximab. Am. J. Hematol. 75:107–109, 2004. © 2004 Wiley‐Liss, Inc.
In vitro approaches for determining mechanisms of toxicity and carcinogenicity by asbestos in the gastrointestinal and respiratory tracts.
Authors: B T Mossman
Journal: Environmental Health Perspectives (1983)

Organ and cell cultures of gastrointestinal and tracheobronchial epithelium have been used to document both the interaction of asbestos with mucosal cells and the sequence of cellular events occurring after exposure of cells to fibers. The biological activity of various types of asbestos in vitro is related to surface charge, crystallization, and dimensional characteristics. These factors also influence adsorption of natural secretions and serum components to fibers, a process that ameliorates cytotoxicity. Although mechanistic studies at the cellular level are lacking using epithelial cells of the digestive tract, asbestos appears to elicit a constellation of morphologic and biochemical changes in tracheal epithelium that resemble effects of classical tumor promoters on target cells.
Inhibition of apical Na+ channels in rabbit cortical collecting tubules by basolateral prostaglandin E2 is modulated by protein kinase C.
Authors: B N Ling, K E Kokko, D C Eaton
Journal: Journal of Clinical Investigation (1992)

We used the cell-attached patch clamp technique to investigate the interaction of exogenous prostaglandins (PG), intracellular [Ca2+]i, and protein kinase C (PKC) on the high selectivity, 4 pS Na+ channel found in the principal cell apical membrane of rabbit cortical collecting tubule (CCT) cultures grown on collagen supports with 1.5 microM aldosterone. Application of 0.5 microM PGE2 to the basolateral membrane decreased mean NP0 (number of channels times the open probability) for apical Na+ channels by 46.5% (n = 9). There was no consistent change in NP0 after apical 0.5 microM PGE2 (n = 12) or after apical or basolateral 0.5 microM PGF2 alpha (n = 8). Release of [Ca2+]i stores with 0.25 microM thapsigargin (n = 7), or activation of apical membrane PKC with apical 0.1 microM 4 beta-phorbol-12-myristate-13-acetate (n = 5) or 10 microM 1-oleyl-2-acetylglycerol (n = 4) also decreased NP0. Depletion of [Ca2+]i stores (0.25 microM thapsigargin pretreatment) (n = 7) or inhibition of apical PKC (100 microM D-sphingosine pretreatment) (n = 8) abolished the inhibitory effects of basolateral PGE2. Conclusions: (a) apical Na+ transport in rabbit CCT principal cells is modulated by basolateral PGE2; (b) the mechanism involves release of IP3-sensitive, [Ca2+]i stores; and (c) Ca(2+)-dependent activation of apical membrane PKC, which then inhibits apical Na+ channels.
A Case of Malignant Disease of the Pancreas
Authors: W. E. Fothergill
Journal: BMJ (1896)

THE following case of primary malignant disease of the pan- creas presents some striking resemblances to the two de- scribecd by Dr. Guthrie Rankin in the BRITlSH MEDICAL JOURNAL of May iith, I895, and, like them, it differs from the classical descriptions of the condition.
ANAPHYLAXIS TO PENICILLIN
Authors: Mardoqueo I. Salomon
Journal: JAMA (1949)

To the Editor:—  I wish to take exception to a clinical note that appeared inThe Journal, February 19, page 526, and that attributes the death of a patient to a (possibly intravenous) injection of penicillin. The author of the note, George L. Waldbott, believes that his patient's death was due to anaphylactic shock caused by the intravenously administered penicillin.  Unfortunately, an autopsy was not performed; moreover, it is to be lamented that the patient's mouth was not opened, because, in my opinion, the case looks much like one of  of the  as manifestation of an angioneurotic reaction. In fact, the signs and symptoms described by Waldbott may well be due to edema of the glottis (tightness in the nose and throat, cyanosis, itching all over—probably first manifestation of a generalized urticaria) and not to anaphylactic shock. Incidentally, this side effect of treatment with penicillin (especially with the
CQC defends rating of Hinchingbrooke as "inadequate"
Authors: M. Limb
Journal: BMJ (2015)

MPs have asked for more evidence to resolve a dispute over the care quality rating of “inadequate” conferred on a privately run NHS hospital.

Hinchingbrooke Health Care NHS Trust, which is managed under contract by the private firm Circle, was heavily criticised in a recent report by the Care Quality Commission.1 2 But the trust’s chief executive, Hisham Abdel-Rahman, told the House of Commons Committee of Public Accounts on 2 February that the report was “problematic” and contained many errors.

He said, “We sent them [the CQC] 300 factual inaccuracies. They agreed with 65% of those, but despite that they did not change the rating.” He said that there were “good explanations” for some of the incidents seen by the CQC during its inspections, but the regulator …
Immunologic Tolerance to Renal Allografts after Bone Marrow Transplants from the Same Donors
Authors: Mohamed H. Sayegh, Neil A. Fine, John L. Smith, Helmut G. Rennke, Edgar L. Milford, Nicholas L. Tilney
Journal: Annals of Internal Medicine (1991)

Excerpt In 1953, Billingham described a state of "actively acquired tolerance" to skin allografts developing after transfer of viable allogeneic cells to fetal or neonatal mice (1). This was followed by the identification by Mitchison of the "radiation chimaera" (2) and the demonstration by Main and Prehn of increased survival of specific donor strain skin allografts in x-irradiated and bone marrow reconstituted hosts (3). More recently, Strober (4) reported the cases of three patients treated with total lymphoid x-radiation who subsequently accepted cadaveric renal allografts. There have been no reports of acquired immunologic tolerance to specific organ allografts in humans. Patient
Trough imatinib plasma levels are associated with both cytogenetic and molecular responses to standard-dose imatinib in chronic myeloid leukemia
Authors: Stephane Picard, Karine Titier, Gabriel Etienne, Emmanuelle Teilhet, Dominique Ducint, Marie-Agnes Bernard, Regis Lassalle, Gerald Marit, Josy Reiffers, Bernard Begaud, Nicholas Moore, Mathieu Molimard, Francois-Xavier Mahon
Journal: Blood (2006)
Thallium 201 imaging and gated cardiac blood pool scans in patients with ischemic and idiopathic congestive cardiomyopathy. A clinical and pathologic study.
Authors: B H Bulkley, G M Hutchins, I Bailey, H W Strauss, B Pitt
Journal: Circulation (1977)

In ischemic cardiomyopathy (CM) fibrosis replaces large segments of myocardium, but in idiopathic congestive CM the myocardium contains only small foci of fibrosis or is morphologically normal. As coronary disease and myocardial infarction may be clinically silent, it is not always possible to distinguish ischemic from idiopathic congestive CM during life without cardiac catheterization. To determine whether noninvasive methods, thallium 201 myocardial (Tl) imaging and technetium 99m gated cardiac blood pool scans (GCBPS), could separate the entities, we evaluated radioisotope images of the heart in 13 patients with ischemic, and eight patients with idiopathic congestive CM, and 14 patients with normal hearts. Diagnosis was setablished by cardiac catherterization and/or autopsy in each of the 35 patients. The 14 normals could be readily distinguished from CM, and ischemic could be distinguished from idiopathic dilated CM in 20 of 21 patients. All patients with myocardiopathy showed hypokinetic and dilated left ventricles, but right ventricular dilatation was evident mainly in those with idiopathic CM. Tl images in the ischemic type had defects of greater than 40% of image circumference which corresponded to segmental wall motion abnormalities on GCBPS, whereas those with the idiopathic congestive form were homogeneous or had defects of less than 20% of image circumference. Autopsy studies in 7 of 35 patients correlated Tl defects of greater than 20% of circumference with transmural myocardial fibrosis.
Measuring Disease-Free Survival and Cancer Relapse Using Medicare Claims From CALGB Breast Cancer Trial Participants (Companion to 9344)
Authors: Elizabeth B. Lamont, James E. Herndon, Jane C. Weeks, I. Craig Henderson, Craig C. Earle, Richard L. Schilsky, Nicholas A. Christakis
Journal: JNCI Journal of the National Cancer Institute (2006)

To determine the accuracy with which Medicare claims data measure disease-free survival in elderly Medicare beneficiaries with cancer, we performed a criterion validation study. We merged gold-standard clinical trial data of 45 elderly patients with node-positive breast cancer who were treated on the Cancer and Leukemia Group B (CALGB) adjuvant breast trial 9344 with Centers for Medicare and Medicaid Services (CMS) data files and compared the results of a CMS-based algorithm with the CALGB disease-free survival information to determine sensitivity and specificity. For 5-year disease-free survival, the sensitivity of the CMS-based algorithm was 100% (95% confidence interval [CI] = 81% to 100%), the specificity was 97% (95% CI = 83% to 100%), and the area under the receiver operator curve was 98[corrected]% (95% CI = 95[corrected]% to 100%). For 2-year disease-free survival, the test characteristics were less favorable: sensitivity was 83% (95% CI = 36% to 100%), specificity was 95% (95% CI = 83% to 100%), and area under the receiver operator curve was 89[corrected]% (95% CI = 72[corrected]% to 100%).
Online Privacy and Your Teen
Authors: Megan A. Moreno
Journal: JAMA Pediatrics (2014)

Most US adolescents use the Internet for homework, entertainment, and to connect with friends.A popular Internet pastime is social media, which is usually described as media that allow interaction among users.Popular forms of social media are social networking sites such as Facebook.Other types include microblogging sites, such as Twitter, and video sharing sites such as YouTube.
European health ministers focus on migration of health workers
Authors: Rory Watson
Journal: BMJ (2011)

Hungary, which currently holds the six month, rotating presidency of the European Union, is drawing attention to the problems caused by the exodus of health professionals from eastern to western Europe. The migration was at the centre of the informal meeting of European Union health ministers at Godollő near Budapest on 4 and 5 April.

Miklos Szocska, Hungary’s minister for healthcare, warned that migration from central and eastern European countries is so great that the very safety of some national health systems is at risk. Doctors …
The Chilling Effect: How Do Researchers React to Controversy?
Authors: Joanna Kempner
Journal: PLoS Medicine (2008)

Background Can political controversy have a “chilling effect” on the production of new science? This is a timely concern, given how often American politicians are accused of undermining science for political purposes. Yet little is known about how scientists react to these kinds of controversies. Methods and Findings Drawing on interview (n = 30) and survey data (n = 82), this study examines the reactions of scientists whose National Institutes of Health (NIH)-funded grants were implicated in a highly publicized political controversy. Critics charged that these grants were “a waste of taxpayer money.” The NIH defended each grant and no funding was rescinded. Nevertheless, this study finds that many of the scientists whose grants were criticized now engage in self-censorship. About half of the sample said that they now remove potentially controversial words from their grant and a quarter reported eliminating entire topics from their research agendas. Four researchers reportedly chose to move into more secure positions entirely, either outside academia or in jobs that guaranteed salaries. About 10% of the group reported that this controversy strengthened their commitment to complete their research and disseminate it widely. Conclusions These findings provide evidence that political controversies can shape what scientists choose to study. Debates about the politics of science usually focus on the direct suppression, distortion, and manipulation of scientific results. This study suggests that scholars must also examine how scientists may self-censor in response to political events.
Cytotoxic T-cell responses in mice infected with influenza and vaccinia viruses vary in magnitude with H-2 genotype.
Authors: P C Doherty, W E Biddison, J R Bennink, B B Knowles
Journal: The Journal of Experimental Medicine (1978)

Secondary effector T-cell populations generated by cross-priming with heterologous influenza A viruses operate only in H-2K or H-2D compatible situations, when assayed on SV40-transformed target cells infected with a range of influenza A viruses. The H2-Kb allele is associated with a total failure in the generation of influenza-immune cytotoxic T cells, though this is not seen for the primary response to vaccinia virus. In both influenza and vaccinia development of effector T cells operating at H-2Db is greatly depressed in B10.A(2R) (kkkddb) and B10.A(4R) (kkbbbb), but not in B10 (bbbbbb), mice. However, there is no defect in viral antigen expression at either H-2Kk or H-2Db in B10.A(2R) target cells. This apparently reflects some inadequacy in the stimulator environment, as (A/J X B6) F1 T cells can be induced to respond at H-2Db when exposed to vaccinia virus in an irradiated B6 but not in a B10.A(4R) recipient. The present report, together with the accompanying paper by Zinkernagel and colleagues, records the first rigorous demonstration of both a nonresponder situation and a probable Ir-gene effect for conventional infectious viruses. Possible implications for the evolution of H-2 polymorphism and mechanisms of Ir gene function are discussed.
Recurrent Mycobacterium avium infection after seven years of latency in a HIV-infected patient receiving efficient antiretroviral therapy
Authors: Guillaume Bussone, Florence Brossier, Laurent Roudiere, Emmanuelle Bille, Nawal Sekkal, Caroline Charlier, Jacques Gilquin, Fanny Lanternier, Marc Lecuit, Olivier Lortholary, Emilie Catherinot
Journal: Journal of Infection (2012)
The TNF-Family Receptor DR3 is Essential for Diverse T Cell-Mediated Inflammatory Diseases
Authors: Françoise Meylan, Todd S. Davidson, Erin Kahle, Michelle Kinder, Krishika Acharya, Dragana Jankovic, Virgilio Bundoc, Marcus Hodges, Ethan M. Shevach, Andrea Keane-Myers, Eddie C.Y. Wang, Richard M. Siegel
Journal: Immunity (2008)
Development of a Novel Peptide Nanoparticle Inhibitor for Human CCR3/Eotaxin-Mediated Eosinophil Migration
Authors: Kimberly G. Laffey, Boris Garnier, Ben Hitchinson, Nadya Tarasova, Vadim Gaponenko, Steven J. Ackerman
Journal: Journal of Allergy and Clinical Immunology (2015)
Lysis of major histocompatibility complex class I-bearing cells in Borna disease virus-induced degenerative encephalopathy.
Authors: O Planz, T Bilzer, M Sobbe, L Stitz
Journal: The Journal of Experimental Medicine (1993)

CD8+ as well as CD4+ T cells and macrophages are of crucial importance for the pathogenesis of Borna disease in rats. This virus-induced immunopathological disease of the brain is characterized by neurological symptoms in the acute phase and chronic debility associated with severe loss of brain tissue in the late stage. We demonstrate here the cytotoxic activity of T lymphocytes in the brain of intracerebrally infected rats. T cells isolated from the brain of infected rats lyse major histocompatibility complex (MHC) class I-bearing target cells in the absence of MHC class II. Borna disease virus (BDV)-infected syngeneic skin cells and astrocytes, the latter one of the relevant target cells in vivo, were significantly lysed whereas infected allogeneic target cells were not. Most relevant to the in vivo situation, primary brain cell cultures propagated from the hippocampus of BDV-infected rats containing considerable numbers of neurons were lysed in vitro. Blocking experiments using antibodies directed against MHC class I antigen provided further evidence for the presence and activity of classical cytotoxic T lymphocytes. Antibodies against MHC class II antigen did not influence lysis of skin target cells but had an effect on lysis of astrocytes at late time points. Lymphocytes isolated from spleen, peripheral blood, or lymph nodes did not show cytotoxic activity. These results verify, on the cellular level, earlier findings that strongly suggest the involvement of CD8+ T cells in brain cell lesions, resulting in brain atrophy long after infection of rats with BDV. This is further evidenced by the presence of CD8+ T cells in direct proximity to neuronal cell lesions. Interestingly, the cytolytic capacity, demonstrated in vitro and strongly correlated to organ destruction, does not result in elimination of the virus but the virus persists in the central nervous system.
Comparison of Oral Agents for Treatment of Pneumocystis carinii Pneumonia
Authors: Sharon Safrin
Journal: Annals of Internal Medicine (1997)

Letters1 March 1997Comparison of Oral Agents for Treatment of Pneumocystis carinii PneumoniaSharon Safrin, MD and Dianne Finkelstein, PhDSharon Safrin, MDUniversity of California, San Francisco, San Francisco, CA 94110Harvard University School of Public Health, Boston, MA 02115Search for more papers by this author and Dianne Finkelstein, PhDUniversity of California, San Francisco, San Francisco, CA 94110Harvard University School of Public Health, Boston, MA 02115Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-126-5-199703010-00012 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Because space constraints made it necessary to select the categories of toxicity to be reported in our article, hyperkalemia was not specifically reported. In response to Dr. Perazella's query, however, we specifically looked at the occurrence of hyperkalemia in patients receiving clindamycin-primaquine, dapsone-trimethoprim, or trimethoprim-sulfamethoxazole in the ACTG (AIDS Clinical Trials Group) 108 trial.Table 1 summarizes all categories of hyperkalemia that occurred in study patients while they were actually receiving assigned therapy. No grade IV toxicities occurred. A single instance of grade III hyperkalemia occurred in a patient receiving dapsone-trimethoprim; this patient had the one case of ... Author, Article, and Disclosure InformationAuthors: Sharon Safrin, MD; Dianne Finkelstein, PhDAffiliations: University of California, San Francisco, San Francisco, CA 94110Harvard University School of Public Health, Boston, MA 02115 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited bySuccessful Conservative Management of Trimethoprim Induced Life-Threatening Hyperkalaemia in a Patient with Pneumocystis jirovecii PneumoniaTrimethoprim-Induced HyperkalaemiaMiscellaneous antibacterial drugsAntiprotozoal drugs 1 March 1997Volume 126, Issue 5Page: 407-408KeywordsAIDSBody weightClinical trialsPneumocystis carinii pneumoniaPotassiumToxicity ePublished: 15 August 2000 Issue Published: 1 March 1997 Copyright & PermissionsCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...