tbuckley/cabot-search huggingface dataset:
Effect of Inhaled Leukotriene D<sub>4</sub> on Airway Eosinophilia and Airway Hyperresponsiveness in Asthmatic Subjects
Authors: ALMA MULDER, GAIL M. GAUVREAU, RICK M. WATSON, PAUL M. O'BYRNE
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Inhaled cysteinyl leukotrienes may cause recruitment of eosinophils into asthmatic airways. We compared the effects of inhaled leukotriene D4 (LTD4), methacholine, and allergen on airway eosinophils in 10 nonsmoking, atopic, mildly asthmatic subjects in a double-blind, diluent-controlled, randomized crossover study. Concentrations of LTD4, methacholine, and allergen resulting in a 30% decrease in FEV1, and diluent controls (ethanol and saline), were inhaled with at least 7 d between challenges. Spirometry was conducted for 4 h after inhalation challenge, and airway hyperresponsiveness (AHR) to methacholine was measured before and 24 h after challenge. Sputum was induced before and 4 h, 7 h, and 24 h after challenge. The maximum decrease in FEV1 was 31.4 ± 1.8% with LTD4, 39.4 ± 2.8% with methacholine, and 30.1 ± 3.4% with allergen. AHR to methacholine, at the provocative concentration causing a 20% decrease in FEV1 (PC20), was enhanced 24 h after allergen challenge, but remained unchanged 24 h after LTD4 and methacholine (p > 0.05). The percentage of eosinophils in sputum was increased after inhalation of allergen at 7 h and 24 h (p = 0.003), but not after LTD4 or methacholine (p = 0.70). We demonstrated that neither inhalation of LTD4 nor of methacholine at concentrations causing submaximal bronchoconstriction increases the number of sputum eosinophils in the airways of mildly asthmatic subjects. However, LTD4 may still be an important cofactor for eosinophil recruitment in asthma.
Specialists or Generalists? The Medical Outcomes Study-Reply
Authors: Roger A. Rosenblatt
Journal: JAMA (1992)

In Reply.  —Although the recent intensity of attention to primary care medicine cited by Dr Balestra may be unusual, the problem of specialty maldistribution in the United States is not new. National health personnel policy has revolved around this issue for much of the last 20 years. 1 What is new is the realization that the growing disarray of our medical care system is in some measure a consequence of the decline of the role of the generalist in American medicine.  Balestra certainly is correct in his observation that the solution to the problem is neither simple nor likely to be solved by any single intervention. Physician specialty choice is influenced by preferences of admission committees, the shape and emphasis of medical school curricula, the availability and attractiveness of residency slots, and the differential rewards that society confers on those who follow disparate paths. Only by addressing the problem at
Characterization of the effects of hepatitis C virus nonstructural 5A protein expression in human cell lines and on interferon-sensitive virus replication
Authors: Stephen J. Polyak, Denise M. Paschal, Susan McArdle, Michael J. Gale, Darius Moradpour, David R. Gretch
Journal: Hepatology (1999)

The hepatitis C virus (HCV) nonstructural 5A (NS5A) protein has been implicated in the inherent resistance of HCV to interferon (IFN) antiviral therapy in clinical studies. Biochemical studies have demonstrated that NS5A interacts in vitro with and inhibits the IFN-induced, RNA-dependent protein kinase, PKR, and that NS5A interacts with at least one other cellular kinase. The present study describes the establishment and characterization of various stable NS5A-expressing human cell lines, and the development of a cell culture-based assay for determining the inherent IFN resistance of clinical NS5A isolates. Human epithelioid (Hela) and osteosarcoma (U2-OS) cell lines were generated that express NS5A under tight regulation by the tetracycline-dependent promoter. Maximal expression of NS5A occurred at 48 hours following the removal of tetracycline from the culture medium. The half-life of NS5A in these cell lines was between 4 to 6 hours. NS5A protein expression was localized cytoplasmically, with a staining pattern consistent with the location of the Golgi apparatus and endoplasmic reticulum. In the majority of cell lines, no obvious phenotypic changes were observed. However, three genotype 1b NS5A-expressing osteosarcoma cell lines exhibited cytopathic effect and severely reduced proliferation as a result of high-level NS5A expression. Full-length NS5A protein isolated from a genotype 1b IFN-nonresponsive patient (NS5A-1b) was capable of rescuing encephalomyocardititis virus replication during IFN challenge up to 40-fold, whereas a full-length NS5A-1a and an interferon sensitivity determining region (ISDR) deletion mutant (NS5A-1a-triangle upISDR) isolated from a genotype 1a IFN-nonresponsive patient showed no rescue activity. The NS5A-1b and NS5A-1a proteins also rescued vesicular stomatitis virus replication during IFN treatment by two- to threefold. These data cummulatively suggest that NS5A expression alone can render cells partially resistant to the effects of IFN against IFN-sensitive viruses, and that in some systems, these effects may be independent of the putative ISDR. A scenario is discussed in which the NS5A protein may employ multiple strategies contributing to IFN resistance during HCV infection.
P1235 BASELINE/EARLY PRESENCE OF KNOWN AND NOVEL RESISTANCE MUTATIONS IS ASSOCIATED WITH VIRAL FAILURE IN DIFFICULT-TO-TREAT PATIENTS TREATED WITH FIRST GENERATION PROTEASE INHIBITORS
Authors: V. Cento, V.C. Di Maio, D. Di Paolo, V. Micheli, M. Tontodonati, F. De Leonardis, M. Aragri, F.P. Antonucci, A. Mancon, D. Armenia, M.C. Bellocchi, I. Lenci, A. Manunta, G. Taliani, A. Di Biagio, L.A. Nicolini, L. Nosotti, C. Sarrecchia, M. Siciliano, S. Landonio, A. Pellicelli, A. Gasbarrini, J. Vecchiet, C.F. Magni, S. Babudieri, M.S. Mura, M. Andreoni, G. Parruti, G. Rizzardini, M. Angelico, C.F. Perno, F. Ceccherini-Silberstein
Journal: Journal of Hepatology (2014)
Mesothelioma in Scotland
Authors: J. McEwen, A. Finlayson, A. Mair, A. A. M. Gibson
Journal: BMJ (1970)

In a retrospective study of the incidence of mesothelioma in Scotland for 1950-67 80 cases were traced from pathological reports and biopsy material of malignant tumours invading the pleura and peritoneum. These cases were matched with two sets of controls. Detailed histories of residence, occupation, and degree of exposure to asbestos confirmed that the incidence of mesothelioma in Scotland is similar to that in other parts of Britain.
A transposon-based chromosomal engineering method to survey a large cis-regulatory landscape in mice
Authors: Chikara Kokubu, Kyoji Horie, Koichiro Abe, Ryuji Ikeda, Sumi Mizuno, Yoshihiro Uno, Sanae Ogiwara, Masato Ohtsuka, Ayako Isotani, Masaru Okabe, Kenji Imai, Junji Takeda
Journal: Nature Genetics (2009)
ANOTHER TRICHO VICTIM
Authors: Howard Fox
Journal: JAMA (1931)

<h3>To the Editor:</h3> —Here is another "Tricho" case: M. C., 35 years old, a saleswoman, consulted the "Tricho Institute" cf New York City six years ago for hypertrichosis beneath the chin. She stated that she was treated weekly for about twenty-five weeks. After approximately fifteen treatments had been given, the irradiated area became red and inflamed. She was advised by the doctor at the institute to use warm applications and to continue treatment. The present eruption appeared about two years after the last treatment. She was told by the doctor at the institute that this was due to "dissolving of moles," of which she had many on the face and other parts of the body. The present eruption consisted of an area of profuse and disfiguring telangiectasia, mostly beneath the chin, measuring six by three inches. There was also a moderate amount of telangiectasia on the right cheek. One area
Combined radiotherapy and immunotherapy using CPG oligodeoxynucleotides and indolamine 2,3 dioxygenase (IDO) blockade
Authors: Arta M Monjazeb, Steven K Grossenbacher, Gail D Sckisel, Robert Canter, Ellen E Sparger, William Culp, Michael S Kent, William J Murphy
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts Pre-clinical and clinical data demonstrate the effectiveness of combining RT and CpG immunotherapy. There is data to suggest that the effectiveness of CpG immunotherapy may be limited by induction of the immunosuppressive enzyme, IDO. We test the efficacy and safety of combining
Natural killer T cells regulate the homing of chemokine CXC receptor 3-positive regulatory T cells to the liver in mice
Authors: Tania Santodomingo-Garzon, Jinglan Han, Tai Le, Yang Yang, Mark G. Swain
Journal: Hepatology (2008)

Natural killer T (NKT) cells and regulatory T cells (Tregs) are both found within the liver and are known to exhibit immune regulatory functions. Hepatic NKT cells are activated early during inflammatory responses and release cytokines, including interferon gamma (IFN-gamma), which we speculated could regulate Treg recruitment to the liver. To examine this, we treated C57BL/6 mice with a specific NKT cell activating ligand alpha galactosyl-C18-ceramide (alphaGal-C18-Cer) and examined the hepatic recruitment of Tregs. We found a time-dependant increase in the hepatic recruitment of Tregs after NKT cell activation, which was absent in NKT cell-deficient mice. Most recruited Tregs expressed interleukin (IL) 10, and to a lesser extent transforming growth factor beta (TGF-beta). Because IFN-gamma induces the production of chemokine (C-X-C motif) ligand 10 (CXCL10), and Tregs can express the cognate receptor for CXCL10 (that is, CXCR3), we considered that CXCL10 might mediate the hepatic recruitment of Tregs after NKT cell activation. Hepatic CXCL10 levels were markedly increased after alphaGal-C18-Cer administration in wild-type but not in NKT cell-deficient mice. Moreover, approximately 50% of Tregs recruited to the liver after alphaGal-C18-Cer administration expressed CXCR3 and CXCR3+ Treg recruitment into the liver was significantly inhibited in IFN-gamma KO mice, and after CXCL10 neutralization. In addition, prevention of CXCR3+ Treg recruitment into the liver enhanced inflammatory effector cell recruitment into the liver after alphaGal-C18-Cer treatment.These results show that activated NKT cells can induce the hepatic recruitment of Tregs through a cytokine-to-chemokine pathway, which could be relevant in the development of chemokine blocking or NKT cell activating strategies to treat liver diseases.
HIGH PLATELET REACTIVITY IN ST SEGMENT ELEVATION MYOCARDIAL INFARCTION POST THROMBOLYSIS: A PHARMACODYNAMIC COMPARISON OF TICAGRELOR VERSUS HIGH DOSE OF CLOPIDOGREL
Authors: Ioanna Xanthopoulou, Angelos Perperis, Stavros Karanikas, Ioanna Koniari, Sotirios Patsilinakos, Periklis Davlouros, George Hahalis, Dimitrios Alexopoulos
Journal: Journal of the American College of Cardiology (2014)
A Practical Handbook of Joint Fluid Analysis
Authors: George E. Ehrlich
Journal: JAMA (1985)

This handy little volume is long overdue. It brings to the realm of the office what previously was the province of the research laboratory. Any physicians who have occasion to see patients who have rheumatic diseases and arthritis in its many manifestations should have the book handy, for their own use or for their laboratory assistants to test the only material that gives relatively specific answers. (Most abnormalities we find in blood tests are nonspecific, and even biopsy specimens and roentgenograms cannot home in on the diagnosis as well as synovianalysis can.)  The book details how to prepare for a sterile aspiration (elaborate surgical technique may be eschewed, and providone iodine [Betadine] should be used, not the familiar red solutions that cannot guard as well against infection). Single needle, substituted syringe techniques are ideal for aspirating fluid and introducing medication thereafter. If the guidelines are followed, most aspirations should be
Autocrine Glutamate Signaling Promotes Glioma Cell Invasion
Authors: Susan A. Lyons, W. Joon Chung, Amy K. Weaver, Toyin Ogunrinu, Harald Sontheimer
Journal: Cancer Research (2007)

Malignant gliomas have been shown to release glutamate, which kills surrounding brain cells, creating room for tumor expansion. This glutamate release occurs primarily via system xC, a Na+-independent cystine-glutamate exchanger. We show here, in addition, that the released glutamate acts as an essential autocrine/paracrine signal that promotes cell invasion. Specifically, chemotactic invasion and scrape motility assays each show dose-dependent inhibition of cell migration when glutamate release was inhibited using either S-(4)-CPG or sulfasalazine, both potent blockers of system xC. This inhibition could be overcome by the addition of exogenous glutamate (100 micromol/L) in the continued presence of the inhibitors. Migration/invasion was also inhibited when Ca2+-permeable alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPA-R) were blocked using GYKI or Joro spider toxin, whereas CNQX was ineffective. Ca2+ imaging experiments show that the released glutamate activates Ca2+-permeable AMPA-R and induces intracellular Ca2+ oscillations that are essential for cell migration. Importantly, glioma cells release glutamate in sufficient quantities to activate AMPA-Rs on themselves or neighboring cells, thus acting in an autocrine and/or paracrine fashion. System xC and the appropriate AMPA-R subunits are expressed in all glioma cell lines, patient-derived glioma cells, and acute patient biopsies investigated. Furthermore, animal studies in which human gliomas were xenographed into scid mice show that chronic inhibition of system xC-mediated glutamate release leads to smaller and less invasive tumors compared with saline-treated controls. These data suggest that glioma invasion is effectively disrupted by inhibiting an autocrine glutamate signaling loop with a clinically approved candidate drug, sulfasalazine, already in hand.
A Phase I Study of Irinotecan As a 3-Week Schedule in Children With Refractory or Recurrent Solid Tumors
Authors: Gilles Vassal, Francois Doz, Didier Frappaz, Karima Imadalou, Evelyne Sicard, Alexandre Santos, John O’Quigley, Caroline Germa, Marie-Laure Risse, Dominique Mignard, Francois Pein
Journal: Journal of Clinical Oncology (2003)

A phase I study was performed to determine the maximum-tolerated dose (MTD) and safety profile of irinotecan (CPT-11) administered as a single intravenous infusion every 3 weeks in children with recurrent or refractory solid tumors.Eighty-one patients were enrolled, including 48 less heavily, and 33 heavily pretreated patients (cranial irradiation and/or high-dose chemotherapy). Children received CPT-11 as a 120-minute infusion at doses ranging from 200 to 720 mg/m2. The dose-limiting toxicities (DLT) on first cycle were determined in both cohorts.One hundred twenty-two cycles and 81 cycles were administered in less heavily, and heavily pretreated patients, respectively. The primary DLT was delayed diarrhea in less heavily pretreated patients, and neutropenia in heavily pretreated patients. MTD was 600 mg/m2 in both cohorts. Grade 3 to 4 neutropenia occurred in 33% and 38% of cycles in less heavily, and heavily pretreated patients, respectively. Grade 3 to 4 nonhematologic toxicities included nausea/vomiting (7% and 4% of cycles in less heavily, and heavily pretreated patients, respectively), asthenia (7% and 4% of cycles, respectively), and delayed diarrhea (6% and 2.5% of cycles, respectively). Four partial responses at 600 mg/m2 (high-grade glioma, neuroblastoma, medulloblastoma, and rhabdomyosarcoma) and 21 minor responses and stable diseases were observed. Pharmacokinetic analysis of CPT-11 and SN-38 was performed in 77 patients. The mean +/- standard deviation (SD) CPT-11 plasma clearance was 20.7 +/- 9.5 L/h/m2 (range, 5 to 54). The mean +/- SD SN-38 metabolic ratio was 1.5% +/- 1.1% (range, 0.15% to 5.55%).The recommended phase II dose of CPT-11 in a 3-week schedule is 600 mg/m2 in less heavily, and heavily pretreated children with solid tumors.
Landmark article June 14, 1941: Sulfadiazine. Therapeutic evaluation and toxic effects on four hundred and forty-six patients. By Maxwell Finland, Elias Strauss, and Osler L. Peterson
Authors: M. Finland
Journal: JAMA (1984)

Sulfadiazine (2-sulfanilamidopyrimidine), the pyrimidine analogue of sulfapyridine and sulfathiazole, is one of a group of heterocyclic derivatives of sulfanilamide synthesized by Roblin and his co-workers.<sup>1</sup>Laboratory studies on animals indicated that this drug has less toxicity than sulfapyridine and sulfathiazole and is highly effective against experimental infections with common pathogens.<sup>2</sup>Preliminary observations in this clinic<sup>3</sup>and in a number of others in which sulfadiazine was made available<sup>4</sup>indicated that this drug was worthy of extensive trial in the therapy of human bacterial infections. This paper deals mainly with a report of the clinical use of sulfadiazine in 446 adult patients treated at the Boston City Hospital prior to March 1, 1941. The results of laboratory studies will be reviewed briefly. <h3>ANIMAL EXPERIMENTS</h3> Feinstone and his associates<sup>2</sup>have shown that sulfadiazine is considerably less toxic than sulfapyridine or sulfathiazole both in acute experiments on mice and
Hydantoin-Induced Pseudo-Pseudolymphoma
Authors: RICHARD A. GAMS
Journal: Annals of Internal Medicine (1968)

A patient developed lymphadenopathy while receiving diphenylhydantoin therapy that histologically resembled malignant lymphoma. Adenopathy regressed when diphenylhydantoin was discontinued but subsequently recurred as a fatal, malignant lymphoma. Previous reports of hydantoin-induced lymphadenopathy were reviewed and classified. It was found that no consistent clinical or histologic criteria existed to differentiate benign from malignant lymphoid reactions.
Feasibility of Web-Based Self-Triage by Parents of Children With Influenza-Like Illness
Authors: Rebecca Anhang Price, Daniel Fagbuyi, Racine Harris, Dan Hanfling, Frederick Place, Todd B. Taylor, Arthur L. Kellermann
Journal: JAMA Pediatrics (2012)

Self-triage using web-based decision support could be a useful way to encourage appropriate care-seeking behavior and reduce health system surge in epidemics. However, the feasibility and safety of this strategy have not previously been evaluated.To assess the usability and safety of Strategy for Off-site Rapid Triage (SORT) for Kids, a web-based decision support tool designed to translate clinical guidance developed by the Centers for Disease Control and Prevention to help parents and adult caregivers determine if a child with influenza-like illness requires immediate care in an emergency department (ED).Prospective pilot validation study conducted between February 8 and April 30, 2012. Staff who abstracted medical records and made follow-up calls were blinded to the SORT algorithm's assessment of the child's level of risk.Two pediatric emergency departments in the National Capital Region.Convenience sample of 294 parents and adult caregivers who were at least 18 years of age; able to read and speak English; and the parent or legal guardian of a child 18 years or younger presenting to 1 of 2 EDs with signs and symptoms meeting Centers for Disease Control and Prevention criteria for influenza-like illness.Completion of the SORT for Kids survey.Caregiver ratings of the website's usability and the sensitivity of the underlying algorithm for identifying children who required immediate ED management of influenza-like illness, defined as receipt of 1 or more of 5 essential clinical services.Ninety percent of participants reported that the website was "very easy" to understand and use. Ratings did not differ by respondent race, ethnicity, or educational attainment. Of the 15 patients whose initial ED visit met explicit criteria for clinical necessity, the Centers for Disease Control and Prevention algorithm classified 14 as high risk, resulting in an overall sensitivity of 93.3% (exact 95% CI, 68.1%-99.8%). Specificity of the algorithm was poor.This pilot study suggests that web-based decision support to help parents and adult caregivers self-triage children with influenza-like illness is feasible. However, prospective refinement of the clinical algorithm is needed to improve its specificity without compromising patient safety.
A CASE OF STREPTOCOCCIC CONJUNCTIVITIS
Authors: H. H. B. Cunningham
Journal: BMJ (1907)

CONJUNCTIVITIS due to a pure or almost pure streptococcic infection does not appear to be a common disease, and in view of the virulence of the affection and the unfortunate termination of the case here recorded, one is thankful that these cases are not more numerous.A. F., aged 2 years, was brought to the hospital on March 12th, 1907, the motherstating that the child had suffered from a sore eye (laft) for the previous three weeks ; she lids were glued together on some mornings, but this was not a marked symptom.There was an eruption on the face, dry in character, situated on the forehead, cheeks, and chin, which the mother stated had been there before the' eye be£ame affected.On examining the eyes, the right eye ind its, appendages were apparently healthy;
The Influence of Market Economics on Primary Health Care in Vietnam
Authors: George A. Gellert
Journal: JAMA (1995)

THE SOCIALIST Republic of Vietnam first cautiously introduced economic reforms in 1986 to reverse the economic deterioration of the previous 15 years. A more extensive and consistent program of reforms, commonly referred to as the introduction of a market economy, began in 1989 as an expression of Vietnamese national policy. The reform programs enacted new monetary, price, and exchange rate policies; tightened credit; decontrolled prices; and abolished or substantially reduced subsidies to state enterprises and consumers as private enterprises emerged. The year 1993 marked a particularly important milestone in the transition to a market economy as Vietnam once again obtained access to concessional international finance.<sup>1</sup> <h3>PRIVATIZATION AND A NEW MARKET ECONOMY</h3> The promise of privatization and market forces in Vietnam, with its industrious and well-educated workforce, should promote socioeconomic development. Sustained economic growth in the range of 8% per year may continue throughout the decade of the 1990s.<sup>1</sup>
Effects of an Adrenergic Blocking Agent (Dibenzyline) upon Clinical Manifestations of Arterial Insufficiency in the Extremities
Authors: LOTHAR WERTHEIMER, WALTER REDISCH, J. MURRAY STEELE
Journal: Circulation (1954)

Adrenergic blocking with Dibenzyline measurably enhances the healing of ischemic ulcers. Eleven cases of obliterative arterial disease and two cases of Raynaud's disease were closely observed and are reported in detail. In six of the individuals suffering from obliterative arterial disease, changes in blood flow were documented by plethysmography. Dibenzyline measurably influenced intermittent claudication only after prolonged administration (three to four months) in four out of eight closely observed patients without ulcers. The results of the physiologic tests suggest that during the early phases of adrenergic blocking the increase in blood flow is mostly in the skin, while in the later phases increase in blood flow through the muscle predominates.