tbuckley/cabot-search huggingface dataset:
Phase I Study of Low-Dose Interleukin-2, Fludarabine, and Cyclophosphamide for Previously Untreated Indolent Lymphoma and Chronic Lymphocytic Leukemia
Authors: Yvette L. Kasamon, Ian W. Flinn, Michael R. Grever, Louis F. Diehl, Elizabeth Garrett-Mayer, Steven N. Goodman, Margaret S. Lucas, John C. Byrd
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Fludarabine and cyclophosphamide is an effective combination but increases the risk of opportunistic infections due to depressed lymphocyte counts. In an attempt to preserve CD4 counts, we conducted a phase I, double-blind, placebo-controlled trial of recombinant interleukin-2 (IL-2) added to fludarabine and cyclophosphamide in patients with treatment-naive indolent lymphomas or chronic lymphocytic leukemia. Experimental Design: Subcutaneous IL-2 (days 1-21 of each 28-day cycle) was combined with cyclophosphamide (600 mg/m2, day 8) and fludarabine (20 mg/m2, days 8-12) at four dose levels: 0.8, 1.0, 1.2, and 1.4 × 106 IU/m2/d. IL-2 dose was escalated in cohorts of four to six patients, with one patient per cohort receiving placebo. Results: Twenty-three patients, median age 50, were enrolled, of whom 30% had chronic lymphocytic leukemia/small lymphocytic lymphoma and 52% had follicular lymphomas. The combination was generally well tolerated, with mainly hematologic toxicities. CD4 counts typically declined substantially during the early weeks of treatment and remained suppressed for months afterward. In the 18 evaluable patients who received IL-2, the mean absolute CD4 count was 999 cells/μL (range, 97-3,776) pretreatment, 379 cells/μL (range, 54-2,599) at day 14, and 98 cells/μL (range, 17-291) at end of treatment. In longitudinal linear models, the changes in CD4 counts were not significantly different across IL-2 dose levels. Conclusions: The addition of low-dose IL-2 to fludarabine and cyclophosphamide does not seem immunoprotective. New approaches are needed to reduce the cellular immunosuppression and infectious complications associated with purine analogues.
Aerosolized human neutrophil elastase induces airway constriction and hyperresponsiveness with protection by intravenous pretreatment with half-length secretory leukoprotease inhibitor.
Authors: T Suzuki, W Wang, J T Lin, K Shirato, H Mitsuhashi, H Inoue
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

This study was designed to determine the effects of inhaled human neutrophil elastase (HNE) on airway constriction and airway responsiveness, and to examine the protection by an intravenous recombinant half-length secretory leukoprotease inhibitor, r1/2SLPI in guinea pigs. Aerosol inhalation of HNE (250 microgram/ml, for 3 min) caused a transient but significant airway constriction, in which lung resistance (RL) increased from 194 +/- 18 (mean +/- SEM) to 461 +/- 42 cm H2O/L/s (p < 0.001). Thirty minutes after the end of HNE inhalation, airway responsiveness to intravenous 5-hydroxytryptamine (5-HT) was significantly increased. The provocative dose causing a 200% increase in RL (PD200) was significantly decreased from 10.0 +/- 1.2 to 6.5 +/- 0.8 microgram/kg (p < 0.001). Forty-five minutes after the end of HNE inhalation, total cells in bronchoalveolar lavage fluid (BALF) were significantly increased (p < 0.05). Histologic study of intrapulmonary bronchi demonstrated an acute inflammatory response characterized by damage to the epithelium, airway obstruction by mucus plugs, and recruitment of mononuclear and polymorphonuclear cells to the bronchial epithelium. r1/2SLPI (30 mg/kg) injected 5 min before the initiation of HNE inhalation significantly inhibited the airway constriction (p < 0.05), the airway hyperresponsiveness (p < 0.01), and the increase of cells in BALF (p < 0.05). The present data suggest that HNE plays a role in the induction of airway constriction and airway hyperresponsiveness in various inflammatory lung diseases with pulmonary neutrophil infiltration, such as chronic obstructive pulmonary diseases (COPD) and possibly bronchial asthma. r1/2SLPI may be useful as an antiprotease treatment.
Rivaroxaban for Thromboprophylaxis in Acutely Ill Medical Patients
Authors: Alexander T. Cohen, Theodore E. Spiro, Harry R. Büller, Lloyd Haskell, Dayi Hu, Russell Hull, Alexandre Mebazaa, Geno Merli, Sebastian Schellong, Alex C. Spyropoulos, Victor Tapson
Journal: New England Journal of Medicine (2013)

The clinically appropriate duration of thromboprophylaxis in hospitalized patients with acute medical illnesses is unknown. In this multicenter, randomized, double-blind trial, we evaluated the efficacy and safety of oral rivaroxaban administered for an extended period, as compared with subcutaneous enoxaparin administered for a standard period, followed by placebo.
Comparable Survival Between pN0 Breast Cancer Patients Undergoing Sentinel Node Biopsy and Extensive Axillary Dissection: A Report From the Korean Breast Cancer Society
Authors: Hyeong-Gon Moon, Wonshik Han, Dong-Young Noh
Journal: Journal of Clinical Oncology (2010)

Recent studies showing survival benefit of extensive axillary lymph node dissection (ALND) in pN0 breast cancer have challenged the concept of sentinel node biopsy (SNB). In this study, the survival and recurrence after SNB alone and ALND in pN0 Korean breast cancer patients were investigated.Using information from two large databases, including a Korean nationwide registry, we assessed survival relative to the extent of ALND in pN0 breast cancer patients. We also compared the survival of pN0 patients who underwent SNB alone with survival in those who underwent varying degrees of ALND.In an analysis of 1,607 pN0 patients from a single institution, less extensive ALND significantly increased the risks of breast cancer death and systemic recurrence but not of locoregional recurrence. These findings were validated by an analysis of nationwide registry data on 17,672 pN0 patients; patients with > 20 dissected lymph nodes had significantly better overall survival (OS) and breast cancer-specific survival (BCSS) than those with 10 to 20 or < 10 dissected lymph nodes. Patients who underwent SNB alone showed OS (hazard ratio [HR], 1.03; 9% CI, 0.08 to 1.56) and BCSS (HR, 1.15; 95% CI, 0.75 to 1.78) similar to those of patients who underwent extensive ALND (> 20 dissected lymph nodes), despite the small number of lymph nodes removed.Extensive ALND is associated with better survival and less systemic recurrence than less extensive ALND in patients with pN0 breast cancer. However, SNB alone showed excellent survival results, similar to those of extensive ALND, supporting the long-term oncologic safety of SNB.
Changes in exercise characteristics, maximal voluntary contraction, and explosive strength during prolonged tennis playing
Authors: O Girard, G Lattier, J-P Micallef, G P Millet
Journal: British Journal of Sports Medicine (2006)

Objectives: To examine changes in exercise characteristics, maximal voluntary contraction, and explosive strength during prolonged tennis playing. Methods: Maximal isometric voluntary contraction (MVC), leg stiffness (hopping), and peak power in squat (SJ) and countermovement (CMJ) jumps were measured before, every 30 minutes during, and 30 minutes after a three hour tennis match in 12 well trained players. Heart rate (HR), the effective playing time (EPT), rating of perceived exertion (RPE), and muscle soreness of knee extensors were also measured. Results: Decreases in MVC (−9%; p&lt;0.05) and leg stiffness (−9%; p = 0.17) were observed after the match and were significantly correlated ( r = 0.66; p = 0.05). Peak power in SJ and CMJ tests was maintained during the match but was lower (p&lt;0.001) 30 minutes after. Average HR and EPT were 144 (8) beats/min and 21 (4)% respectively. A strong correlation was found between EPT and HR ( r = 0.93; p&lt;0.05). RPE and muscle soreness increased linearly during the exercise and were significantly correlated ( r = 0.99; p&lt;0.001). Conclusions: Progressive reductions in maximal voluntary strength and leg stiffness highly correlated with increases in perceived exertion and muscle soreness were observed throughout a three hour tennis match, whereas explosive strength was maintained and decreased only after the match. These alterations may result in less efficient on-court movement and stroke production. They are, however, lower than those reported during continuous exercise of the same duration. The intermittent pattern of tennis and the numerous stretch-shortening cycle movements partly explain these results.
β2-Adrenergic Agonists Suppress Rat Autoimmune Myocarditis
Authors: Mototsugu Nishii, Takayuki Inomata, Hiroe Niwano, Hitoshi Takehana, Ichiro Takeuchi, Hironari Nakano, Hisahito Shinagawa, Takashi Naruke, Toshimi Koitabashi, Jun-ichi Nakahata, Tohru Izumi
Journal: Circulation (2006)

The therapeutic potential of beta2-adrenergic receptor (AR) agonists in the treatment of autoimmune diseases has been reported. However, the role of these drugs in the myocardial structure-induced autoimmune process, which is thought to play a crucial role in the progression of myocarditis to subsequent complications, has not been elucidated.Experimental autoimmune myocarditis (EAM) was induced in rats by immunization with cardiac myosin. On daily administration from day 0 after immunization, the beta2-selective AR agonists formoterol or salbutamol ameliorated EAM on day 21 and increased myocardial interleukin-10/interferon-gamma mRNA levels. Propranolol, a nonselective beta-AR antagonist, aggravated EAM on day 21 and decreased mRNA levels, whereas metoprolol, a beta1-selective AR antagonist, showed no effect. These results were reflected in vivo by the proliferation of cardiac myosin-primed lymph node cells from drug-treated rats. In vitro addition of beta2-selective AR agonists inhibited the activation of cardiac myosin fragment-specific myocarditogenic T lymphocytes, and this effect was reversed by ICI118,551, a beta2-selective AR antagonist. Furthermore, treatment with 2 different beta2-selective AR agonists starting on day 14 also ameliorated EAM on day 21.beta2-AR stimulation suppressed the development of EAM by inhibiting cardiac myosin-specific T-lymphocyte activation in lymphoid organs and by shifting the imbalance in Th1/Th2 cytokine toward Th2 cytokine. Furthermore, it also ameliorated established myocardial inflammation. beta2-AR-stimulating agents may represent important immunomodulators of the cardiac myosin-induced autoimmune process and have potential as a new therapy for myocarditis.
Penicillin-resistant gonococcal polyarthritis
Authors: M. I. Liftik
Journal: JAMA (1978)

PENICILLIN has been the preferred treatment of gonococcal infections for years. However, in 1976, reports from Great Britain and the United States described patients with uncomplicated genitourinary infections due to penicillin-resistant<i>Neisseria gonorrhoeae</i>, which produced β-lactamase (penicillinase).<sup>1,2</sup>We describe a patient with infection of the pharynx and destructive polyarthritis due to a β-lactamase—producing strain of<i>N gonorrhoeae</i>. <h3>Report of a Case</h3> A 25-year-old man was admitted to a US Navy Hospital in the Philippine Islands on Aug 15, 1976, with a two-day history of fever, migratory arthritis, and transient red papules on his limbs. He had an effusion of the left knee, with a WBC count of 14,300/cu mm, with 85% polymorphonuclear leukocytes. Gram's stain and cultures of the synovial fluid were negative, and roentgenograms of his joints were normal. He was treated with oral penicillin G potassium, salicylates, and prednisone for possible acute rheumatic fever. Temperatures of 38
Molecular and functional analysis of Shiga toxin–induced response patterns in human vascular endothelial cells
Authors: Andreas Matussek, Joerg Lauber, Anna Bergau, Wiebke Hansen, Manfred Rohde, Kurt E. J. Dittmar, Matthias Gunzer, Michael Mengel, Patricia Gatzlaff, Maike Hartmann, Jan Buer, Florian Gunzer
Journal: Blood (2003)
Identification of two collagen domains within the bullous pemphigoid autoantigen, BP180.
Authors: G J Giudice, H L Squiquera, P M Elias, L A Diaz
Journal: Journal of Clinical Investigation (1991)

Bullous pemphigoid (BP) is an autoimmune disease characterized by subepidermal vesicles and the presence of autoantibodies directed against the epidermal basement membrane zone. Previous studies have identified two protein components of the hemidesmosome, BP180 and BP230, as the primary antigenic targets of BP autoantibodies. We have recently reported the isolation of a 1.0-kb BP180 cDNA. Sequence analysis presented in this report reveals that this partial BP180 cDNA encodes two protein domains which have primary structures that are characteristic of the triple helical domains of collagens, i.e., glycine appears at every third position and over one-third of the remaining residues are proline. The two collagen domains have lengths of 242 and 30 amino acids and are separated by a noncollagen stretch of 12 amino acids. Collagenase digestion of the BP180 cDNA-encoded fusion protein generated a peptide fragment with a size that was consistent with the predicted locations of the collagenase digestion sites. A possible physiological function for the collagen domains of the BP180 hemidesmosomal protein may be to form stable interactions with constituents of the extracellular matrix of the cutaneous basement membrane zone. Such interactions may provide the molecular framework for the adhesion between the basal keratinocyte and the basal lamina.
Waiting list management in general practice: a review of orthopaedic patients
Authors: G. J. Elwyn, L A Williams, S. Barry, P. Kinnersley
Journal: BMJ (1996)

<h3>Abstract</h3> <b>Objective</b>: To review all patients on a current general practice orthopaedic waiting list for outpatient appointments with regard to accuracy of the list, clinical priority, and need for further radiological investigation before hospital attendance. <b>Design</b>: Record review by one general practitioner and a radiologist, and discussion with patients of management alternatives. <b>Setting</b>: Six partner city centre urban fund-holding general practice, list size 8651 (29% low deprivation payment status). <b>Subjects</b>: 116 adults on an orthopaedic waiting list. <b>Main outcome measures</b>: List accuracy (patient details and status on waiting list); clinical priority (severity of condition); further investigations (results of tests after radiological review). <b>Results</b>: 32 patients (28%) were removed from the waiting list because of inaccuracies. 14 patients were considered to be high priority and referred to other hospitals by utilising waiting list initiative funds. Of these patients, five agreed to referral to another hospital (treatment completed on average within three months of rereferral), six did not wish to be rereferred, and two did not attend to discuss the offer and remained on the original waiting list. One prioritised patient had further radiological investigations, was reassured, and was taken off the waiting list. 10 patients had further investigations. These resulted in six patients being referred to other hospitals, three being taken off the waiting list, and one seeking private care. <b>Conclusions</b>: Systematic review of patients on an orthopaedic waiting list of one general practice, though time consuming, led to the identification of inaccuracies in the list and changes in management. Costs need further evaluation, but if the findings occur widely substantial benefits could be achieved for patients. <h3>Key messages</h3> Key messages Waiting lists contain patients who have differing clinical priorities It is possible to develop practice based lists Increased use of elaborate investigation tech- niques may eliminate the need for referral and can identify those patients who have clinical priority ”Active waiting list management” is possible in general practice but there are substantial opportu- nity costs
Heterogeneity in Fanconi anemia: evidence for 2 new genetic subtypes
Authors: Marieke Levitus, Martin A. Rooimans, Jûrgen Steltenpool, Nicolle F. C. Cool, Anneke B. Oostra, Christopher G. Mathew, Maureen E. Hoatlin, Quinten Waisfisz, Fré Arwert, Johan P. de Winter, Hans Joenje
Journal: Blood (2003)
On the Results of Recent Researches in the Treatment of Phthisis
Authors: I. B. Yeo
Journal: BMJ (1877)

But what are we to say to those who are falling or to fall in a true fight, whose life is expended in a noble despair, who have tempered fret- fulness with, wisdom and resignation, and whose passions are purified ?Simply this: that we are born to war and not to peace ; but we must see that we spend ourselves to some good purpose.A generous ardour is no safeguard against errors of aim; and we find that men and women often die rather like the bird which beats its wings against the cage, than by the defeat of well-directed effort.Manv of us must fight, knowing that victory is impossible; and in constant strife there can be no joy or fruition ; still, in a good cause, no wise effort can be wholly in vain, and a consciousness of this is a healing salve more powerful than any we can give.We shall be but blind physicians if we preach cowardice or inaction as the secret of health ; let us rather urge upon those who seek our help in times of trial, to fix their affections on no selfish, unworthy, or transitory desires; to spend tlhemselves, if their lives must be prematurely spent, in the cause of others, and for ends uhich are not visionary but attainable; and, finally, to possess their souls in patience and steadfastness.I know, in many cases, you may as well bid the wind cease to whistle; but, in others, by economising effort, by purifying suffering, and by lessening defeat, you may not oiily keep reason on its throne, but you may save the body from the inroads of organic disease, and from that disease more particularly on which to-day I have ventured to address you.
Communicative Disorders Related to Cleft Lip and Palate
Authors: Susan S. Laber
Journal: JAMA (1980)

Written to supplant the first edition published in 1971, this volume embodies such dramatic changes that a new title might have been in order. Dr Bzoch proposes this book for those studying in graduate programs in communicative disorders. It assumes a good background in normal and pathological language as well as the anatomy and physiology of the speech mechanism. The authors cite recent references and present the viewpoint of other members involved in management of persons with cleft lip and palate. This exposure to the writing of specialists can only enrich the speech and language therapist's background. Most conspicuously absent, however, is a contribution by a plastic surgeon. The text is well organized under headings dealing with the general, diagnostic, and habilitative aspects of communication disorders. The chapters are short and lucid. Bzoch's drollery and wit characterize the sections he has written. The segment on anatomy and physiology is brief
Clinical and diagnostic tests for shoulder disorders: a critical review
Authors: Edward G McFarland, Juan Garzon-Muvdi, Xiaofeng Jia, Pingal Desai, Steve A Petersen
Journal: British Journal of Sports Medicine (2009)

The shoulder is one of the most complex joints in the human body and, as such, presents an evaluation and diagnostic challenge. The first steps in its evaluation are obtaining an accurate history and physical examination and evaluating conventional radiography. The use of other imaging modalities (eg, ultrasound, magnetic resonance imaging and computed tomography) should be based on the type of additional information needed. The goals of this study were to review the current limitations of evidence-based medicine with regard to shoulder examination and to assess the rationale for and against the use of diagnostic physical examination tests.
NO suppresses while peroxynitrite sustains NF-κB: a paradigm to rationalize cytoprotective and cytotoxic actions attributed to NO
Authors: Y HATTORI, K KASAI, S GROSS
Journal: Cardiovascular Research (2004)

NO has both cytoprotective and cytotoxic effects. A key cytoprotective action of NO is attributed to inhibition of nuclear factor-kappaB (NF-kappaB)-mediated gene expression; this potentially endows NO with ubiquitous anti-inflammatory activity. Since immunostimulant-induced iNOS gene expression is itself dependent on NF-kappaB, NO is expected to limit its own synthesis. On the other hand, many cytotoxic actions of NO have been attributed to the chemical reactivity of peroxynitrite (ONOO-) formed from NO by near diffusion-limited reaction with O2-. To assess whether ONOO- shares the ability of NO to inhibit NF-kappaB activation and consequent iNOS gene expression, we compared effects of NO donors (NOR3 and SNAP), an ONOO- donor (SIN-1), and pure ONOO- on LPS-induced responses in vascular smooth muscle cells (VSMC).NO donors, but not ONOO-, suppressed LPS-induced NF-kappaB activation and expression of a murine iNOS promoter/reporter construct. An NO donor also suppressed NF-kappaB activation when induced by IL-1beta or TNFalpha. Northern blot and RT-PCR analyses showed that NO, but not ONOO- or 8-bromo-cGMP, decreases LPS-induced expression of iNOS mRNA. Electrophoretic mobility shift assays (EMSA) and immunocytochemical analyses confirmed that NO but not ONOO- inhibits nuclear translocation of NF-kappaB. Although ONOO- generation from SIN-1 did not inhibit NF-kappaB activation, conversion of SIN-1 to a pure NO donor (by addition of excess superoxide dismutase) resulted in potent inhibition of NF-kappaB activation. Dose-response analyses suggest that the inhibitory effect of NO on iNOS gene transcription results specifically from inhibition of NF-kappaB activation, and is mediated by a G-cyclase-independent mechanism that is unavailable to ONOO-. LPS stimulates IkappaB-alpha phosphorylation by inducing IkappaB kinase (IKK) activity, and NO, but not ONOO-, inhibits LPS-induced IkappaB-alpha phosphorylation and IKK activity.We demonstrate that only NO inhibits the activation of NF-kappaB and suppresses iNOS gene expression. This distinction provides a novel paradigm to rationalize cytoprotective and cytotoxic actions attributed to NO.
Regulation of Immunity Toward Allogeneic Tumors in Mice. I. Effect of Antiserum Fractions on Tumor Growth&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: M. Takasugi, W. H. Hildemann
Journal: JNCI Journal of the National Cancer Institute (1969)

Hyperimmune serum produced in host mice against allogeneic tumor antigens inhibited and enhanced tumor growth. Fractionation of the antiserum by column chromatography established that immunoglobulin M was primarily responsible for inhibition and immunoglobulin G γ2 for enhancement. Since only one class of immunoglobulin can cause enhancement, mere blocking of the immune response at the peripheral tumor-cell level was rejected in favor of a more central feedback mechanism of control. The functions of distinctive immunoglobulin classes are considered in relation to alloimmune rejection and in the regulation of the overall immune response.