tbuckley/cabot-search huggingface dataset:
P178 Validation of a novel synthetic absorptive matrix (SAM) for sampling nasal mucosal lining fluid
Authors: D. Jackson, Y. Clements, S. L. Johnston, T. T. Hansel
Journal: Thorax (2010)

<h3>Introduction</h3> An improved method for sampling nasal mucosal lining fluid (MLF), termed nasosorption, utilises a synthetic absorptive matrix (SAM) (Accuwick Ultra, Pall). Conventionally, Whatman9s filter paper has been used for absorption of nasal MLF, but this natural cellulose source has the capacity to bind mediators, causing eluted fluid to have decreased and variable detectable levels of mediators. Nasal lavage has the problem of diluting MLF and this also causes detectable levels of mediators to be low. Strips of Accuwick are effective for nasosorption in adults following nasal allergen challenge and for sampling children with active rhinitis. However, Accuwick is no longer manufactured and we wished to validate an alternative SAM (Leukosorb, Pall). <h3>Methods</h3> Sputum supernatant (40 μl) from a subject with COPD as well as a standard preparation of cytokines was spiked onto Accuwick and Leukosorb strips. Following elution by spin filter centrifugation, the MesoScale Diagnostics (MSD) multi-immunoassay platform was used to assess levels of IFN-γ, IL-10, IL-12 p70, IL-6, IL-8, and TNFα. After absorption to Accuwick and Leukosorb, elution was compared with and without buffer (PBS with BSA (1%) and Triton X (1%)), prior to immunoassay of the recovered sample. <h3>Results</h3> Without buffer the recovery of 7 cytokines after the sputum supernatant was applied to Accuwick was a mean of 17.6% (range 1–100%), while recovery was a mean of 20.2% (range 2.9–92.5%) using Leukosorb. Addition of the buffer prior to elution of the fluid increased mean recovery to 61.8% when employing the Leukosorb system. Finally, in a direct comparison when employing Leukosorb and Accuwik for nasosorption in different nostrils after nasal allergen challenge in a single subject, Leukosorb resulted in higher detectable IL-5 levels in MLF. <h3>Conclusion</h3> Leukosorb appears to be a superior alternative to Accuwick Ultra for nasosorption in terms of recovery of cytokines. Addition of a buffer containing detergent and protein prior to elution significantly increases recovery. SAM has the potential to be employed in the upper and lower respiratory tract to sample undiluted MLF.
Computer Processing of Pediatric Emergency Room Data
Authors: Edward F. Lenoski
Journal: JAMA (1968)

This communication describes a rapid, uncomplicated method of coding diagnosis which is based on anatomical site, condition, and specific etiology of diseases seen most frequently in a pediatric emergency room. Significant information has been obtained with a minimum of expense and time expended. The emergency room (ER) staff has accepted the method, probably because of its simplicity. Data obtained by computer analysis of coded pediatric ER records are valuable in assessing the demography and needs of the population served, the quality of medical practice in the ER, and the temporal assignment of auxiliary personnel. Problems of data input are related to the amount of time expended by physicians and other relevant information.
1064. Haute Couture Vectors: Solving Clinical Problems with Custom Designed AAV Vectors
Authors: Dawn E. Bowles, Chengwen Li, Paul E. Monahan, Joseph E. Rabinowitz, Mavis McKenna, Jude Samulski
Journal: Molecular Therapy (2006)

Compelling evidence that therapeutic transgene levels can be achieved from adeno-associated virus (AAV) vectors has not been observed in any human gene therapy application to date. We show that AAV capsids can be tailored to solve such clinical problems and describe here a new generation of AAV vectors approved for use in clinical studies.
COMPARISON OF HEALTH OUTCOMES AT A HEALTH MAINTENANCE ORGANISATION WITH THOSE OF FEE-FOR-SERVICE CARE
Authors: JohnE. Ware, WilliamH. Rogers, AllysonRoss Davies, GeorgeA. Goldberg, RobertH. Brook, EmmettB. Keeler, CathyDonald Sherbourne, Patricia Camp, JosephP. Newhouse
Journal: The Lancet (1986)
On the Control of Heart Disease in Childhood
Authors: M. F. Lowenfeld
Journal: BMJ (1926)

tr eatment of rihleumatoid arthlritis by in-jection of non- speei-fic proteins.we have no precise knowledge of the actutal mechanism of these focal reactions in the inhfected subject, though imianiy hypotheses have been put forward.It is genierally believed that the uiltimate effect in any case is to produce ai greater flow of blood thlrough any inidolenit inflamumatory foci that nwy be presenit, w-ithi the result that the normal cellular and humoral defences are allows-ed to come into p1da.Possibly it accomplishes for the unseen indolent iesion what the surgeon's bistoury does for the visible carlbuncle.Non-specific protein therapy lhas really a very long hiistory if all tlhe phenomiiena provisionially assigned to this category do rightly belong to it.We have tlle mutual initer action of concuirrent inifectiolns with the ousting of the more chronic by the more acutoe as eviden'ced by olservations on erysipelas stuperveniing oin miiore chlronic processes.The use *of Coley's flu-id was an attempt to alpply this principle to the tr eatment of sarcoma.The evxerimental induction of malaria for the amiielioration or c-ure of general paralysis is another instance of prolonged and repeated protein shock tlherapy.So also is the Schiotz ti eatinient for diplhtheria carriers wlichli would seem to lepend for any attenidant success-on the inflammatory r eaction produced by the staphylococci sprayed on the tlhroat.Many other phienomena, suclh as thle occasional dramatic effect of niormal lhorse serum in septicaemias, the .so of auto-serotlierapy anid of multiple bleedings, come probably into the same category.I conclude, therefore, that so far as tlho early effects (euphoria, focal and genleral reactions, etc.) followvinig an injection of vaccile are conicerned, tlle action is entirely non-specific.There is no warrant I for assuming that the Organism, a vaccinio of which happenis to give a focal reaction in a particular caso, is etiologically related to the case.Onie bacterial colloid can be more potent tlhani anotlher in tlle production of imnmiiediate pllysiological ( ffOct5.In maany cases it is the action of the nol-specific elemcnt of the vaccinle that we wish to elicit wi-ith a view to cure.This is certainly so in the acute inifections and in the more chronic infections (for example, the artlhritic) also; we gather that the object now ustually aimed at is to produce focal and general reactions bv repeated adminis- tration of nonl-specific substances in appropriato dose.
Theory and practice of decision making in coronary care in general practice.
Authors: A E Stephenson, D M Fergusson, A R Hornblow, D W Beaven, S J Chetwynd
Journal: BMJ (1985)

Decisions about coronary care made by 39 randomly selected general practitioners in New Zealand over one year were investigated. Demographic variables and variables relating to the patient9s condition, history, and social circumstances were assessed for 113 patients, and practitioners9 belief about the relevance of each variable to the decision was elicited. A comparison was made between the objective criteria found to be related to the decision, the criteria believed by the practitioners to be relevant to the decision, and a theoretical model of what should govern the decision to admit. The theoretical model was found to be built into the beliefs of the practitioners, but the objective model was far simpler. Further research is needed to determine whether the use of the more complex, theoretical models will confer any benefit, in terms of patient wellbeing, over the pragmatic model in use at present.
Salmeterol in nocturnal asthma: a double blind, placebo controlled trial of a long acting inhaled beta 2 agonist.
Authors: M F Fitzpatrick, T Mackay, H Driver, N J Douglas
Journal: BMJ (1990)

OBJECTIVE--To determine whether inhaled salmeterol, a new long acting inhaled beta adrenergic agonist, reduces nocturnal bronchoconstriction and improves sleep quality in patients with nocturnal asthma. DESIGN--Randomised, double blind, placebo controlled crossover study. SETTING--Hospital outpatient clinics in Edinburgh. SUBJECTS--Twenty clinically stable patients (13 women, seven men) with nocturnal asthma, median age 39 (range 18-60) years. INTERVENTIONS--Salmeterol 50 micrograms and 100 micrograms and placebo taken each morning and evening by metered dose inhaler. Rescue salbutamol inhalers were provided throughout the run in and study periods. MAIN OUTCOME MEASURES--Improvement in nocturnal asthma as measured by peak expiratory flow rates and change in sleep quality as measured by electroencephalography. RESULTS--Salmeterol improved the lowest overnight peak flow rate at both 50 micrograms (difference in median values (95% confidence interval for difference in medians) 69 (18 to 88) l/min) and 100 micrograms (72 (23 to 61) l/min) doses twice daily. While taking salmeterol 50 micrograms twice daily patients had an objective improvement in sleep quality, spending less time awake or in light sleep (-9 (-4 to -44) min) and more time in stage 4 sleep (26 (6-34) min). CONCLUSIONS--Salmeterol is an effective long acting inhaled bronchodilator for patients with nocturnal asthma and at a dose of 50 micrograms twice daily improves objective sleep quality.
Up-regulation of a HOXA-PBX3 homeobox-gene signature following down-regulation of miR-181 is associated with adverse prognosis in patients with cytogenetically abnormal AML
Authors: Zejuan Li, Hao Huang, Yuanyuan Li, Xi Jiang, Ping Chen, Stephen Arnovitz, Michael D. Radmacher, Kati Maharry, Abdel Elkahloun, Xinan Yang, Chunjiang He, Miao He, Zhiyu Zhang, Konstanze Dohner, Mary Beth Neilly, Colles Price, Yves A. Lussier, Yanming Zhang, Richard A. Larson, Michelle M. Le Beau, Michael A. Caligiuri, Lars Bullinger, Peter J. M. Valk, Ruud Delwel, Bob Lowenberg, Paul P. Liu, Guido Marcucci, Clara D. Bloomfield, Janet D. Rowley, Jianjun Chen
Journal: Blood (2012)
Effectiveness of rotavirus vaccine against hospital admission for rotavirus diarrhoea in Brazilian children: a case-control study
Authors: Maria Yury T Ichihara, Laura C Rodrigues, Carlos Antonio S Teles Santos, Maria da Gloria L Cruz Teixeira, Sandra R de Jesus, Sheila M Alvim de Matos, José P Gagliardi Leite, Mauricio L Barreto
Journal: The Lancet (2014)
Matters of life and death and quality of life
Authors: D. K. Sokol
Journal: BMJ (2012)

Hospital doctors hold no monopoly in dealing with matters of consequence

Some doctors deal with matters of life and death on a regular basis. If the cardiac surgeon ignores the leaking aneurysm, the patient will die in minutes. If the anaesthetist fails to intubate at once, the patient will asphyxiate. In an emergency department in the United States I was present when a patient shot through the back was admitted by helicopter, his chest opened up within seconds of landing, and his heart pumped manually by a trauma physician. It was impressive, high octane medicine. In the course of a recent conversation with one of those life and death doctors, I lamented the plight of a young woman who had lost a leg in a road crash. Her life had been forever changed. She could no longer do things that we take for granted, such as swimming or taking the train or wearing certain clothes. The doctor remarked, to my surprise, that, though regrettable, “it wasn’t a matter of life and death.”

This dismissive attitude …
Radiation and women of child bearing potential
Authors: B. Bury, A. Hufton, J. Adams
Journal: BMJ (1995)

<h3>BACKGROUND AND PURPOSE:</h3> While posttraumatic anosmia is not uncommon, the olfactory function evaluation has strongly relied on subjective responses given by patients. We aimed to examine the utility of fMRI as an objective tool for diagnosing traumatic anosmia. <h3>MATERIALS AND METHODS:</h3> Sixteen patients (11 men and 5 women; mean age, 42.2 ± 10.4 years) with clinically diagnosed traumatic anosmia and 19 healthy control subjects (11 men and 8 women; mean age, 29.3 ± 8.5 years) underwent fMRI during olfactory stimulation with citral (a pleasant odor) or β-mercaptoethanol (an unpleasant odor). All patients were subjected to a clinical olfactory functional assessment and nasal endoscopic exploration. Two-sample <i>t</i> tests were conducted with age as a covariate to examine group differences in brain activation responses to olfactory stimulation (false discovery rate–corrected <i>P</i> &lt; .05). <h3>RESULTS:</h3> Compared with healthy control subjects, patients with traumatic anosmia had reduced activation in the bilateral primary and secondary olfactory cortices and the limbic system in response to β-mercaptoethanol stimulation, whereas reduced activation was observed only in the left frontal subgyral region in response to citral stimulation. <h3>CONCLUSIONS:</h3> Brain activation was decreased in the bilateral primary and secondary olfactory cortices as well as the limbic system in response to olfactory stimulation in patients with traumatic anosmia compared with healthy control subjects. These preliminary results may shed light on the potential of fMRI for the diagnosis of traumatic anosmia.
Genomic Analyses of Pneumococci from Children with Sickle Cell Disease Expose Host-Specific Bacterial Adaptations and Deficits in Current Interventions
Authors: Robert Carter, Joshua Wolf, Tim van Opijnen, Martha Muller, Caroline Obert, Corinna Burnham, Beth Mann, Yimei Li, Randall T. Hayden, Tamara Pestina, Derek Persons, Andrew Camilli, Patricia M. Flynn, Elaine I. Tuomanen, Jason W. Rosch
Journal: Cell Host & Microbe (2014)
Asthma and Nonsteroidal Anti-inflammatory Drugs
Authors: RICHARD S. FARR
Journal: Annals of Internal Medicine (1978)

Letters and Corrections1 October 1978Asthma and Nonsteroidal Anti-inflammatory DrugsRICHARD S. FARR, M.D., SHELDON L. SPECTOR, M.D., CAROLYN WANGAARD, R.N.RICHARD S. FARR, M.D.Search for more papers by this author, SHELDON L. SPECTOR, M.D.Search for more papers by this author, CAROLYN WANGAARD, R.N.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-89-4-577_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: We read with interest the case report of Daniel Kordansky and colleagues (Ann Intern Med 88:508-511, 1978) "Asthma Improved by Nonsteroidal Anti-Inflammatory Drugs".For the past 5 years at National Jewish Hospital, we have challenged a great many asthmatic patients with aspirin, placebo, tartrazine, sodium salicylate, and acetaminophen. Of 230 aspirin challenges, 44 or 19% led to significant bronchospasm. We found only one patient or 0.4% who was helped by aspirin. Unlike the authors, we did not test that patient with indomethacin, mefanamic acid, ibuprofen, or phenylbutazone. When historical information on aspirin idiosyncrasy is gathered, one obtains...References1. FALLIERS C: Aspirin and subtypes of asthma: risk factor analysis. J Allergy Clin Immunol 52:141-147, 1973 CrossrefMedlineGoogle Scholar2. SETTIPANECHAFFEEKLEIN GFD: Aspirin intolerance. II. A prospective study in an atopic and normal population. J Allergy Clin Immunol 53:200-204, 1974 CrossrefMedlineGoogle Scholar3. SPECTORFARRHARNETT SRJ: Aspirin idiosyncrasy, asthma and urticaria, in Allergy: Principles and Practice, edited by MIDDLETON E, REED C, ELLIS E. St. Louis, C.V. Mosby Co., 1978, pp. 1008-1022. Google Scholar4. VEDANTHANMENONBELLBERGIN PMTD: Aspirin and tartrazine oral challenge: incidence of adverse response in chronic childhood asthma. J Allergy Clin Immunol 60:8-13, 1977. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: National Jewish Hospital and Research Center Denver, CO 80206 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByDrug-Induced Respiratory DisordersAspirin-induced asthma in a patient with asthma previously improved by non-steroidal anti-inflammatory drugsEfecto broncodilatador de los antiinflamatorios no esteroideos en el asma. Comunicacion de un casoNeutrophil chemotactic factor of anaphylaxis (NCF-A) release in aspirin-induced asthma 1 October 1978Volume 89, Issue 4Page: 577-578KeywordsAspirinAsthmaDrugsIbuprofenPatientsSalicylatesSodium Issue Published: 1 October 1978 PDF DownloadLoading ...
Atopy and wheeze in children according to parental atopy and family size.
Authors: J B Davis, C J Bulpitt
Journal: Thorax (1981)

The relationship between atopy and wheeze was examined in children, together with the possible influence on these conditions of parental atopy and family size. Children with a repeated history of wheezing were selected from an urban general practice population. The children, their first degree relatives, and a control group were examined for atopic status, atopy being defined as more than one positive immediate skin prick test response. The prevalence of wheeze in boys was 15.5%, in girls 7.6%, and of atopy in boys 19.7% and in girls 8.1%. Of 110 atopic children 70% had no atopic parent, 27% had one atopic parent, and in 3% both parents were atopic. The presence of parental atopy was associated with an increased prevalence of wheeze in boys but not in girls, 12.0% of boys having a history of wheezing if neither parent was atopic and 27.5% if either or both parents were atopic (p less than 0.05). The presence of parental atopy was associated with an increased prevalence of atopy in girls but not in boys, 6.1% of girls having atopy if neither parent was atopic and 18.9% if either or both parents were atopic (p less than 0.01). There was a strong association between atopy and wheeze for both sexes and no statistically significant difference in the prevalence of atopy or wheeze in children whether they were from two, three, or four child families.
A8.18 Tissue specific pro-drug for the next generation of anti-TNF therapy in rheumatoid arthritis
Authors: M Ferrari, SC Onuoha, D Sblattero, C Pitzalis
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and objective</h3> Despite the obvious success of current anti-TNFα agents in Rheumatoid Arthritis (RA) treatment, high number of non-responders and systemic adverse effects (e.g. reactivation of tuberculosis) highlight the need of broader efficacy and improved safety profiles. Recently the importance of angiogenesis in the progression of arthritis has been unveiled. Angiogenesis can be exploited for tissue selective drug delivery approaches to drive <i>in-situ</i> drug accumulation, reducing systemic side effects. Towards this end we developed a bispecific antibody pro-drug platform with ICAM1 specificity to deliver an anti-TNFα payload to the arthritic tissue, allowing anti-TNFα activation selectively in the arthritic synovium and avoiding systemic TNFα engagement. <h3>Materials and methods</h3> The anti-ICAM1 variable region was subcloned in fusion with the anti-TNFα antibody Adalimumab in dual variable domain (DVD) bispecific format. The linker between the outer and inner variable domain was engineered to be short and bear an MMP1 cleavable site, forming an activatable DVD (aDVD) antibody. Reactivity with RA human synovium was determined using immunohistochemistry on tissue sections. MMP1-mediated antibody activation was tested using RA synovial fluids and RA synovial fibroblasts. Activity and biological functionality of the anti-TNFα moiety was assessed <i>in-vitro</i> using ELISA, Biacore and L-929 TNFα-cytotoxicity assays. <h3>Results</h3> The aDVD bispecific antibody was able to maintain synovial microvascular targeting, conveyed by the anti-ICAM1 variable domain, in RA synovial tissue sections. The intact molecule however, showed a reduced capacity to bind TNFα with 500-fold affinity decrease caused by steric hindrance of the outer variable region. Digestion with physiologically relevant concentrations of MMP1 was sufficient to restore 100% anti-TNFα activity (EC50 53 pM), comparable to the parent Adalimumab antibody (49 pM). Further, the un-processed aDVD antibody was significantly impaired in rescuing the L-929 cell line from TNFα-induced cytotoxicity. Digestion with MMP1 and activation of the anti-TNFα domain restored the anti-TNFα biological activity with an IC50 of 0.1 nM comparable to Adalimumab IgG (IC50 0.1 nM). <h3>Conclusions</h3> Our results demonstrate the development of a synovium-specific pro-drug delivery system for RA. The impaired TNFα binding capacity of the intact molecule ensures a decreased systemic TNFα engagement. Presence of metalloproteinases in RA synovium would activate and deliver the anti-TNFα activity locally in the site of disease. This strategy may allow greater therapeutically-relevant doses to be delivered in the synovium, increasing pharmacological potency, allowing reduction in the dosage and/or administration frequency, with the ultimate goal of reducing systemic exposure, achieve better therapeutic index and decreasing healthcare costs.
Echocardiography and Nuclear Cardiac Imaging in the Critical Care Unit
Authors: Margaret M. Parker
Journal: JAMA (1985)

AN ESSENTIAL function of the intensive care unit (ICU) is to couple immediate diagnosis with rapid therapeutic reversal of acute abnormalities of vital organ function. Much of conventional ICU technology monitors rapid changes in the cardiovascular system. Continuous electrocardiographic monitoring facilitates immediate detection and reversal of arrhythmias. Indwelling arterial catheters provide continuous measurement of arterial pressure. The balloon-tipped, flow-directed thermodilution pulmonary artery catheter permits frequent assessment of ventricular filling pressure and cardiac output, as well as calculation of vascular resistance in the systemic and pulmonary circulations. The major purpose of this cardiovascular monitoring is to allow recognition and correction of major derangements in cardiovascular function before serious compromise of vital organ systems can develop. During the past few years, the diagnostic and therapeutic capabilities of cardiovascular medicine have become more and more sophisticated. This enhanced diagnostic capability stems in part from the application of ultrasound and nuclear-medicine techniques to image