tbuckley/cabot-search huggingface dataset:
Randomized comparison of neoadjuvant cisplatin and fluorouracil infusion followed by radiation versus concomitant treatment in advanced head and neck cancer.
Authors: S G Taylor, A K Murthy, J M Vannetzel, P Colin, M Dray, D D Caldarelli, S Shott, E Vokes, J L Showel, J C Hutchinson
Journal: Journal of Clinical Oncology (1994)

PURPOSE To compare two published schedules of cisplatin plus fluorouracil (5-FU) infusion and radiation as either sequential or concomitant treatment for toxicity and efficacy in patients with unresectable head and neck cancer. PATIENTS AND METHODS This was a randomized trial between cisplatin 100 mg/m2 over 15 minutes on day 1 plus 5-FU 1.0 g/m2 by continuous infusion on days 1 to 5, repeated every 3 weeks for three cycles, followed by 70 Gy of radiation in 7 to 8 weeks, versus cisplatin 60 mg/m2 over 15 minutes on day 1 plus 5-FU 800 mg/m2 by continuous infusion on days 1 to 5 plus radiation 2 Gy on days 1 to 5, repeated every other week for seven cycles. Unresectable head and neck squamous cancer patients not previously treated with radiation or chemotherapy and with a performance status of 0 to 2 were stratified by tumor (T) and node (N) groupings and performance status and randomized. RESULTS Two hundred fifteen patients were entered and 214 analyzed, 107 on each arm. After all treatment, overall response rates were different (P = .003), with similar complete response rates, but more partial responses and fewer patients with no change or progression with concomitant treatment. Cox regression analysis for progression-free survival identified concomitant treatment (P = .003), Radiation Therapy Oncology Group (RTOG) stage III grouping (P &lt; .0001), performance status (P = .0002), concomitant treatment (P = .003), and treating institution (P = .006) as significant. The sequential and concomitant treatments showed similar distant failure patterns (10% and 7%, respectively), but divergent regional failure rates (55% and 39%). Severe and worse toxic events were similar between the treatment programs, but radiation-induced mucositis combined with cisplatin-induced water-losing nephropathy, in the concomitant arm only, demanded more supportive care. Survival duration was similar between the treatment arms, but significantly more patients in the sequential arm died of their cancer (P = .011). CONCLUSION Concomitant treatment offered improved disease control, predominantly of regional disease, but benefit was dependent on the experience of the treating institution. Translation of this benefit into improved survival is not yet evident, with an excess of deaths from other causes in the concomitant arm.
Clinical Tuberculosis 3rd Edition
Authors: M. Woodhead
Journal: European Respiratory Journal (2004)

Clinical Tuberculosis 3rd Edition     Edited by Peter D.O. Davies     Published by Arnold     Pages: 476. Price £110, \#8364;156. ISBN 0-340809167

Infection of one-third of the worlds' population, an interrelationship with HIV infection, new developments in molecular diagnostics and the development of resistance to the usually prescribed therapies are all pertinent reasons why a book like this might be important at this time. Peter Davies' book is now into its third edition after being published for the first time only 10 yrs ago and rightly seeks to remain …
Severe hypercholesterolemia inhibits cyclosporin A efficacy in a dose-dependent manner in children with nephrotic syndrome.
Authors: E Ingulli, A Tejani
Journal: Journal of the American Society of Nephrology (1992)

In order to identify possible markers of cyclosporin A (CSA) efficacy, the use of CSA (6 mg/kg) in 47 children with refractory nephrotic syndrome was reviewed. Response was defined as remission of proteinuria within 2 months. Before CSA administration, nonresponders (N = 13) were found to have more proteinuria (6 versus 3 g/24 h; P less than 0.03) and higher serum creatinine levels (0.9 versus 0.6 mg/dL; P less than 0.03) compared with responders (N = 34). Also, a markedly elevated serum cholesterol level (545 versus 312 mg/dL; P less than 0.001) was noted among nonresponders. Logistic regression analysis of all three parameters isolated serum cholesterol (P less than 0.01) as the only significant predictor of CSA nonresponsiveness. Discriminate analysis identified serum cholesterol to predict 97% of responders and 77% of nonresponders (P less than 0.0005) to conventional CSA doses. The CSA whole-blood trough HPLC levels were subtherapeutic among nonresponders (71 ng/mL) compared with responders (162 ng/mL) (P less than 0.001). Thus, a high serum cholesterol level may prevent the achievement of therapeutic CSA blood levels with conventional doses. On the basis of this, seven of the nonresponders were re-treated by titration of the CSA dose (10 to 14 mg/kg) with their serum cholesterol level. Their mean highest trough CSA level was 286 ng/mL. Five patients responded within 2 months. No elevation in serum creatinine or evidence of nephrotoxicity on repeat biopsy was seen after 2 months of therapy in all seven patients. It was concluded that severe hypercholesterolemia in nephrotic syndrome patients necessitates the titration of the CSA dose with the serum cholesterol level to achieve remission.
Ultrasound measurement of quadriceps wasting in patients with GOLD stage II COPD and its relationship to physical activity
Authors: Dinesh Shrikrishna, Rebecca Tanner, Mehul Patel, Anna V.J. Donaldson, Cayley Smith, Zudin A. Puthucheary, John M. Seymour, Paul S. Sidhu, Nicholas Hart, John Moxham, Michael I. Polkey, Nicholas S. Hopkinson
Journal: European Respiratory Journal (2011)

Introduction:  Ultrasound measurement of rectus femoris cross-sectional area (USRF CSA ) is a radiation-free measure of muscle bulk that relates to quadriceps strength. 1  A recent study reported that a significant proportion of GOLD stage II patients have quadriceps weakness. 2  We hypothesised that quadriceps wasting, measured by USRF CSA , would be observed in GOLD stage II patients and would correlate with daily physical activity levels.   Methods:  USRF CSA  and quadriceps maximum voluntary contraction (QMVC) were measured as described by Seymour  et al  1 . Physical activity was recorded for six consecutive days using a multisensor biaxial accelerometer, SenseWear Pro Armband™. Fat free mass (FFM) was estimated using bioelectrical impedance and a disease specific regression equation.   Results:  We studied 100 patients with stable COPD, (GOLD stage II-33%, III-34%, IV-33%), mean (SD) age 65 (9) years, 57% male and 23 age-matched healthy controls. USRF CSA  was significantly reduced (517mm 2  vs 626mm 2 ; p=0.005) in Stage II patients compared to controls. USRF CSA  was also significantly reduced in stage III (500mm 2 ; p=0.0006) and IV (522mm 2 ; p=0.007) disease. Using a stepwise regression model in all patients, FEV 1 % predicted and USRF CSA , but not FFM index and QMVC, correlated with daily physical activity (steps) (r 2 =0.4, p   Conclusion:  USRF CSA  is reduced in GOLD stage II COPD and is related to daily physical activity. USRF CSA  provides a bedside method for identifying quadriceps muscle loss in less severe disease and may guide the application of pulmonary rehabilitation in these patients.  1. Seymour JM  et al , Thorax 2009;64:418-23.  2. Seymour JM  et al , Eur Resp J 2010;36:81-8.
The Emerging Role of Spinal Dynorphin in Chronic Pain: A Therapeutic Perspective
Authors: Sonia Podvin, Tony Yaksh, Vivian Hook
Journal: The Annual Review of Pharmacology and Toxicology (2016)

Notable findings point to the significance of the dynorphin peptide neurotransmitter in chronic pain. Spinal dynorphin neuropeptide levels are elevated during development of chronic pain and sustained during persistent chronic pain. Importantly, knockout of the dynorphin gene prevents development of chronic pain in mice, but acute nociception is unaffected. Intrathecal (IT) administration of opioid and nonopioid dynorphin peptides initiates allodynia through a nonopioid receptor mechanism; furthermore, antidynorphin antibodies administered by the IT route attenuate chronic pain. Thus, this review presents the compelling evidence in the field that supports the role of dynorphin in facilitating the development of a persistent pain state. These observations illustrate the importance of elucidating the control mechanisms responsible for the upregulation of spinal dynorphin in chronic pain. Also, spinal dynorphin regulation of downstream signaling molecules may be implicated in hyperpathic states. Therapeutic strategies to block the upregulation of spinal dynorphin may provide a nonaddictive approach to improve the devastating condition of chronic pain that occurs in numerous human diseases.
Interleukin-18 is elevated in the horny layer in patients with atopic dermatitis and is associated with Staphylococcus aureus colonization
Authors: Y. Inoue, M. Aihara, M. Kirino, I. Harada, J. Komori-Yamaguchi, Y. Yamaguchi, Y. Nagashima, Z. Ikezawa
Journal: British Journal of Dermatology (2010)

An increase in interleukin (IL)-18 production from epidermal cells has been reported in an atopic dermatitis (AD) mouse model, and subsequent topical application of Staphylococcus aureus results in severe dermatitis.To reveal the relationship between S. aureus colonization of skin lesions and keratinocyte IL-18 production, particularly in AD with relatively low serum IgE levels. We also aimed to establish a simple and noninvasive method of assaying IL-18 produced by epidermal keratinocytes to evaluate local skin inflammation and therapeutic effects in patients with AD.IL-18 in the horny layer of the skin was collected via a tape-stripping method and measured in 95 patients with AD and 40 healthy controls by enzyme-linked immunosorbent assay (ELISA). Clinical severity, blood data and S. aureus skin colonization were evaluated before and after treatment.IL-18 levels in the horny layer were significantly higher in the skin lesions of patients with AD than in healthy controls and correlated with SCORAD, levels of serum IL-18, IgE, lactate dehydrogenase, thymus and activation-regulated chemokine, blood eosinophils and transepidermal water loss. In the AD group with serum IgE < 1500 IU mL(-1) , significantly higher IL-18 levels were observed in the horny layer of patients colonized with S. aureus compared with those who were not.Epidermal IL-18 production was associated with the severity of AD. Staphylococcus aureus colonization seems to contribute to this IL-18 production, especially in the AD group with relatively low IgE production. Tape stripping provides an easy and noninvasive method to assess epidermal IL-18 production by ELISA.
A Blood Based Egfr Mutation Analysis in Circulating Plasma Dna for Prediction of Primary Tumour Mutations in Lung Cancer
Authors: M. Freydin, D.V. Freydina, D. Chudasama, M. Leung, S. Popat, D. Gonzalez-De-Castro, A. Rice, A. Montero Fernandez, A.G. Nicholson, E. Lim
Journal: Annals of Oncology (2014)
Broad-spectrum antibodies against self-antigens and cytokines in RAG deficiency
Authors: Jolan E. Walter, Lindsey B. Rosen, Krisztian Csomos, Jacob M. Rosenberg, Divij Mathew, Marton Keszei, Boglarka Ujhazi, Karin Chen, Yu Nee Lee, Irit Tirosh, Kerry Dobbs, Waleed Al-Herz, Morton J. Cowan, Jennifer Puck, Jack J. Bleesing, Michael S. Grimley, Harry Malech, Suk See De Ravin, Andrew R. Gennery, Roshini S. Abraham, Avni Y. Joshi, Thomas G. Boyce, Manish J. Butte, Kari C. Nadeau, Imelda Balboni, Kathleen E. Sullivan, Javeed Akhter, Mehdi Adeli, Reem A. El-Feky, Dalia H. El-Ghoneimy, Ghassan Dbaibo, Rima Wakim, Chiara Azzari, Paolo Palma, Caterina Cancrini, Kelly Capuder, Antonio Condino-Neto, Beatriz T. Costa-Carvalho, Joao Bosco Oliveira, Chaim Roifman, David Buchbinder, Attila Kumanovics, Jose Luis Franco, Tim Niehues, Catharina Schuetz, Taco Kuijpers, Christina Yee, Janet Chou, Michel J. Masaad, Raif Geha, Gulbu Uzel, Rebecca Gelman, Steven M. Holland, Mike Recher, Paul J. Utz, Sarah K. Browne, Luigi D. Notarangelo
Journal: Journal of Clinical Investigation (2015)

Patients with mutations of the recombination-activating genes (RAG) present with diverse clinical phenotypes, including severe combined immune deficiency (SCID), autoimmunity, and inflammation. However, the incidence and extent of immune dysregulation in RAG-dependent immunodeficiency have not been studied in detail. Here, we have demonstrated that patients with hypomorphic RAG mutations, especially those with delayed-onset combined immune deficiency and granulomatous/autoimmune manifestations (CID-G/AI), produce a broad spectrum of autoantibodies. Neutralizing anti–IFN-α or anti–IFN-ω antibodies were present at detectable levels in patients with CID-G/AI who had a history of severe viral infections. As this autoantibody profile is not observed in a wide range of other primary immunodeficiencies, we hypothesized that recurrent or chronic viral infections may precipitate or aggravate immune dysregulation in RAG-deficient hosts. We repeatedly challenged Rag1S723C/S723C mice, which serve as a model of leaky SCID, with agonists of the virus-recognizing receptors TLR3/MDA5, TLR7/-8, and TLR9 and found that this treatment elicits autoantibody production. Altogether, our data demonstrate that immune dysregulation is an integral aspect of RAG-associated immunodeficiency and indicate that environmental triggers may modulate the phenotypic expression of autoimmune manifestations.
Ventilatory efficiency: An independent mechanism affected in exercise of GOLD 1 and 2 COPD patients
Authors: Iván Caviedes Soto, Rodrigo Soto
Journal: European Respiratory Journal (2013)

Background: we demonstrated the influence of Ventilatory inefficiency over exercise capacity in COPD (Resp Care 2012; 57: 583)

Purpose: to show ventilatory efficiency as a different mechanism affected in GOLD I-II patients.

Methods: 23 Gold I-II patients, mean age, FEV1/CVF, FEV1 and DCO of 65, 63.6, 84 and 60.5% respectively, compared with16 normal individuals. A stress test measuring Power, VO2max, Anaerobic threshold, Oxygen pulse, Ventilatory efficiency (VE/VCO2), expiratory flow limitation (EFL) and dynamic hyperinflation (DEELV) was performed comparing both groups. Correlations between EFL, DEELV and VE/VCO2 were calculated in patients with hyperinflation.

Results: COPD patients ended the test with leg fatigue and dyspnea (Borg 5 and 4) with normal Power, VO2max, Anaerobic threshold and Oxygen pulse (mean: 83, 82, 48.5 and 91% respectively), without difference with controls.

COPD patients presented an increased VE/VCO2 (mean 35.9) in oposition to controls (32.4) p < 0.005. 13 patients presented hyperinflation (mean 0.17 L). No significant correlation between EEFL, DEELV and VE/VCO2 was suggested (r 0.16 and 0.47).

Conclusions: Ventilatory efficiency is a different mechanism tampered during exercise in COPD patients, proposing another pathophysiological way to influence their exercise capacity.

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Hypnotics and Triazolobenzodiazepines - Best Predictors of High-Dose Benzodiazepine Use: Results from the Luxembourg National Health Insurance Registry
Authors: Jean-Marc Cloos, Valéry Bocquet, Isabelle Rolland-Portal, Paul Koch, Guy Chouinard
Journal: Psychotherapy and Psychosomatics (2015)

Benzodiazepines are not all the same concerning their risk of high-dose use.We studied benzodiazepine use from the Luxembourg national records of all insured. We calculated the 12-year prevalence from 1995 to 2007. Benzodiazepine users were divided into 3 groups, short-term with no longer than 3-month intake, intermediate with multiple administration with at least a 1-year interruption, and continuous who never stopped. A high-dose user (HDU) was defined as a patient who received a higher dose than the yearly maximum usual therapeutic dose.An average of 16.0% of the adult insured population received at least 1 benzodiazepine annually, 42.9% were older than 50, 55.9% were women, and 5.4% were HDUs. We found that 32.6% were short-term users, 49.0% intermediate and 18.4% continuous. Compared to diazepam, hypnotics had higher risks for high-dose use in at least 1 age group at first-benzodiazepine intake, the risks being greater in elderly subjects and women, the highest risks being with triazolam (adjusted odds ratio = 215.85; 95% confidence interval = 133.75-348.35) in the 69- to 105-year-old group at first-benzodiazepine intake. Anxiolytics had a low risk except for alprazolam and prazepam in the 69- to 105-year-old group at first-benzodiazepine intake, clonazepam and clobazam had the lowest risk in 18- to 43-year-olds at first-benzodiazepine intake. Alprazolam had dispensed volumes increased by threefold over the 12-year period.All hypnotics had higher risks for high-dose use compared to diazepam in continuous users. Two anxiolytics, clonazepam and clobazam, had the lowest risks. Hypnotics and the triazolobenzodiazepines alprazolam and triazolam were most problematic. Elderly subjects and women are at greater risks.
Chromosomally integrated human herpesvirus 6 in heart failure: prevalence and treatment
Authors: Uwe Kühl, Dirk Lassner, Nina Wallaschek, Ulrich M. Gross, Gerhard R.F. Krueger, Bettina Seeberg, Benedikt B. Kaufer, Felicitas Escher, Wolfgang Poller, Heinz‐Peter Schultheiss
Journal: European Journal of Heart Failure (2014)
Prenatal Particulate Air Pollution and Asthma Onset in Urban Children. Identifying Sensitive Windows and Sex Differences
Authors: Hsiao-Hsien Leon Hsu, Yueh-Hsiu Mathilda Chiu, Brent A. Coull, Itai Kloog, Joel Schwartz, Alison Lee, Robert O. Wright, Rosalind J. Wright
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

The influence of particulate air pollution on respiratory health starts in utero. Fetal lung growth and structural development occurs in stages; thus, effects on postnatal respiratory disorders may differ based on timing of exposure.
Proof of In Vivo Fusion of Murine Tumor Cells With Host Cells by Universal Fusers: Brief Communication 2
Authors: Rosalie Ber, Francis Wiener, Eva-Maria Fenyö
Journal: JNCI Journal of the National Cancer Institute (1978)

Journal Article Proof of In Vivo Fusion of Murine Tumor Cells With Host Cells by Universal Fusers: Brief Communication Get access Rosalie Ber, Rosalie Ber 5 3Department of Tumor Biology, Karolinska Institutet, S-104 01 Stockholm 60, Sweden 4Address reprint requests to Dr. Ber at Technion -Abba Khoushi, School of Medicine, Haifa, Israel. Search for other works by this author on: Oxford Academic PubMed Google Scholar Francis Wiener, Francis Wiener 3Department of Tumor Biology, Karolinska Institutet, S-104 01 Stockholm 60, Sweden Search for other works by this author on: Oxford Academic PubMed Google Scholar Eva-Maria Fenyö Eva-Maria Fenyö 3Department of Tumor Biology, Karolinska Institutet, S-104 01 Stockholm 60, Sweden Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 60, Issue 4, April 1978, Pages 931–933, https://doi.org/10.1093/jnci/60.4.931 Published: 01 April 1978 Article history Received: 20 October 1977 Accepted: 07 November 1977 Published: 01 April 1978
Altered Host-Allograft Relationships for Mouse Tumors Modified by Prior Passage In Vitro and In Vivo. II. Reactivity of Lymphoid Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Barbara B. Jacobs
Journal: JNCI Journal of the National Cancer Institute (1972)

Tumors modified by short-term passage in vitro or in vivo were established as serially transplantable lines in untreated histoincompatible mice. The morphology of lymphoid tissues from DBA/1 mice bearing progressive growths of BALB/c tumor allografts was not notably different from that of BALB/c animals bearing syngeneic grafts of the same tumor line. Spleen cells from the DBA/1 allograft recipients induced an unaltered graft-versus-host reaction in (BALB/c × DBA/1)F1 mice. These data do not support the view that there is a tolerant state associated with deletion of a reactive cell population. DBA/1 animals pre-exposed to the altered tumor allografts often accept grafts of the nonmodified tumor counterpart and manifest a delayed rejection of BALB/c skin grafts, which suggests that their cellular immune capacity has been modified. However, we were unable to induce allograft acceptance in mice by passive transfer of lymphoid tissues from allografted donors, nor were we able to inhibit tumor growth by inoculation of lymphoid cells from DBA/1 mice hyperimmunized against unmodified BALB/c tumor. Therefore, it is proposed that adaptations of both the tumor and the host perpetuate successful allograft survival and that these changes may be similar to those favoring the survival of the fetus as an allograft.—J Natl Cancer Inst 49: 1085–1091, 1972.
Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications
Authors: Larry M. Baddour, Walter R. Wilson, Arnold S. Bayer, Vance G. Fowler, Imad M. Tleyjeh, Michael J. Rybak, Bruno Barsic, Peter B. Lockhart, Michael H. Gewitz, Matthew E. Levison, Ann F. Bolger, James M. Steckelberg, Robert S. Baltimore, Anne M. Fink, Patrick O’Gara, Kathryn A. Taubert
Journal: Circulation (2015)

Infective endocarditis is a potentially lethal disease that has undergone major changes in both host and pathogen. The epidemiology of infective endocarditis has become more complex with today's myriad healthcare-associated factors that predispose to infection. Moreover, changes in pathogen prevalence, in particular a more common staphylococcal origin, have affected outcomes, which have not improved despite medical and surgical advances.This statement updates the 2005 iteration, both of which were developed by the American Heart Association under the auspices of the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease of the Young. It includes an evidence-based system for diagnostic and treatment recommendations used by the American College of Cardiology and the American Heart Association for treatment recommendations.Infective endocarditis is a complex disease, and patients with this disease generally require management by a team of physicians and allied health providers with a variety of areas of expertise. The recommendations provided in this document are intended to assist in the management of this uncommon but potentially deadly infection. The clinical variability and complexity in infective endocarditis, however, dictate that these recommendations be used to support and not supplant decisions in individual patient management.
Reductive Effect of Aspirin Treatment on Primary Tumor Growth and Metastasis of Implanted Fibrosarcoma in Rats2
Authors: Will J. Kort, Lorette O. M. Hulsman, Wim P. van Schalkwljk, Ineke M. Weijma, Pieter E. Zondervan, Dick L. Westbroek
Journal: JNCI Journal of the National Cancer Institute (1986)

Journal Article Reductive Effect of Aspirin Treatment on Primary Tumor Growth and Metastasis of Implanted Fibrosarcoma in Rats Get access Will J. Kort, Will J. Kort Search for other works by this author on: Oxford Academic PubMed Google Scholar Lorette O. M. Hulsman, Lorette O. M. Hulsman Search for other works by this author on: Oxford Academic PubMed Google Scholar Wim P. van Schalkwljk, Wim P. van Schalkwljk Search for other works by this author on: Oxford Academic PubMed Google Scholar Ineke M. Weijma, Ineke M. Weijma Search for other works by this author on: Oxford Academic PubMed Google Scholar Pieter E. Zondervan, Pieter E. Zondervan Search for other works by this author on: Oxford Academic PubMed Google Scholar Dick L. Westbroek Dick L. Westbroek Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 76, Issue 4, April 1986, Pages 711–720, https://doi.org/10.1093/jnci/76.4.711 Published: 01 April 1986 Article history Received: 30 April 1985 Revision received: 29 October 1985 Accepted: 06 December 1985 Published: 01 April 1986