tbuckley/cabot-search huggingface dataset:
Oxidative stress in cystic fibrosis lung disease: an early event, but worth targeting?
Authors: Andreas Hector, Matthias Griese, Dominik Hartl
Journal: European Respiratory Journal (2014)

A recent study showed that oxidative stress occurs early in CF lung disease and represents a potential drug target http://ow.ly/vdH2POxidative stress is a universal biological response, which plays a major role in a variety of inflammatory disease conditions, such as cardiovascular diseases or sepsis.In the lung, harmful oxidative stress mainly occurs in nonresolving pathologies, such as cystic fibrosis (CF) lung disease [1,2] or, to a lesser extent, chronic obstructive pulmonary disease [3,4].In CF, neutrophils are continuously recruited to the airways and liberate their toxic ingredients, particularly proteases and oxidants, in an uncontrolled fashion [5].Anti-proteases and anti-oxidants shield the lung from free proteolytic and oxidative damage [6].However, in CF the amount and duration of neutrophilic inflammation overwhelms these defence systems [2,7].The released proteases and reactive oxygen species, physiologically the neutrophil's major armamentarium to kill intracellular pathogens, as evidenced in patients with chronic granulomatous disease [8], degrade extracellular matrix components and immune receptors and oxidise proteins in the CF airway microenvironment in an uncontrolled manner.Glutathione is the major antioxidant shield in the epithelial lining fluid of the human lung and protects this vulnerable area from oxidative stress.Previous reports supported the concept that the cystic fibrosis transmembrane conductance regulator (CFTR) itself transports glutathione, providing a potential explanation for the low glutathione levels in CF airways [9][10][11].Alternatively to this CFTR-linked mechanism, activated neutrophils are also capable of oxidising and thereby disabling glutathione [12].To date, the relative contribution of these two mechanisms and the time-point when glutathione loss occurs in CF lung disease in vivo remains poorly understood.In this issue of the European Respiratory Journal, KETTLE et al.[13] take a closer look at the relationship between glutathione and neutrophilic inflammation by studying bronchoalveolar lavage fluid from 167 infants with CF with a mean age of 3 years.KETTLE et al. [13] studied a whole panel of glutathione oxidation products and neutrophil-derived enzymes that can oxidise glutathione.This study provides evidence that: 1) loss of glutathione occurs early in CF lung disease; 2) oxidised glutathione closely correlates with neutrophil-derived products, mainly hypochlorous acid; and 3) pulmonary infection enhances oxidative stress and oxidative loss of glutathione.The question arises of how specific are these findings for CF and what are the therapeutic consequences?We know that glutathione levels in airway lining fluids are low in a number of inflammatory conditions beyond CF, including severe asthma [14].In previous studies, glutathione levels were found to be decreased in
Associations of health related behaviour, social relationships, and health status with persistent physical activity and inactivity: a study of Finnish adolescent twins
Authors: M Aarnio, T Winter, U Kujala, J Kaprio
Journal: British Journal of Sports Medicine (2002)

Objective: To examine the association between leisure time physical activity over a three year period and health related behaviour, social relationships, and health status in late adolescence as part of a nationwide longitudinal study. Methods: Five birth cohorts of adolescent twins aged 16 at baseline (n = 5028; 2311 boys and 2717 girls) participated in the study. Questionnaires on leisure time physical activity, other health related behaviour, social relationships, and health status were sent to the twins on their 16th and 17th birthdays and six months after their 18th birthday. The combined response rate to the three questionnaires was 75.8% for boys and 81.7% for girls. Those who answered in all three questionnaires that their frequency of physical activity was 4–5 times a week or more were defined as persistent exercisers, and those who exercised at most twice a month in all three were defined as persistently inactive. Logistic regression analyses were used to identify baseline variables associated with outcome measures. Results: Overall, 20.4% of boys and 13.0% of girls were persistent exercisers and 6.5% of boys and 5.3% of girls were persistently inactive. In both sexes, smoking, irregular breakfast eating, attending vocational school, and poor self perceived current health were significantly associated with persistent inactivity. Conclusions: Persistent physical inactivity in adolescents is associated with a less healthy lifestyle, worse educational progression, and poor self perceived health. Tailoring methods to promote physical activity may prove useful for influencing other health habits. Such programmes are indicated for vocational schools in particular.
Menopause and Hypothalamic-Pituitary Sensitivity to Estrogen
Authors: Gerson Weiss, Joan H Skurnick, Laura T Goldsmith, Nanette F Santoro, Susanna J Park
Journal: JAMA (2004)

ContextThe onset of human menopause is thought to be caused solely by ovarian failure and oocyte depletion. However, clinical symptoms and certain recent data in perimenopausal women suggest central nervous system involvement.ObjectiveTo determine if modifications of hypothalamic-pituitary response to estrogen feedback mechanisms occur in older reproductive-age women as a mechanism of the onset of menopause.Design, Setting, and ParticipantsThe Study of Women’s Health Across the Nation (SWAN) is a multiethnic observational cohort study of the menopausal transition in 3302 women at 7 US sites. Of the subcohort of 840 women who participated in the Daily Hormone Study between 1997 and 1999, 680 women had evidence of luteal activity. The remaining 160 women (19%) did not have luteal activity and are the subject of this report.Main Outcome MeasuresDaily urinary hormone levels of estrogen and progesterone metabolites, luteinizing hormone (LH), and follicle-stimulating hormone (FSH).ResultsThree groups of women were studied: those with estrogen increases with an LH surge, those with estrogen increases without an LH surge, and those with neither. There were no differences in age or ethnicity among the 3 groups of women. Women in the third group (no increases) experienced more menopausal symptoms (hot flashes) than did women in the other groups with estrogen increases. In older reproductive-age women, the frequent existence of anovulatory cycles with estrogen peaks, equivalent to those that result in LH surges in younger women, yet in which no LH surges occur, indicates failure of estrogen-positive feedback on LH secretion. In other anovulatory cycles, follicular-phase estrogen levels did not lower LH secretion as occurs in cycles of younger women, indicating decreased estrogen-negative feedback on LH secretion.ConclusionOur findings are compatible with hypothalamic-pituitary insensitivity to estrogen in aging perimenopausal women.
Echolucent Plaques Are Associated With High Risk of Ischemic Cerebrovascular Events in Carotid Stenosis
Authors: Ellisiv B. Mathiesen, Kaare H. Bønaa, Oddmund Joakimsen
Journal: Circulation (2001)

Background —The purpose of the study was to assess in a prospective design whether plaque morphology is associated with risk of ischemic stroke and other cerebrovascular events in subjects with carotid stenosis. Methods and Results —A total of 223 subjects with carotid stenosis (123 with 35% to 49% degree of stenosis, 100 with 50% to 99% stenosis) and 215 control subjects matched by age and sex who participated in a population health survey at baseline were followed up for 3 years. Plaque echogenicity was assessed by ultrasound at baseline and scored as echolucent, predominantly echolucent, predominantly echogenic, or echogenic. Forty-four subjects experienced ≥1 ischemic cerebrovascular events in the follow-up period. Plaque echogenicity, degree of stenosis, and white blood cell count were independent predictors of cerebrovascular events. The unadjusted relative risk for cerebrovascular events was 13.0 (95% CI 4.5 to 37.4) in subjects with echolucent plaques and 3.7 (95% CI 0.7 to 18.2) in subjects with echogenic plaques when subjects without stenosis were used as the reference. The adjusted relative risk for cerebrovascular events in subjects with echolucent plaques was 4.6 (95% CI 1.1 to 18.9), and there was a significant linear trend ( P =0.015) for higher risk with increasing plaque echolucency. The adjusted relative risk for a 10% increase in the degree of stenosis was 1.2 (95% CI 1.04 to 1.4). Conclusions —Subjects with echolucent atherosclerotic plaques have increased risk of ischemic cerebrovascular events independent of degree of stenosis and cardiovascular risk factors. Subjects at high risk for ischemic vascular events may be identified by ultrasound assessment of plaque morphology.
RE: Meta-analysis of the Relationship Between Dose and Benefit in Phase I Targeted Agent Trials
Authors: Rajul K. Jain, J. Jack Lee, David Hong, Razelle Kurzrock
Journal: JNCI Journal of the National Cancer Institute (2013)

multi-institutional with findings across sites determining MTDs. MDACC sponsors included pharmaceutical corporations, NCI-CTEP, and foundations, entities with diverse approaches to clinical trials, whereas NCI-CTEP trials had one sponsor. Regarding sample size, in the NCICTEP study, 32% of subjects had gastric cancer, and two categories (gastric and leukemia/lymphoma) comprised 59% of the 1908 patients. In the MDACC study, the five most common tumors (breast, colorectal, melanoma, non–small cell lung, and thyroid cancers) comprised only 50% of the 683 patients. Regarding follow-up, patients were enrolled between May 2000 and December 2009 in the NCI-CTEP study and between October 2004 and June 2008 in the MDACC study. Given that overall survival is usually of short duration in phase I populations (3–5), the MDACC result will not change much with longer follow-up. Although MTD dosing has been a successful paradigm for cytotoxic agents, it is not clear this model applies to targeted agents (6,7). Toxicity considerations are important when evaluating patient benefit. Patients receiving MTD doses may endure increased toxicity without increased target modulation, as reflected by our time to treatment failure findings and findings that 2% to 3% of patients receiving low doses vs 10% to 15% of patients receiving high doses discontinued study for toxicity (P ≤ .01) (2). Furthermore, in addition to traditional response criteria, sustained stable disease can also be a meaningful efficacy measure. In view of the above, results of these studies may not be as contradictory as Gupta et al. suggest. Although the studies have differences in patient populations, institutions, sponsors, and outcome measures, our study clearly demonstrated that lower doses did not yield worse outcomes
Use of Stents to Treat Extracranial Cerebrovascular Disease
Authors: Philip M. Meyers, H. Christian Schumacher, Randall T. Higashida, Megan C. Leary, Louis R. Caplan
Journal: Annual Review of Medicine (2005)

Stent-assisted carotid angioplasty (CAS) is increasingly utilized for hemodynamically significant stenoses of the extracranial carotid artery. Carotid endarterectomy (CEA) is still considered the gold standard in the management of symptomatic hemodynamically significant carotid stenoses. However, endovascular device technology is rapidly evolving and the recent introduction of embolic filtration devices (EFD) proved to reduce periprocedural stroke rates in CAS considerably. Several randomized multicenter trials are currently recruiting patients to compare CAS with EFD to carotid endarterectomy in different cohorts, such as patients at high surgical risk for CEA and those with asymptomatic stenosis. The review presents current developments in CAS.
Colour doppler ultrasound assessment of arteriovenous haemodialysis fistulas
Authors: B. Nonnast-Daniel, O. Lindert, A. Mügge, J. Schaeffer, K.-M. Koch, W.G. Daniel, H. v d Lieth, E. Söchtig, M. Galanski, R.P. Martin
Journal: The Lancet (1992)
Effect of recombinant activated factor VII on perioperative blood loss in patients undergoing retropubic prostatectomy: a double-blind placebo-controlled randomised trial
Authors: Philip W Friederich, Christiaan P Henny, Embert J Messelink, Mark G Geerdink, Tymen Keller, Karl-Heinz Kurth, Harry R Büller, Marcel Levi
Journal: The Lancet (2003)
Risk factors for hospitalisation and poor outcome with pandemic A/H1N1 influenza: United Kingdom first wave (May-September 2009)
Authors: J. S. Nguyen-Van-Tam, P. J. M. Openshaw, A. Hashim, E. M. Gadd, W. S. Lim, M. G. Semple, R. C. Read, B. L. Taylor, S. J. Brett, J. McMenamin, J. E. Enstone, C. Armstrong, K. G. Nicholson
Journal: Thorax (2010)

<h3>Background</h3> During the first wave of pandemic H1N1 influenza in 2009, most cases outside North America occurred in the UK. The clinical characteristics of UK patients hospitalised with pandemic H1N1 infection and risk factors for severe outcome are described. <h3>Methods</h3> A case note-based investigation was performed of patients admitted with confirmed pandemic H1N1 infection. <h3>Results</h3> From 27 April to 30 September 2009, 631 cases from 55 hospitals were investigated. 13% were admitted to a high dependency or intensive care unit and 5% died; 36% were aged &lt;16 years and 5% were aged ≥65 years. Non-white and pregnant patients were over-represented. 45% of patients had at least one underlying condition, mainly asthma, and 13% received antiviral drugs before admission. Of 349 with documented chest x-rays on admission, 29% had evidence of pneumonia, but bacterial co-infection was uncommon. Multivariate analyses showed that physician-recorded obesity on admission and pulmonary conditions other than asthma or chronic obstructive pulmonary disease (COPD) were associated with a severe outcome, as were radiologically-confirmed pneumonia and a raised C-reactive protein (CRP) level (≥100 mg/l). 59% of all in-hospital deaths occurred in previously healthy people. <h3>Conclusions</h3> Pandemic H1N1 infection causes disease requiring hospitalisation of previously fit individuals as well as those with underlying conditions. An abnormal chest x-ray or a raised CRP level, especially in patients who are recorded as obese or who have pulmonary conditions other than asthma or COPD, indicate a potentially serious outcome. These findings support the use of pandemic vaccine in pregnant women, children &lt;5 years of age and those with chronic lung disease.
Genetic factors on quitting habits and smoking characteristics: A twin study
Authors: David Laszlo Tarnoki, Adam Domonkos Tarnoki, Zsofia Lazar, Kinga Karlinger, Andrea Agnes Molnar, Zsolt Garami, Viktor Berczi, Ildiko Horvath
Journal: European Respiratory Journal (2012)

Introduction: It is well known that quitting has a genetic background; however, no detailed information is available in this field. Our aim was to investigate different quitting and smoking charasteristics of monozygotic (MZ) and dizygotic (DZ) twins in order to investigate the genetic contribution.  Methods: Smoking 72 twin pairs (65 Hungarian and 7 American, 44 MZ and 28 DZ; mean age 44±17 years±standard deviation/SD/) filled in a questionnaire concerning smoking and quitting habits. The prevalence of concordant answers was calculated from the answers of 9 MZ and 3 DZ twin pairs whose both members quitted smoking. Significantly higher rate of concordant answers in MZ twins compared to DZ twins suggested a genetic influence.  Results: No significant difference was observed in the concordant answers concerning quitting attempts and duration of quitting period in MZ versus DZ twins (63% vs. 70%; 2.9±4.0 versus 1.9±1.5 years, p>0.05). Similarly, no significant difference was found in concordant answers regarding the history of quitting, mean difference in first cigarette smoking after wake-up, self-reported tobacco dependence, and certain smoking characteristics (what part of the cigarette is smoked, depth of imbibing the smoke, frequency of taking sniffs; and the frequency of thoughts concerning quitting smoking, harmful effects of smoking on other persons or him/herself, harmful operation of tobacco factories, cost of smoking) in MZ versus DZ twin pairs (p>0.05 for all characteristics).  Conclusions: In conclusion, this small twin study indicates no genetic influence on certain quitting habits, thoughts and smoking characteristics. A larger study sample is warranted.
A Synovial Sarcoma-Specific Preoperative Nomogram Supports a Survival Benefit to Ifosfamide-Based Chemotherapy and Improves Risk Stratification for Patients
Authors: Robert J. Canter, Li-Xuan Qin, Robert G. Maki, Murray F. Brennan, Marc Ladanyi, Samuel Singer
Journal: Clinical Cancer Research (2008)

Abstract Purpose: To identify prognostic factors related to outcome in 255 patients with synovial sarcoma and to construct a preoperative nomogram to predict the risk of disease-specific death. Design: Between July 1982 and June 2006, 301 patients underwent treatment at our institution for primary synovial sarcoma of all anatomic sites and 255 patients with localized disease at presentation were resected with curative intent. Data were collected prospectively and analyzed retrospectively. Results: Five-, 10-, and 15-year disease-specific survival (DSS) was 72%, 60%, and 53%, respectively. Multivariate analysis revealed size and primary tumor site as the only independent adverse predictors of disease-specific death. A nomogram based on preoperative data for surgical patients not receiving anthracycline-ifosfamide (AI) chemotherapy (n = 196) estimates 3- and 5-year DSS with a concordance index of 77.3%. For the first 3 years following diagnosis, the observed DSS for patients treated with AI chemotherapy (n = 59) was greater than that predicted by the preoperative nomogram based on patients not receiving AI chemotherapy. SYT-SSX fusion transcript data were available for 132 patients. Multivariate analysis of this subset showed that SYT-SSX1 fusion type was predictive of early, but not late, distant recurrence. Conclusion: Size and location govern prognosis in primary synovial sarcoma resected with curative intent. A nomogram based on preoperative variables provides individualized patient survival estimates and shows an early survival benefit to chemotherapy that may dissipate over time. This nomogram may improve decision-making with regards to selecting patients most likely to benefit from neoadjuvant/adjuvant chemotherapy.
Effects of beraprost sodium, an oral prostacyclin analogue, in patients with pulmonary arterial hypertension: a randomized, double-blind, placebo-controlled trial
Authors: Nazzareno Galiè, Marc Humbert, Jean-Luc Vachiéry, CarmineDario Vizza, Meinhard Kneussl, Alessandra Manes, Olivier Sitbon, Adam Torbicki, Marion Delcroix, Robert Naeije, Marius Hoeper, Ari Chaouat, Sophie Morand, Bruno Besse, Gerald Simonneau
Journal: Journal of the American College of Cardiology (2002)
Does non-cystic fibrosis bronchiectasis (nCF-BCt) determine extrapulmonary manifestations?
Authors: Anderson Alves de Camargo, Tatiane Soares Amaral, Rodrigo Abensur Athanazio, Samia Zahi Rached, Fernanda de Cordoba Lanza, Jenifer dos Santos, Dirceu Costa, Alberto Cukier, Regina Maria Carvalho-Pinto, Celso Ricardo Fernandes Carvalho, Rafael Stelmach, Simone Dal Corso
Journal: European Respiratory Journal (2013)

Introduction: Although nCF-BCt is a chronic and debilitating disease, its extrapulmonary effects have been poorly described in the literature. Objective: To evaluate the effects of nCF-BCt on exercise capacity, peripheral muscle strength, physical activity in daily life (PADL), and health-related quality of life (HRQoL) in adult subjects. Methods: Eighty subjects (50 women; 44 ± 14 yrs; fat-free mass index: 17 ± 2 kg/m²) with nCF-BCt and 30 healthy subjects (18 women; 44 ± 15 yrs; fat-free mass index: 17 ± 2 kg/m²) were evaluated. The subjects performed maximum voluntary isometric contraction of the quadriceps femoris (MVIC-QF), the incremental shuttle walking test (ISWT), and a maximum cardiopulmonary exercise test. PADL was assessed by the number of steps taken, calculated over three consecutive days (Yamax, PW-610 model, Tokyo, Japan). Dyspnea was rated according to the Medical Research Council (MRC) scale, and HRQoL was assessed using the SF-36 Health Survey Questionnaire. Results: Compared with the controls, the subjects with nCF-BCt presented with reduced aerobic capacity (VO2: 81 ± 15 vs 63 ± 13% pred; p < 0.001), functional capacity (ISWT distance: 73 ± 15 vs 52 ± 13% pred; p < 0.001), and MVIC-QF (26 ± 11 Kg vs 22 ± 10 Kg; p= 0.046). Lower PADL was also observed in the nCF-BCt patients (9526 ± 5843 vs 12009 ± 6031; p = 0.052), as well as poor HRQoL in most domains (statistically significant), except for pain and mental health. Conclusion: nCF-BCt is associated with extrapulmonary manifestations characterized by reduced exercise capacity, muscle strength, and PADL beyond impairment of HRQoL.
The Social Breakdown Syndrome-Some Origins
Authors: ERNEST M. GRUENBERG
Journal: American Journal of Psychiatry (1967)

Some patients manifest progressive chronic deterioration chiefly by behavior changes which are observable as modifications of personal and social behavior. Thus, studies of inner psychic connection underlying symptom formation can be complemented by investigating how social functioning breaks down. Six years' study suggests that the social breakdown syndrome (SBS) occurs when certain reactions to the patient interact and resonate with some of his efforts to do what he feels will be acceptable. There is evidence that properly conducted mental health center services can interrupt this process.
Identification of IL-16 as the lymphocyte chemotactic activity in the bronchoalveolar lavage fluid of histamine-challenged asthmatic patients
Authors: Margaret Vallen Mashikian, Robert E. Tarpy, Jussi J. Saukkonen, Kaiser G. Lim, Gregg D. Fine, William W. Cruikshank, David Center
Journal: Journal of Allergy and Clinical Immunology (1998)

Objective: We have previously demonstrated that the earliest lymphocyte chemotactic factors present in bronchoalveolar lavage fluid (BALF) of subjects with atopic asthma after subsegmental antigen challenge are IL-16 and MIP-1α, of which IL-16 appears to contribute a majority of the chemotactic activity. Because IL-16 is released in vitro after histamine stimulation of CD8+ T cells and epithelial cells, we evaluated the potential role of histamine in the release of IL-16 into the airways of allergic asthmatics in vivo. Methods: Eight allergic asthmatic subjects, six normal subjects, and six atopic nonasthmatic subjects were challenged with saline in the lingula and with serial concentrations of histamine (1 × 10-7 to 5 × 10-5 mol/L) in the right middle lobe followed by bronchoalveolar lavage (BAL) 15 minutes and 6 hours later. Results: The BALF from saline- and histamine-challenged lobes of normal subjects and atopic nonasthmatic subjects contained no significant lymphocyte chemoattractant activity. In six of the eight atopic asthmatic subjects, the histamine-challenged but not saline-challenged segment contained IL-16 chemotactic activity but no other identifiable lymphocyte chemoattractant activities at 6 hours. Conclusions: IL-16 appears in the airways after histamine challenge and therefore could contribute to the earliest infiltration of CD4+T cells and eosinophils observed after antigen challenge due to histamine release from mast cells. (J Allergy Clin Immunol 1998;101:786-792.)