tbuckley/cabot-search huggingface dataset:
Assessment of Exhaled Breath Condensate pH in Exacerbations of Asthma and Chronic Obstructive Pulmonary Disease
Authors: Balazs Antus, Imre Barta, Tamas Kullmann, Zsofia Lazar, Marta Valyon, Ildiko Horvath, Eszter Csiszer
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Exhaled breath condensate pH has been proposed as a noninvasive marker of airway inflammation. However, due to standardization difficulties in pH measurement techniques, different pH readings were obtained in previous studies.In this longitudinal study we assessed condensate pH in patients with an exacerbation of asthma or chronic obstructive airway disease using the very precise carbon dioxide standardization method that negates the effect of this gas on condensate acidity.Condensate pH, fractional exhaled nitric oxide, lung function, and blood gases were measured in 20 nonsmoking patients with asthma and 21 smoking and 17 ex-smoking patients with chronic obstructive airway disease first at hospital admission due to an acute exacerbation of the disease and again at discharge after treatment. Condensate pH was also assessed in 18 smoking and 18 nonsmoking healthy control subjects.In patients with asthma, condensate pH was significantly decreased at the time of exacerbation compared with nonsmoking control subjects and increased with treatment. In patients with chronic obstructive airway disease, condensate pH remained unchanged during exacerbation, both in smokers and ex-smokers. Nevertheless, condensates collected from smokers were more acidic than those of ex-smokers. A similar difference was observed between smoker and nonsmoker healthy control subjects. No correlations were found between condensate pH and fractional exhaled nitric oxide or lung function variables measured either at admission or discharge.Our data suggest that exacerbation of asthma, but not chronic obstructive airway disease, is associated with acidification of breath condensate.
P-219 The role of the putative tumor suppressor protein spinophilin in colorectal cancer
Authors: V. Stiegelbauer, A. Ress, D. Schwarzenbacher, A. Deutsch, S. Perakis, H. Ling, C. Ivan, G. Calin, A. Gerger, B. Rinner, M. Pichler
Journal: Annals of Oncology (2015)
Mass screening and age-specific incidence of neuroblastoma in Saitama Prefecture, Japan.
Authors: K Yamamoto, Y Hayashi, R Hanada, A Kikuchi, M Ichikawa, M Tanimura, S Yoshioka
Journal: Journal of Clinical Oncology (1995)

PURPOSE To provide the population-based incidence rate of neuroblastoma and to determine the effect of mass screening on the annual age-specific incidence of the tumor in Saitama Prefecture, Japan, from 1981 to 1992. METHODS Data on screened infants and patients detected by the screening were obtained from the records of the Prefectural Screening Center. Data on neuroblastomas in this area were obtained from the Children's Cancer Registry of the Saitama Prefectural Government (Prefectural Registry) and from the Japan Children's Cancer Registry (National Registry). Population data were obtained from the Prefectural Census. Mass screening for 6-month-old infants was performed by qualitative assessment of urinary vanillylmandelic acid (VMA) from June 1981 to September 1989 and by quantitative measurement of VMA/creatinine (Cre) and homovanillic acid (HVA)/Cre from October 1989 to December 1992. RESULTS Between 1981 and 1992, 199 cases of neuroblastoma, which include 74 cases detected by mass screening, were identified in Saitama Prefecture. The incidence rate for children under 15 years of age increased from 6.4/10(6) to 20.1/10(6), that for children 0 to 4 years of age increased from 17.0/10(6) to 64.1/10(6), and that for infants under 1 year of age increased from 27.9/10(6) to 260.4/10(6) during these 12 years. No significant reduction in the incidence rate was observed for children over 1 year of age. CONCLUSION The incidence rate for children under 15 years of age increased with mass screening. The rate for infants was sharply increased, with no corresponding decrease in the rate for children at older ages. These data suggest that there is a subset of neuroblastoma that can be detected by mass screening at 6 months of age but would not be diagnosed later clinically.
Prime study : a randomised phase 3 study of panitumumab with Folfox4 versus Folfox4 alone as first line treatment for metastatic colorectal cancer (mCRC)
Authors: Salvatore Siena, Jean-Yves Douillard, Josef Tabernero, James Cassidy, Ronald Burkes, Mario E. Barugel, Yves Humblet, David Cunningham, Michael Wolf, Jennifer Gansert
Journal: Annals of Oncology (2010)
Different effects of inhaled amiloride and frusemide on airway responsiveness to dry air challenge in asthmatic subjects
Authors: LT Rodwell, SD Anderson, J du Toit, JP Seale
Journal: European Respiratory Journal (1993)

Amiloride, a Na+ channel blocker, and frusemide, an inhibitor of the Na+/K+/2Cl- co-transporter on the basolateral surface of airway epithelial cells, have the potential to affect water transport across the airway epithelium. As isocapnic hyperventilation challenge (ISH) with dry air may provoke airway narrowing in asthmatic subjects by dehydrating the airways, inhaled amiloride and frusemide may reduce airway responsiveness by effecting airway hydration. Fifteen asthmatic subjects (6 females, 9 males), who had a fall in forced expiratory volume in one second (FEV1) of 20% after ISH, inhaled amiloride (11 mg), or its vehicle, from a Fisoneb ultrasonic nebulizer, within 10 min before ISH. On a separate day, eight of these subjects inhaled frusemide (38 mg), from the same Fisoneb, 10 min before ISH. After breathing, 30 l at resting ventilation, subjects breathed at 30% of their maximum voluntary ventilation (MVV i.e. predicted FEV1x35), then at 60% MVV, and finally at MVV for 3 or 4 min. FEV1 was measured 1, 3, 5, 7 and 9 min after each period, or until it was stable. Airway sensitivity was expressed as the ventilation (l-min-1) which provoked a 10, 15, 20 or 30% fall in FEV1, (PVE10, PVE15, PVE20 and PVE30, respectively). There was no significant difference in the PVE10,15,20,30 between the vehicle and amiloride treatment day; however, in the 8 subjects who inhaled frusemide, frusemide caused a significant increase in the PVE20 when compared to amiloride. In conclusion, inhaled amiloride failed to protect against ISH, whereas frusemide was effective at reducing airway responsiveness. Further studies are needed to explain the mechanism of action of frusemide.
Ribonucleotide reductase-mediated increase in dATP improves cardiac performance via myosin activation in a large animal model of heart failure
Authors: Shin Kadota, John Carey, Hans Reinecke, James Leggett, Sam Teichman, Michael A. Laflamme, Charles E. Murry, Michael Regnier, Gregory G. Mahairas
Journal: European Journal of Heart Failure (2015)
Spontaneous Lymphomas in SJL/J-(v&lt;sup&gt;+&lt;/sup&gt;) Mice: Ecotropic and Dualtropic Virus Expression in Normal and Lymphomatous Tissues&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: Anita De Rossi, Emma D'Andrea, Alfonso Colombatti, Peter J. Fischinger, Luigi Chieco-Bianchi
Journal: JNCI Journal of the National Cancer Institute (1981)

Approximately 60% of inbred SJL/J-(v+) adult mice having high levels of ecotropic endogenous XC+ virus showed virus activation within the first month of life, while the others produced virus at comparable levels later on, in an attempt to correlate the time of virus activation with the incidence and latency of lymphomas, the tails of 57 1- and 2-month-old mice were tested for virus presence, and the mice were then observed for lymphoma appearance. While all 2-month-old mice expressed ecotropic virus, only 63% of the 1-month-old mice were virus-positive. However no relationship existed between early virus production (within 1 month) or late virus production and lymphoma latency, total lymphoma incidence, and histopathology. In contrast with high titers of XC+ virus in tail tissues of diseased mice, a markedly low virus content was found in lymphomatous organs. This difference was not due to selective growth of poor virus-producer cells or to inhibitory factors possibly released by the inflammatory cell component. Viral protein content and XC+ virus titer were not closely correlated in the neoplastic organs. Search for XC- viruses revealed that only 1 of 6 aged normal and 16 of 19 lymphomatous mice produced viruses that grew on mink lung cells. By use of a standard limiting dilution cloning procedure, four isolates were obtained that showed tropism for both murine and heterologous cells. Three of these isolates induced cytopathic changes similar to those induced by MCF viruses on mink lung cells but not on mouse cells. Interference and neutralization assays performed to better characterize the virus envelope properties further indicated that SJL/J isolates had features typical of MCF dualtropic viruses.
Variance and covariances of the numbers of synonymous and nonsynonymous substitutions per site.
Authors: T Ota, M Nei
Journal: Molecular Biology and Evolution (1994)

Nei and Gojobori (1986) developed a simple method to estimate the numbers of synonymous (ds) and nonsynonymous (dN) substitutions per site. In the present paper, we have developed a method for computing variances and covariances of ds's and dN's and of the proportions of synonymous (ps) and nonsynonymous (pN) differences. We also have developed a method for computing the variances of mean dS, dN, pS, pN, without constructing a phylogenetic tree of the genes. We have conducted computer simulations based on simple evolutionary models and have shown that the new method gives good estimates of variances and covariances.
Nitrazepam in patients with sleep apnoea: a double-blind placebo-controlled study
Authors: U Hoijer, J Hedner, H Ejnell, R Grunstein, E Odelberg, M Elam
Journal: European Respiratory Journal (1994)

We wanted to assess whether benzodiazepines worsen sleep apnoea, since their use in such patients has been controversial. Fourteen male patients with mild to moderate obstructive sleep apnoea were investigated in a placebo-controlled, double-blind study evaluating the influence of nitrazepam (NIT) on apnoea frequency and severity. Each patient was given oral nitrazepam 5 or 10 mg, or corresponding placebo, in a randomized order on three separate nights. Wash-out time was one week. A complete sleep study was undertaken at each study night. Eleven patients completed the study. Although there were individuals with marked variability in apnoea index between the three study nights, there was no significant change in apnoea index or minimum arterial oxygen saturation with any of the two nitrazepam dosages studied. Only 3 out of 11 patients had a higher apnoea index after both nitrazepam doses compared to placebo, and in these patients the increase in sleep-disordered breathing was of marginal clinical significance. Nitrazepam caused a modest increase in total sleep time and a decrease in rapid eye movement (REM) sleep. These results demonstrate that nitrazepam does not worsen sleep apnoea in patients with mild to moderate sleep apnoea. The previously reported sleep apnoea promoting effects of benzodiazepines may be restricted to a small subgroup of patients with sleep-disordered breathing.
Adjuvant randomized trials of doxorubicin/cyclophosphamide versus doxorubicin/cyclophosphamide/tamoxifen and CMF chemotherapy versus tamoxifen in women with node-positive breast cancer.
Authors: M Kaufmann, W Jonat, U Abel, J Hilfrich, H Caffier, R Kreienberg, G Trams, K Brunnert, J Schermann, W Kleine
Journal: Journal of Clinical Oncology (1993)

PURPOSE We report two randomized trials of adjuvant systemic therapy in 747 patients &lt; or = 65 years of age with histologically proven node-positive breast cancer. PATIENTS AND METHODS Patients were selected for the two trials on the basis of lymph node and hormone receptor status. The only stratification was based on the treating institution. In patients with a lower probability of recurrence (n = 276), a comparison between endocrine therapy (tamoxifen [Tam] 30 mg/d for 2 years) and chemotherapy (cyclophosphamide, methotrexate, and fluorouracil [CMF] intravenously [IV], six cycles every 4 weeks) was performed. In patients with a higher risk of recurrence (n = 471), a comparison between chemotherapy alone (doxorubicin plus cyclophosphamide [AC] i.v., eight cycles every 3 weeks) and the same chemotherapy plus Tam was made. RESULTS Overall, we found that CMF and Tam are equally effective in a subgroup of patients with a relatively good prognosis (low-risk patients). However, in the subset of women &lt; or = 49 years old, a significantly greater disease-free survival (DFS) rate (P = .01) and overall survival (OS) rate (P = .002) was observed following therapy with CMF compared with Tam. In patients &gt; or = 50 years old, the opposite was found, and Tam appeared to be superior to CMF (DFS, P = .003; OSm P = .5). These results must be interpreted cautiously, since a post-hoc stratification of patients by age (&lt; or = 49, &gt; or = 50) was performed, and significantly more younger, low-risk patients were randomized to receive chemotherapy alone and more older patients to receive Tam alone. Among patients with a relatively poor prognosis (high-risk patients), a combination of AC plus Tam was equivalent to AC and, when women were analyzed by age, this was found to be true of patients &lt; or = 49 years as well. However, the addition of Tam to AC in women age &gt; or 50 years resulted in a statistically significantly higher DFS (P = .01) and a trend toward better OS compared with women who received AC alone. CONCLUSION Further trials are required to analyze the role of combined simultaneous or sequential chemoendocrine adjuvant treatment or each single therapy alone in defined risk-adapted subsets of node-negative and node-positive patients.
β2-microglobulin is a systemic pro-aging factor that impairs cognitive function and neurogenesis
Authors: Lucas K Smith, Yingbo He, Jeong-Soo Park, Gregor Bieri, Cedric E Snethlage, Karin Lin, Geraldine Gontier, Rafael Wabl, Kristopher E Plambeck, Joe Udeochu, Elizabeth G Wheatley, Jill Bouchard, Alexander Eggel, Ramya Narasimha, Jacqueline L Grant, Jian Luo, Tony Wyss-Coray, Saul A Villeda
Journal: Nature Medicine (2015)
Safety, tolerability and efficacy of intravenous aminophylline in adult patients with pulmonary exacerbations of cystic fibrosis
Authors: Peter Waddingham, Nicholas Simmonds, Diana Bilton
Journal: European Respiratory Journal (2014)

Background: Intravenous aminophylline (IVA) is sometimes used in the treatment of pulmonary exacerbations of cystic fibrosis (CF), however there is limited evidence for its benefit and small scale data suggest higher dosing may be needed for therapeutic effects (Isles et al 1983). We aimed to assess the safety, tolerability and efficacy of IVA in our large adult CF centre.  Methods: Retrospective pilot study of consecutive patient admissions receiving IVA over 5 months (Oct 2013-Feb 2014) including assessment of dose prescribed, serum levels, and side effects; with an observational subgroup analysis of efficacy (spirometry pre/post IVA and sputum clearance) in 15 patients prospectively.  Results: 30 patients received IVA. Median (range) duration of treatment was 8 (3-16) days. All infusions commenced at ≥0.5mg/kg/hour. Of 240 serum levels: 59.6% were sub therapeutic, 40% therapeutic (10-20mg/L) and 0.4% high. Side effects were common (60%) but did not lead to drug cessation (n=0).  % Predicted FEV1 and FVC improved from median (range) 33 (17-52) to 41 (22-63) and 49 (20-85) to 69 (29-108), respectively. Median change in % predicted of FEV1 7.5 (0-16) and FVC 12.5 (0-59). Improved sputum clearance was reported in 67% (n=10) of patients. 80% (n=12) of patients had therapeutic levels, not clearly linked to sputum clearance or improved spirometry.  Conclusion: High doses are required to achieve therapeutic levels in most patients although toxicity is extremely rare. Side effects are common but tolerance to these is high. Efficacy data suggests potential benefit with IVA regardless of serum levels; this now needs to be tested in a prospective controlled study.
Managing asthma in the outpatient clinic - Athletes with exercise-induced asthma
Authors: Asger Sverrild, Celeste Porsbjerg, Lise Stensen, Birgitte Nybo, Vibeke Backer
Journal: European Respiratory Journal (2012)

BACKGROUND  In athletes with exercise-induced asthma, confirmation of the disease with an objective test is required as part of the Therapeutic Use Exemption (TUE) application. An objective diagnosis often requires multiple testing with bronchial provocations and lung function measurements. Currently no guidelines exist on a diagnostic strategy in this group of subjects.  AIM  To evaluate the use of diagnostic tests in newly referred athletes with possible exercise-induced asthma in a specialized outpatient clinic.  METHODS  Medical records on all patients with a suspected diagnosis of asthma referred to the outpatient clinic at Bispebjerg Hospital, Copenhagen, Denmark in 2010 where reviewed, and data on reversibility to beta2-agonist and airway hyperresponsiveness (AHR) to inhaled mannitol, methacholine and eucapnic hyperventilation was collected. Subjects with exercise-induced symptoms that reported to spend at least 10 hours a week on their sports were defined as athletes and were included in the analysis.  RESULTS  Of 221 subjects referred with possible asthma to the outpatient clinic, 51 (23%) were athletes with possible exercise-induced asthma. A total of 39/51 (72%) was concluded to have asthma, based on a specialist9s assessment. Among these subjects the final diagnosis was confirmed by an objective test in 31/39 (80%). The number of tests required to confirm the presence of disease was one in 9 (29%) subjects, two in 15 (48%) subjects, three in 6 (19%) and four in 1 (3%) subject.  CONCLUSION  In more than eight out of ten athletes with exercise induced asthma, more than one test for AHR or reversibility was necessary as part of the diagnostic process.
Combination therapy with a <scp><i>T</i></scp><i>mprss6</i><scp>RNA</scp>i‐therapeutic and the oral iron chelator deferiprone additively diminishes secondary iron overload in a mouse model of β‐thalassemia intermedia
Authors: Paul J. Schmidt, Tim Racie, Mark Westerman, Kevin Fitzgerald, James S. Butler, Mark D. Fleming
Journal: American Journal of Hematology (2015)

β‐thalassemias result from diminished β‐globin synthesis and are associated with ineffective erythropoiesis and secondary iron overload caused by inappropriately low levels of the iron regulatory hormone hepcidin. The serine protease TMPRSS6 attenuates hepcidin production in response to iron stores. Hepcidin induction reduces iron overload and mitigates anemia in murine models of β‐thalassemia intermedia. To further interrogate the efficacy of an RNAi‐therapeutic downregulating Tmprss6 , β‐thalassemic Hbb th3/+ animals on an iron replete, an iron deficient, or an iron replete diet also containing the iron chelator deferiprone were treated with Tmprss6 siRNA. We demonstrate that the total body iron burden is markedly improved in Hbb th3/+ animals treated with siRNA and chelated with oral deferiprone, representing a significant improvement compared to either compound alone. These data indicate that siRNA suppression of Tmprss6 , in conjunction with oral iron chelation therapy, may prove superior for treatment of anemia and secondary iron loading seen in β‐thalassemia intermedia. Am. J. Hematol. 90:310–313, 2015. © 2015 The Authors. American Journal of Hematology Published by Wiley Periodicals, Inc.
Serum antibody responses to pneumococcal colonization in the first 2 years of life: results from an SE Asian longitudinal cohort study
Authors: P. Turner, C. Turner, N. Green, L. Ashton, E. Lwe, A. Jankhot, N.P. Day, N.J. White, F. Nosten, D. Goldblatt
Journal: Clinical Microbiology and Infection (2013)

Assessment of antibody responses to pneumococcal colonization in early childhood may aid our understanding of protection and inform vaccine antigen selection. Serum samples were collected from mother-infant pairs during a longitudinal pneumococcal colonization study in Burmese refugees. Maternal and cord sera were collected at birth and infants were bled monthly (1–24 months of age). Nasopharyngeal swabs were taken monthly to detect colonization. Serum IgG titres to 27 pneumococcal protein antigens were measured in 2624 sera and IgG to dominant serotypes (6B, 14, 19F, 19A and 23F) were quantified in 864 infant sera. Antibodies to all protein antigens were detect ablein maternal sera. Titres to four proteins (LytB, PcpA, PhtD and PhtE) were significantly higher in mothers colonized by pneumococci at delivery. Maternally-derived antibodies to PiuA and Spr0096 were associated with delayed pneumococcal acquisition in infants in univariate,but not multivariate models. Controlling for infant age and previous homologous serotype exposure, nasopharyngeal acquisition of serotypes 19A, 23F, 14 or 19F was associated significantly with a ≥2-fold antibody response to the homologous capsule (OR 12.84, 7.52,6.52, 5.33; p <0.05). Acquisition of pneumococcal serotypes in the nasopharynx of infants was not significantly associated with a ≥2-fold rise in antibodies to any of the protein antigens studied. In conclusion, nasopharyngeal colonization in young children resulted in demonstrable serum IgG responses to pneumococcal capsules and surface/virulence proteins. However, the relationship between serum IgG and the prevention of, or response to, pneumococcal nasopharyngeal colonization remains complex. Mechanisms other than serum IgG are likely to have a role but are currently poorly understood.
Respiratory viruses are more prevalent among urban preschoolers
Authors: Doxa Kotzia, Apostolos Giotas, Christine Kottaridi, Konstantinos Douros, Vasilis Grammeniatis, Vasiliki Matziou, Achileas Attilakos, Peter Karakitsos, Andreas Fretzayas, Konstantinos N. Priftis
Journal: European Respiratory Journal (2013)

Aim: Examine if there is any difference in incidence of respiratory virus detection among daycare attending children, living in urban or rural environment and second-hand tobacco smoke exposed.  Methods: The study population consisted of 233 preschool aged children, attending nursery: 120 children living in a rural area with low air-pollution (Viotia) and 113 in a metropolitan city (Athens). Urine cotinine was measured in the beginning of the study and 2 months later. The mean value was considered as a reliable index of tobacco smoke exposure. Nasal-pharyngeal swabs (NPS) were collected from 7 th  to 21 st  December 2010 and examined with RT-PCR for Adenovirus, Bocavirus, Coronavirus, Enteroviruses, Influenza (A, B, C) viruses, Metapneumovirus, Parainfluenza (1, 2, 3, 4) viruses, Rhinovirus, and RSV (A, B). Children were generally well during the study, only some had minor coryzal symptoms. We used logistic regression to investigate for differences in the viral distribution among the 2 groups and ordinal logistic regression for differences in the viral detection.  Results: Children from rural area had less viruses isolated (OR:0.48, CI:0.25-0.88, p=0.018). The most prevalent virus was Bocavirus (26/120 and 44/113 respectively, p=0.005) followed by Rhinovirus (4/120 and 12/113 respectively, p=0.028). In multivariable analysis, the distribution of Bocavirus was related to the living area (OR:0.43, CI:0.21-0.85, p=0.015) but not to cotinine levels. The distribution of all other viruses was not affected either by the living area or cotinine levels.  Conclusion: Urban living does favor the presence of respiratory viruses in NPS among preschool-aged children. No safe risk-free level of exposure to secondhand smoke was confirmed.