tbuckley/cabot-search huggingface dataset:
Is early diagnosis of COPD possible? Preliminary results of early COPD study
Authors: Sara Job, Rocco Francesco Rinaldo, Maria Adelaide Roggi, Alice Claudia Repossi, Silvia Dellafiore, Mirta Cavallini, Martina Piluso, Fabiano Di Marco, Stefano Centanni
Journal: European Respiratory Journal (2014)

COPD diagnosis is based on spirometric detection of irreversible airway obstruction. However, the wide pulmonary functional reserve may make spirometry insensitive.  Aim of the study is to assess whether second-level pulmonary functional tests and exercise testing allow an early diagnosis of COPD.  3 groups of subjects were enrolled: 1) EARLY: high pre-test probability of COPD (smoking history ≥ 10 py and exertional dyspnea not related to heart disease, and FEV1/FVC between the 5th and the 20th percentile of predicted values); 2) mild-to-moderate COPD; 3) HEALTHY (asymptomatic, smoking history ≤ 10 py, normal spirometry). All patients underwent a detailed anamnestic assessment, global spirometry, DLCO, single breath nitrogen wash-out (SBN 2 ), forced oscillation technique (FOT), six-minutes walking test (6MWT, with continuous flow and volumes evaluation) and cardiopulmonary exercise test (CPET).  19 patients were recruited: 6 EARLY, 7 HEALTHY and 6 COPD patients. Between EARLY and HEALTHY subjects, no significant difference in terms of dynamic hyperinflation and ventilatory reserve at 6MWT and CPET. However, we found a significant difference between groups in terms of SBN 2  slope (p ‹ 0.001). FOT, thoracic gas volume and FEF 25-75% values were different, although not statistically significant.  Our preliminary results show a sensitivity gap in the exertional pulmonary functional tests for early diagnosis of COPD. The SBN 2  slope could early identify small airway obstruction.
Abnormalities in lung clearance index in CF infants diagnosed by newborn screening
Authors: Padmaja Subbarao, Felix Ratjen, Renee Jensen, Per Gustafsson, Meghan Brown, Sanja Stanojevic
Journal: European Respiratory Journal (2012)

Newborn screening (NBS) in CF offers the potential to prevent lung damage before the onset of clinical symptoms. The lung clearance index (LCI), measured by multiple breath washout has shown promise as a marker of early lung disease in patients with CF.Therefore we aimed to determine whether LCI could be used to distinguish between subjects with CF and healthy subjects in the first 2 years of life. Healthy infants (3 months – 2 years) completed MBW testing as part of the infant pulmonary function protocol of the Canadian Healthy Infant Longitudinal Development Study (CHILD Study). Infants (3 months – 2 years) with diagnosed CF attending the Respiratory Medicine Clinic at the Hospital for Sick Children were invited to complete MBW testing. MBW was measured 51 healthy infants and 18 infants with CF diagnosed by NBS. Despite NBS, infants born with CF were smaller (Height-for-age z-score (-1.19 (-0.58; -1.81) and lighter (mean difference weight-for-age z-score (-0.40 (-0.98; 0.19) compared with healthy controls. The LCI was on average 0.4 units higher in CF (mean LCI 7.32 (SD 0.91)) compared to healthy infants (6.92 (SD 0.61)). Adjusting for the relationship between LCI and height in the first 2 years of life, LCI was 0.67 (95%CI -1.34; -0.01) z-scores higher in CF compared to healthy infants, although overlap was considerable (Figure). Therefore, despite newborn screening early abnormalities in LCI are present in CF patients LCI underscoring the need for new treatment approaches to address early lung disease.  Supported by CIHR and the Lynn and Arnold Irwin Foundation.
An attempt to evaluate lung aggression in monkey silicosis: hydrolases, peroxidase and antiproteases activities in serial bronchoalveolar lavages
Authors: MH Hannothiaux, A Scharfman, A Wastiaux, L Cornu, E van Brussel, JJ Lafitte, P Sebastien, P Roussel
Journal: European Respiratory Journal (1991)

Exposure to silica can induce fibrosis and/or emphysema. Various factors such as proteases, other hydrolases and oxidants may be involved in the destruction of lung parenchyma. On the other hand, antiproteases play an important role in the protection of lung parenchyma against the action of proteases. We have developed an animal model of silicosis in monkey Macacus cynomolgus and followed these factors by bronchoalveolar lavage (BAL). We have studied glycosidases activities, elastase-like activity, immunoreactive alpha 1-protease inhibitor (alpha 1PI), neutrophil elastase inhibitory capacity (NEIC) and myeloperoxidase. Bronchoalveolar cells in serial BAL were also studied. Six monkeys were exposed to quartz aerosols (100 mg.m-3) for 18 wks. They were followed until they developed X-ray changes, which occurred between 21-64 wks after the end of the dust exposure. Cellular "silicotic nodules" were observed in lung biopsies. A control animal underwent serial BAL. Changes were seen in the differential cell count. The release of superoxide anion by bronchoalveolar cells obtained during the experiment was increased. Separation on a gradient of Percoll showed the presence of young macrophages, which exhibited enhanced release of superoxide anion as compared to the totality of bronchoalveolar cells. The biochemical analysis of BAL fluids obtained during and after the period of dust exposure showed an increase in glycosidases, alpha 1PI and NEIC. Some free elastase-like activity was simultaneously detected in BAL fluids from exposed animals but not from the control. This elastase-like activity was very low compared to NEIC. The increase in enzymatic and antiprotease activities occurred at different points in time for each animal, suggesting large differences in individual responses to dust, but occurred before the chest X-ray abnormalities.
Role of cytokines in the innate immune response to intracellular pathogens
Authors: S Stenger, M Röllinghoff
Journal: Annals of the Rheumatic Diseases (2001)

Intracellular pathogens live inside host cells, and survival is dependent on coexistence with the host. In their intracellular niche these pathogens are well shielded from the effector cells of the cellular immune system. However, microbial proteins are processed and presented, thus promoting activation of T lymphocytes. These T lymphocytes determine resistance, susceptibility, and often immunopathogenesis of intracellular infections. Pathogenic intracellular bacteria and parasites include different species of Listeria , Mycobacteria , Salmonella , Chlamydia , Rickettsia , Trypanosoma , and Leishmania . Although CD4+ lymphocytes are central to acquired resistance, an increasing amount of evidence is emerging showing crucial contributions by CD8+ T cells as well as unconventional T cells. These include CD4−, CD8− TCRαβ+ T cells recognising mycobacterial lipid antigens, T cells expressing the TCRγδ or natural killer T cells, which are thought to have a regulatory function in the early immune response. Facultative intracellular microbes favour mononuclear phagocytes as their biotope, but can survive in the extracellular environment. In contrast, obligate intracellular bacteria such as Rickettsiae and Chlamydiae must enter host cells, because their metabolism requires nutrients of the eukaryotic cell.

The different types of immune response fall into two categories: innate immune response and adaptive immune responses (table1).

View this table:

Table 1 
Different types of immune response



The major difference between innate and acquired immune responses is that the latter are highly specific for a particular pathogen. Moreover, although the innate immune response does not alter on repeated exposure to a given infectious agent, the adaptive response improves with each successive encounter with the same pathogen. Because innate immunity functions at times before adaptive immunity, its major role is likely to be to initiate defence early during primary infections. There is growing appreciation of the immunoregulatory role of the innate immune responses both in activating cellular constituents of innate …
Clinically “small” effects of air pollution on FVC have a large public health impact
Authors: N Kunzli, U Ackermann-Liebrich, O Brandli, JM Tschopp, C Schindler, P Leuenberger
Journal: European Respiratory Journal (2000)

Epidemiological studies have repeatedly established adverse health effects due to long-term exposure to ambient air pollution. The Swiss Study on Air Pollution and Lung Disease in Adults (SAPALDIA) published a -3.14% decrease in forced vital capacity (FVC) per 10 microg x m(-3) increment in particulate matter (particles with a 50% cut-off aerodynamic diameter of 10 microm (PM(10)). Compared to the within-subject variability of FVC, the effect may be considered small. This individual (or clinical) perspective is, however, misleading. The purpose of this study was to demonstrate the public health relevance of apparently "small" effects, using the impact of PM10 on FVC as an example. The scenario compares a population A, exposed to an annual mean PM10 of 20 microg x m(-3), with a population B exposed to 30 microg x m(-3) mean PM10. A shift of -3.14% in the population distribution of FVC increases the number of subjects in the lower tail of the distribution. In population B a relative increase was expected of 47% (16-91%) in the prevalence of "FVC &lt;80% predicted", (i.e., from 5.17 to 7.59% and 5.88 to 8.65% among males and females, respectively). The relative increase in the prevalence of "FVC &lt;70% predicted" (approximately 1% of population) was 63% (30-98%, males) and 57% (21-86%, females). An epidemiological estimate of a change in the mean value of the population distribution should not be misinterpreted as an effect on the individual level. However, the impact of a 10 microg x m(-3) increase in particles with a 50% cut-off aerodynamic diameter of 10 microm (PM10) on the number of subjects with a clinically relevant reduction in lung function is quantitatively important.
Granulocyte colony-stimulating factor stimulates recovery of granulocytes in patients receiving dose-intensive chemotherapy without bone marrow transplantation.
Authors: J Neidhart, A Mangalik, W Kohler, C Stidley, J Saiki, P Duncan, L Souza, M Downing
Journal: Journal of Clinical Oncology (1989)

Bone marrow colony-stimulating factors (CSF) ameliorate hematologic toxicity of standard chemotherapy regimens and may allow relatively safe use of intensive and more efficacious doses of anticancer drugs. Twenty-four patients with cancers for which no standard regimens were likely to be effective received repeated courses of a combination of cisplatin (150 mg/m2), etoposide (1,500 mg/m2), and cyclophosphamide (5,000 mg/m2) at doses for which bone marrow transplantation is usually used. A total of 10 patients received escalating doses of recombinant human granulocyte CSF (rhG-CSF); 11 patients receiving identical chemotherapy and supportive therapy without rhG-CSF served as controls for the first cycle of therapy. Five of these patients and 3 additional patients also served as their own controls, receiving rhG-CSF for all cycles after the first. No patient received bone marrow transplantation. rhG-CSF shortened the median duration of severe granulocytopenia (less than or equal to 100/mm3) in a dose-related fashion (P less than .03; Kruskal-Wallis test). Patients not receiving rhG-CSF had a median of 8.5 days of granulocytopenia. Those receiving 40 micrograms/kg of rhG-CSF for approximately 20 days from the third day after chemotherapy had a median of 7.0 days (P less than .23) and those receiving 60 micrograms/kg had a median of 5.5 days (P less than .007) of granulocytopenia. An rhG-CSF dose of 20 micrograms/kg had no effect. Recovery to a granulocyte count of at least 500/mm3 took a median of 12 days in the control group and 8 days (P less than .03) in patients receiving rhG-CSF at a dose of 60 mg/kg. The duration of antibiotic therapy (a median, 9.0 days v 5.0 days) was shortened with the two higher and effective doses of rhG-CSF compared with control patients. The duration of hospitalization (median of 20 days v 19 days) was not shortened. These findings that rhG-CSF decreases the risk of granulocytopenia associated with this particular dose-intensive chemotherapy regimen therapy administered without bone marrow transplantation.
Practitioners should embrace, not ignore, health apps
Authors: E. Hickey, B. McMillan, C. Mitchell
Journal: BMJ (2015)

We are currently exploring two of the concerns raised by Husain and Spence—the regulation of health apps and evidence for their effectiveness.1 Android and iOS app stores currently contain more than 100 000 health apps, and the number is constantly increasing.2 The NHS Choices Health Apps Library contains verified apps with trusted information that are clinically safe and comply with data …
Pathologic analysis of autofluorescence bronchoscopy between heavy smokers with or not airway obstruction
Authors: Eunwoo Lee, Sungryong Kim, Minsun Beom
Journal: European Respiratory Journal (2013)

Background : The best prognosis for lung cancer can be expected by diagnosis at an early stage of the disease. Although low dose computed tomographic screening is known to reduces mortality from lung cancer, but may not reduce mortality in central lesions. autofluorescence bronchoscopy is known to be useful to detect central lung cancer. However, because of its invasiveness, its use is very limited. Also, It is known the presence of COPD in heavy smokers is an important factor to develop lung cancer. However, about central bronchial lesions, researches on the meaning of the presence of chronic obstructive pulmonary disease (COPD) are rare.

Methods : In this study, 139 participants (adults> 50 years old who had smoked at least 30 pack-years with respiratory symptoms) underwent screening with LDCT, autofluorescence bronchoscopy and from September 2008 through November 2011. We divided into two groups, one is group with airway obstruction, and another is group without airway obstruction. Airway obstruction criteria is postbronchodilator FEV1/FVC <0.7, pathologic abnormality is defined above metaplasia change.

Results : group with airway obstruction, total number is 39 person, the mean age of the patients was 65.0±27.1 years. Smoking history 51.9±29 pack-years, pathologic abnormality 5 person, a group without airway obstruction, total number is 100 person, the mean age of the patients was 59±9.6 years, smoking history 43.8±17.3 pack-years, pathologic abnormality 6 person.

Conclusion :

This study suggested that regardless of age and smoking history, chronic obstructive pulmonary disease (COPD) are considered as independent factors of central bronchial lesion (odds ratio 2.02).
Hundreds are arrested for Medicare fraud totalling $712m
Authors: O. Dyer
Journal: BMJ (2015)

A nationwide sweep led by the Medicare Fraud Strike Force has led to charges being laid against 243 people accused of submitting fraudulent Medicare bills totalling $712m (£450m; €625m), the new US attorney general, Loretta Lynch, has announced. Forty six of the accused are licensed medical professionals.

Flanked by Sylvia Mathews Burwell, secretary of health and human services, and James Comey, director of the FBI, Lynch said that the defendants charged included “doctors, patient recruiters, home healthcare providers, pharmacy owners, and others. They billed for equipment that wasn’t provided, for care that wasn’t needed, and for services that weren’t rendered.

“In the days ahead, the US Department of Justice will continue our focus on preventing wrongdoing …
Iron deficiency in non-anemic patients with chronic obstructive pulmonary disease
Authors: Matthias Urban, Otto Chris Burghuber, Wolfgang Hübl, Georg-Christian Funk
Journal: European Respiratory Journal (2011)

Background:  Iron deficiency contributes to reduced exercise capacity in patients with heart failure. The repletion of iron improves cognitive, symptomatic, and exercise performance in these patients independent of hemoglobin. COPD shares many functional features of heart failure. Thus iron deficiency could be a potential therapeutic target in COPD.   Aims and objectives:  The aim of this study was to determine the prevalence of iron deficiency in non-anemic patients with COPD.   Methods:  Serum markers of iron status were measured in 53 stable non-anemic (hemoglobin>12 g/L) COPD patients (53% males; mean age 64±8 years, mean FEV1predicted 41±18%; GOLD stage II, III, and IV was 34%, 32%, and 34%, respectively). Iron deficiency was diagnosed when the serum ferritin level was either    Results:  The serum ferritin level was    Conclusions:  Iron deficiency is present in half of the patients with stable COPD. A randomized, placebo-controlled trial should clarify whether repletion of iron stores improves functional performance in COPD patients with iron deficiency.
Identification of a New Susceptibility Locus for Systemic Lupus Erythematosus on Chromosome 12 in Individuals of European Ancestry
Authors: F. Yesim Demirci, Xingbin Wang, Jennifer A. Kelly, David L. Morris, M. Michael Barmada, Eleanor Feingold, Amy H. Kao, Kathy L. Sivils, Sasha Bernatsky, Christian Pineau, Ann E. Clarke, Rosalind Ramsey‐Goldman, Timothy J. Vyse, Patrick M. Gaffney, Susan Manzi, M. Ilyas Kamboh
Journal: Arthritis & Rheumatology (2015)

Objective Genome‐wide association studies (GWAS) in individuals of European ancestry identified a number of systemic lupus erythematosus (SLE) susceptibility loci using earlier versions of high‐density genotyping platforms. Followup studies on suggestive GWAS regions using larger samples and more markers identified additional SLE loci in subjects of European descent. This multistage study was undertaken to identify novel SLE loci. Methods In stage 1, we conducted a new GWAS of SLE in a North American case–control sample of subjects of European ancestry (n = 1,166) genotyped on Affymetrix Genome‐Wide Human SNP Array 6.0. In stage 2, we further investigated top new suggestive GWAS hits by in silico evaluation and meta‐analysis using an additional data set of subjects of European descent (&gt;2,500 individuals), followed by replication of top meta‐analysis findings in another data set of subjects of European descent (&gt;10,000 individuals) in stage 3. Results As expected, our GWAS revealed the most significant associations at the major histocompatibility complex locus (6p21), which easily surpassed the genome‐wide significance threshold ( P &lt; 5 × 10 −8 ). Several other SLE signals/loci previously implicated in Caucasians and/or Asians were also confirmed in the stage 1 discovery sample, and the strongest signals were observed at 2q32/ STAT4 ( P = 3.6 × 10 −7 ) and at 8p23/ BLK ( P = 8.1 × 10 −6 ). Stage 2 meta‐analyses identified a new genome‐wide significant SLE locus at 12q12 (meta P = 3.1 × 10 −8 ), which was replicated in stage 3. Conclusion Our multistage study identified and replicated a new SLE locus that warrants further followup in additional studies. Publicly available databases suggest that this newly identified SLE signal falls within a functionally relevant genomic region and near biologically important genes.
A model of laboratory surveillance for neuro-arbovirosis applied during 2012 in the Emilia-Romagna region, Italy
Authors: A. Pierro, M.P. Landini, P. Gaibani, G. Rossini, C. Vocale, A.C. Finarelli, R. Cagarelli, V. Sambri, S. Varani
Journal: Clinical Microbiology and Infection (2013)
Neodymium-YAG Laser Iridotomy
Authors: D J Brazier
Journal: Journal of the Royal Society of Medicine (1986)

Results of neodymium-YAG laser iridotomy in 34 eyes with narrow drainage angles are reported. Iridotomies appeared patent on slit-lamp examination in 32 (94%) eyes. Complications included failed patency of iridotomy and acute elevation of intraocular pressure.
LSC 2013 abstract - The role of alveolar macrophages during the resolution of house dust mite induced allergic airways disease
Authors: Sara Mathie, Tracy Hussell, Clare Lloyd
Journal: European Respiratory Journal (2013)

In spite of sharing common risk factors, in particular cigarette smoking, and aetiological substratum like low-grade systemic inflammation, chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) have been studied mostly separately. We investigated the coexistence of left ventricular dysfunction in COPD patients and of airway obstruction in CHF patients. Patients aged ≥50 years and with ≥10 pack/years of cigarette smoking presenting with a diagnosis of stable COPD (n=70) or stable CHF (n=124) were recruited. All COPD patients underwent routine echocardiographic assessment and Nt-pro brain natriuretic peptide (BNP) measurements, and all CHF patients underwent routine spirometry. Also, plasma levels of high sensitivity C reactive protein (hs-CRP), interleukin (IL)-6, IL-1β and its decoy receptor (IL-1RII), and pentraxin 3 (PTX3) were determined by using a sandwich enzyme-linked immunosorbent assay in all patients and in 24 healthy smokers. We did not detect ventricular dysfunction in COPD patients, whereas the occurrence of airway obstruction among CHF patients was 34%. COPD patients had higher plasma levels of hs-CRP and IL-1β as compared with CHF and healthy subjects (p  COPD coexists frequently in CHF patients; routine spirometry therefore seems to be worth in CHF subjects. COPD outpatients showed a low-grade systemic inflammation, but not left ventricular dysfunction.  Supported by the Ministry of Health and CFR.
Abstract 11564: Increased Expression of MiR-130a Improves Cardiac Function and Reduces Ventricular Remodeling Following Myocardial Infarction
Authors: Chen Lu, Xiaohui Wang, Tuanzhu Ha, Li Liu, Xia Zhang, Race Kao, John Kalbfleisch, David Williams, Chuanfu Li
Journal: Circulation (2013)

MicroRNA130a has been reported to promote angiogenesis which is an important factor in cardiac repair following myocardial infarction (MI). This study examined the role of miR-130a in cardiac function and cardiac remodeling following MI. Lentivirus expressing miR-130 (LmiR-130a) was delivered into mouse hearts (n=11) through the right carotid artery. Lentivirus expressing control miR (LmiR-con) served as transfection control (n=9). Seven days after transfection, the mice were subjected to MI by permanent ligation of LAD. Untransfected MI mice (n=24) served as MI control. Cardiac function was assessed by echocardiography before and after MI (1, 3, 7, 14, and 21 days). In LmiR-130a transfected MI group, EF% and %FS were significantly greater (~50%) than in LmiR-con and MI groups. LVESD and LVEDD values in LmiR-130a MI mice were markedly lower than in LmiR-con and MI groups. LmiR-130 transfection markedly increased the number of capillaries and decreased fibrotic deposition in the myocardium compared with LmiR-con and MI controls. To examine the effect of miR-130a on myocardial infarction, we induced myocardial ischemia (45 min) followed by reperfusion (24 h). Infarct size was analyzed by TTC staining. Transfection of LmiR-130a (n=8) significantly reduced myocardial infarct size by 53% compared with untransfected I/R group (n=7). LmiR-con transfection did not alter I/R induced infarct size (n=7). In a separate experiment, mice transfected with LmiR-130a (n=6) or LmiR-con (n=6) and untransfected (n=6) were subjected to MI for 3 days. Sham surgical operation served as sham controls (n=4/groups). Hearts were harvested and cellular proteins were prepared for Western blot analysis. LmiR-130a transfection suppressed PTEN expression, increased the levels of phospho-Akt and phospho-GSK-3β, enhanced VEGF and decreased HoxA5 levels, when compared with LmiR-con and MI groups. In addition, LmiR-130a transfection significantly reduced myocardial apoptosis, increased Bcl2 and prevented MI-increased Bax levels.  We concluded that miR-130a improves cardiac function and reduces cardiac remodeling following MI. The mechanisms involve activation PI3K/Akt signaling, stimulation of angiogenesis, and attenuation of MI-induced apoptosis.