tbuckley/cabot-search huggingface dataset:
Diagnostics of lung cancer in antituberculosis departments
Authors: Pavel Kryvanos, Halina Tamashakina, Dzmitry Kryvanos
Journal: European Respiratory Journal (2011)

Aim:  To study information of different examination methods for lung cancer diagnostics in patients of antituberculosis departments   Methods:  We analyzed results of medical examinations (clinical, roentgen and bronchological) of 2516 patients in hospital departments of Scientific Practical Centre for Pulmonology and Phthisiology in 2006-2008   Results:  Incidence rate of bronchologic cancer was 1,7% (43 patients); average patient age was 60,3 years; males – 76,7%, females – 23,3%. 74,4% cases with lung changes were revealed during the patient visited to physishian and only 25,6% (11 patients) during the systematic R-examination. 18 persons had tuberculosis, the rest patients were examined for specific or nonspecific process. According to made examinations 33 patients had tumour lung lesion, 10 had combination of lung tuberculosis and cancer. Central cancer was suspected in 44,2% patients and peripheral cancer in 50% during the rauting R-examination. Computed tomography increased diagnostics of central lung cancer to 68,4%. In peripheral cancer data of computed tomography was informative in 7 of 9 patients. Bronchoscopy with lung and bronch bicepsy permited to determine lung cancer in 88.9-100%. We had the most difficulties in lung cancer diagnostics because its combination with active tuberculosis and bacilli shedding.   Conclusion:  Early diagnostics of lung cancer in antituberculosis departments is possible with availability of timely bronchoscopy and oncologic alert in physicians.
Inhaled Aztreonam Lysine for Chronic Airway <i>Pseudomonas aeruginosa</i> in Cystic Fibrosis
Authors: Karen S. McCoy, Alexandra L. Quittner, Christopher M. Oermann, Ronald L. Gibson, George Z. Retsch-Bogart, A. Bruce Montgomery
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

The effectiveness and safety of aztreonam lysine for inhalation (AZLI) in patients with cystic fibrosis (CF) on maintenance treatment for Pseudomonas aeruginosa (PA) airway infection was evaluated in this randomized, double-blind, placebo-controlled study.To evaluate the safety and efficacy of inhaled aztreonam lysine in controlling PA infection in patients with CF.After randomization and a 28-day course of tobramycin inhalation solution (TIS), patients (n = 211; > or =6 yr; > or =3 TIS courses within previous year; FEV(1) > or = 25% and < or =75% predicted values) were treated with 75 mg AZLI or placebo, twice or three times daily for 28 days, then monitored for 56 days. The primary efficacy endpoint was time to need for additional inhaled or intravenous antipseudomonal antibiotics. Secondary endpoints included changes in respiratory symptoms (CF Questionnaire-Revised [CFQ-R] Respiratory Scale), pulmonary function (FEV(1)), and sputum PA density. Adverse events and minimum inhibitory concentrations of aztreonam for PA were monitored.AZLI treatment increased median time to need for additional antipseudomonal antibiotics for symptoms of pulmonary exacerbation by 21 days, compared with placebo (AZLI, 92 d; placebo, 71 d; P = 0.007). AZLI improved mean CFQ-R respiratory scores (5.01 points, P = 0.02), FEV(1) (6.3%, P = 0.001), and sputum PA density (-0.66 log(10) cfu/g, P = 0.006) compared with placebo; no AZLI dose-response was observed. Adverse events reported for AZLI and placebo were comparable and consistent with CF lung disease. Susceptibility of PA to aztreonam at baseline and end of therapy were similar.AZLI was effective in patients with CF using frequent TIS therapy. AZLI delayed time to need for inhaled or intravenous antipseudomonal antibiotics, improved respiratory symptoms and pulmonary function, and was well tolerated. Clinical trial registered with www.clinicaltrials.gov (NCT 00104520).
Th17/Treg Imbalance in Murine Cystic Fibrosis Is Linked to Indoleamine 2,3-Dioxygenase Deficiency but Corrected by Kynurenines
Authors: Rossana G. Iannitti, Agostinho Carvalho, Cristina Cunha, Antonella De Luca, Gloria Giovannini, Andrea Casagrande, Teresa Zelante, Carmine Vacca, Francesca Fallarino, Paolo Puccetti, Cristina Massi-Benedetti, Gloria Defilippi, Maria Russo, Luigi Porcaro, Carla Colombo, Luigi Ratclif, Fernando M. De Benedictis, Luigina Romani
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Mutations in the cystic fibrosis (CF) transmembrane conductance regulator affect the innate epithelial immune function of the lung, resulting in exaggerated and ineffective airway inflammation that fails to eradicate pathogenic fungi. The appreciation of whether such fungi are primarily responsible for or a consequence of ineffective airway inflammation is important for future therapeutics development.To characterize the impact of the tryptophan/kynurenine pathway on pathogenic airway inflammation preventing effective fungal clearance in CF.We studied the expression of indoleamine 2,3-dioxygenase (IDO), the first enzyme in the kynurenine pathway of tryptophan degradation, in human and murine CF, the impact of IDO on lung inflammation and immunity in murine CF, and the potential role of tryptophan catabolism in pathogenesis and therapy of fungus-associated lung inflammation.IDO was defective in murine and human CF. Genetic and transcriptional regulatory mechanisms contributed to dysfunctional IDO activity that, in turn, correlated with imbalanced Th17/Treg-cell responses to Aspergillus fumigatus in murine CF. Treatments enhancing IDO function or preventing pathogenic Th17-cell activation restored protective immunity to the fungus and improved lung inflammation in murine CF.This study provides a link between tryptophan catabolism and lung immune homeostasis in murine CF, representing a proof-of-concept that targeting pathogenic inflammation via IDO-mimetic drugs may benefit patients with CF.
The new ‘connexin’ to the pathogenesis of <i>E coli</i> diarrhoea
Authors: Alastair J M Watson
Journal: Gut (2010)

Infectious diarrhoea is a major cause of morbidity and mortality causing 1.5 million deaths worldwide in 2005.1 Thus the pathobiology of diarrhoea is of considerable interest. However, despite considerable research over the last 50 years, significant gaps remain in our knowledge of the pathogenic diarrhoea mechanisms of specific microorganisms.

Diarrhoea can be regarded simply as an excess of water in faeces. The healthy adult intestine must absorb approximately 7 litres per 24 h to produce a normal stool. Failure of absorption or, alternatively, secretion of water into the intestine or a combination of the two will cause diarrhoea.

Vibrio cholerae or enterotoxogenic Escherichia coli (ETEC) secrete toxins which cause the accumulation of the second messenger cyclic AMP or, in the case of ETEC, cyclic GMP in intestinal epithelial cells. These second messengers cause secretion of water into the intestinal lumen through a couple of mechanisms. Secretion occurs predominately in the intestinal crypts. They can directly open an anion channel on the apical membrane of epithelial cells called cystic fibrosis transmembrane conductance regulator (CFTR) allowing the efflux of chloride ions resulting in osmotic gradients that pull water into the intestinal lumen; a process called electrogenic chloride secretion.2 They also activate a neural reflex within …
Risk of solid cancer in patients exposed to anti-tumour necrosis factor therapy: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis
Authors: Louise K Mercer, Mark Lunt, Audrey L S Low, William G Dixon, Kath D Watson, Deborah P M Symmons, Kimme L Hyrich
Journal: Annals of the Rheumatic Diseases (2014)

Background Patients with rheumatoid arthritis (RA) have an increased risk of certain solid cancers, in particular lung cancer, compared to the general population. Treatment with tumour necrosis factor (TNF) inhibitors (TNFi) may further enhance this risk. Objectives To compare the risk of solid cancer in patients with RA treated with TNFi to that in patients treated with non-biologic (synthetic) disease modifying antirheumatic drugs (sDMARDs). Methods Patients with a physician diagnosis of RA enrolled in the British Society for Rheumatology Biologics Register, a national prospective cohort study established in 2001 to monitor the long-term safety of TNFi, were followed via record linkage with the national cancer registries until first solid cancer, death, for 5 years, or until 2011. Rates of solid cancers in 11 767 patients without prior cancer who received TNFi were compared to those in 3249 patients without prior cancer treated with sDMARDs. Results 427 solid cancers were reported in 52 549 patient-years follow-up for the TNFi group (81 (95% CI 74 to 89) per 10 000 patient-years) and 136 cancers were reported in 11 672 patient-years in the sDMARD cohort (117 (95% CI 98 to 138) per 10 000 patient-years). After adjusting for differences in baseline characteristics there was no difference in risk of solid cancer for TNFi compared to sDMARD treated patients: HR 0.83 (95% CI 0.64 to 1.07). There was no difference in the relative risk of cancer for any of the individual TNFi drugs. Conclusions The addition of TNFi to sDMARD does not alter the risk of cancer in RA patients selected for TNFi in the UK.
A Chronic Illness Characterized by Fatigue, Neurologic and Immunologic Disorders, and Active Human Herpesvirus Type 6 Infection
Authors: Dedra Buchwald, Paul R Cheney, Daniel L Peterson, Berch Henry, Susan B Wormsley, Ann Geiger, Dharam V Ablashi, S Zaki Salahuddin, CArl Saxinger, Royce Biddle, Ron Kikinis, Ferenc A Jolesz, Thomas Folks, N Balachandran, James B Peter, Robert C Gallo, Anthony L Komaroff
Journal: Annals of Internal Medicine (1992)

▪ Objective:To conduct neurologic, immunologic, and virologie studies in patients with a chronic debilitating illness of acute onset. ▪ Design: Cohort study with comparison to matched, healthy control subjects. ▪ Patients: We studied 259 patients who sought care in one medical practice; 29% of the patients were regularly bedridden or shut-in. ▪ Main Outcome Measures: Detailed medical history, physical examination, conventional hematologic and chemistry testing, magnetic resonance imaging (MRI) studies, lymphocyte phenotyping studies, and assays for active infection of patients' lymphocytes with human herpesvirus type 6 (HHV-6). ▪ Main Results: Patients had a higher mean (± SD) CD4/CD8 T-cell ratio than matched healthy controls (3.16 ± 1.5 compared with 2.3 ± 1.0, respectively; P < 0.003). Magnetic resonance scans of the brain showed punctate, subcortical areas of high signal intensity consistent with edema or demyelination in 78% of patients (95% CI, 72% to 86%) and in 21% of controls (CI, 11% to 36%) (P < 10-9). Primary cell culture of lymphocytes showed active replication of HHV-6 in 79 of 113 patients (70%; CI, 61% to 78%) and in 8 of 40 controls (20%; CI, 9% to 36%) (P < 10-8), a finding confirmed by assays using monoclonal antibodies specific for HHV-6 proteins and by polymerase chain reaction assays specific for HHV-6 DNA. ▪ Conclusions: Neurologic symptoms, MRI findings, and lymphocyte phenotyping studies suggest that the patients may have been experiencing a chronic, immunologically mediated inflammatory process of the central nervous system. The active replication of HHV-6 most likely represents reactivation of latent infection, perhaps due to immunologic dysfunction. Our study did not directly address whether HHV-6, a lymphotropic and gliotropic virus, plays a role in producing the symptoms or the immunologic and neurologic dysfunction seen in this illness. Whether the findings in our patients, who came from a relatively small geographic area, will be generalizable to other patients with a similar syndrome remains to be seen.
Crystal Structure of the Cysteine-Rich Domain of Mannose Receptor Complexed with a Sulfated Carbohydrate Ligand
Authors: Yang Liu, Arthur J. Chirino, Ziva Misulovin, Christine Leteux, Ten Feizi, Michel C. Nussenzweig, Pamela J. Bjorkman
Journal: The Journal of Experimental Medicine (2000)

The macrophage and epithelial cell mannose receptor (MR) binds carbohydrates on foreign and host molecules. Two portions of MR recognize carbohydrates: tandemly arranged C-type lectin domains facilitate carbohydrate-dependent macrophage uptake of infectious organisms, and the NH2-terminal cysteine-rich domain (Cys-MR) binds to sulfated glycoproteins including pituitary hormones. To elucidate the mechanism of sulfated carbohydrate recognition, we determined crystal structures of Cys-MR alone and complexed with 4-sulfated-N-acetylgalactosamine at 1.7 and 2.2 Å resolution, respectively. Cys-MR folds into an approximately three-fold symmetric β-trefoil shape resembling fibroblast growth factor. The sulfate portions of 4-sulfated-N-acetylgalactosamine and an unidentified ligand found in the native crystals bind in a neutral pocket in the third lobe. We use the structures to rationalize the carbohydrate binding specificities of Cys-MR and compare the recognition properties of Cys-MR with other β-trefoil proteins.
Alzheimer's Disease and Parkinson's Disease
Authors: Robert L. Nussbaum, Christopher E. Ellis
Journal: New England Journal of Medicine (2003)

Although most cases of Alzheimer's and Parkinson's disease are sporadic, some cases are clearly familial. This review, part of the Genomic Medicine series, examines the genetics of these familial forms. Although the inherited forms are rare, the knowledge derived from investigating their pathobiology has improved our understanding of the pathobiology of the more common, sporadic forms of the diseases.
Physical activity and cardiovascular risk factors in children
Authors: Lars Bo Andersen, Chris Riddoch, Susi Kriemler, Andrew Hills
Journal: British Journal of Sports Medicine (2011)

A number of recent systematic reviews have resulted in changes in international recommendations for children's participation in physical activity (PA) for health. The World Health Authority (WHO) has recently released new recommendations. The WHO still recommends 60 min of moderate to vigorous physical activity (MVPA), but also emphasises that these minutes should be on top of everyday physical activities. Everyday physical activities total around 30 min of MVPA in the quintile of the least active children, which means that the new recommendations constitute more activity in total compared with earlier recommendations.To summarise evidence justifying new PA recommendation for cardiovascular health in children.The results of recent systematic reviews are discussed and supplemented with relevant literature not included in these reviews. PubMed was searched for the years 2006-2011 for additional topics not sufficiently covered by the reviews.PA was associated with lower blood pressure and a healthier lipid blood profile in children. The association was stronger when a composite risk factor score was analysed, and the associations between physical fitness and cardiovascular disease (CVD) risk factors were even stronger. Muscle strength and endurance exercise each had an effect on blood lipids and insulin sensitivity even if the effect was smaller for muscle strength than for aerobic exercise. New evidence suggests possible effects of PA on C-reactive protein.There is accumulating evidence that PA can have beneficial effects on the risk factors of CVD in children. Public health policy to promote PA in children, especially the most sedentary children, may be a key element to prevent the onset of CVD later in the children's lives.
Effect on mortality of switching from cigarettes to pipes or cigars
Authors: B R. O'Driscoll, M. J Jarvis, R. Edwards, M. Jakubovic, J. H Lubin, J. F Fraumeni, N J Wald, H C Watt
Journal: BMJ (1998)

Editor—In their study of lung cancer and other diseases in male pipe and cigar smokers, Wald and Watt seem to have underestimated the difference in the risk of lung cancer between male current smokers and lifelong non-smokers (a 16-fold difference in their study).1 Non-smokers accounted for seven of 102 lung cancers in the study (figures for most ex-smokers were not supplied). This is very different from the experience of Capewell et al, who studied 3070 Scottish patients with lung cancer.2 Only 0.7% of men with lung cancer were lifelong non-smokers. My experience in Salford (three (0.8%) non-smokers and 217 current smokers among 380 men with lung cancer) is almost identical with that of Capewell et al. On the basis of local data on the prevalence of smoking, I calculate a 62-fold increased risk of lung cancer for Salford smokers compared with non-smokers. Capewell et al’s figures would also imply a risk of cancer of at least 50-fold for current smokers. 

There are several possible explanations for the high proportion of non-smokers with lung cancer in Wald and Watt’s study. Firstly, this was an elite group of subjects (business and professional men), of whom only a fifth smoked; one would therefore expect proportionally more cancers among non-smokers. In a previous study of professional British male subjects (the British doctors study), however, only seven (1.6%) of 441 deaths from lung cancer occurred in non-smokers.3 Secondly, the number of lung cancers in Wald and Watt’s study was small (102 cases), so the finding of seven cancers in non-smokers (compared with an expected finding of one or two cancers based on the above studies) may have occurred by chance. Thirdly, some long term ex-smokers in Wald and Watt’s study may have described themselves as non-smokers (Capewell et al found that at least a quarter of “non-smokers” were really ex-smokers). 

Whatever the explanation, Wald and Watt seem likely to have overestimated the risk of lung cancer in lifelong non-smokers compared with that in larger British studies. It is therefore important to emphasise to smokers in the general population that their risk of lung cancer is far more than 16 times that of a non-smoker and that this risk can be reduced greatly by stopping smoking. It is also likely that pipe and cigar smokers (and long term ex-cigarette smokers) are at greater relative risk of lung cancer compared with non-smokers than suggested in the authors’ study.
Pim-1 kinase is a target of miR-486-5p and eukaryotic translation initiation factor 4E, and plays a critical role in lung cancer
Authors: Wenshuai Pang, Xin Tian, Fan Bai, Ruiyu Han, Juan Wang, Haitao Shen, Xianghong Zhang, Yueping Liu, Xia Yan, Feng Jiang, Lingxiao Xing
Journal: Molecular Cancer (2014)

Pim-1 kinase is a proto-oncogene and its dysregulation contributes to tumorigenesis and progression of a variety of malignancies. Pim-1 was suggested as a therapeutic target of cancers. The functional relevance of Pim-1 and the mechanism underlying its dysregulation in lung tumorigenesis remained unclear. This study aimed to investigate if Pim-1 has important functions in non-small-cell lung cancer (NSCLC) by: 1) evaluating the clinicopathologic significance of Pim-1 through analysing its expression in 101 human NSCLCs tissues using quantitative PCR, Western Blot and immunohistochemical studies, 2) determining its role in NSCLC and drug resistance using in vitro assays, and 3) investigating the regulatory mechanism of Pim-1 dysregulation in lung tumorigenesis.Pim-1 was upregulated in 66.2% of the lung tumor tissues and its expression was significantly related to advanced stage (P = 0.019) and lymph node metastasis (P = 0.026). Reduced Pim-1 expression suppressed NSCLC cell growth, cell cycle progression and migration in vitro. Pim-1 was a novel target of miR-486-5p determined by luciferase report assay, and ectopic miR-486-5p expression in cancer cells reduced Pim-1 expression. Furthermore, eukaryotic translation initiation factor 4E (eIF4E) controlled the synthesis of Pim-1 in NSCLC cells, and its expression was positively associated with that of Pim-1 in NSCLC tissue specimens (r = 0.504, p < 0.001). The downregulated miR-486-5p and upregulated eIF4E in NSCLC cells led to the overexpression of Pim-1 by relieving the inhibitory effect of the 3'-UTR or 5'-UTR of Pim-1 mRNA, respectively. Moreover, Pim-1 knockdown sensitized NSCLC cells to cisplatin and EGFR tyrosine kinase inhibitor, gefitinib.Pim-1 kinase could be a critical survival signaling factor in NSCLC, and regulated by miR-486-5p and eIF4E. Pim-1 kinase may provide a potential target for diagnosis and treatment for lung cancer.
VALsartan In Acute myocardial iNfarcTion (VALIANT) trial: baseline characteristics in context
Authors: Eric J. Velazquez, Marc A. Pfeffer, John V. McMurray, Aldo P. Maggioni, Jean‐Lucien Rouleau, Frans Van de Werf, Lars Kober, Harvey D. White, Karl Swedberg, Jeffrey D. Leimberger, Paul Gallo, Mary Ann Sellers, Susan Edwards, Marc Henis, Robert M. Califf
Journal: European Journal of Heart Failure (2003)
Severe episodic dyspnoea and abnormal flow-volume loop
Authors: C Bucca, B Culla, S Asioli, F Rabbia, A Milan, G Limerutti, G Guida
Journal: Thorax (2009)

A 78-year-old never-smoking Caucasian woman presented with a 4-month history of persistent dry cough and episodic severe dyspnoea with inspiratory stridor and chest pain. She had visited the emergency department several times, where no significant abnormalities were noted. A suspected vocal cord dysfunction was excluded by fibreoptic laryngoscopy. Two months later spirometric examination showed moderate airway obstruction (forced …
Leukotriene receptor antagonists: useful in acute asthma?
Authors: L M KUITERT
Journal: Thorax (2000)

The leukotriene receptor antagonists (LTRAs) constitute the first completely new class of drugs for use in asthma for 25 years. Their development was based on the recognition that cysteinyl leukotrienes exhibit biological activities that mimic some of the clinical features of asthma and are detectable in increased amounts in asthmatic patients, particularly during exacerbations of asthma. Potent and specific LTRAs have been developed and marketed for use in the treatment of asthma in the UK. Their use by clinicians in the UK is usually as “add-on” therapy in chronic asthma at steps 3, 4, or 5 of the BTS asthma guidelines.

In this issue of Thorax Dockhorn et al compare the effect of intravenous and oral administration of the LTRA montelukast on airway function.1 Their results confirm those of previous studies that have shown improved pulmonary function after administration of an LTRA in asthmatic patients, and they also found that intravenous montelukast had a rapid onset of action and a duration of action of about 24 hours in 51 patients with mild to moderate asthma.

Early studies with the LTRAs showed that administration of a single dose (orally or intravenously) was predictably associated with an improvement in lung function.2 3 This suggested that, in patients with asthma, leukotrienes were contributing to the increase in airway smooth muscle tone. This is in contrast to that of normal subjects in whom the LTRAs …