tbuckley/cabot-search huggingface dataset:
Mechanisms of Dyspnea during Cycle Exercise in Symptomatic Patients with GOLD Stage I Chronic Obstructive Pulmonary Disease
Authors: Dror Ofir, Pierantonio Laveneziana, Katherine A Webb, Yuk-Miu Lam, Denis E O'Donnell
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Smokers with a relatively preserved FEV(1) may experience dyspnea and activity limitation but little is known about underlying mechanisms.To examine ventilatory constraints during exercise in symptomatic smokers with GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage I chronic obstructive lung disease (COPD) so as to uncover potential mechanisms of dyspnea and exercise curtailment.We compared resting pulmonary function and ventilatory responses (breathing pattern, operating lung volumes, pulmonary gas exchange) with incremental cycle exercise as well as Borg scale ratings of dyspnea intensity in 21 patients (post-bronchodilator FEV(1), 91 +/- 7% predicted, and FEV(1)/FVC, 60 +/- 6%; mean +/- SD) with significant breathlessness and 21 healthy age- and sex-matched control subjects with normal spirometry.In patients with COPD compared with control subjects, peak oxygen consumption and power output were significantly reduced by more than 20% and dyspnea ratings were higher for a given work rate and ventilation (P < 0.05). Compared with the control group, the COPD group had evidence of extensive small airway dysfunction with increased ventilatory requirements during exercise, likely on the basis of greater ventilation/perfusion abnormalities. Changes in end-expiratory lung volume during exercise were greater in COPD than in health (0.54 +/- 0.34 vs. 0.06 +/- 0.32 L, respectively; P < 0.05) and breathing pattern was correspondingly more shallow and rapid. Across groups, dyspnea intensity increased as ventilation expressed as a percentage of capacity increased (P < 0.0005) and as inspiratory reserve volume decreased (P < 0.0005).Exertional dyspnea in symptomatic patients with mild COPD is associated with the combined deleterious effects of higher ventilatory demand and abnormal dynamic ventilatory mechanics, both of which are potentially amenable to treatment.
Phospholipase A<sub>2</sub> in Eicosanoid Generation
Authors: EDWARD A. DENNIS
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Phospholipase A 2  (PLA 2 ) catalyzes the hydrolysis of the sn-2 fatty acyl bond of phospholipids, liberating free fatty acids and lysophospholipids (for a review see Reference 1). Its presence in pancreatic juices and in cobra venom was discovered around the beginning of the twentieth century (for a review see Reference 2). The role of these secreted PLA 2 s in digestion and envenomization has since been well documented. Evidence began to appear in the last several decades that PLA 2 s are also present in most types of cells and that they are involved in many different cellular functions including general lipid metabolism and membrane homeostasis. During this same period the view of phospholipids has also changed. What were once considered the inert building blocks of cellular membranes are now known to be important metabolic entities. Phospholipids and their metabolites are involved in a large number of important cellular control systems. This discovery has elevated PLA 2 s from being simple maintenance enzymes to being important players in such crucial systems as signal transduction and eicosanoid production. Through these systems, the actions of PLA 2 s affect a wide range of human physiological functions and diseases including asthma and allergy, the initiation and maintenance of parturition, blood clotting, atherosclerosis, sepsis, asthma, inflammatory bowel disease, and arthritis and other inflammatory diseases (for a review see Reference 3). The development of PLA 2  inhibitors is being vigorously pursued. A drug that modulates PLA 2  activity would have a large number of potential uses, especially as a nonsteroidal antiinflammatory agent (for a review see Reference 4). Such an inhibitor could supplement the current armament of cyclooxygenase inhibitors and new cyclooxygenase 2 inhibitors being developed to block prostaglandin biosynthesis and the multitude of approaches (for a review see Reference 5) currently being explored for the inhibition of enzymes responsible for leukotriene biosynthesis and leukotriene receptor antagonists as illustrated in Figure 1.
Dramatic increase in the numbers of functionally mature dendritic cells in Flt3 ligand-treated mice: multiple dendritic cell subpopulations identified.
Authors: E Maraskovsky, K Brasel, M Teepe, E R Roux, S D Lyman, K Shortman, H J McKenna
Journal: The Journal of Experimental Medicine (1996)

Dendritic cells (DC) are the most efficient APC for T cells. The clinical use of DC as vectors for anti-tumor and infectious disease immunotherapy has been limited by their trace levels and accessibility in normal tissue and terminal state of differentiation. In the present study, daily injection of human Flt3 ligand (Flt3L) into mice results in a dramatic numerical increase in cells co-expressing the characteristic DC markers-class II MHC, CD11c, DEC205, and CD86. In contrast, in mice treated with either GM-CSF, GM-CSF plus IL-4, c-kit ligand (c-kitL), or G-CSF, class II+ CD11c+ cells were not significantly increased. Five distinct DC subpopulations were identified in the spleen of Flt3L-treated mice using CD8 alpha and CD11b expression. These cells exhibited veiled and dendritic processes and were as efficient as rare, mature DC isolated from the spleens of untreated mice at presenting allo-Ag or soluble Ag to T cells, or in priming an Ag-specific T cell response in vivo. Dramatic numerical increases in DC were detected in the bone marrow, gastro-intestinal lymphoid tissue (GALT), liver, lymph nodes, lung, peripheral blood, peritoneal cavity, spleen, and thymus. These results suggest that Flt3L could be used to expand the numbers of functionally mature DC in vivo for use in clinical immunotherapy.
Inflammatory pattern in bacteriemic community-acquired pneumonia
Authors: Beatriz Montull, Rosario Menéndez, Eva Polverino, Soledad Reyes, Jose Miguel Sahuquillo, Juan Ginés Cόrdoba, Catia Cilloniz, Raquel Martínez, Rosaly Moreno, Antoni Torres, Jacobo Sellares, María Άngeles Marcos
Journal: European Respiratory Journal (2011)

Background: The inflammatory response in community-acquired pneumonia (CAP) depends on the host response, causal microorganism and severity of infection.

Objective: To analyze in a prospective study the pattern of inflammatory cytokines and biomarkers PCT and CRP (procalcitonin and C-reactive protein) in bacteriemic CAP in hospitalized CAP patients.

Results: 685 patients were included: 40 of them with bacteremia. The medians of CRP, PCT, TNF and IL-6 were significantly higher in those with bacteriemia (Table 1). PCT ≥0.36 to predict positive blood cultures showed sensitivity (S) of 85%, specificity (E) 42% and negative predictive value (NPV) of 98% (ROC area 0.70). The threshold of IL-6 ≥ 150 for predicting bacteremic CAP showed: 60% sensitivity, 70% and 96% negative predictive value (ROC area 0.65).

View this table:

Biomarkers and citokines in CAP





Conclusions: Bacteriemic CAP is associated with higher inflammatory cytokine systemic. PCT showed the highest diagnostic value. A cutoff ≥0.36 has high sensitivity. Lower initial PCT levels rule out bacteriemic CAP with a high negative predictive value.
Active eosinophilic esophagitis is characterized by epithelial barrier defects and eosinophil extracellular trap formation
Authors: D. Simon, S. Radonjic-Hösli, A. Straumann, S. Yousefi, H.-U. Simon
Journal: Allergy (2015)

Eosinophilic esophagitis (EoE) exhibits esophageal dysfunction owing to an eosinophil-predominant inflammation. Activated eosinophils generate eosinophil extracellular traps (EETs) able to kill bacteria. There is evidence of an impaired barrier function in EoE that might allow pathogens to invade the esophagus. This study aimed to investigate the presence and distribution of EETs in esophageal tissues from EoE patients and their association with possible epithelial barrier defects.Anonymized tissue samples from 18 patients with active EoE were analyzed. The presence of DNA nets associated with eosinophil granule proteins forming EETs and the expression of filaggrin, the protease inhibitor lympho-epithelial Kazal-type-related inhibitor (LEKTI), antimicrobial peptides, and cytokines were evaluated by confocal microscopy following immune fluorescence staining techniques.Eosinophil extracellular trap formation occurred frequently and was detected in all EoE samples correlating with the numbers of infiltrating eosinophils. While the expression of both filaggrin and LEKTI was reduced, epithelial antimicrobial peptides (human beta-defensin-2, human beta-defensin-3, cathelicidin LL-37, psoriasin) and cytokines (TSLP, IL-25, IL-32, IL-33) were elevated in EoE as compared to normal esophageal tissues. There was a significant correlation between EET formation and TSLP expression (P = 0.02) as well as psoriasin expression (P = 0.016). On the other hand, a significant negative correlation was found between EET formation and LEKTI expression (P = 0.016).Active EoE exhibits the presence of EETs. Indications of epithelial barrier defects in association with epithelial cytokines are also present which may have contributed to the activation of eosinophils. The formation of EETs could serve as a firewall against the invasion of pathogens.
THYMECTOMY IN THE RABBIT
Authors: Chester M. Van Allen
Journal: The Journal of Experimental Medicine (1926)

Thymectomy in the rabbit is a comparatively simple procedure. The open method described above offers many advantages over any of the closed methods and success depends largely upon the observance of a few precautions; chief among these is the avoidance of haste and the observance of aseptic technique. The operative mortality in our series of rabbits was 10 per cent and there was an additional loss of useful animals, due to secondary complications, amounting to 16 per cent. Among the last 29 rabbits, however, there was only 1 operative death, in an old animal, and 2 cases of slight infection. It appears, therefore, that with some experience the operation can be carried out successfully in nearly all animals, especially so if comparatively young rabbits are used. Old rabbits present greater difficulties on account of the presence of dense fibrous tissue within the field of operation. While the animals of this series showed no immediate symptoms or alteration in physical condition that could be referred to thymoprivia, it is not to be assumed that removal of the thymus is entirely without effect even on rabbits of mature age. Our observations on the reaction of thymoprivic rabbits to disease show that this is not the case and that in all probability decided effects can be demonstrated if the problem is approached on another basis. The object of the present investigation was, however, to determine whether the thymus could be completely removed from rabbits of certain ages without producing any serious disturbance of health which would interfere with their use in other experiments or complicate the interpretation of results. It was found that this could be done.
Health effects of passive smoking. 4. Parental smoking, middle ear disease and adenotonsillectomy in children
Authors: D. P. Strachan, D. G. Cook
Journal: Thorax (1998)

BACKGROUND: A systematic quantitative review was conducted of evidence relating parental smoking to acute otitis media, recurrent otitis media, middle ear effusion, and adenoidectomy and/or tonsillectomy. METHODS: Forty five relevant publications were identified after consideration of 692 articles selected by electronic search of the Embase and Medline databases using keywords relevant to passive smoking in children. The search was completed in April 1997 and identified 13 studies of acute otitis media, nine of recurrent otitis media, five of middle ear effusion, nine of glue ear surgery, and four of adenotonsillectomy. A quantitative meta-analysis was possible for all outcomes except acute otitis media, using random effects modelling where appropriate to pool odds ratios from each study. RESULTS: Evidence for middle ear disease is remarkably consistent, with pooled odds ratios if either parent smoked of 1.48 (95% CI 1.08 to 2.04) for recurrent otitis media, 1.38 (1.23 to 1.55) for middle ear effusion, and 1.21 (0.95 to 1.53) for outpatient or inpatient referral for glue ear. Odds ratios for acute otitis media are in the range 1.0 to 1.6. No single study simultaneously addresses selection bias, information bias and confounding, but where these have been investigated or excluded in the design or analysis, the associations with parental smoking persist virtually unchanged. Large French and British studies are inconsistent with regard to the association of parental smoking and tonsillectomy. CONCLUSIONS: There is likely to be a causal relationship between parental smoking and both acute and chronic middle ear disease in children.
Merkel Cell Carcinoma: Incidence, Mortality, and Risk of Other Cancers
Authors: J. Kaae, A. V. Hansen, R. J. Biggar, H. A. Boyd, P. S. Moore, J. Wohlfahrt, M. Melbye
Journal: JNCI Journal of the National Cancer Institute (2010)

Merkel cell carcinoma (MCC) is a rare skin cancer that was recently found to be associated with a polyomavirus and with immunosuppression, provoking new interest in its epidemiology. We conducted a nationwide study in Denmark to describe MCC incidence and mortality and the association between MCC and other cancers. We used data from Danish national health and population registers on MCC diagnoses, deaths, and population counts during the study period (1978–2006) to calculate MCC incidence rates, cumulative risks of MCC at age 100 years, and MCC mortality rates by tumor stage. We used Poisson regression to estimate the excess mortality rate ratio attributable to MCC and examined associations between MCC and other cancers diagnosed before and after the MCC diagnosis using standardized incidence rate ratios (SIRs). All statistical tests were two-sided. Between January 1, 1978, and December 31, 2006, 185 persons were diagnosed with MCC in Denmark. MCC incidence between 1995 and 2006 was 2.2 cases per million person-years. In the first year after MCC diagnosis, 22% of persons with localized disease died compared with 54% of patients with nonlocalized disease; by 5 years after diagnosis, the proportions of MCC patients who had died increased to 55% and 84%, respectively. MCC incidence was statistically significantly increased more than 1 year after a diagnosis of squamous cell carcinoma of the skin (SIR = 14.6, 95% confidence interval [CI] = 8.4 to 25.6), basal cell carcinoma (SIR = 4.3, 95% CI = 2.7 to 6.6), malignant melanoma (SIR = 3.3, 95% CI = 1.1 to 10.3), chronic lymphocytic leukemia (SIR = 12.0, 95% CI = 3.8 to 37.8), Hodgkin lymphoma (SIR = 17.6, 95% CI = 2.5 to 126), and non-Hodgkin lymphoma (SIR = 5.6, 95% CI = 1.4 to 22.4). Squamous cell carcinoma (SIR = 12.1, 95% CI = 5.1 to 29.1) and chronic lymphocytic leukemia (SIR = 14.7, 95% CI = 3.7 to 58.8) occurred in statistically significant excess more than 1 year after MCC diagnosis. These results support the existence of shared risk factors for MCC and other cancers. Heightened awareness of the association between MCC and other cancers, particularly squamous cell carcinoma and chronic lymphocytic leukemia, may facilitate earlier clinical detection and treatment of MCC, thereby improving patient survival.
Reduced Cortical Folding in Schizophrenia: An MRI Morphometric Study
Authors: Paulo C Sallet, Helio Elkis, Tânia M Alves, José R Oliveira, Erlei Sassi, Claudio Campi de Castro, Geraldo F Busatto, Wagner F Gattaz
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: Although well documented, regional brain structural abnormalities in schizophrenia are nonspecific, and morphometric parameters show significant overlapping between patients and healthy comparison subjects. An increasing number of studies have focused on supraregional models involving abnormalities of the neuronal circuitry between cortical regions in schizophrenia. The aim of the present study was to investigate cortical folding as an index of the neuronal wiring in different subtypes of schizophrenia. METHOD: Magnetic resonance imaging measures of gyrification index in intervals of 3.6 mm along the total cerebral cortex were compared in 40 patients with DSM-IV schizophrenia and 20 healthy subjects. Psychopathology was assessed with the Positive and Negative Syndrome Scale, Brief Psychiatric Rating Scale, and the Negative Symptom Rating Scale. RESULTS: The schizophrenia patients showed significantly reduced bilateral cortical folding relative to healthy comparison subjects. Such reductions were more pronounced in those with the disorganized subtype and showed an inverse correlation with negative symptoms and a positive correlation with positive symptoms. The paranoid subtype showed reduced cortical folding that was restricted to the left hemisphere. CONCLUSIONS: These results from a larger patient group confirm a previous report of reduced cortical folding in schizophrenia patients. They also suggest a distinct pattern of abnormality between schizophrenia subtypes regarding the process of cerebral lateralization and are in agreement with the neurodevelopmental hypothesis of schizophrenia.
Cetuximab rechallenge in metastatic colorectal cancer patients: how to come away from acquired resistance?
Authors: D. Santini, B. Vincenzi, R. Addeo, C. Garufi, G. Masi, M. Scartozzi, A. Mancuso, A.M. Frezza, O. Venditti, M. Imperatori, G. Schiavon, G. Bronte, G. Cicero, F. Recine, E. Maiello, S. Cascinu, A. Russo, A. Falcone, G. Tonini
Journal: Annals of Oncology (2012)
Lymphoma mimicking cardiomegaly.
Authors: G D Angelini, E G Butchart
Journal: Thorax (1984)

As many as 20% of patients dying with lymphoma are found to have cardiac disease at postmortem examina- tion.' 2 The clinical signs and symptoms of cardiac dysfunc- tion in these cases may be few and non-specific and are not always related to the lymphoma.'-3Several authors have reported necropsy findings with three patterns of cardiac spread-namely, pericardial, epicardial-adventitial, and diffuse interstitial-perivascular.45 Each of these patterns may be correlated with one of the three proposed mechanisms by which lymphoma and malignant neoplasm in gen- eral may spread to affect the heart: direct extension, retrograde flow through cardiac lymphatics, and
Acne prevalence, knowledge about acne and psychological morbidity in mid-adolescence: a community-based study
Authors: A. Smithard, C. Glazebrook, H.C. Williams
Journal: British Journal of Dermatology (2001)

Acne vulgaris is a distressing condition that affects the majority of adolescents, but its impact on mental health in this age group is poorly understood.To determine the prevalence of acne, knowledge about acne and rates of help-seeking behaviour in English teenagers. It was hypothesized that presence of acne would be associated with higher rates of emotional and behavioural difficulties.Three hundred and seventeen pupils (80% response rate) aged 14-16 years participated from a comprehensive school in Nottingham. An age-appropriate, validated measure of emotional well-being, the Strengths and Difficulties Questionnaire (SDQ), and an Acne Management Questionnaire were used to assess participants' psychological health, level of acne knowledge and help-seeking behaviour. Acne severity was by graded by visual facial examination using an adaptation of the Leeds Acne Grading Technique.There was a prevalence of acne in 50% of the study sample, with 11% of participants having moderate to severe acne (> 20 inflammatory lesions). Participants with definite acne (12+ lesions) (P < 0.01) and girls (P < 0.05) had higher levels of emotional and behavioural difficulties. Participants with acne were nearly twice as likely as those without acne to score in the abnormal/borderline range of the SDQ (32% vs. 20%; odds ratio 1.86, 95% confidence interval 1.03-3.34). Knowledge about the causes of acne was low (mean 45%), and was unrelated to acne status. Fewer than a third of participants with definite acne had sought help from a doctor.Acne is a common disorder in English adolescents and appears to have a considerable impact on emotional health in this age group. Low levels of acne knowledge and poor acne management are concerns that could be amenable to a school-based education programme.
Minor H Antigen HA-1–specific Regulator and Effector CD8+ T Cells, and HA-1 Microchimerism, in Allograft Tolerance
Authors: Junchao Cai, Junglim Lee, Ewa Jankowska-Gan, Richard Derks, Jos Pool, Tuna Mutis, Els Goulmy, William J. Burlingham
Journal: The Journal of Experimental Medicine (2004)

The role of the hematopoietic lineage-restricted minor histocompatibility (H) antigen HA-1 in renal allograft tolerance was explored. We obtained peripheral blood samples from three recipients of histocompatibility leukocyte antigen (HLA)–matched, HA-1–mismatched renal transplants, one of which had discontinued immunosuppression &amp;gt;30 yr ago while sustaining normal kidney function. Peripheral blood mononuclear cells (PBMCs) were injected into the footpads of severe combined immunodeficiency mice to measure human delayed type hypersensitivity (DTH) responses. All three patients manifested regulated DTH responses to HA-1H peptide. By differential tetramer staining intensities, we observed two distinct minor H antigen HA-1–specific CD8+ T cell subsets. The one that stained dimly had the characteristics of a T regulatory (TR) cell and produced interleukin (IL) 10 and/or transforming growth factor (TGF) β. These HA-1–specific TR cells coexisted with bright tetramer-binding CD8+ T effector (TE) cells. The CD8+ TE cells mediated HA-1–specific DTH and produced interferon-γ. Suppression of these TE functions by TR cells was TGFβ, IL-10, and cytotoxic T lymphocyte–associated antigen 4 dependent. In addition, HA-1 microchimerism was detected in two recipients, primarily in the dendritic cell fraction of the PBMCs. This is the first demonstration of coexisting CD8+ memory TR and TE cells, both specific for the same HA-1 antigen, in the context of renal allograft tolerance.
Need for a New Trial to Evaluate Adjuvant Postoperative Radiotherapy in Non–Small-Cell Lung Cancer Patients With N2 Mediastinal Involvement
Authors: Cecile Le Péchoux, Ariane Dunant, Jean-Pierre Pignon, Dirk De Ruysscher, Françoise Mornex, Suresh Senan, Francesc Casas, Allan Price, Bernard Milleron
Journal: Journal of Clinical Oncology (2007)
Late-breaking abstract: Risk factors for osteoporosis in patients with COPD: 2008-2010 Korean NHANES
Authors: Seok Jeong Lee, Kyoung Ae Kong, Yon Ju Ryu, Jin Hwa Lee, Jung Hyun Chang
Journal: European Respiratory Journal (2014)

Background  Osteoporosis is an important comorbid disease in patients with COPD. It sometimes results from inhaled or oral medications used for airway disease management. Development of osteoporosis and its complication such as fracture in patients with COPD cause poor quality of life and even mortality. It becomes a big burden in society. We designed this study to investigate risk factors of osteoporosis in patients with COPD.  Methods  We used the data from the 2008-2010 Korean National Health and Nutrition Examination Survey. Subjects who aged 40 or more and performed pulmonary function test appropriately and BMD were included in this study.  Result  Total 6192 subjects were enrolled in this study. Among them, 782 were COPD patients. When comparing the frequency, COPD patients showed higher ratio of osteoporosis (T-score ≤-2.5) than non-COPD group (15.4 vs 11.5%, p  Conclusion  Besides age and sex, low BMI, lack of exercise, and anemia were risk factors for osteoporosis in patients with COPD.