tbuckley/cabot-search huggingface dataset:
Neutrophil elastase-activated host defence peptide prodrugs kill pseudomonas aeruginosa in a cystic fibrosis lung milieu
Authors: Eanna Forde, Hilary Humphreys, Catherine Greene, Deirdre Fitzgerald-Hughes, Marc Devocelle
Journal: European Respiratory Journal (2014)

Background:  Host defence peptides (HDPs) are short antimicrobial components of the innate immune system. In cystic fibrosis (CF), deficiencies in HDPs rationalises exogenous application but cytotoxicity limits development as therapeutics. Previously, neutrophil elastase (NE)-labile HDP prodrugs were designed with a promoiety successfully reducing cytotoxicity (1). However, remaining issues with selectivity and cytotoxicity require the optimisation of the promoiety and peptide sequence. This study further refines design.   Methods:  Lability to purified NE was confirmed with HPLC and MALDI-TOF MS. New HDPs were incorporated into the prodrug model. The susceptibility of  Pseudomonas aeruginosa  to the peptides was compared with/without NE-rich CF bronchoalveolar lavage (BAL) fluid. The effect of the promoiety on cytotoxicity was determined with CF bronchial epithelial (CFBE41o-) cells.   Results:  The use of new peptide sequences yielded the required improvements. One pro-HDP, pro-WMR, maintained low antimicrobial activity in the absence of NE, performing better than the previous pro-HDPs, with a bactericidal activity at 25μg/ml that increased from 8.4% to 91.5% with the addition of 25%v/v BAL (p=0.0008). Selectivity was also greatly improved (IC 50  against CFBE cells ≥300μM).   Conclusions:  Selective activation by a host disease-associated enzyme at physiological concentrations was demonstrated here and the promoiety successfully reduced cytotoxicity. The study has produced pro-HDPs, with greatly reduced host toxicity, that function in the challenging conditions of the CF lung.  1. Forde et al. Antimicrobial agents and chemotherapy. 2014;58(2):978-85.
Calculation of half-life of carcinoembryonic antigen after lung tumour resection: a case report
Authors: J Verhelst, E Vanden Broecke, J Van Meerbeeck, W De Backer, P Blockx, P Vermeire
Journal: European Respiratory Journal (1991)

Since little is known about carcinoembryonic antigen (CEA) half-life in humans, we followed changes in CEA levels after curative resection of a small bronchial adenocarcinoma in a 54 yr old man with an unusually high preoperative serum CEA level of 1,199 ng.ml-1. Serum CEA followed a four phase curve with an initial increase, attributed to release of CEA from the tumour, a rapid fall during four days (CEA half-life 3.2 days), a slower exponential decay to normal levels during almost three months (CEA half-life 11 days) and eventually maintenance of normal levels for 14 months. These results are consistent with data from animal experiments and a single report on CEA half-life in humans, but CEA half-life seems longer in man than in animals. This observation also suggests that a very high serum CEA level should not in itself preclude curative surgical resection of a primary bronchogenic carcinoma.
Effects of Oxygen on Growth in Several Established Cell Lines<xref ref-type="fn" rid="fn1">2</xref>
Authors: Donald M. Pace, James R. Thompson, W. A. Camp
Journal: JNCI Journal of the National Cancer Institute (1962)

Studies were made on the effects of various O2 concentrations on 4 established cell lines: strain L (NCTC 929), mouse liver epithelium (NCTC 1469), HeLa, and human skin (NCTC 1769). In 100 percent O2 some strain L cells survived up to 14 days; mouse liver cells, 9 days; HeLa cells, 3 days; human skin cells, 8 days. There was practically no proliferation in 100 percent O2, and all liver, HeLa, and skin cells died before termination of the experiment. In95 percent O2 + 5 percent CO2, the only significant proliferation was in the strain L cultures; all others decreased in number and finally died out. Of the 4 lines tested, human skin and HeLa cells appeared more sensitive to high O2 tensions than strain L or mouse liver cells. Cell proliferation in the presence of CO2 and 95 percent N2 was not so severely inhibited as that in 100 percent N2.
Abstract 347: Glutathione-S-Transferase P Regulates Bone Marrow Derived Endothelial Progenitor Cell (EPC) Function and Neovascularization in the Infarcted Heart
Authors: Guihua Zhou, Hai Zhong, Yixin Wu, Chiao-Wang Sun, Timothy M Townes, Sumanth D Prabhu
Journal: Circulation Research (2014)

Glutathione-S-transferase P (GSTP) modulates proliferation of bone marrow (BM) myeloid progenitors via non-catalytic inhibition of c-Jun N-terminal kinase (JNK); however, its effects on BM-derived EPCs are unknown. We hypothesized that GSTP supports EPC mobilization while suppressing inflammatory cells, thereby promoting tissue neovascularization. We generated chimeric mice using BM-ablated wild-type (WT) mice reconstituted with either GSTP-/- (GSTP-/-c) or WT (WTc) BM. GSTP-/-c and WTc mice underwent coronary ligation or sham operation (n = 8-15/group). Compared to WTc sham, 4 w after surgery, WTc HF mice exhibited significant (p &lt; 0.05): LV dilatation, dysfunction, and fibrosis; increased mortality; and augmented circulating pro-inflammatory CD11b+Ly6Chi monocytes, but comparable circulating CD34+VEGFR2+ EPCs. In contrast, compared to WTc HF, GSTP-/-c HF hearts had significant (p &lt; 0.01): 1) worsening of LV dilatation (LVEDV 118 ± 30 vs 88 ± 13 μL), dysfunction (LVEF 21 ± 4 vs 32 ± 9 %), wall thinning (anterior wall thickness 0.41 ± 0.06 vs 0.49 ± 0.1 mm), and LV hypertrophy (LV/tibia length 4.9 ± 0.5 vs 4.5 ± 0.6 mg/mm); 2) increased remote zone fibrosis by trichrome staining (1.3 ± 0.2 vs 0.61 ± 0.3 %); 3) reduced capillary density (476 ± 60 vs 544 ± 37 capillary/mm2) and increased capillary area (14 ± 1.1 vs 12 ± 1.2 μm2); 4) diminished gene expression of VEGF A, VEGF B, and VEGF C; 5) and increased IL-1β, IL-6 gene expression. GSTP-/-c mice also exhibited (p &lt; 0.01) increased BM JNK activation, reduced circulating EPCs (0.18±0.07 vs 0.24±0.06%), increased CD11b+Ly6Chi monocytes (2.25±0.5 vs 1.8±0.6%), but comparable anti-inflammatory CD11b+Ly6Clow monocytes at baseline as compared with WTc mice. Moreover, at 3 and 7 d after ligation, GSTP-/-c HF mice exhibited fewer circulating EPCs and anti-inflammatory monocytes, and significantly higher pro-inflammatory monocytes as compared with WTc HF mice. We conclude that GSTP promotes EPC and reparative monocyte mobilization, thereby improving angiogenic gene expression, neovascularization and LV remodeling after myocardial infarction. This suggests that GSTP polymorphisms can impact cardiac reparative capacity in humans, and that enhancing GSTP function after infarction may yield therapeutic benefit.
Treating peripheral eosinophilia in asthma: Simple and effective
Authors: Ding Yew, Kimberly Su, Rajesh Yadavilli, Mithun Murthy, Hassan Burhan
Journal: European Respiratory Journal (2013)

Background:  Escalating steroid treatment in asthma based on sputum eosinophilia has been shown to reduce admissions. While sputum cell counting is not practical in all patients, increasing steroid treatment in those asthmatic patients with peripheral eosinophilia is straight forward. We assessed our patient database to see whether those patients with eosinophilia were prescribed more steroid and whether this led to better control.  Methods:  A retrospective analysis of 100 patients from a dedicated asthma clinic, using case note review, spirometry results, serum eosinophils and total IgE, mini Asthma Quality of Life Questionnaire (AQLQ) and Asthma Control Test (ACT) questionnaire results was carried out. Hypothesis testing using two-way unpaired student’s t test for continuous variables and z-test for proportions.  Results:  The mean age of our asthmatic population was 49.3years, 77% were female. A significantly greater proportion of patients with blood eosinophilia were on maintainence oral corticosteroids.  Conclusions:  Patients with a blood eosinophilia tend to be on higher BTS Step treatment and a significantly greater portion are on maintainence oral corticosteroids. Perhaps as a consequence of this, there are no significant differences between those with and without eosinophilia with regards to BMI, QoL, control or FEV 1  % predicted.
The Council on Professions and Associations
Authors: ROBERT S. GARBER
Journal: American Journal of Psychiatry (1973)

DR. NORMAN ROSENZWEIG presented the report of the Council on International Affairs for Dr. Rome, who was unable to be present. The continuing activities of the Inter-American Council of Psychiatric Associations, a group representative of psychiatry in the Americas, was reviewed by the Council. The plans for a Second Inter-American Congress on the Mental Health of Children and Youth, which was to be held in Puerto Rico, September 28-October 3, 1972, were highlighted. The format of the congress was reviewed in detail, including the innovation ofits two-part program: I) the Working Conference-concerned with the collation of the mutual committees’ reports on four topical areas, and 2) the Institute-composed of invited participants who would not have previously panticipatcd in the preparation of data but who would have had the opportunity under the aegis of the Preparatory Commission to discuss the items developed at the plenary session of the institute. The next meeting of the Inter-American Council was planned for Mexico City, January 4-5, 1973. The scientific session, which is a regular pant of the meeting, was to have as its theme “Inter-American Cooperative Studies of Drug Abuse Prevcntion,” arranged by Dr. Guido Belsasso. It was anticipated that the new constitution would have been ratified by all of the signatory associations and would provide a smoother organizational procedure. A proposal to the Council by Dr. Norman Rosenzwcig had to do with the establishment of an International Liaison Task Force. Its purpose would be to create a more formal network of members in APA to facilitate an interchange of mental health in formation. Dr. Rosenzweig was delegated to contact the district branches to learn who from their membership might be intercsted in this communications activity. Jorge Velasco-Alzaga described at length his plan for the
Alterations in static lung volumes during methacholine challenge (MCH) tests, assessed by whole-body plethysmography using the aerosol provocation system (APS)
Authors: Richard Kraemer, Gaby Giger, Thomas Sigrist, Martin Frey
Journal: European Respiratory Journal (2012)

Rationale.  Airway hyperreactivity (AHR) is a characteristic feature of asthma, and methacholine challenge tests (MCT) are well established in asthma diagnostics and research, to quantitate AHR. Cut points have arbitrarily been selected, defining a fall of 20% in FEV 1  as PC 20 . By this technical approach, however, changes in end-expiratory resting level cannot be detected. MCT using APS technology integrated in the Jaeger whole-body plethysmograph features the possibility to evaluate changes of airway dynamics concomitantly with changes of lung volumes [1].   Objectives.  We aimed to assess changes of FRC pleth , IC, ERV and hence RV and TLC during MCT, and comparing changes of effective specific airway conductances (sG eff , sG 0.5 , sG tot ) in relation to changes effected to FEV 1  and MEF 50 .   Methods.  We retrospectively analysed data from our hospital database including 140 test persons (asthmatics and controls; 59 males; 81 females; age: 11 to 82 y), in whom MCT have been performed. Methacholine was administered during 3 consecutive cumulative challenge levels (P1:0.2 mg; P2:1.0 mg; P3:2.2 mg) computerized by the APS system.   Results.  During MCT not only airway mechanics, but also static lung volumes (FRC pleth , IC) changed consistently.   Conclusions.  In the assessment of AHR by MCT sG eff  and and sG tot  qualified as most sensitive target parameter, taking into account changes of airway dynamics concomitantly with changes of lung volumes. Comparison between volume-time and flow-volume parameters with plethysmographically assessed sG eff , sG 0.5  during MCT is presented in abstract 850930.  [1]. Matthys H, et al.: Respiration: 1975;32(2):121-134.
Adjuvant interferon alfa-2a treatment in resected primary stage II cutaneous melanoma. Austrian Malignant Melanoma Cooperative Group.
Authors: H Pehamberger, H P Soyer, A Steiner, R Kofler, M Binder, P Mischer, W Pachinger, J Auböck, P Fritsch, H Kerl, K Wolff
Journal: Journal of Clinical Oncology (1998)

PURPOSE Patients with primary cutaneous melanoma with a Breslow thickness &gt; or = 1.5 mm have only a 30% to 70% probability of survival after surgery, and no adjuvant therapy has so far improved this outcome. Since interferon alfa-2a (IFNalpha2a) exhibits antitumor activity in metastatic melanoma, we investigated whether adjuvant IFNalpha2a diminishes the occurrence of metastases and thus prolongs disease-free survival in melanoma patients after excision of the primary tumor. PATIENTS AND METHODS In a prospective randomized study, 311 melanoma patients with a Breslow thickness &gt; or = 1.5 mm were assigned to either adjuvant IFNalpha2a treatment (n = 154) or observation (n = 157) after excision of the primary tumor. IFNalpha2a was given daily at a dose of 3 mIU subcutaneously (s.c.) for 3 weeks (induction phase), after which a dose of 3 mIU s.c. three times per week was given over 1 year (maintenance phase). RESULTS Prolonged disease-free survival was observed in patients treated with IFNalpha2a versus those who underwent surgery alone. This difference was significant (P = .02) for all patients enrolled onto the study (intention-to-treat analysis) at a mean observation time of 41 months. Subgroup analysis showed that Breslow tumor thickness had no influence on treatment results in the groups of patients investigated. CONCLUSION Adjuvant IFNalpha2a treatment diminishes the occurrence of metastases and thus prolongs disease-free survival in resected primary stage II cutaneous melanoma patients.
Partial Characterization of a Herpes-Type Virus (K9V) Derived From Kaposi's Sarcoma2
Authors: Ronald Glaser, Laszlo Geder, Stephen St. Jeor, Susan Michelson-Fiske, Francoise Haguenau
Journal: JNCI Journal of the National Cancer Institute (1977)

A herpes-type virus that was originally isolated from a cell culture (designated K9V) derived from a tumor biopsy specimen from a patient with Kaposi's sarcoma was partially characterized. The host range of K9V, as determined by the induction of virus-specific cytopathology, synthesis of antigens, and plaque formation, was limited to human cells and particularly to fibroblasts. Immunofluorescence and complement fixation assays confirmed the specificity of the presence of cytomegalovirus (CMV)-type antigens in K9V-infected human fibroblasts. In addition, the density of K9V DNA was consistent with the density of CMV DNA. However, some peculiarities were observed in the K9V strain of CMV. The virus seemed more cell-associated in human fibroblasts than were known laboratory strains: The spread of cytopathology was slow and did not always involve the whole cell sheet, and the total regression of cytopathology with the establishment of a persistent infection was common. Similar characteristics have recently been observed in the Mj strain of CMV, which has been shown to be oncogenic in human fibroblasts.
Safety and performance of the second-generation drug-eluting absorbable metal scaffold in patients with de-novo coronary artery lesions (BIOSOLVE-II): 6 month results of a prospective, multicentre, non-randomised, first-in-man trial
Authors: Michael Haude, Hüseyin Ince, Alexandre Abizaid, Ralph Toelg, Pedro Alves Lemos, Clemens von Birgelen, Evald Høj Christiansen, William Wijns, Franz-Josef Neumann, Christoph Kaiser, Eric Eeckhout, Soo Teik Lim, Javier Escaned, Hector M Garcia-Garcia, Ron Waksman
Journal: The Lancet (2015)
Does CT screening for lung cancer assist smokers to stop
Authors: N Jayasekera
Journal: Thorax (2004)

▴ Cox LS, Clark MM, Jett JR, et al . Change in smoking status after spiral chest computed tomography scan screening. Cancer2003;98:2495–501

[OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4]



Smoking cessation is of paramount importance in the prevention of lung cancer. Attendance for cancer screening may provide a “teachable moment”. This study aimed to evaluate changes in smoking status following lung cancer screening in a large group of both current and ex-smokers. 1520 subjects were enrolled and underwent low dose spiral chest CT scan screening for …

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Benign lung tumors: Presentation, diagnosis, and outcome
Authors: Cecília Pacheco, Hans Dabo, Gabriela Fernandes, Pedro Bastos, Adriana Magalhães
Journal: European Respiratory Journal (2013)

Background: Benign tumors of the lung are uncommon and can be diagnostically challenging.Methods:Retrospective analysis of the clinicopathologic data and outcome of patients with benign lung tumors diagnosed in the last 10 years. Results:72 patients were included, 68% male,mean age 55 years.Most of the patients were assymptomatic. In 23,6% of patients with endoscopic abnormalities appeared respiratory symptoms such as shortness of breath and obstructive pneumonia. CT scan showed a solitary pulmonary nodule in 73,6%.Endoscopic abnormalities were found in 16 patients.Tumors were more frequently located at main bronchus.Most lesions appeared as exophytic lesion or polyps.BB was diagnostic for hamartoma (n=7),papilloma (n=4),granular cell myoblastoma (n=3),leiomyoma (n=1) and inflammatory pseudotumor (n=1).In 7 cases, bronchial biopsy removed the entire tumor.Transthoracic needle biopsy (TNB) was performed in 26 patients and was diagnostic for hamartoma in 13 cases and mixoid tumor in 1 case.Forty seven patients were treated surgically,most with lobectomies and segmentectomies.Pathological diagnosis revealed 32 hamartomas,5 solitary fibrous tumors,2 lymphangiomas,2 adenomas,1 chondroma,1 myofibroblastic tumor,1 papilloma,1 inflammatory pseudotumor,1 granular cell myoblastoma and 1 desmoid tumor.In 18 cases, although diagnostic confirmation, has not been performed surgical therapy. In 11 cases surgical treatment was refused by the patient.Conclusion:Benign lung tumors are usually assymptomatic and do not pose a significant health problem. The purpose of surgical intervention for benign lung tumors is to avoid missing potentially malignant lesions. In some situations, these tumors can be diagnosed and treated endoscopically.
Benefits of a new device for inspiratory muscle training in COPD
Authors: Voicu Tudorache, Cristian Oancea, Nicoleta Bertici, Ovidiu Fira-Mladinescu, Monica Marc, Claudiu Avram, Alexandru Somesan
Journal: European Respiratory Journal (2012)

In chronic obstructive pulmonary disease (COPD), inspiratory muscle weakness may occur as a result of the combined effects of increased work of breathing, malnutrition, hypercapnia/hipoxemia and others. The benefit of inspiratory muscle training (IMT) depends on patients phenotype but also on the type exercise methods.  The aim of the study was the evaluation of medium (3 months) and short-term (at the end of a pulmonary rehabilitation program, PRP) effects of IMT using the TrainAir® electronic system.  47 patients with COPD (GOLD stage III, IV) without any previously PRP were divided in 2 groups. Both groups followed one month a comprehensive PRP, but to the group of patients that initially presented lower values of the respiratory maximal pressures IMT was added. Patients9 assessment consisted of: spirometry, maximum inspiratory and expiratory pressures (MIP, MEP), 6-minute walk test (6MWT), body composition, MRC scale, and COPD Assessment Test (CAT).  Our results demonstrated in both groups the increase of exercise capacity on short and medium term (p=0.025) measured by the distance expressed in meters walked to 6MWT as compared to the initial value (500±37 and 488±46 vs. 457±51 for the IMT group; 492±99, and 479±87 vs. 452±105 for the control group). IMT significantly reduced the difference between groups for MIP (kPa) (from 2.91±0.74 to 2.35±0.75, p=0.002), and the effect had been maintained over the medium term (p=0.016). Also, CAT score reduces more significantly on medium term in the presence of IMT (from 21.27±4.13 to 16.91±2.21 vs. from 22.25±2.19 to 19.50±1.85 in control group, p   In conclusion, in COPD patients, in addition to the improvement of MIP, IMT was beneficial for patients9 symptomatology.
Predicting mortality in patients hospitalised with acute exacerbations of COPD (AECOPD) requiring assisted ventilation
Authors: John Steer, John Gibson, Stephen Bourke
Journal: European Respiratory Journal (2012)

Background  Prognostic studies in AECOPD requiring assisted ventilation often select patients by place of care and predict failure of non-invasive ventilation (NIV), not mortality. Improved mortality prediction for unselected patients requiring ventilation for AECOPD is needed.  Objective  Identify mortality predictors in patients with AECOPD requiring ventilatory assistance.  Methods  Clinical data were collected on consecutive patients hospitalised with AECOPD requiring assisted ventilation (NIV or invasive ventilation) for acidaemic respiratory failure (ARF) during their hospital stay. Independent predictors of in-hospital mortality were identified.  Results  199 received ventilatory assistance: mean (SD) age = 73.9 (9.8) years; FEV 1  38.1 (16.1) % predicted and 61.3% were female. 49 (24.6%) patients died in hospital.  Older age, an ineffective cough, and severe stable-state dyspnoea were the strongest mortality predictors. The regression model (table 1) showed excellent discrimination for mortality (AUROC = 0.92, 0.88 to 0.96).  Conclusion  Mortality in patients hospitalised with AECOPD requiring assisted ventilation is high but can be accurately predicted using simple to measure indices.