tbuckley/cabot-search huggingface dataset:
The clinical significance of variant-morphology small-cell carcinoma of the lung.
Authors: S C Aisner, D M Finkelstein, D S Ettinger, M D Abeloff, J C Ruckdeschel, J C Eggleston
Journal: Journal of Clinical Oncology (1990)

Past attempts to subclassify small-cell lung cancer (SCCL) histology (oat cell, fusiform, polygonal, intermediate, etc) have not been useful because of interrater variability and a lack of clinical significance. A review of outcome in a previous series suggested that a different histologic subtype, small-cell/large-cell (SC/LC) conferred an inferior response and survival analogous to the relative chemotherapy and radiation resistance seen in the variant-morphology (SC/LC) cultured cell lines. To evaluate the clinical impact of SC/LC we applied the proposed International Association for the study of Lung Cancer (IASLC) histology subclassification that incorporates the SC/LC category for patients with extensive-disease SCCL entering Eastern Cooperative Oncology Group (ECOG) protocol 1582. All cases were reviewed for eligibility by one pathologist, and all possible SC/LC (variant) plus 10% of all cases were reviewed together with a second pathologist; 577 of the 628 patients who entered were eligible, of whom 550 had histologic material submitted for review and are considered for this analysis. Initial review disclosed 24 cases with SC/LC (4.4%) and 526 with "classic" histology. The second review showed 100% agreement for classic form, but only 11 SC/LC cases with concordance between the reviewing pathologists. Eight of 24 (33%) cases from first review and three of 11 (27%) with concordance on second review achieved complete response (CR) compared with 101 of 526 (19%) for "classic" SCCL (P = .11 and .45, respectively, for the first and second review groups).(ABSTRACT TRUNCATED AT 250 WORDS)
Return to Work in Out-of-Hospital Cardiac Arrest Survivors
Authors: Kristian Kragholm, Mads Wissenberg, Rikke Normark Mortensen, Kirsten Fonager, Svend Eggert Jensen, Shahzleen Rajan, Freddy Knudsen Lippert, Erika Frischknecht Christensen, Poul Anders Hansen, Torsten Lang-Jensen, Ole Mazur Hendriksen, Lars Kober, Gunnar Gislason, Christian Torp-Pedersen, Bodil Steen Rasmussen
Journal: Circulation (2015)

Background— Data on long-term function of out-of-hospital cardiac arrest survivors are sparse. We examined return to work as a proxy of preserved function without major neurologic deficits in survivors. Methods and Results— In Denmark, out-of-hospital cardiac arrests have been systematically reported to the Danish Cardiac Arrest Register since 2001. During 2001–2011, we identified 4354 patients employed before arrest among 12 332 working-age patients (18–65 years), of whom 796 survived to day 30. Among 796 survivors (median age, 53 years [quartile 1–3, 46–59 years]; 81.5% men), 610 (76.6%) returned to work in a median time of 4 months [quartile 1–3, 1–19 months], with a median time of 3 years spent back at work. A total of 74.6% (N=455) remained employed without using sick leave during the first 6 months after returning to work. This latter proportion of survivors returning to work increased over time (66.1% in 2001–2005 versus 78.1% in 2006–2011; P =0.002). In multivariable Cox regression analysis, factors associated with return to work with ≥6 months of sustainable employment were as follows: (1) arrest during 2006–2011 versus 2001–2005, hazard ratio (HR), 1.38 (95% CI, 1.05–1.82); (2) male sex, HR, 1.48 (95% CI, 1.06–2.07); (3) age of 18 to 49 versus 50 to 65 years, HR, 1.32 (95% CI, 1.02–1.68); (4) bystander-witnessed arrest, HR, 1.79 (95% CI, 1.17–2.76); and (5) bystander cardiopulmonary resuscitation, HR, 1.38 (95% CI, 1.02–1.87). Conclusions— Of 30-day survivors employed before arrest, 76.6% returned to work. The percentage of survivors returning to work increased significantly, along with improved survival during 2001–2011, suggesting an increase in the proportion of survivors with preserved function over time.
Past dust and gas/fume exposure and COPD in Chinese: The Guangzhou Biobank cohort study
Authors: Kin Bong Hubert Lam, Peng Yin, Chao Qiang Jiang, Wei Sen Zhang, Peymané Zdab, Martin Miller, G. Neil Thomas, Jon G. Ayres, Tai Hing Lam, Kar Keung Cheng
Journal: European Respiratory Journal (2011)

Background:  The impact of occupational dust and gas/fume exposure on chronic obstructive pulmonary disease (COPD) has been described in Western populations but the extent has not been quantified in developing countries.   Aims:  We examined the relationship between past dust and fume exposure and prevalence of COPD and respiratory symptoms in a Chinese population sample. We have calculated the population attributable fraction for COPD due to previous occupation exposures.   Methods:  Baseline data from the Guangzhou Biobank Cohort Study (2003-6; n = 8,219) were analysed. Self-reported intensity and duration of dust and gas/fume exposure was obtained from which a cumulative exposure index was derived. COPD was defined based on spirometry using lower limit of normal. Respiratory symptoms were assessed by the MRC questionnaire.   Results:  In this sample (27.3% men, mean age 61.9±6.8 years), COPD was associated with dust or gas/fume exposure in a dose-response manner with no evidence of effect modification by smoking (adjusted OR for high level exposure = 1.49; 95% CI 1.21-1.91). Similar associations were found for chronic cough/phlegm (1.60; 1.18-2.17) and dyspnoea (1.38; 1.21-1.58). The population attributable fraction for COPD due to occupational exposure was 11.2% (95% CI 1.4%-20.0%).   Conclusion:  Occupational dust and gas/fume exposure is associated with an increased prevalence of COPD in this Chinese sample, independent of smoking. The magnitude is similar to that reported in other populations.
Do infants with bronchiolitis get any benefit with nebulized salbutamol
Authors: Elpis Hatziagorou, Vasiliki Avramidou, Fotis Kirvassilis, Antigoni Mavroudi, John Tsanakas
Journal: European Respiratory Journal (2011)

Background:  The results of nebulized salbutamol in hospitalized infants with bronchiolitis are controversial. Rint is a standardized method of evaluation of airways broncho-constricion in infants.   Aim:  1). To compare expiratory interrupter resistance (Rint) among 19 infants with bronchiolitis and 21 healthy controls. 2). To assess the effect of nebulized salbutamol on Rint among infants with bronchiolitis.   Methods:  Nineteen infants with bronchiolitis and positive history of atopy, family history of asthma and high total serum IgE levels were studied. Twenty one age-matched healthy infants were used as controls. Expiratory interrupter resistance (Rint) was measured before and 20 minutes after nebulized salbutamol.   Results:  19 infants with bronchiolitis (mean age 9.25±6.34 months, 57% boys) and 21 age-matched healthy control infants were studied. 90.1% of them had eczema and 18.2% of them had milk allergy. Mean total serum IgE was 180.4±33.5 IU/ml. 82% of them had siblings with asthma, while 55% of them had a history of maternal asthma. As compared to controls, infants with bronchiolitis had significantly higher Rint, (2.64±0.0.78 vs 1.26±0.12 kPa L -1  second, p   Conclusions:  Infants with bronchiolitis, positive family history of asthma and positive personal history of atopy might benefit from nebulized salbutamol, as shown by the improvement of Rint values.
Regulation and localization of the telomerase enzyme-complex and the shelterin-telosom-complex in sporadic idiopathic pulmonary fibrosis (IPF)
Authors: Martina Korfei, Ulas Tenekeci, Oleksiy Klymenko, Clemens Ruppert, Walter Klepetko, Ludger Fink, Werner Seeger, Andreas Guenther
Journal: European Respiratory Journal (2013)

Introduction: IPF is an adult-onset, lethal lung disease of unknown etiology. Reports linking telomerase mutations to familial IPF suggest that reduced telomerase activity and telomere shortening are key factors in disease pathogenesis. Accelerated telomere shortening is also observed in sporadic IPF in the absence of gene mutations. We therefore aimed to analyze the expression of the Telomerase- [TERT,TERC,DKC1,NOP10,NHP2] and the Shelterin-complex [TERF1/-2,POT1,TIN2,PTOP,RAP1] in lungs from sporadic IPF-patients (n=30) and organ donors (n=12). Methods: Lung tissue was analyzed by RT-PCR, immunoblotting and immunohistochemistry (IHC). Results: Gene expression analysis for TERT and the telomerase RNA-component TERC by RT-PCR indicated a significant downregulation in IPF-lungs. Surprisingly, we could not detect any protein expression of Telomerase- and Shelterin-components in type-II cells of IPF- and donor lungs using conventional IHC. Instead, we observed a strong TERT expression in a subset of Clara-cells (CC10-positive) in IPF- and donor lungs, and expression of POT1 (protection of telomeres1) was exclusively localized in a subset of TERT-negative Clara-cells in both categories. The other Shelterin-members revealed strong expression in fibroblast foci and in basal cells at sites of aberrant bronchiolar proliferation. Conclusion: We suggest that the robust expression of TERT in CC10-positive cells of IPF- and donor lungs might indicate a cell population with stem cell characteristics. Due to the reduced expression of TERT and TERC in IPF lungs, we conclude that the regenerative capacity of TERT-positive Clara cells is impaired in IPF.
Safety, pharmacokinetic and pharmacodynamic profile of RV568, a narrow spectrum kinase inhibitor, following repeat inhaled dosing in COPD patients
Authors: Paul Russell, Lindsey Cass, Kazuhiro Ito, Catherine Charron, Pete Strong, Garth Rapeport, Dave Singh
Journal: European Respiratory Journal (2013)

RATIONALE   To evaluate the safety, pharmacokinetic (PK) and pharmacodynamic (PD) profile of RV568 in GOLD stage II/III Chronic Obstructive Pulmonary Disease (COPD) patients.   METHODS   30 COPD patients aged 40–75 years were recruited. Inhaled RV568 50mg, 100mg or placebo were given daily for 14 days. Forced expiratory volume in 1 second (FEV1) was recorded primarily for safety; PK was measured on Days (D) 1, 7 and 14. PD included 54 sputum and 20 serum biomarkers measured by Luminex, biochemical assay or ELISA.   RESULTS    Twenty eight subjects completed the study, 2 met the withdrawal criterion of decrease in FEV1 >20%. One subject [placebo] had a serious adverse event (hospitalised for COPD exacerbation) otherwise no clinically significant safety signals attributable to RV568 were reported. On D14 compared to baseline, RV568 showed a significant (p  PK data showed plasma exposure was approximately 2 fold greater on D14 than D1, the effective half-life was 19-29 h and steady state was reached by D7.  RV568 showed a significant (p  In serum RV568 showed a significant (p   CONCLUSIONS   The safety, PK and PD profile support progression of inhaled RV568 into further clinical studies in COPD.
Emergency prebiopsy radiation for mediastinal masses: impact on subsequent pathologic diagnosis and outcome.
Authors: J S Loeffler, K A Leopold, A Recht, H J Weinstein, N J Tarbell
Journal: Journal of Clinical Oncology (1986)

From 1968 to 1983, 19 patients were treated at the Joint Center for Radiation Therapy for symptomatic mediastinal masses before a biopsy was obtained. This study evaluates the impact of radiation on the ability to establish a pathologic diagnosis and the results of subsequent empirical therapy if no diagnosis was established. Eight of the 19 (42%) patients were not able to have a histologic diagnosis established at the time of biopsy. Seven of these eight patients went on to receive empiric therapy for what was thought to be the most likely diagnosis on clinical grounds. Four of the seven have not relapsed; three who have relapsed were found to have the diagnosis for which they were empirically treated. The untreated patient relapsed with seminoma. Thus, the use of emergency irradiation for mediastinal masses is sometimes associated with the loss of pathologic diagnosis. These patients likely have a radioresponsive disease (ie, lymphoma or seminoma) that may be treated successfully on the presumed clinical diagnosis even when the histologic diagnosis is lost secondary to prebiopsy irradiation.
Prognostic significance of age, MYCN oncogene amplification, tumor cell ploidy, and histology in 110 infants with stage D(S) neuroblastoma: the pediatric oncology group experience--a pediatric oncology group study.
Authors: H M Katzenstein, L C Bowman, G M Brodeur, P S Thorner, V V Joshi, E I Smith, A T Look, S T Rowe, M B Nash, T Holbrook, C Alvarado, P V Rao, R P Castleberry, S L Cohn
Journal: Journal of Clinical Oncology (1998)

PURPOSE Although a high rate of spontaneous regression is observed in infants with stage D(S) neuroblastoma (NB), survival is not uniform. To determine the prognostic relevance of age at diagnosis, therapy, and tumor biology in infants with stage D(S) NB, we reviewed the Pediatric Oncology Group (POG) experience. PATIENTS AND METHODS A review of patients diagnosed with stage D(S) NB registered on POG protocols was performed. Survival according to age at diagnosis, treatment, and tumor biology was determined. RESULTS Between 1987 and 1996, 110 infants with stage D(S) NB had an estimated 3-year survival rate of 85% +/- 4%; survival rate was 71% +/- 8% for infants 2 months of age or younger, and 68% +/- 12%, 44% +/- 33%, and 33% +/- 19% for patients with diploid, MYCN-amplified, and unfavorable histology tumors, respectively. Survival rates were similar for patients who received adjuvant chemotherapy versus those who did not (82% +/- 5% v 93% +/- 6%, respectively; P = .187). Furthermore, there was no statistical difference in survival rate for patients who underwent complete resection of their primary tumor compared with those who underwent partial resection or biopsy only (90% +/- 5% v 78% +/- 7%, respectively; P = .083). CONCLUSION Our review confirmed that the survival of infants with stage D(S) NB is excellent. However, subsets of patients with poor prognosis can be identified by young age and unfavorable biologic factors. More effective therapy is needed for the group of stage D(S) infants who show unfavorable clinical and biologic features.
Current use of bisphosphonates in oncology. International Bone and Cancer Study Group.
Authors: J J Body, R Bartl, P Burckhardt, P D Delmas, I J Diel, H Fleisch, J A Kanis, R A Kyle, G R Mundy, A H Paterson, R D Rubens
Journal: Journal of Clinical Oncology (1998)

PURPOSE The purpose of this article is to review the recent data on bisphosphonate use in oncology and to provide some guidelines on the indications for their use in cancer patients. DESIGN The group consensus reached by experts on the rationale for the use of bisphosphonates in cancer patients and their current indications for the treatment of tumor-induced hypercalcemia and metastatic bone pain in advanced disease and for the prevention of the complications of multiple myeloma and of metastatic bone disease are reviewed. RESULTS Bisphosphonates are potent inhibitors of tumor-induced osteoclast-mediated bone resorption. They now constitute the standard treatment for cancer hypercalcemia, for which we recommend a dose of 1,500 mg of clodronate or 90 mg of pamidronate; the latter compound is more potent and has a longer lasting effect. Intravenous bisphosphonates exert clinically relevant analgesic effects in patients with metastatic bone pain. Regular pamidronate infusions can also achieve a partial objective response by conventional International Union Against Cancer criteria and enhance the objective response rate to chemotherapy. In breast cancer, the prolonged administration of oral clodronate 1,600 mg daily reduces the frequency of morbid skeletal events by more than one fourth, whereas monthly pamidronate infusions of 90 mg for only 1 year in addition to chemotherapy reduce by more than one third the frequency of all skeletal-related events. The use of bisphosphonates to prevent bone metastases remains experimental. Last, bisphosphonates in addition to chemotherapy are superior to chemotherapy alone in patients with stages II and III multiple myeloma and can reduce the skeletal morbidity rate by approximately one half. CONCLUSION Bisphosphonate use is a major therapeutic advance in the management of the skeletal morbidity caused by metastatic breast cancer or multiple myeloma, although many questions remain unanswered, notably regarding the optimal selection of patients and the duration of treatment.
Psychogenic cough in children: Clinical, laboratory characteristics and follow- up
Authors: Elpis Hatziagorou, Dimitris Nasioudis, Fotis Kirvasillis, Theofoanis Tsiligiannis, John Tsanakas
Journal: European Respiratory Journal (2013)

Aim – Method: Clinical and laboratory characteristics of 201 children, (51.2% boys), aged 4.5 - 18 years with psychogenic cough were analyzed retrospectively. Children were seen as outpatients, over an eleven year period (2002-2012). Half of the children were re-evaluated 6.95 (±3.4) years later via a telephone conduct.

Results:. Clinical characteristics: mean duration of the cough: 5.26 ± 3.1 months harsh and explosive (75%), croupy and barking (7.96%), exacerbating in the presence of medical staff (62%), disappearing with sleep (98%), not exacerbated with exercise (82%), not accompanied with wheeze (96.5%). Fifty –two percent of children appeared to be under psychological stress. Fifty-five percent of the children had received antitussives, beta-2 agonists, inhaled steroids, anti-leucotrienes, anti-histamines, or oral steroids, with no response. Physical examination and lung function tests were normal (FEV1: 101.9± 13.8% and FVC: 104.3 ±15.7%). Explanation of the origin of the cough and re-assurance were helpful for 82% of the patients. Ninety-three of the 201 children (46.3%) were evaluated 6.95 (±3.4) years later. Cough was completely resolved among 86% of them. Fifteen percent of the children, whose cough was resolved, had 1-3 relapses, responding to anti-asthmatic treatment.

Conclusions: The recognition of the characteristic pattern of the psychogenic cough in a child of school age with chronic non-specific cough will result in the early diagnosis and treatment, avoiding unnecessary and expensive tests. Re-assurance and explanation of the origin of the cough result in resolution of the cough among the majority of the cases.
Do Changes of 6-Minute Walk Distance Predict Clinical Events in Patients With Pulmonary Arterial Hypertension?
Authors: Gianluigi Savarese, Stefania Paolillo, Pierluigi Costanzo, Carmen D'Amore, Milena Cecere, Teresa Losco, Francesca Musella, Paola Gargiulo, Caterina Marciano, Pasquale Perrone-Filardi
Journal: Journal of the American College of Cardiology (2012)
Exhaled NO but not eosinophilic inflammation is reduced by inhaled corticosteroid treatment in COPD
Authors: Andrei Malinovschi, Gunnar Johansson, Per Venge, Hans Hedenström, Christer Janson, Kjell Alving
Journal: European Respiratory Journal (2013)

Exhaled NO (FeNO) is a marker of airways inflammation that relates to eosinophilic inflammation in asthma. A subgroup of subjects with COPD has elevated FeNO levels, but no studies have analysed the relation between FeNO and eosinophilic inflammation in COPD. Therefore, we studied the relation between FeNO and markers of eosinophil activity, as well as their response to inhaled corticosteroid (ICS) treatment, in patients with COPD.

FeNO, serum ECP and blood eosinophils (B-Eos) were measured in 36 steroid-naive, ex-smoking patients with COPD, aged 54 to 79 yrs, before and after 4 weeks of treatment with 800 μg mometasone furoate/day in a double-blind, placebo-controlled, crossover study. Patients were grouped as having normal FeNO (<25 ppb) (n=19) and intermediate-increased FeNO (≥25 ppb) (n=17).

ECP levels (μg/L, median (IQR)) were similar in both FeNO groups (25 (12.7, 106) vs 44.3 (14.6, 82.9), p=0.60) and no relation was found between serum ECP and FeNO in all subjects (rho=0.04, p=0.82). Similarly, no differences between FeNO groups were found in B-Eos (109/L, median (IQR)) (0.2 (0.1, 0.3) vs 0.2 (0.1, 0.2), p=0.46) nor was any relation found between B-Eos and FeNO in all subjects (rho=-0.17, p=0.32). The decrease of FeNO levels (ppb, median(IQR)) during ICS treatment was significantly larger than during placebo treatment (-4.5 (-11.5, -1) vs 0.8 (-2.3, 6), p=0.008) while no such differences were found for ECP or B-Eos (p=0.35 and p=0.31).

In conclusion, exhaled NO did not relate to markers of eosinophilic inflammation in COPD. Furthermore only exhaled NO was decreased by ICS treatment. This suggests a dissociation between exhaled NO and eosinophilic inflammation in COPD.
Inhibition of Phorbol Ester-Induced Tumor Promotion in Mice by Vitamin A Analog and Anti-inflammatory Steroid&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: C. E. Weeks, Thomas J Slaga, H. Hennings, G. L. Gleason, W. M. Bracken
Journal: JNCI Journal of the National Cancer Institute (1979)

The effects of a vitamin A analog, TMMP ethyl retl-noate [or ethyl-9-(4-methoxy-2,3,6-trlmethylphenyl)-3,7-dlmeth-yl-trans-2,4,6,8-nonatetraenoate] (abbreviated Ro 10-9359), and an anti-inflammatory steroid, fluoclnolone acetonlde for 6α,9α-difluoro-11β,16α,17,21-tetrahydroxypregna-1,4-diene-3,20-dione cyclic 16,17-acetal) (abbreviated FA), given alone or together were studied in a two-stage carclnogenesls system. The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) was used as the tumor promoter in a 7,12-dlmethylbenz[a]anthracene (DMBA)-inltlated mouse skin system. Two stocks of female mice, CD®-1 and Sencar, which differ in their degrees of sensitivity to skin carclnogenesis, were used. A dose-dependent inhibition of carcinogenic expression, as determined by a decreased number of papillomas per animal, was observed in each mouse stock with the use of both FA and Ro 10-9359 when given alone. When FA and Ro 10-9359 were given together, an enhanced effect on the lowering of tumor Incidence was noted. FA effectively inhibited tumor formation in the sensitive mouse stock even when the steroid was given 1 day prior to TPA treatment under conditions of unusually high doses of initiator (DMBA) and/or promoter (TPA). These results suggest that both anti-inflammatory steroids and retinolds inhibit tumor promotion and can be effectively used as a combination regimen for increased chemopreventive response.
In vitro and in vivo identification of ABCB1 as an efflux transporter of bosutinib
Authors: Sara Redaelli, Pietro Perini, Monica Ceccon, Rocco Piazza, Roberta Rigolio, Mario Mauri, Frank Boschelli, Athina Giannoudis, Carlo Gambacorti-Passerini
Journal: Journal of Hematology & Oncology (2015)

Bosutinib is a recently approved ABL inhibitor. In spite of the well-documented effectiveness of BCR-ABL inhibitors in treating chronic myeloid leukemia, development of resistance is a continuous clinical challenge. Transporters that facilitate drug uptake and efflux have been proposed as one potential source of resistance to tyrosine kinase inhibitor treatment. Our aim was to determine which carriers are responsible for bosutinib transport. K562S cells overexpressing the drug transporters ABCB1, ABCG2, and SLC22A1 were generated, characterized and used in proliferation assay and intracellular uptake and retention assay (IUR). In vivo experiments were performed in nude mice injected with K562S, K562DOX cells (overexpressing ABCB1), and K562DOX silenced for ABCB1 (K562DOX/sh P-GP). The IUR assay using C-14 bosutinib showed that only ABCB1 was responsible for active bosutinib transport. K562DOX cells showed the lowest intracellular level of bosutinib, while K562DOX cells treated with the ABCB1 inhibitor verapamil showed intracellular bosutinib levels comparable with parental K562S. Proliferation assays demonstrated that K562DOX are resistant to bosutinib treatment while verapamil is able to restore the sensitivity to the drug. Nude mice injected with K562DOX and treated with bosutinib showed very limited response and quickly relapsed after stopping treatment while K562S as well as K562DOX/sh P-GP remained tumor-free. Our data suggest that the analysis of ABCB1 expression levels might help determine treatment options for patients exhibiting resistance to bosutinib.