tbuckley/cabot-search huggingface dataset:
The effects of human lung mast cell products on the synthetic functions of lung fibroblasts
Authors: Hatem Alkhouri, Michael Wai-Shing, David Krimmer, Brian Oliver, Carol Armour, J. Margaret Hughes
Journal: European Respiratory Journal (2012)

Activated mast cell numbers are generally increased in the bronchial wall and alveolar parenchyma of people with asthma. Mast cells release a wide variety of cytokines and mediators that may modulate the activities of structural cells such as fibroblasts and contribute to airway remodelling in asthma. Objective: To examine the effects of human lung mast cell (HLMC) products on the synthetic functions of airway and parenchymal fibroblasts. Methods: HLMC were stimulated with IgE/anti-IgE and their supernatants (SN) collected after 2 and 24h. The SN were added to serum-deprived airway and parenchymal fibroblasts for up to 48h. Fibroblast and mast cell cytokine release and extracellular matrix (ECM) deposition were measured using ELISAs. Results: Both 2 and 24h HLMC SN significantly increased the synthetic functions of parenchymal and airway fibroblasts in a concentration-related manner. Release of CXCL8 was increased up to 3.9 and 3.1-fold from parenchymal fibroblasts by the 2 and 24h SN respectively. The 2 and 24h SN respectively also increased IL-6 release from parenchymal [5.8 and 6.6-fold] and airway [8.7 and 22.6-fold] fibroblasts in a similar manner. Interestingly, although fibronectin deposition was unchanged, both the 2 and 24h SN significantly increased collagen IV deposition by airway, but not parenchymal, fibroblasts up to 1.5- fold, whereas only the 24h SN increased tenascin-C deposition [1.8-fold] by the airway cells. Conclusions: HLMC products increase lung fibroblast cytokine release and differentially regulate airway and parenchymal fibroblast ECM deposition. Thus HLMC may promote further inflammation and airway remodelling in asthma.
Is there a need for prolonged follow up in mono-drug resistant TB?
Authors: Jayne Ellis, Hugo Farne, Douglas Fink, Dean Creer
Journal: European Respiratory Journal (2014)

Background  Latest NICE guidance recommends 12 month follow up post-treatment completion for mono-drug resistant TB because patients on non-standard regimens have a potentially higher relapse  This creates a significant resource burden. Yet there is little evidence that patients are less adherent, more prone to relapse, or that follow up results in earlier detection and treatment of relapses. We audited practice at a London hospital with a large immigrant population and significant incidence of TB.  Methods  We used the London TB Register to identify cases notified at Barnet & Edgware Hospitals between 2002-14 (n=885) that were resistant to one first line agent on culture (n=36). 5 patients moved out of area and 1 was lost prior to treatment. 30 patients were treated locally. We audited the notes to review antibiotic regimen, duration, length of follow up, and relapse/reinfection.  Results  28/30 were isoniazid resistant, with 1 each rifampicin and pyrazinamide resistant. They received a median 12 months treatment (range 9-17). At completion 8/30 were not offered follow up, 1 died (ischaemic heart disease) but 6 did not attend. The remaining 15/30 received a median 9 months follow up (one ongoing). There were no relapses/reinfection. Antibiotic treatment was concordant with guidelines.  Discussion  Our small and retrospective study suggests that mono-drug resistance does not impact negatively upon compliance with TB treatment, demonstrated by the 100% completion rate. Post-treatment follow up is logistically challenging: 20% (6/30) did not attend the first appointment. The lack of relapses despite a median 9 months active monitoring post-treatment suggests prolonged follow up may not be warranted in the UK.
P-161 A phase I-trial assessing several schedules of Oral S-1 combined with fixed doses of Oxaliplatin and Irinotecan in patients with advanced or metastatic digestive adenocarcinoma as first- or second-line treatment
Authors: E. Samalin, S. Thezenas, J.-P. Delord, A. Italiano, D. Smith, F. Portales, T. Mazard, E. Assenat, S. Poujol, I. Solassol, S. Khier, P. Chalbos, M. Ychou
Journal: Annals of Oncology (2015)
Which children have the strongest longitudinal associations between early exposure to environmental tobacco smoke and age of asthma development
Authors: Elinor Simons, Teresa To, Rahim Moineddin, David Stieb, Sharon Dell
Journal: European Respiratory Journal (2012)

Objective: We sought to understand the effects of risk factors such as atopy on the longitudinal association between early-life exposure to environmental tobacco smoke (ETS) and age of physician-diagnosed asthma (PDA) development in childhood.  Methods: In the Toronto Child Health Evaluation Questionnaire, parents of 5619 grades 1-2 students reported age of PDA development, exposure to ETS during pregnancy and the first year of life, history and family history of atopy and demographic information. Using Cox proportional hazard models, we conducted stratified analyses by potential effect modifiers.  Results: Household ETS exposure prevalence was 8.3% during pregnancy and 10.6% in the first year of life; 15.5% of children developed PDA, 31.2% had a history of atopy and 9.8% had a history of maternal asthma. Children exposed to ETS during pregnancy developed asthma sooner [adjusted hazard ratio (aHR) 1.27, 95% confidence interval (CI): 1.00-1.61]. Stronger associations were seen among children without a history of atopy (aHR 1.92, 95% CI: 1.42-2.61) and without maternal asthma (aHR 1.74, 95% CI: 1.34-2.25); these relationships persisted for ETS exposure in the first year of life (aHR 1.52, 95% CI: 1.12-2.07 and 1.39, 95% CI: 1.08-1.79, respectively).  Conclusions: Longitudinal associations between ETS exposure during pregnancy or the first year of life and age of PDA development are stronger in children without a history of atopy and without maternal asthma. Greater understanding of these associations may guide hypotheses regarding possible mechanisms of association and suggest strategies for exposure reduction in higher-risk children.
Telemedicine-based strategy for sleep apnea management: A multicenter randomized controlled trial
Authors: Valentina Isetta, Carmen León, Cristina Embid, Monica de la Peña, Roser Cambrodí, F Javier Puertas, Ramon Farré, Josep M. Montserrat
Journal: European Respiratory Journal (2014)

INTRODUCTION: Continuous Positive Airway Pressure (CPAP) therapy compliance is essential to treat patients with Obstructive Sleep Apnea (OSA). CPAP therapy prevalence is estimated at two-thirds of all home respiratory therapies, but health resources assigned to promote therapy compliance are reduced. A telemedicine-based approach for CPAP therapy management could be of great benefit for OSA patients. METHODS: In a multicenter randomized clinical trial (RCT) we compared two groups of recently diagnosed OSA patients receiving face-to-face vs Internet-based CPAP follow-up, where a web platform we previously developed (Isetta, ATS2012) supports the follow-up and visits are via videoconference. Both groups answer periodical surveys about sleep time, CPAP side effects, lifestyle and have two follow-up visits (month 1 and 3). At the end of the study (6 months) main outcomes will be CPAP compliance, quality of life and cost-effectiveness. RESULTS: Considering patients who finalized the trial (72/140) compared with baseline, at 6 months face-to-face group reported improvement in sleepiness (Epworth 10.7±5.2 vs 5.4±3.6;p
Clinical Utility of Quantitative Gleason Grading in Prostate Biopsies and Prostatectomy Specimens
Authors: Guido Sauter, Stefan Steurer, Till Sebastian Clauditz, Till Krech, Corinna Wittmer, Florian Lutz, Maximilian Lennartz, Tim Janssen, Nayira Hakimi, Ronald Simon, Mareike von Petersdorff-Campen, Frank Jacobsen, Katharina von Loga, Waldemar Wilczak, Sarah Minner, Maria Christina Tsourlakis, Viktoria Chirico, Alexander Haese, Hans Heinzer, Burkhard Beyer, Markus Graefen, Uwe Michl, Georg Salomon, Thomas Steuber, Lars Henrik Budäus, Elena Hekeler, Julia Malsy-Mink, Sven Kutzera, Christoph Fraune, Cosima Göbel, Hartwig Huland, Thorsten Schlomm
Journal: European Urology (2015)
Comparing analysis software versions in infant multiple breath washout
Authors: Anne-Marie Ebdon, Billy Skoric, Colin Robertson, Sarath Ranganathan
Journal: European Respiratory Journal (2013)

Background:  An elevated functional residual capacity (FRC) measured in infants with cystic fibrosis may help identify gas-trapping, frequently identified on chest computed tomography in this population.   Aims : To examine the difference in values for FRC and LCI (lung clearance index) measured by multiple breath washout, analysed using 2 different versions of a commercially available software package.   Methods : Infant lung function was performed at 3 months, 1 year and 2 years of age under sedation with chloral hydrate. Both FRC and LCI were measured using 4% sulphur hexafluoride (Exhalyzer® D, Eco Medics, Switzerland). Data were acquired using Spiroware Wbreath and analysed using both versions 3.19 and 3.28 (Ndd Medizintechnik AG).   Results : 34 infants of mean age 14.9 months (range 3.0-26.5 months) were tested. Using v3.19 the mean (SD) FRC was 20.9 (4.8) mls/kg, coefficient of variation (CV) 4.2%. Using v3.28 the FRC was 22.7 (4.5) mls/kg, CV 3.5%. The mean (SD) difference between the FRC measurements (v3.28-v3.19) was 1.8 (2.1) mls/kg. In most subjects agreement was within ±2SD but in 3/34 agreement for FRC was outside the limits of agreement (>2SD). The mean (SD) difference between the LCI measurements (v3.28-v3.19) was -0.12 (0.3) and in 2/34 subjects agreement was outside the limits of agreement (>2SD).   Conclusion : Variability in FRC and LCI values arise when using different versions of the same analysis software package and requires consideration when inter-centre comparisons are made.
Randomized study of initial versus late chest irradiation combined with chemotherapy in limited-stage small-cell lung cancer. Aarhus Lung Cancer Group.
Authors: E Work, O S Nielsen, S M Bentzen, K Fode, T Palshof
Journal: Journal of Clinical Oncology (1997)

PURPOSE To evaluate if the timing of chest irradiation with respect to chemotherapy would influence survival and local and distant control in patients with limited-stage small-cell lung cancer (LSCLC). PATIENTS AND METHODS From 1981 to 1989, 199 consecutive patients with LSCLC were randomly allocated to receive initial chest irradiation (ICI; n = 99) or late chest irradiation (LCI; n = 100) given 18 weeks delayed. Both groups received the same nine cycles of combination chemotherapy: three cycles of cisplatin and etoposide and six cycles of cyclophosphamide, doxorubicin, and vincristine. In the first part of the study, prophylactic cranial irradiation (PCI) was only given to patients randomized to ICI, but after inclusion of 42 patients in the LCI arm, the protocol was changed, so that all patients received PCI independent of the timing of the chest irradiation (CI). A total of 157 patients received PCI with a radiation dose of 25 Gy in 11 fractions. RESULTS The timing of radiotherapy had no significant effect on the 2-year overall survival rate (20% after ICI v 19% after LCI, P = .4) or the 2-year in-field recurrence rate (72% after ICI v 68% after LCI, P = .2). Median survival durations were 10.5 (ICI) and 12.0 (LCI) months. Similarly, no difference in the 2-year incidence of CNS recurrences was found between the 2 arms in patients who received PCI (19% after ICI v 13% after LCI, P = .24). Bone marrow toxicity was acceptable, as 15% developed World Health Organization (WHO) grade 4 leukocytopenia and 4% grade 4 thrombocytopenia. Grade 4 leukocytopenia was more pronounced in the ICI group. There was no difference in the frequency and severity of other toxicities between the 2 groups. CONCLUSION Timing of CI did not significantly influence the incidence of in-field recurrences, CNS recurrences, or overall survival.
A phase 2, randomized, double‐blind, multicenter study comparing siltuximab plus best supportive care (BSC) with placebo plus BSC in anemic patients with International Prognostic Scoring System low‐ or intermediate‐1–risk myelodysplastic syndrome
Authors: Guillermo Garcia‐Manero, Gary Gartenberg, David P. Steensma, Martin R. Schipperus, Dimitri A. Breems, Raquel de Paz, David Valcárcel, Britte Kranenburg, Manjula Reddy, Rami S. Komrokji
Journal: American Journal of Hematology (2014)

Interleukin‐6 (IL‐6) may play an important role in the pathophysiology of anemia of inflammation associated with myelodysplastic syndrome (MDS). This double‐blind, placebo‐controlled, phase 2 study assessed the efficacy and safety of siltuximab, a chimeric anti–IL‐6 monoclonal antibody, in patients with low‐ and intermediate‐1–risk MDS who require transfusions for MDS anemia. Patients were randomized in a 2:1 ratio to siltuximab 15 mg kg −1 every 4 weeks + best supportive care (BSC) or placebo + BSC for 12 weeks. The primary endpoint was reduction in red blood cell (RBC) transfusions to treat MDS anemia, defined as ≥50% relative decrease and ≥2‐unit absolute decrease in RBC transfusions. Fifty and 26 patients were randomized to the siltuximab and placebo groups, respectively. The study did not meet its prespecified hypothesis, with six (12%) patients in the siltuximab group and one (3.8%) in the placebo group having reductions in RBC transfusions ( P = 0.271). At the time of the planned futility analysis, the prespecified cutoff criteria were not met, and the study was terminated early due to lack of efficacy. No unexpected safety findings were observed. In conclusion, compared to placebo, treatment with siltuximab did not reduce RBC transfusions in transfusion‐dependent patients with low‐ and intermediate‐1–risk MDS. Future studies might explore siltuximab in patients with less iron overload and with elevated IL‐6 levels and/or using higher doses for MDS. Am. J. Hematol. 89:E156–E162, 2014. © 2014 Wiley Periodicals, Inc.
T wave normalization in infarct-related electrocardiographic leads during exercise testing for detection of residual viability
Authors: Gianni Mobilia, Pierluigi Zanco, Alessandro Desideri, Gianfilippo Neri, Ferdinando Alitto, Gianleone Suzzi, Franca Chierichetti, Leopoldo Celegon, Giorgio Ferlin, Riccardo Buchberger
Journal: Journal of the American College of Cardiology (1998)
The Combined Accelerated Program in Psychiatry: A Progress Report
Authors: WALTER WEINTRAUB, GEORGE BALIS, JAMES MACKIE
Journal: American Journal of Psychiatry (1974)

The authors report on the nature and progress of the Combined Accelerated Program in Psychiatry (CAPP), now in its fourth year of operation. The program involves three and a half years of undergraduate and two and a half of postgraduate training. Participants begin clinical training in the freshman year and supervised psychotherapy in the sophomore year. Test results comparing CAPP students with their non-CAPP fellow students and with psychiatric residents indicate that CAPP students in the middle of their junior year score higher than residents after one and a half to two years of training. The authors present and respond to criticisms of the program, observing that the true test will lie in the careers of CAPP graduates and in the program's impact on psychiatric education.
Abstract 2769: PKC/MARCKS pathway is a novel therapeutic target associated with breast cancer malignancy potential and paclitaxel resistance
Authors: Ching-Hsien Chen, Muhammad Arif, Wen-Hsin Chang, Yuan Yuan, Jing Zhai, David K. Ann, Reen Wu
Journal: Cancer Research (2014)

Abstract Increasing evidence had suggested important roles of protein kinase C (PKC)-mediated phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS) in modulating various cellular processes, including cancer cell growth and metastasis. However, there is a lack of information regarding to the roles of MARCKS and its pSer 159/163 phosphorylated product in breast cancer cells and tissues. To tackle this concern, we recently initiated both immunohistochemical and western blot analyses on a series of clinical specimens and several breast cancer cell lines. We have observed a significant elevation of phospho-MARCKS associated with advanced-stage breast cancer tissues as compared with benign ones, particularly in triple-negative breast cancer (TNBC) tissues and cell lines. Knockdown of MARCKS expression resulted in suppressions of lamellipodia/filopodia formation and migration/invasion as well as down-regulation of Src activity in these TNBC cell lines. Of note, MARCKS-silenced TNBC cells grew much more slowly and more sensitive to paclitaxel than the control and parental cells. Treatment with paclitaxel was shown to induce MARCKS phosphorylation in a dose-dependent manner, which may be related to an enhanced paclitaxel resistance in some of TNBC cells. However, PKC inhibitors were able to abrogate paclitaxel-induced MARCKS phosphorylation. Consistent with this potential, treatments of TNBC cells with a MARCKS N-terminus sequence peptide, namely MANS, to down regulate PKC/MARCKS pathway not only attenuated the associated aggressive phenotype but also synergistically enhanced paclitaxel-induced cytotoxicity in vitro and in vivo. These results demonstrate an association of PKC-mediated MARCKS phosphorylation with breast cancer malignancy potential and MARCKS phosphorylation as a predictor of paclitaxel resistance in TNBC cells. It is suggestive that an inhibition of PKC/MARCKS pathway may serve as an alternative therapeutic strategy for enhancing efficacy of chemotherapy. Citation Format: Ching-Hsien Chen, Muhammad Arif, Wen-Hsin Chang, Yuan Yuan, Jing Zhai, David K. Ann, Reen Wu. PKC/MARCKS pathway is a novel therapeutic target associated with breast cancer malignancy potential and paclitaxel resistance. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2769. doi:10.1158/1538-7445.AM2014-2769
Serum albumin concentration is not a marker of nutritional status
Authors: E. Chojnowska
Journal: BMJ (1996)

EDITOR,—In their paper on postoperative enteral feeding in patients undergoing bowel resection Cornelia S Carr and colleagues used serum albumin concentrations as one of six markers of nutritional status.1 Doweiko and Nompleggi and Klein show that although protein energy …
P1050 : Association of family history of metabolic traits with age at diagnosis and severity of non alcoholic steatohepatitis (NASH) related cirrhosis
Authors: A.S. Bhadoria, C.K. Kedarisetty, V. Shasthry, M.K. Sharma, J. Benjamin, G. Kumar, A. Bhardwaj, S. Muralikrishna Shasthry, T. Vyas, S. Sarin
Journal: Journal of Hepatology (2015)
Intracranial Meningiomas: State of the Art
Authors: F. D’Andrea, F. Maiuri
Journal: Neuro-Oncology (1991)

The epidemiological, clinical, diagnostic and therapeutic features of intracranial meningiomas seem to be appreciably modified in the last years. The frequency of these tumors is considerably increased, as confirmed by our cooperative study with other 21 italian neurosurgical centers, which has shown an average incidence of about 27% of all intracranial tumors. The radiological diagnosis is still based on computed tomography and angiography, whereas magnetic resonance does not provide relevant improvement in the diagnostic accuracy of meningiomas. The use of ultrasonic aspiration and preoperative embolization may improve the surgical treatment. Radiosurgery may be useful in selected cases of residual or recurrent meningiomas. Hormonal studies have confirmed the influence of the progesterone on the cell growth; an hormonal treatment by antiprogestin drugs may be useful in cases of residual, aggressive or malignant meningiomas.
Effective salvage therapy (T-GX) for pancreatic cancer patients after treatment with GTX
Authors: D. R. Fogelman, S. Schreibman, R. L. Fine
Journal: Journal of Clinical Oncology (2004)

4268 Background: Alternating T-GX is a salvage therapy for patients who have failed or could not tolerate GTX. The regimen is based upon our laboratory evidence of circumventing cell cycle drug resistance by separating G1/S agents (gemcitabine, capecitabine) from G2/M agents (docetaxel) as originally described by Skipper et al in the 1960's. The mechanism of T-GX may be mediated by p38 MAP kinase. By separating these cell cycle specific agents, responses can occur despite previously failing the same agents. The regimen is docetaxel 40mg/m2 on the Wednesdays of weeks 1 and 3; capecitabine 1500mg/m2/day M-F of weeks 2 and 4, gemcitabine 750mg/m2/75 min on the Wednesday of weeks 2 and 4. A two week break is given after each cycle; response is assessed after 2 cycles. Methods: We performed a retrospective chart review of all identifiable patients treated with T-GX after prior treatment with GTX. Responses were measured per WHO criteria; survival was measured from the first dose of chemotherapy. Toxicities were recorded from the chart notes. Results: 15 patients were treated; 13 with metastatic disease and two with unresectable disease. Seven patients were treated for disease progression on or after GTX; 5 began the regimen for intolerable symptoms on GTX. Three switched to reduce chemotherapy exposure. There were 2 CRs and 2 PRs for a response rate of 27% on an intent to treat basis. 5 other patients were judged to have stable disease (33%) for a clinical benefit rate of 60%. Nine patients are still alive; median survival is at least 5.5 months from the start of the salvage therapy. Toxicity data is available for 14 patients and include 4 grade 3 leukopenias (no grade 4), 1 grade 3 thrombocytopenia (no grade 4), and no grade 3–4 anemia. Diarrhea (n=4) and abdominal cramps (n=3) were the most common toxicities; three patients experienced a DVT. Conclusions: The alternating T-GX regimen has significant efficacy in pts who have failed or cannot tolerate GTX chemotherapy with an acceptable toxicity profile. A phase II study is planned. No significant financial relationships to disclose.