tbuckley/cabot-search huggingface dataset:
Effectiveness of software-based patient education on inhaler technique: A clinical study
Authors: Romil Shah, Luis Velez
Journal: European Respiratory Journal (2014)

National asthma guidelines to improve asthma outcomes rely on inhaled medications. However, it has been commonly recorded that the majority of asthma patients use inhalers incorrectly and that poor inhaler technique is correlated with poor asthma control. Common inhaler education is written instruction, but some patients receive no training. We tested the effectiveness of a computer based training solution versus traditional written instruction on inhaler technique. An example of a computer based training solution used was videos found at www.use-inhalers.com. We hypothesize that it can increase a provider's ability to deliver high quality instruction to all patients without increasing time burden on providers. Our controls were patients without any training and patients given written training. Videotapes of patients using their inhalers before and after training were created and analyzed by a fixed rubric and given a score. 50 patients were recruited in the Junta De Beneficencia Hospital in a randomized, unblinded enrollment process. Analysis was done through multivariate regression analysis where the different trainings were binomial indicator variables. Video training improved inhaler technique by more than 70% (p .05), and on average, only improved technique by less than 10%. We conclude that (1) written instruction may not be enough to instruct patients for inhaler technique education (in fact, most patients missed more than 50% of the necessary steps) and (2) a computer-based alternative can have the desired educational effect without an increased time effort.
Tumoral-reduced folates and clinical resistance to fluorouracil-based treatment in head and neck cancer patients.
Authors: S Chéradame, M C Etienne, P Formento, M Schneider, O Dassonville, F Demard, G Milano
Journal: Journal of Clinical Oncology (1997)

PURPOSE To describe the distribution of tumoral-reduced folates in cancer patients and to analyze the link between this parameter and antitumor efficacy of fluorouracil (FU)-based induction chemotherapy. PATIENTS AND METHODS Ninety-five patients with head and neck squamous cell carcinoma were included in the present study and 41 received induction treatment with FU-based chemotherapy (35 men and six women; mean age, 59 years; range, 40 to 76). Thymidylate synthase (TS) activity was measured according to the tritium-release assay. Reduced folates (5-10 methylenetetrahydrofolate [CH2FH4] plus tetrahydrofolate) were measured according to the entrapment assay. RESULTS Among the whole group of patients, reduced folates ranged from nondetectable (&lt; 0.3) to 17.7 pmol/mg protein; CH2FH4 ranged from nondetectable (&lt; 0.3) to 8.2 pmol/mg protein. There was no significant link between tumoral levels of reduced folates and the severity of disease stage. Among 41 treated patients, there were 12 (29%) complete responses (CRs), 18 (44%) partial responses (PRs), and 11 patients (27%) with no response (NR). No statistically significant relationship was observable between TS activity and response. The distribution of CH2FH4 in tumors was significantly higher for complete responders in comparison to patients with a PR or NR. CONCLUSION The present clinical data demonstrate the importance of basal tumoral-reduced folates for the achievement of optimal efficacy of FU-based treatment. They may have implications for the identification of patients resistant to FU chemotherapy and for a better understanding and management of FU modulation by folinic acid (FA).
Neo-tAnGo: A neoadjuvant randomized phase III trial of epirubicin/cyclophosphamide and paclitaxel ± gemcitabine in the treatment of women with high-risk early breast cancer (EBC): First report of the primary endpoint, pathological complete response (pCR)
Authors: H. M. Earl, A. Vallier, L. Hiller, N. Fenwick, M. Iddawela, L. Hughes-Davies, E. Provenzano, K. McAdam, T. Hickish, C. Caldas
Journal: Journal of Clinical Oncology (2009)

522 Background: Neo-tAnGo used a 2-by-2 factorial design, addressing: (i) gemcitabine (G) in a sequential neoadjuvant chemotherapy (CT) regimen of epirubicin/cyclophosphamide (EC) and paclitaxel (T); and (ii) the sequencing of these treatment components (EC then T ± G versus T ± G then EC). Methods: Patients (Pts) with early breast cancer (T2 tumours or above) were randomised to EC then T, T then EC, EC then TG or TG then EC. All components were given x 4 cycles. (E= 90 mg/m 2 day (d)1 every (q) 21d; C = 600 mg/m 2 d1 q21d; T = 175 mg/m 2 d1 q14d; G = 2,000 mg/m 2 d1 q14d.) The primary endpoint was pCR, defined as absence of invasive disease in the breast and axillary lymph nodes. 800 pts were required to detect 10% differences in the primary endpoint pCR rates, at the 5% (2-sided) significance level with 85% power. Stratification was by age, inflammatory/locally advanced disease, tumour size, clinical involvement of axillary nodes and oestrogen receptor (ER) status. Results: Between January 2005 and September 2007, 831 pts were randomised by 88 consultants from 57 UK centres. Characteristics were balanced across groups: 63% &lt;50 years old, 25% had inflammatory and/or locally advanced disease, 79% of tumours &lt;50 mm, 50% node positive and 34% ER negative. Two-reader review of 813 (98%) eligible pts'. pathology reports, blinded to treatment arm, were carried out. pCR rates were 17% (95% CI 14–21) for EC&amp;T pts and 17% (95% CI 14–21) for EC&amp;TG pts (p = 0.98). However the sequence T±G then EC, showed pCR of 20% (95% CI 16–24) compared with 15% (95% CI 11–18) for EC then T±G pts (p = 0.03). Adjustment by stratification did not alter results. Conclusions: The Neo-tAnGo results confirm those of the adjuvant tAnGo trial in terms of gemcitabine effect (ASCO 2008). The sequence of T±G-first has demonstrated a significant advantage in pCR compared with the more conventional anthracycline-first sequencing. [Table: see text]
Induction of DT-Diaphorase by Anticarcinogenic Sulfur Compounds in Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: A M Benson, P B Barretto, J S Stanley
Journal: JNCI Journal of the National Cancer Institute (1986)

The effects of the dietary administration of four anticarcinogenic sulfur compounds on the activity of DT-diaphorase, a protective enzyme in quinone and quinoneimine detoxification, have been investigated in female CD-1 mice. Bisethylxanthogen, disulfiram, sodium diethyldithiocarbamate, and benzylisothiocyanate, administered at 0.5% of the diet (by weight) for 14 days, each induced significant increases in DT-diaphorase specific activities in cytosol fractions of lung, kidney, urinary bladder, proximal small intestine, and colon. Cytosolic DT-diaphorase of the fore-stomach was elevated in response to bisethylxanthogen, disulfiram, and benzylisothiocyanate. The increases in cytosolic DT-diaphorase activities in organs of mice fed 0.5% bisethylxanthogen were similar in magnitude to those observed previously in response to 0.75% butylated hydroxyanisole. Liver cytosol DT-diaphorase specific activity was enhanced sevenfold by 0.5% bisethylxanthogen, twofold by 0.5% benzylisothiocyanate, and 2.6-fold by 1% disulfiram but was not significantly increased by disulfiram or sodium diethyldithiocarbamate at 0.5% of the diet. Diets containing 0.5% bisethylxanthogen or 0.5% benzylisothiocyanate also elevated microsomal DT-diaphorase specific activities in several organs. Even at the tenfold-lower concentration of 0.05% of the diet, bisethylxanthogen induced significant increases in DT-diaphorase specific activities in cytosol fractions of liver, lung, kidney, and small intestine and in liver and kidney microsomes. The protective function of DT-diaphorase in limiting free-radical formation and oxidative damage to cells suggests that the induction of this enzyme contributes to the anticarcinogenic effects of the four sulfur compounds studied.
High prevalence of mumps in Lao People’s Democratic Republic
Authors: J.M. Hübschen, K. Vilivong, C. Souvannaso, A.P. Black, N. Lütteke, B. Samountry, V. Phongsavath, B. Khamphaphongphane, J. Denny, C. Sayyavong, G.K.S. Woo, K. Sengsaya, A. Sausy, P. Vongphrachanh, P. Jutavijittum, D. Phonekeo, C.P. Muller
Journal: Clinical Microbiology and Infection (2014)
Foreign Body Aspiration of a Press-Through Package That Lodged between the Vocal Cords
Authors: Ha Youn Lee, Sun Mi Choi
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Figure 1. (A) A cervical spine radiography demonstrating a round object with a radio-opaque rim. (B) Computed tomographic image of the neck showing a hyperdense foreign body located in the supraglottic larynx. (C) A bronchoscopic view of the vocal cords, revealing a pill in a press-through package. A 63-year-old man presented at the emergency department with sudden onset of a sore throat and expectoration of reddish sputum after consuming medicine that had been administered by his caretaker. He had recently been diagnosed with extensive-stage small-cell lung cancer that had metastasized to multiple mediastinal lymph nodes, the liver, and bones (T4N3M1). He had had a productive cough for 1 month and a history of recurrent aspiration owing to recurrent laryngeal nerve involvement, due to the lung cancer. A physical examination revealed stridor, while plain radiography of the cervical spine revealed a round object with a radio-opaque rim (Figure 1A). Computed tomography of the neck revealed a hyperdense foreign body located in the supraglottic larynx (Figure 1B), which was not visible during laryngoscopic examination. Fiberoptic bronchoscopy revealed a pill in a pressthrough package, lodged between the vocal cords (Figure 1C). This 1.5-cm foreign body was successfully removed from the vocal cords using bronchoscopic forceps, after which the stridor immediately resolved. Foreign body aspiration leading to obstruction of the airway can have various consequences. If it is undetected or left untreated, severe airway damage can occur (1, 2). This case highlights the importance of obtaining a detailed medical history and exploring causes other than the most obvious ones (e.g., the advanced-stage lung cancer in this case) in cases of stridor. n
FK506-Binding Protein 10, a Potential Novel Drug Target for Idiopathic Pulmonary Fibrosis
Authors: Claudia A. Staab-Weijnitz, Isis E. Fernandez, Larissa Knüppel, Julia Maul, Katharina Heinzelmann, Brenda M. Juan-Guardela, Elisabeth Hennen, Gerhard Preissler, Hauke Winter, Claus Neurohr, Rudolf Hatz, Michael Lindner, Jürgen Behr, Naftali Kaminski, Oliver Eickelberg
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: Increased abundance and stiffness of the extracellular matrix, in particular collagens, is a hallmark of idiopathic pulmonary fibrosis (IPF). FK506-binding protein 10 (FKBP10) is a collagen chaperone, mutations of which have been indicated in the reduction of extracellular matrix stiffness (e.g., in osteogenesis imperfecta).Objectives: To assess the expression and function of FKBP10 in IPF.Methods: We assessed FKBP10 expression in bleomycin-induced lung fibrosis (using quantitative reverse transcriptase–polymerase chain reaction, Western blot, and immunofluorescence), analyzed microarray data from 99 patients with IPF and 43 control subjects from a U.S. cohort, and performed Western blot analysis from 6 patients with IPF and 5 control subjects from a German cohort. Subcellular localization of FKBP10 was assessed by immunofluorescent stainings. The expression and function of FKBP10, as well as its regulation by endoplasmic reticulum stress or transforming growth factor-β1, was analyzed by small interfering RNA–mediated loss-of-function experiments, quantitative reverse transcriptase–polymerase chain reaction, Western blot, and quantification of secreted collagens in the lung and in primary human lung fibroblasts (phLF). Effects on collagen secretion were compared with those of the drugs nintedanib and pirfenidone, recently approved for IPF.Measurements and Main Results: FKBP10 expression was up-regulated in bleomycin-induced lung fibrosis and IPF. Immunofluorescent stainings demonstrated localization to interstitial (myo)fibroblasts and CD68+ macrophages. Transforming growth factor-β1, but not endoplasmic reticulum stress, induced FKBP10 expression in phLF. The small interfering RNA–mediated knockdown of FKBP10 attenuated expression of profibrotic mediators and effectors, including collagens I and V and α-smooth muscle actin, on the transcript and protein level. Importantly, loss of FKBP10 expression significantly suppressed collagen secretion by phLF.Conclusions: FKBP10 might be a novel drug target for IPF.
Human respiratory muscles: fibre morphology and capillary supply
Authors: M Mizuno
Journal: European Respiratory Journal (1991)

In man the diaphragm (DIA) and abdominal muscles comprise approximately 50% slow-twitch (ST) fibres, whereas a higher proportion (60%) is found in intercostal muscles and the scalenes. All respiratory muscles show an equal distribution of fast-twitch (FTa and b) fibres with the exception of the expiratory intercostal muscles which have few FTb fibres. The inspiratory muscles have a uniformly small fibre size, in contrast to the expiratory intercostal muscle fibres which are large. The fibre size of the inspiratory muscles is maintained with ageing, whereas that of the expiratory intercostal muscles appears to be reduced after the age of 50 yrs. Capillary supply is most abundant in the expiratory muscles followed by DIA and the inspiratory intercostal muscles. In patients with chronic obstructive pulmonary disease (COPD) it is unknown whether a reduction in fibre size of the thoracic respiratory muscles is caused by extreme use due to increased ventilatory work, or by disuse due to an increased involvement of the extrathoracic respiratory muscles. Histochemical characteristics suggest that, in normal humans, the load on the inspiratory muscles is relatively small during contractions, whereas the expiratory intercostal muscles are exposed to severe continuous activity with a heavy load.
Breast cancer patients' attitudes about rationing postlumpectomy radiation therapy: applicability of trade-off methods to policy-making.
Authors: V A Palda, H A Llewellyn-Thomas, R G Mackenzie, K I Pritchard, C D Naylor
Journal: Journal of Clinical Oncology (1997)

PURPOSE Along with evidence, clinical policies must take patients' values into account. Particularly where evidence is limited and where assumptions of utility-maximizing behavior may not be valid, new methods such as trade-off techniques (TOTs), which allow elicitation of patients' treatment alternatives, might be useful in policy formulation. We used TOTs to assess breast cancer patients' attitudes toward two clinical policies designed to ration adjuvant postlumpectomy breast radiation therapy. METHODS Cross-sectional interviews were performed in a tertiary cancer center. A total of 102 patients were presented with information about the side effects and benefits associated with two hypothetical decisions: (1) willingness to receive treatment elsewhere to shorten the wait for radiation therapy, and (2) foregoing radiation therapy in the face of small marginal benefits. For each scenario, a TOT was used to identify the maximal acceptable wait time (MAWT) for therapy and the benefit threshold at which the patient would forego therapy. Associations of clinical and demographic factors with these decisions were determined by regression analysis. RESULTS Patients would be willing to wait, on average, 7 weeks before wanting to leave their city for radiation therapy, less than the 13-week delay our patients actually faced. Older patients were less willing to wait (P = .013); 46% of patients would not give up radiation therapy, even in the face of no stated benefit. Willingness to give up radiation therapy was predicted by willingness to accept delay (odds ratio [OR], 1.84; 95% confidence interval [CI], 1.05 to 3.37) and being employed (OR, 2.61; 95% CI, 1.08 to 6.54). Patients with larger tumors were less willing to give up radiation therapy (OR, 0.57; 95% CI, 0.31 to 0.97). CONCLUSION Even in difficult decisions such as rationing postlumpectomy breast cancer radiation therapy, TOTs can inform policy formulation by indicating the distributions of patients' preferences.
Hepatomas in CBA/Cb/Se Mice and Liver Lesions in Golden Hamsters Induced by Hydrazine Sulfate&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Cesare Biancifiori
Journal: JNCI Journal of the National Cancer Institute (1970)

Hydrazine sulfate (HS), administered daily in scalar doses to intact virgin CBA/Cb/Se mice of both sexes, raised the hepatoma incidence as follows: 1.13 mg, 60% in males and 62.5% in females; 0.56 mg, 48% in males and 66.6% in females; 0.28 mg, 28% in males and 8% in females; and 0.14 mg, 3.8% in males and 0% in females. Most tumors were highly vascularized hepatocarcinomas; however, 4 mice that received 1.13 mg HS daily also had lung metastases. HS administered to intact virgin golden hamsters of both sexes caused liver reticuloendothelial cell proliferation and cirrhosis, bile duct proliferation, and degeneration of fibrous cells in the hyalinized sclerotic tissue. But no liver lesions were observed in the untreated controls.
Aberrant Expression of MHC Class II in Melanoma Attracts Inflammatory Tumor-Specific CD4+ T- Cells, Which Dampen CD8+ T-cell Antitumor Reactivity
Authors: Marco Donia, Rikke Andersen, Julie W. Kjeldsen, Paolo Fagone, Shamaila Munir, Ferdinando Nicoletti, Mads Hald Andersen, Per thor Straten, Inge Marie Svane
Journal: Cancer Research (2015)

In the absence of a local inflammatory response, expression of MHC class II molecules is restricted mainly to hematopoietic cells and thymus epithelium. However, certain tumors, such as melanoma, may acquire aberrant constitutive expression of MHC class II. In a set of primary melanoma cell populations and correspondingly expanded autologous tumor-infiltrating lymphocytes (TIL), we show how MHC class II expression on melanoma cells associates with strong MHC class II-restricted CD4(+) T-cell responses that are specific for tumors. Notably, we found that tumor-specific CD4(+) T-cell responses were dominated by TNF production. TNF reduced CD8(+) T-cell activation in IFNγ-rich environments resembling a tumor site. Conversely, direct CD4(+) T-cell responses had no influence on either the proliferation or viability of melanoma cells. Taken together, our results illustrate a novel immune escape mechanism that can be activated by aberrant expression of MHC class II molecules, which by attracting tumor-specific CD4(+) T cells elicit a local inflammatory response dominated by TNF that, in turn, inhibits cytotoxic CD8(+) T-cell responses
Socieconomic factors affecting the acceptance of continuous positive airway pressure in sleep apnoea syndrome patients
Authors: Vasileios Michailidis, Dimitra Siopi, Nikolaos Moisiadis, Eleni Perantoni, Andreas Kosmas, Evaggelia Serasli, Venetia Tsara
Journal: European Respiratory Journal (2012)

Background: CPAP therapy is often associated with suboptimal adherence rates and the assessment of patients9 motivations and barriers is important for the treatment. The aim of this study was to investigate factors which may affect the acceptance of CPAP among patients with SAS.Patients-Methods: One hundred and nine patients who were diagnosed with SAS and prescribed CPAP during the last 2 years did not come to the follow-up visit despite the instructions. We contacted them via telephone and asked about the acceptance and the adherence to CPAP therapy.Results: From 109 patients, 62(56.8%) (age 49.2±11.3 years, 93.5% male) were found and answered the questions.Twenty two patients(35.5%) did not purchase the CPAP device(group1) mainly(50%) due to economic restriction, 12 patients(19.4%) abandoned CPAP therapy over time(group2) mainly(50%) due to subjective perception of treatment ineffectiveness and 28 patients(45.1%) continue CPAP but they ignored the follow-up procedure(group3).No significant correlations were observed between anthropometric characteristics, severity of SAS, socioeconomic and employment issues and the decision about the CPAP treatment in each group, but group 1 had lower education level than the two others(basic level 36.4% vs 16,6% vs 25%).No significant differences were noted between the 3 groups with respect to method of CPAP titration, age,BMI,AHI but the ESS was higher in group 3(p
Comparison of pulmonary versus extrapulmonary models of induced acute lung injury in rat
Authors: Laura Chimenti, Ferranda Puig, Maria Neus Gómez, Jessica Tijero, Thomas Lebouvier, Maria Elisa Quílez, Josefina López-Aguilar, Lluis Blanch, Antonio Artigas
Journal: European Respiratory Journal (2013)

BACKGROUND. Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are caused by a variety of pathological processes that may affect the lung either directly or indirectly. Most animal models of ALI are based on clinicals disorders that are associated with ALI/ARDS in humans, however none of them fully simulate the human disease. AIM. To compare different types of ALI animal models reproducing mechanisms which may injury the lung directly or indirectly. METHODS. Adult male Sprague-Dawley rats (250-300 g; n=3 for group) underwent:1) intratracheal administration (IA) of HCl (0.1 N, pH=1.4) to mimic acid aspiration, 2) IA of LPS (10 μg/g of rat) to mimic bacterial infection, 3) HCl and LPS as a potential synergistic double hit, 4) IA of saline in control animals, 5) cecal ligation and puncture (CLP) to induce sepsis. 24h after the injury the animals were sacrificed and bronchoalveaolar lavage fluid (BALF) inflammatory cells were assessed. RESULTS. Simultaneous IA of HCl and LPS or LPS alone significantly increased total neutrophil counts compared to control rats (7.7±0.1 vs 0.3±0.1 x 10 6 cells/ml, p 6 cells/ml, p  Grant acknowledgements: FIS-PI12/02548 and Fundacio Parc Tauli.
Cancer chemoprevention: Evidence of a nonlinear dose response for the protective effects of resveratrol in humans and mice
Authors: Hong Cai, Edwina Scott, Abeer Kholghi, Catherine Andreadi, Alessandro Rufini, Ankur Karmokar, Robert G. Britton, Emma Horner-Glister, Peter Greaves, Dhafer Jawad, Mark James, Lynne Howells, Ted Ognibene, Michael Malfatti, Christopher Goldring, Neil Kitteringham, Joanne Walsh, Maria Viskaduraki, Kevin West, Andrew Miller, David Hemingway, William P. Steward, Andreas J. Gescher, Karen Brown
Journal: Science Translational Medicine (2015)

Resveratrol is widely promoted as a potential cancer chemopreventive agent, but a lack of information on the optimal dose prohibits rationally designed trials to assess efficacy. To challenge the assumption that "more is better," we compared the pharmacokinetics and activity of a dietary dose with an intake 200 times higher. The dose-response relationship for concentrations generated and the metabolite profile of [(14)C]-resveratrol in colorectal tissue of cancer patients helped us to define clinically achievable levels. In Apc(Min) mice (a model of colorectal carcinogenesis) that received a high-fat diet, the low resveratrol dose suppressed intestinal adenoma development more potently than did the higher dose. Efficacy correlated with activation of adenosine monophosphate-activated protein kinase (AMPK) and increased expression of the senescence marker p21. Nonlinear dose responses were observed for AMPK and mechanistic target of rapamycin (mTOR) signaling in mouse adenoma cells, culminating in autophagy and senescence. In human colorectal tissues exposed to low dietary concentrations of resveratrol ex vivo, we measured enhanced AMPK phosphorylation and autophagy. The expression of the cytoprotective NAD(P)H dehydrogenase, quinone 1 (NQO1) enzyme was also increased in tissues from cancer patients participating in our [(14)C]-resveratrol trial. These findings warrant a revision of developmental strategies for diet-derived agents designed to achieve cancer chemoprevention.