tbuckley/cabot-search huggingface dataset:
A qualitative study of self-management in COPD: Attitudes and priorities of patients for making health behaviour changes
Authors: Julia Walters, Helen Cameron-Tucker, Helen Courtney-Pratt, Richard Wood-Baker, Andrew Robinson, Jenn Scott, Paul Turner, Mark Nelson, E. Haydn Walters
Journal: European Respiratory Journal (2011)

Pivotal to successful chronic disease self-management is achieving adoption and maintenance of health behaviours that influence disease progression and impact.   Aim:  To evaluate patients9 uptake and attitudes to health behaviour change in the SNAPPS framework consisting of the items: smoking, nutrition, alcohol consumption, physical activity, psychosocial wellbeing and symptom management.   Methods:  Community nurse mentors trained in a self-management approach, mentored 90 participants with COPD for up to 12 months by telephone. Participants9 views were sought during semi-structured interviews with a purposive representative sample. Data analysis by two independent authors used an Iterative Thematic approach. Health status was measured using SGRQ, HADS and MRC scales.   Results:  In 20 participants (50% male, 50% current smokers) with COPD (GOLD stage: moderate 15, severe 5), mean age 65.4 years, the SGRQ overall score was 45.0 (SD 23.8). We found three groups related to health behaviour change attitudes: 8 (40%) subjects were actively making changes; 9 (45%) subjects were open to making changes and 3 (15%) subjects were more resistant. Severity of COPD and current smoking status were not major influences on attitude. Mentoring increased awareness of COPD effects and helped develop and personalise behaviour change strategies, importantly even in those not actively making changes. Physical activity was most frequently targeted for changes. 50% of current smokers developed plans targeting smoking. Motivation to maintain changes was increased by mentor support.   Conclusions:  Health behaviour change in COPD at all stages can be supported by regular telephone mentoring.
Effect of erdosteine on airflow obstruction and symptom recovery in severe COPD exacerbations
Authors: Maurizio Moretti, Maria Ballabio
Journal: European Respiratory Journal (2011)

Introduction: Acute COPD exacerbations (AECOPD) represent an important cause of morbidity and mortality. Early and effective interventions may improve their outcome and patients' health status.

Objective: This study evaluated the effect of erdosteine, an anti-oxidant mucolytic agent, on airflow limitation and symptom recovery at AECOPD

Methods: 15 COPD patients hospitalized for an acute exacerbation randomly received erdosteine 900 mg daily (E) or placebo (P) for 10 days in combination with standard steroid, antibiotic and bronchodilator treatment. Pulmonary function test including spirometry (FVC, FEV1, FEF25–75) and breathlessness, cough, and sputum scale (BCSS) were measured at hospital admission, and at 10 and 30 days post-exacerbation.

Results: 

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The improvement of lung function parameters and symptom scores from baseline was significantly greater in patients receiving erdosteine. Symptom score recovery significantly correlated to improvement of airway obstruction at time 10 and 30 in the erdosteine group.

Conclusions: Treatment with erdosteine plus standard therapy in AECOPD proved to be effective in improving both clinical symptoms, and large and small airway impairment. Mucolytic agents with relevant antioxidant activity may allow a more rapid and complete recovery of exacerbated patients by reducing the burst of airway inflammation.
424. Development of a Scalable Column Chromatography-Based Purification Process To Manufacure Empty Capsid-Free AAV Vectors
Authors: Guang Qu, Xiaofei Wang, Jac Luna, Sooah Sohr, Floro Cataniag, Fraser J. Wright
Journal: Molecular Therapy (2004)

Recombinant adeno-associated virus (rAAV) has shown great promise as a DNA-based biopharmaceutical agent to treat serious human diseases. In conjunction with efforts in pre-clinical and clinical development, there is a significant need to develop and implement manufacturing processes capable of consistently providing vectors of optimal purity, potency and safety. We have previously reported the development and implementation of a fully scalable rAAV purification process that enabled us to manufacture AAV vectors at a scale to support our clinical development programs. However, like many other reported column-based purification processes, the vectors purified in our second generation purification method contained significant levels of empty capsids. In consideration of the possible deleterious effects of empty capsids, a product-related impurity, on vector efficacy and safety, we have developed a scalable method to separate empty capsids from vector particles. While this separation has been historically achieved using density gradient ultracentrifugation, such methods are not preferred for scalable, cost-effective vector manufacturing. Instead, we have developed a column chromatograpy-based technique to separate empty capsids from DNA containing vector particles. AAV vectors expressing human coagulation factor IX (AAV-hFIX16) were produced using helper virus-free triple transfection of HEK293 cells in roller bottles, and purified using anion exchange chromatography. This empty capsid-containing material was used as the starting point to screen various ion exchange resins to identify conditions that could differentiate between empty and full AAV2 particles. These studies indicated that the surface characteristics of the two particle types are very similar. However, identification of subtle, pH-dependent differences in binding to selected resins, in conjunction the selective use of chaotropic agents, allowed us to separate these two populations effectively. Our data indicated that more than 90% of the empty particles were removed from the purified vector using this newly developed column chromatography technique, with approximately 60% recovery of the DNA-containing vector particles. This new column step, in combination with the column-based scalable method that we previously reported, now enables us to efficiently manufacture empty capsid-free recombinant AAV using a fully scalable process.
Modulation of gene expression by soy phytochemicals in orthotopic bladder tumors in mice by using affymetrix microarray assay.
Authors: Ajita V. Singh, Hasan Otu, Towia Libermann, Jin-Rong Zhou
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

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Bladder cancer is the fifth most common malignancy diagnosed in the United States. With the unknown etiological factors for bladder cancer carcinogenesis and the fact that bladder cancer patients are facing both threat of metastases and uncontrolled local recurrence after treatment, additional efforts to define dietary intervention or chemoprevention programs for bladder cancer progression/recurrence and metastasis are urgently needed. A role of diet and nutrition in bladder cancer development and progression is biologically plausible since most substances or metabolites are excreted through the urinary tract, and are consequently in direct contact with the mucosa of the bladder. In previous studies we have shown that soy bioactive components significantly inhibit the bladder cancer cell growth both in vitro and in an orthotopic bladder tumor model. Mice treated with genistin and the genistein-rich soy phytochemical concentrate (SPC) had reduced final tumor weights by 56% (P<0.05) and 52% (P<0.05) respectively, associated with induction of tumor cell apoptosis and inhibition of tumor angiogenesis in vivo. In addition, SPC treatment, but not genistin treatment, significantly inhibited lung metastases by 95% (P<0.01). To further investigate the molecular mechanisms behind anti-growth and anti-metastasis of soy components, we performed microarray assays by using the tumor samples. Total RNA was extracted by using RNeasy Mini Kit From Qiagen Inc. First and second strand cDNA were synthesized from 5-15mg of total RNA using superscript double stranded cDNA synthesis kit and oligo-dt24-T7 primer according to the manufacturer's instructions. Affymetrix microarray assay was performed in HG-U133 plus 2.0 arrays. Data were analyzed by using Affymetrix Netafex analysis as well as cluster analysis. We observed differential expression of certain genes that are specifically related to angiogenesis, cell cycle, apoptosis and metastasis between the treated and the control groups. We also identified several new candidate genes whose activities in bladder cancer were not previously reported. We are performing gene function assays to determine the functional roles of these modulated genes in anti-growth and anti-metastasis activities of soy bioactive components.
Introduction to Clinical Examination.
Authors: John Macleod, E. B. French, J. F. Munro
Journal: Annals of Internal Medicine (1975)

The approach to the patient - the history, psychiatric assessment, the physical examination, the sequence of the learning process the cardiovascular system the respiratory system the alimentary and genito-urinary systems the nervous system the locomotor system the intergation and completion of the physical examination - the examination of the hands and upper limbs, head, neck, breasts, trunk and lower limbs, a swelling, the skin, the use of the ophthalmoscope, the methods in practice, case recording.
Genetics of Susceptibility to Plasmacytoma Induction. I. BALB/cAnN (C), C57BL/6N (B6), C57BL/Ka (BK), (C × B6)F 1 , (C × BK) F 1 , and C × B Recombinant-Inbred Strains
Authors: Michael Potter, Janet G. Pumphrey, Donald W. Bailey
Journal: JNCI Journal of the National Cancer Institute (1975)

Plasmacytomas were found in 58% of 373 BALB/cAnN (C) mice given three 0.5-ml doses of mineral oil (Bayol F or light mineral oil) or 2,6,10,14-tetramethylpentadecane (pristane) ip. The incidence of plasmacytomas in C57BL/6N (B6), C57BL/Ka (BK), (C times B6)F1 and (C times BK)F1 was 6.4, 0, 11.5, and 16.5%, respectively. The plasmacytomas occurred in old B6 mice, in contrast to their early appearance in strain C mice. The incidence of plasmacytomas in mineral oil-treated or pristane-treated C times B recombinant-inbred (Rl) strain mice was 28.3% in C times BD, 17.5% IN C times BE, 36.5% IN C times BG, 0% in C times BH, 2.9% in C times Bl, 48% in C times BJ, and 4.3% in C times BK. C times BD, C times BG, and C times BJ strains were considered susceptible to plascytoma induction by mineral oil or pristane; C times BE had a low susceptibility, and C times BH, C times Bl, and C times BK were resistant. The results suggested that there were only a few gene difference between C and B6 or BK that determined susceptibility or resistance to plasmacytoma induction, and that B6 and BK have at least one dominant resistance gene. The distribution pattern of susceptibility and resistance in the C times B Rl strains suggested the presence of a resistance gene on chromosome 9, linkage group II.
Abstract 2809: Absence of Flow-Limiting Coronary Artery Disease Among Patients Undergoing Emergent Cardiac Catheterization For ST Segment Elevation Myocardial Infarction in the National Cardiovascular Data Registry CathPCI Registry: Implications for Primary Angioplasty Programs
Authors: Kalon K Ho, H. V Anderson, Richard E Shaw, Lloyd W Klein, James H Beachy, Christopher P Cannon, Harlan M Krumholz, Susan Fitzgerald, Anthony Hermann, Kristi Mitchell, John Rumsfeld, Ralph G Brindis
Journal: Circulation (2007)

Background : Many hospitals have established primary angioplasty programs with a goal of providing consistently timely reperfusion for patients with suspected acute ST segment elevation myocardial infarction (STEMI). As the locus of control for activation of the cardiac catheterization laboratory moves from the cardiologist to the emergency department and even to pre-hospital activation by emergency medical services, concerns have been raised about ``false positive” activations of the primary angioplasty team, yet there has been little data on the frequency of this occurence. Objective : We sought to estimate how often flow-limiting coronary artery disease (CAD) was NOT found among patients undergoing emergent cardiac catheterization in a large multi-center registry. Methods and Results : The National Cardiovascular Data Registry (NCDR) CathPCI Registry is a cardiac catheterization and angioplasty quality improvement and outcomes database with over 800 participating institutions. Among 131,211 patients undergoing emergent or salvage coronary angiography from 1/1/2005 -12/31/2006, 9.8% had no lesions of ≥50% diameter stenoses in the major epicardial coronary arteries. No angiographically visualized coronary stenoses at all were reported in 5.2% of these cases. Detailed data were not readily available on whether the primary indication for the procedure was suspected acute STEMI vs. other reasons such as hemodynamic instability or refractory arrhythmia. Conclusions : Among patients undergoing emergent or salvage diagnostic catheterizations nationwide in the NCDR CathPCI Registry, finding NO angiographically-apparent flow-limiting CAD was uncommon (&lt;10%). While no clinical finding or test will perfectly discriminate STEMI from ``STEMI mimics”, current clinical practice appears to activate primary angioplasty teams with reasonable specificity.
Arcus Not So Senilis
Authors: P V Macaraeg, L Lasagna, None Snyderb
Journal: Annals of Internal Medicine (1968)

A survey of two populations of negroes and whites has revealed a higher frequency of corneal arcus in the negro. While both races show a tendency to develop the lesion with advancing age, some negro men and women will show lesions relatively early in life. The corneal lesion seems not to be a useful predictor of diastolic hypertension, myocardial infarction, or cerebrovascular accidents. It is suggested that in the negro at least, the development of arcus is genetically determined, rather than a reflection of a generalized lipid disturbance or of generalized vascular disease. It would appear desirable to label this lesion arcus corneae rather than arcus senilis or gerontoxon.
Apoptotic cells overexpress vinculin and induce vinculin-specific cytotoxic T-cell cross-priming
Authors: Antonella Propato, Giovanna Cutrona, Vittorio Francavilla, Massimo Ulivi, Enrico Schiaffella, Olfert Landt, Rod Dunbar, Vincenzo Cerundolo, Manlio Ferrarini, Vincenzo Barnaba
Journal: Nature Medicine (2001)
Abstract 11532: Randomized Trial of the Association Between Low Dose Statins and Nutraceuticals in High intensity Statin. intolerRant patiENts With Very High Risk Coronary Artery disease (ADHERENCE)
Authors: giuseppe marazzi, francesco pelliccia, maurizio volterrani, giuseppe campolongo, salvatore rosanio, rosalba massaro, luca cacciotti, silvia quattrino, barbara sposato, giuseppe rosano
Journal: Circulation (2014)

Background: Several trials have shown that in patients (pts) with atherosclerotic cardiovascular disease, reduction of LDL-C level with statin is associated with significant reductions in mortality and cardiovascular events. In clinical practice, however, high dose statin (HDS) treatment is often discontinued by pts due to side effects. Indeed, in statin intolerant pts alternative therapies such as nutraceuticals are available. Purpose: The primary objective of this study is to compare the efficacy and tollerability of low dose statin (LDS) therapy vs the association between a LDS and a nutraceuticals in HDS intollerant pts with CAD deemed to be at high risk. Methods: A randomised, prospective, parallel group, double blind trial was designed. The inclusion criteria were pts with CAD that underwent to PCI and that do not achieved at least a 50% reduction in LDL C and were HDS intolerant in treatment with LDS. These pts were randomized 1:1 in 2 groups: group NS received an association with LDS and a commercially available nutraceutical pill (1 tablet/day containing red yeast rice 200 mg, policosanol 10 mg and berberine 500 mg) and group S continued LDS (10 to 20 mg/day of simvastatin or 5 to 10 mg/day atorvastatin or 5 mg/day rosuvastatin). At baseline and after 3 months all pts underwent to clinical evaluation and blood exams. Results: 100 pts were consecutively enrolled. Baseline clinical features and lipid profiles were similar between groups. At the 3° month, the 2 groups significantly differed for LDL-C, total cholesterol and triglycerides, with lower levels in the NS group than in the S group; also, the 2 groups differed for HDL-C values but not significantly, with higher levels in the NS group than in the S group (Table 1). Morever, in both group the treatment tolerance was high: in each groups only 3 pts discontinued therapy. Conclusion: In pts with CAD and HDS intolerant, a treatment with LDS and Nutraceuticals can be a reliable treatment option. (clinicaltrials.gov: NCT02001883)
Protein kinase C δ inhibits the secretion of proteolytic enzymes in murine mammary cells
Authors: Alejandro J. Urtreger, Valeria C. Grossoni, Marcelo G. Kazanietz, Elisa D. Bal de Kier Joffé
Journal: Cancer Research (2006)

4379   PKC isozymes are serine-threonin kinases that control several cell functions, including proliferation, differentiation, malignant transformation, and metastatic dissemination. We have previously shown that overexpression of the novel calcium-independent protein kinase C δ (PKCδ) in normal murine mammary cells (NMuMG) was associated with increased proliferation and resistance to apoptosis induced by cytotoxic drugs or serum starvation. Moreover, PKCδ overexpression led to anchorage-independent growth, a property closely related with the malignant phenotype. In the present work we investigated whether PKCδ could modulate the production of proteolytic enzymes, such as urokinase (uPA) and metalloproteinase-9 (MMP-9), molecules directly associated with the metastatic dissemination process. Two methodologies were used: stable overexpression of PKCδ and PKCδ depletion using RNAi. NMuMG cells overexpressing PKCδ showed a 67% reduction in the secretion of uPA compared to vector-transfected (control) cells, as well as a 63% reduction in MMP-9 secretion. Furthermore, treatment with the PKC activator PMA induced a dose-dependent inhibition of uPA production in NMuMG-PKCδ cells (70% and 95% reduction for 25 and 50 nM PMA respectively). Similar results were observed for the secretion of MMP-9. The production of proteases was not significantly altered in control cells after PMA treatment. On the other hand, cells in which PKCδ had been depleted using RNAi showed a marked increase (4–fold) in uPA levels as well as in MMP-9 secretion (8–fold). Our results demonstrate that PKCδ has a negative modulatory role in the secretion of uPA and MMP-9 in normal murine mammary cells. Although our previous observations showed that PKCδ was inducing changes compatible with a malignant phenotype, the present results strongly suggest that PKCδ plays an important role in limiting metastatic dissemination by inhibiting the secretion of proteolytic enzymes that modulate invasiveness. In summary, PKCδ seems to be playing multiple roles in the control of breast carcinogenesis.
Recent Progress on C‐4‐Modified Podophyllotoxin Analogs as Potent Antitumor Agents
Authors: Ying‐Qian Liu, Jing Tian, Keduo Qian, Xiao‐Bo Zhao, Susan L. Morris‐Natschke, Liu Yang, Xiang Nan, Xuan Tian, Kuo‐Hsiung Lee
Journal: Medicinal Research Reviews (2014)

Abstract Podophyllotoxin (PPT), as well as its congeners and derivatives, exhibits pronounced biological activities, especially antineoplastic effects. Its strong inhibitory effect on tumor cell growth led to the development of three of the most highly prescribed anticancer drugs in the world, etoposide, teniposide, and the water‐soluble prodrug etoposide phosphate. Their clinical success as well as intriguing mechanism of action stimulated great interest in further modification of PPT for better antitumor activity. The C‐4 position has been a major target for structural derivatization aimed at either producing more potent compounds or overcoming drug resistance. Accordingly, numerous PPT derivatives have been prepared via hemisynthesis and important structure–activity relationship (SAR) correlations have been identified. Several resulting compounds, including GL‐331, TOP‐53, and NK611, reached clinical trials. Some excellent reviews on the distribution, sources, applications, synthesis, and SAR of PPT have been published. This review focuses on a second generation of new etoposide‐related drugs and provides detailed coverage of the current status and recent development of C‐4‐modified PPT analogs as anticancer clinical trial candidates.
Cost-effectiveness of sofosbuvir-based triple therapy for untreated patients with genotype 1 chronic hepatitis C
Authors: Salvatore Petta, Giuseppe Cabibbo, Marco Enea, Fabio Salvatore Macaluso, Antonella Plaia, Raffaele Bruno, Antonio Gasbarrini, Antonio Craxì, Calogero Cammà
Journal: Hepatology (2014)

We assessed the cost-effectiveness of sofosbuvir (SOF)-based triple therapy (TT) compared with boceprevir (BOC)- and telaprevir (TVR)-based TT in untreated genotype 1 (G1) chronic hepatitis C (CHC) patients discriminated according to IL28B genotype, severity of liver fibrosis, and G1 subtype. The available published literature provided the data source. The target population was made up of untreated Caucasian patients, aged 50 years, with G1CHC and these were evaluated over a lifetime horizon by Markov model. The study was carried out from the perspective of the Italian National Health Service. Outcomes included discounted costs (in euros at 2013 value), life-years gained (LYG), quality-adjusted life year (QALY), and incremental cost-effectiveness ratio (ICER). Cost of SOF was assumed to be €3,500 per week, i.e., the price generating a willingness-to-pay threshold of €25,000 per LYG compared with TVR in the entire population of untreated G1 patients. The robustness of the results was evaluated by one-way deterministic and multivariate probabilistic sensitivity analyses. SOF was cost-effective compared with BOC in all strategies with the exception of cirrhosis and IL28B CC patients. In comparison with TVR-based strategies, SOF was cost-effective in IL28B CT/TT (ICER per LYG €22,229) and G1a (€19,359) patients, not cost-effective in IL28B CC (€45,330), fibrosis F0-F3 (€26,444), and in cirrhosis (€34,906) patients, and dominated in G1b patients. The models were sensitive to SOF prices and to likelihood of sustained virological response. Conclusion: In untreated G1 CHC patients, SOF-based TT may be a cost-effective alternative to first-generation protease inhibitors depending on pricing. The cost-effectiveness of SOF improved in IL28B CT/TT and G1a patients. SOF was dominated by TVR in G1b patients even if, in clinical practice, this issue could be counterbalanced by the good tolerability profile of SOF and by the shorter treatment duration. (Hepatology 2014;59:1692–1705)
SKIN ULTRASTRUCTURE IN LETTERER-SIWE DISEASE TREATED WITH VINBLASTINE.
Authors: F. GIANOTTI, R. CAPUTO
Journal: British Journal of Dermatology (1971)

Journal Article SKIN ULTRASTRUCTURE IN LETTERER‐SIWE DISEASE TREATED WITH VINBLASTINE: MODE OF PENETRATION OF LANGERHANS GRANULES INTO THE NUCLEUS Get access F. GIANOTTI, F. GIANOTTI Dermatology Clinic and Institute of Pharmacology, University of Milan, Italy Search for other works by this author on: Oxford Academic Google Scholar R. CAPUTO R. CAPUTO Dermatology Clinic and Institute of Pharmacology, University of Milan, Italy Requests for reprints should be addressed to Dr R. Caputo, Clinica Dermatologica, University of Milan, via Pace 9, 20122. Milano, Italy. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 84, Issue 4, 1 April 1971, Pages 335–345, https://doi.org/10.1111/j.1365-2133.1971.tb14229.x Published: 01 April 1971 Article history Accepted: 01 November 1970 Published: 01 April 1971