tbuckley/cabot-search huggingface dataset:
Severe community-acquired pneumonia: assessment of microbial aetiology as mortality factor
Authors: F. Paganin, F. Lilienthal, A. Bourdin, N. Lugagne, F. Tixier, R. Génin, J-L. Yvin
Journal: European Respiratory Journal (2004)

Community-acquired pneumonia (CAP) remains a major cause of mortality. The aetiology of CAP has rarely been identified as a mortality risk factor. A prospective study was conducted to assess the prognostic factors of CAP patients admitted to the intensive care unit (Centre Hospitalier Departmental Felix Guyon, St Denis de la Reunion, France), with a special emphasis on microbial aetiology. All variables assessing severity were collected, with a special emphasis on microbial investigations. Among 112 immunocompetent patients (mean+/-SD age 54.7+/-15.1 yrs), 84% were male. Severity of CAP was demonstrated by mortality rate (43%), shock (48%), simplified acute physiology score (SAPS; 46.4+/-21.6) and mechanical ventilation support (82%). Mean risk factor score was 2.2+/-1.2. Microbiological identification was obtained in 78.6% of cases, with positive blood culture in 33%. Most frequently, microbial agents were Streptococcus pneumoniae and Klebsiella pneumoniae (42% and 22%, respectively). The univariate analysis recorded the usual mortality variables: age, alcohol consumption, SAPS, shock, mechanical ventilation, positive end expiratory pressure level, positive blood culture, multilobar infiltrates on chest radiograph, neutropenia, and acidosis, and found K. pneumoniae (versus S. pneumoniae, and all CAP) as a mortality factor. The multivariate analysis demonstrated that septic shock (relative risk (RR) 141), K. pneumoniae CAP (RR 27), SAPS (RR 10.7) and positive blood culture (RR 2.7) were independent factors related to death. In conclusion, the present study found that the microbial aetiology, Klebsiella pneumoniae, was an independent risk factor for mortality in severe community-acquired pneumonia.
Role of Transforming Growth Factor-β1 in Invasion and Metastasis in Gastric Carcinoma
Authors: Yoshihiko Maehara, Yoshihiro Kakeji, Akira Kabashima, Yasunori Emi, Akihiro Watanabe, Kohei Akazawa, Hideo Baba, Shunji Kohnoe, Keizo Sugimachi
Journal: Journal of Clinical Oncology (1999)

Transforming growth factor-beta1 (TGF-beta1) is a major modulator of cellular proliferation and extracellular matrix formation. We determined the role of TGF-beta1 in invasion and metastasis in gastric cancer.We detected TGF-beta1 expression in primary and lymph node metastatic lesions of gastric cancer, using an antibody and in situ hybridization. The plasma TGF-beta1 levels in the peripheral vein and in the tumor drainage vein were assayed.In the cytoplasm of cancer cells, TGF- beta1 was immunostained in 35.9% (78 of 217) of primary gastric carcinomas, and this expression was confirmed by in situ hybridization. Of 59 gastric carcinomas with a TGF-beta1-negative primary tumor, metastatic lymph nodes were positive for TGF-beta1 staining in 32 cases (54.2%). Positive staining of TGF-beta1 in gastric cancer tissues was closely related to serosal invasion, infiltrative growth, and lymph node metastasis. Multivariate analysis showed that the expression of TGF-beta1 was an independent risk factor for serosal invasion and infiltrative growth of the tumor. The plasma level of TGF-beta1 did not differ between TGF-beta1-negative and -positive groups. There were also no differences in plasma TGF-beta1 levels among each tumor stage, between the peripheral and the tumor drainage veins, and between preoperative and postoperative testings.Transforming growth factor-beta1 is closely related to the invasion and metastasis of gastric cancer, and production of TGF-beta1 in the tumor does not contribute to the total amount of TGF-beta1 in the blood circulation. We interpret our observations to mean that in a tumor microenvironment, TGF-beta1 alters the biologic behavior of the tumor.
Biological and Clinical Relevance of miRNA Expression Signatures in Primary Plasma Cell Leukemia
Authors: Marta Lionetti, Pellegrino Musto, Maria Teresa Di Martino, Sonia Fabris, Luca Agnelli, Katia Todoerti, Giacomo Tuana, Laura Mosca, Maria E. Gallo Cantafio, Vitina Grieco, Gabriella Bianchino, Fiorella D'Auria, Teodora Statuto, Carmela Mazzoccoli, Luciana De Luca, Maria Teresa Petrucci, Massimo Offidani, Francesco Di Raimondo, Antonietta Falcone, Tommaso Caravita, Paola Omede', Fortunato Morabito, Pierfrancesco Tassone, Mario Boccadoro, Antonio Palumbo, Antonino Neri
Journal: Clinical Cancer Research (2013)

Primary plasma cell leukemia (pPCL) is a rare and very aggressive form of plasma cell dyscrasia. To date, no information on microRNA (miRNA) expression in pPCL has been reported. This study aimed at investigating the involvement of miRNAs in pPCL and their possible relationship with higher tumor aggressiveness.Global miRNA expression profiles were analyzed in highly purified malignant plasma cells from 18 pPCL untreated patients included in a prospective clinical trial. MiRNA expression patterns were evaluated in comparison with a representative series of multiple myeloma patients, in relation to the most recurrent chromosomal abnormalities (as assessed by fluorescence in situ hybridization and single-nucleotide polymorphism-array analysis), and in association with clinical outcome. MiRNA expression was also integrated with gene expression profiles in pPCL and multiple myeloma samples.We identified a series of deregulated miRNAs in pPCL (42 upregulated and 41 downregulated) in comparison with multiple myeloma. Some of them, on the basis of their reported functions and putative target genes computed by integrative analysis, might have a role in the pathobiology of pPCL. As regards chromosomal aberrations, the expression of some miRNAs mapped to hotspot altered regions was associated with DNA copy number of the corresponding loci. Finally, 4 miRNA (miR-497, miR-106b, miR-181a*, and miR-181b) were identified as having expression levels that correlated with treatment response, and 4 (miR-92a, miR-330-3p, miR-22, and miR-146a) with clinical outcome.Overall, our study provides insights into the possible contribution of miRNAs in the pathogenesis of pPCL and suggests targets for future therapeutic investigations.
Impact of Completeness of Percutaneous Coronary Intervention Revascularization on Long-Term Outcomes in the Stent Era
Authors: Edward L. Hannan, Michael Racz, David R. Holmes, Spencer B. King, Gary Walford, John A. Ambrose, Samin Sharma, Stanley Katz, Luther T. Clark, Robert H. Jones
Journal: Circulation (2006)

The importance of completeness of revascularization by percutaneous coronary intervention in patients with multivessel disease is unclear in that there is little information on the impact of incomplete revascularization outside of randomized trials. The objective of this study is to compare long-term mortality and subsequent revascularization for percutaneous coronary intervention patients receiving stents who were completely revascularized (CR) with those who were incompletely revascularized (IR).Patients from New York State's Percutaneous Coronary Interventions Reporting System were subdivided into patients who were CR and IR. Then subsets of IR patients were contrasted with CR patients. Differences in long-term survival and subsequent revascularization for CR and IR patients were compared after adjustment for differences in preprocedural risk. A total of 68.9% of all stent patients with multivessel disease who were studied were IR, and 30.1% of all patients had total occlusions and/or > or =2 IR vessels. At baseline, the following patients were at higher risk: those who were older and those with more comorbid conditions, worse ejection fraction, and more renal disease and stroke. After adjustment for these baseline differences, IR patients were significantly more likely to die at any time (adjusted hazard ratio=1.15; 95% confidence interval, 1.01 to 1.30) than CR patients. IR patients with total occlusions and a total of > or =2 IR vessels were at the highest risk compared with CR patients (hazard ratio=1.36; 95% confidence interval, 1.12 to 1.66).IR with stenting is associated with an adverse impact on long-term mortality, and consideration should be given to either achieving CR, opting for surgery, or monitoring percutaneous coronary intervention patients with IR more closely after discharge.
Effect of gas cooking on lung function in adolescents: modifying role of sex and immunoglobulin E
Authors: G M Corbo
Journal: Thorax (2001)

A study was undertaken to investigate the effect of gas cooking on the lung function of adolescents while considering serum IgE level as a possible effect modifier.The cross sectional study was performed in 702 subjects aged 11-13 years from primary and secondary schools in Civitavecchia and Viterbo ( Latium region in Central Italy), categorised according to how often they were in the kitchen while the mother cooked (never, sometimes, often). Data were collected by questionnaire and lung function was measured by spirometric tests. Bronchial hyperresponsiveness was evaluated by the methacholine test, atopic status by a skin prick test, and a blood sample was collected to determine serum IgE levels. The results were analysed separately for boys and girls. Multiple regression analysis was performed, taking functional parameters (FEV(1), FEV(1)/FVC, FEF(25-75), FEF(50), FEF(75)) as the dependent variables and age, height, parental smoking, and father's education as independent variables.There was no association between time spent in the kitchen and lung function level in boys, but a reduction in lung function was detected in girls which was statistically significant for FEF(75) (sometimes -10.3%, often -11.1%). After stratifying boys and girls into four groups on the basis of the IgE serum level (below and above the median value of IgE), the reduction in lung function was significant in girls with a high IgE value whereas no significant deleterious effects were evident in girls with a low IgE value or in boys with either a low or high IgE. The results remained substantially unchanged after excluding girls with a response to methacholine below the concentration of 4 mg/ml, asthmatic patients, and those with positive skin prick tests.Gas cooking has a harmful effect on the lung function of girls with a high serum level of IgE. We do not know whether serum IgE, a marker of allergic susceptibility, is a simple indicator that an inflammatory process is in progress or whether it is involved in the pathogenesis of injury leading to bronchial obstruction.
Cognitive behaviour therapy to prevent harmful compliance with command hallucinations (COMMAND): a randomised controlled trial
Authors: Max Birchwood, Maria Michail, Alan Meaden, Nicholas Tarrier, Shon Lewis, Til Wykes, Linda Davies, Graham Dunn, Emmanuelle Peters
Journal: The Lancet Psychiatry (2014)

Acting on command hallucinations in psychosis can have serious consequences for the individual and for other people and is a major cause of clinical and public concern. No evidence-based treatments are available to reduce this risk behaviour. We therefore tested our new cognitive therapy to challenge the perceived power of voices to inflict harm on the voice hearer if commands are not followed, thereby reducing the hearer's motivation to comply.In COMMAND, a single-blind, randomised controlled trial, eligible participants from three centres in the UK who had command hallucinations for at least 6 months leading to major episodes of harm to themselves or other people were assigned in a 1: 1 ratio to cognitive therapy for command hallucinations + treatment as usual versus just treatment as usual for 9 months. Only the raters were masked to treatment assignment. The primary outcome was harmful compliance. Analysis was by intention to treat. The trial is registered, number ISRCTN62304114.98 (50%) of 197 participants were assigned to cognitive therapy for command hallucinations + treatment as usual and 99 (50%) to treatment as usual. At 18 months, 39 (46%) of 85 participants in the treatment as usual group fully complied with the voices compared with 22 (28%) of 79 in the cognitive therapy for command hallucinations + treatment as usual group (odds ratio 0·45, 95% CI 0·23-0·88, p=0·021). At 9 months the treatment effect was not significant (0·74, 0·40-1·39, p=0·353). However, the treatment by follow-up interaction was not significant and the treatment effect common to both follow-up points was 0·57 (0·33-0·98, p=0·042).This is the first trial to show a clinically meaningful reduction in risk behaviour associated with commanding voices. We will next determine if change in power was the mediator of change. Further more complex trials are needed to identify the most influential components of the treatment in reducing power and compliance.UK Medical Research Council and the National Institute for Health Research.
Weekly paclitaxel as first-line chemotherapy and trastuzumab in patients with advanced breast cancer
Authors: G. Fountzilas, D. Tsavdaridis, A. Kalogera-Fountzila, Ch. Christodoulou, E. Timotheadou, Ch. Kalofonos, P. Kosmidis, A. Adamou, P. Papakostas, H. Gogas, G. Stathopoulos, E. Razis, D. Bafaloukos, D. Skarlos
Journal: Annals of Oncology (2001)
The UK Standardisation of Breast Radiotherapy (START) trials of radiotherapy hypofractionation for treatment of early breast cancer: 10-year follow-up results of two randomised controlled trials
Authors: Joanne S Haviland, J Roger Owen, John A Dewar, Rajiv K Agrawal, Jane Barrett, Peter J Barrett-Lee, H Jane Dobbs, Penelope Hopwood, Pat A Lawton, Brian J Magee, Judith Mills, Sandra Simmons, Mark A Sydenham, Karen Venables, Judith M Bliss, John R Yarnold
Journal: The Lancet Oncology (2013)
Treatment of Tuberculosis with Rifamycin-containing Regimens in Immune-deficient Mice
Authors: Ming Zhang, Si-Yang Li, Ian M. Rosenthal, Deepak V. Almeida, Zahoor Ahmad, Paul J. Converse, Charles A. Peloquin, Eric L. Nuermberger, Jacques H. Grosset
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Daily rifapentine plus isoniazid-pyrazinamide in mice infected with Mycobacterium tuberculosis produces cure in 3 months. Whether cure corresponds to latent infection contained by host immunity or true tissue sterilization is unknown.To determine the length of treatment with rifapentine-isoniazid-pyrazinamide or rifampin-isoniazid-pyrazinamide needed to prevent relapse in immune-deficient mice.Aerosol-infected BALB/c and nude mice were treated 5 days per week with either 2 months of the rifapentine-based regimen followed by rifapentine-isoniazid up to 12 months or the same regimen with rifampin instead of rifapentine. Cultures of lung homogenates were performed during the first 3 months and then every 3 months. Relapse rates were assessed after 3, 6, 9, and 12 months of treatment in BALB/c (± 1 mo of cortisone) and nude mice.All rifapentine-treated mice were lung culture-negative at 3 months but 13% of BALB/c that received cortisone and 73% of nude mice relapsed. After 6, 9, and 12 months of treatment no mouse relapsed. Rifampin-treated BALB/c mice remained culture positive at 3 months. All were culture negative at 6, 9, and 12 months. None, including those receiving cortisone, relapsed. Rifampin-treated nude mice harbored more than 4 log(10) lung cfu at Month 2 and approximately 6 log(10) cfu with isoniazid resistance at Month 3. A supplementary experiment demonstrated that 7 days a week treatment did not prevent isoniazid resistance, whereas addition of ethambutol did.In nude mice, sterilization of tuberculosis is obtained with rifapentine-containing treatment, whereas failure with development of isoniazid resistance is obtained with rifampin-containing treatment.
Autophagy in Toxicology: Cause or Consequence?
Authors: Sten Orrenius, Vitaliy O. Kaminskyy, Boris Zhivotovsky
Journal: The Annual Review of Pharmacology and Toxicology (2012)

Research on autophagy and its effects on cell metabolism and physiology has increased dramatically during recent years. Multiple forms of autophagy have been characterized, and many of the genes involved in the regulation of this process have been identified. The importance of autophagy for embryonic development and maintenance of tissue homeostasis in the adult organism has been demonstrated convincingly, and several human diseases have been linked to deficiencies in autophagy. Most often, autophagy serves as a protective mechanism, but persistent activation of autophagy can result in cell death. This is true for many toxic agents. In fact, there are ample examples of cross talk between autophagy and other modes of cell death after exposure to toxicants. However, the relative contribution of autophagy to the overall toxicity of these compounds is not always clear, and further research is needed to clarify the toxicological significance of this process.
A randomized, controlled exploratory study of clonidine in diarrhea-predominant irritable bowel syndrome
Authors: Michael Camilleri, Doe-Young Kim, Sanna Mckinzie, H.Jae Kim, George M. Thomforde, Duane D. Burton, Phillip A. Low, Alan R. Zinsmeister
Journal: Clinical Gastroenterology and Hepatology (2003)
Efficacy and safety of biweekly i.v. administrations of the Aurora kinase inhibitor danusertib hydrochloride in independent cohorts of patients with advanced or metastatic breast, ovarian, colorectal, pancreatic, small-cell and non-small-cell lung cancer: a multi-tumour, multi-institutional phase II study
Authors: P. Schöffski, B. Besse, T. Gauler, M.J.A. de Jonge, G. Scambia, A. Santoro, C. Davite, M.G. Jannuzzo, A. Petroccione, J.-P. Delord
Journal: Annals of Oncology (2014)
GPs' complaints go unheard
Authors: K. M. Hawking
Journal: BMJ (2013)

Francis criticised local GPs for not raising concerns about Stafford Hospital until asked.1 I’m in a different part of the country, but my experiences are unlikely to be very different. When I have wanted to complain about the care of an individual patient, where should I have gone?

Chief executives and consultants, if they do respond, say they have looked …
Association of Volume and Volume-Independent Factors With Accuracy in Screening Mammogram Interpretation
Authors: C. A. Beam, E. F. Conant, E. A. Sickles
Journal: JNCI Journal of the National Cancer Institute (2003)

Early detection of breast cancer is associated with the accurate reading of screening mammograms, but factors that influence reading accuracy are not well understood. We thus investigated whether reading volume and other factors were independently associated with accuracy in reading screening mammograms in a population of U.S. radiologists.A random selection of 110 of 292 radiologists who agreed to participate, if selected, interpreted screening mammograms from 148 randomly selected women. Original index mammograms (i.e., mediolateral oblique and craniocaudal views of each breast) were used; comparison original mammograms were provided when available. Radiologist-level and facility-level factors were surveyed. Two standard metrics of screening accuracy, both based on receiver operating characteristic curves, were analyzed. The influence of volume on accuracy after controlling for other factors was assessed with multiple regression analysis.Current reading volume was not statistically significantly associated with interpretive accuracy. More recently trained radiologists interpreted mammograms more accurately than those trained earlier (-0.76% [95% confidence interval (CI) = -1.75% to -0.02%] reduction in sensitivity per year since residency). Facility-level factors that were statistically significantly and independently associated with better accuracy were the number of diagnostic breast imaging examinations and image-guided breast interventional procedures performed (0.55% [95% CI = 0.11% to 2.40%] increase in accuracy per examination or procedure offered), being classified as a comprehensive breast diagnostic and/or screening center or freestanding mammography center (1.39% [95% CI = 0.15% to 3.82%] higher than a hospital radiology department or multispecialty medical clinic), and being a facility that practiced double reading (1.61% [95% CI = 1.99% to 11.65%]) higher than in a facility without such practice).Individual radiologists' current reading volume was not statistically significantly associated with accuracy in reading screening mammograms, but several other factors were. Expertise reflects a complex multifactorial process that needs further clarification.
Nonproprietary Nomenclature for Combination Products
Authors: John Andrako
Journal: JAMA (1978)

The United States Adopted Name (USAN) program is generally recognized as having been established in June 1961. Since that time, the USAN Council has, on request and on its own initiative, devoted considerable effort to the problem of appropriate nonproprietary nomenclature for drug products formulated to contain more than one active ingredient. A single, reasonably simple name for a combination product would perform in nonproprietary fashion several functions similar to that which trademarks perform: it would permit convenient reference in oral statements, in prescription writing, in articles prepared for publication, and in medical history entries, inventory control, and fiscal records. Desirable attributes for such nonproprietary names would be (1) that a signal be used (an obviously plural name, an established prefix or suffix such as co- or -mix, or use of a hyphen) to alert health professionals to the fact that the name applied to a combination product and (2)
Generation of functional cholangiocyte‐like cells from human pluripotent stem cells and HepaRG cells
Authors: Noushin Dianat, Hélène Dubois‐Pot‐Schneider, Clara Steichen, Christophe Desterke, Philippe Leclerc, Aurélien Raveux, Laurent Combettes, Anne Weber, Anne Corlu, Anne Dubart‐Kupperschmitt
Journal: Hepatology (2014)

Cholangiocytes are biliary epithelial cells, which, like hepatocytes, originate from hepatoblasts during embryonic development. In this study we investigated the potential of human embryonic stem cells (hESCs) to differentiate into cholangiocytes and we report a new approach, which drives differentiation of hESCs toward the cholangiocytic lineage using feeder-free and defined culture conditions. After differentiation into hepatic progenitors, hESCs were differentiated further into cholangiocytes using growth hormone, epidermal growth factor, interleukin-6, and then sodium taurocholate. These conditions also allowed us to generate cholangiocytes from HepaRG-derived hepatoblasts. hESC- and HepaRG-derived cholangiocyte-like cells expressed markers of cholangiocytes including cytokeratin 7 and osteopontin, and the transcription factors SOX9 and hepatocyte nuclear factor 6. The cells also displayed specific proteins important for cholangiocyte functions including cystic fibrosis transmembrane conductance regulator, secretin receptor, and nuclear receptors. They formed primary cilia and also responded to hormonal stimulation by increase of intracellular Ca 2+ . We demonstrated by integrative genomics that the expression of genes, which signed hESC- or HepaRG-cholangiocytes, separates hepatocytic lineage from cholangiocyte lineage. When grown in a 3D matrix, cholangiocytes developed epithelial/apicobasal polarity and formed functional cysts and biliary ducts. In addition, we showed that cholangiocyte-like cells could also be generated from human induced pluripotent stem cells, demonstrating the efficacy of our approach with stem/progenitor cells of diverse origins. Conclusion : We have developed a robust and efficient method for differentiating pluripotent stem cells into cholangiocyte-like cells, which display structural and functional similarities to bile duct cells in normal liver. These cells will be useful for the in vitro study of the molecular mechanisms of bile duct development and have important potential for therapeutic strategies, including bioengineered liver approaches. (Hepatology 2014;60:700–714)