tbuckley/cabot-search huggingface dataset:
Endoscopic injection sclerotherapy for 1,000 patients with esophageal varices: A nine-year prospective study
Authors: Makoto Hashizume, Seigo Kitano, Nobuhiro Koyanagi, Kazuo Tanoue, Masayuki Ohta, Hiroya Wada, Hirohiko Yamaga, Hidefumi Higashi, Yasunori Iso, Tetsuya Iwanaga, Keizo Sugimachi
Journal: Hepatology (1992)

We report here the results of endoscopic injection sclerotherapy performed in 1,000 consecutively treated Japanese patients with esophageal varices. This prospective study covered the period from 1982 to 1990. Variceal bleeding was controlled in 215 (97.7%) of 220 patients. Esophageal varices were completely eradicated in 778 patients (77.8%); the mean number of sessions was 4.2. In only 3 of the 778 patients did esophageal varices of the same size recur. Small, dilated, venous vessels that required additional sclerotherapy in follow-up endoscopy at 3-mo intervals appeared in 171 (22.2%) of 778 patients. The cumulative nonbleeding rate at 5 yr was 94.5% in patients in whom the varices had been eradicated. Deaths caused by upper gastrointestinal bleeding accounted for 2.6% of cases, whereas the rates of liver failure and hepatoma were 4.6% and 47.3%, respectively. The 5-yr cumulative survival rate was 54.1% in patients without concomitant hepatoma; it was 12.0% in patients with hepatomas. Multivariate analysis showed that hepatoma, Child classification, indication (acute, elective or prophylactic) and eradication were independent factors that significantly influenced survival time. This study clearly shows that close follow-up with endoscopy and complete eradication lead to significant reduction in bleeding from esophageal varices and reduction of mortality related to this bleeding.
Outcome of patients with metastatic renal cell carcinoma treated with targeted therapy without cytoreductive nephrectomy
Authors: S.L. Richey, S.H. Culp, E. Jonasch, P.G. Corn, L.C. Pagliaro, P. Tamboli, K.K. Patel, S.F. Matin, C.G. Wood, N.M. Tannir
Journal: Annals of Oncology (2010)
Development and validation of the RAND Asthma Control Measure
Authors: Marielena Lara, Maria Orlando Edelen, Nicole K. Eberhart, Brian D. Stucky, Cathy D. Sherbourne
Journal: European Respiratory Journal (2014)

Patient-based measures for asthma control are important in assessing the worldwide impact of this highly prevalent chronic illness. We sought to refine an asthma symptom scale that RAND had previously developed to shorten it and validate it further, as well as reflect updated international expert definitions of asthma control. We conducted rigorous psychometric testing of new and adapted self-administered survey items in a sample of 2032 adults with asthma. The reliability and preliminary validity of the resulting measure, henceforth referred to as the RAND Asthma Control Measure (RAND-ACM), matched or exceeded that of the original RAND measure and others in the literature. RAND-ACM scores for worse asthma control were significantly associated with worse asthma-related quality of life, increased asthma-related healthcare use, Hispanic ethnicity and lower educational level. Evidence for internal consistency was strong with a Cronbach’s α of 0.84. We also found adequate concordance between the RAND-ACM and the Global Initiative for Asthma categories of “uncontrolled”, “partly controlled” and “controlled” asthma. The RAND-ACM, a five-item self-reported asthma control survey measure, performs well in a large ethnically-diverse sample of US adults with asthma and provides a cost-free alternative to other asthma control measures currently available.
Day After the Night Before
Authors: Tristan Richardson, Melanie Weiss, Peter Thomas, David Kerr
Journal: Diabetes Care (2005)

There is no evidence to suggest that individuals with type 1 diabetes adopt a different approach to their use of alcohol than the rest of the population. Nevertheless, in patients treated with insulin, alcohol has been implicated in up to one-fifth of hospital attendances with hypoglycemia (1). Recently, in a laboratory-based study, Turner et al. (2) reported that ingestion of alcohol with an evening meal increased the risk of hypoglycemia the next morning in patients with type 1 diabetes. However, this study was small, patients were admitted to a research unit, their “usual” insulin doses were reduced at meal times, and the overnight insulin was administered intravenously in a controlled environment. To date there has been no study examining the effect of alcohol in free-living patients with type 1 diabetes over a 24-h period.

We studied 16 free-living patients with type 1 diabetes aged 39 ± 7 years, with a duration of diabetes of 15 ± 11 years, who consumed alcohol on a regular basis (<28 units/week). All gave written informed consent for the study after approval from the local research ethics committee. All had normal awareness of hypoglycemia and stable glycemic control (HbA1c 8.1 ± 1.0%). The patients wore the continuous glucose monitoring system (CGMS) (Medtronic Minimed, Minneapolis) for 36 h …
Vesicle Trafficking and RNA Transfer Add Complexity and Connectivity to Cell–Cell Communication
Authors: Charles T. Roberts, Peter Kurre
Journal: Cancer Research (2013)

Abstract Cell–cell communication, either in direct proximity or at a distance, generally occurs by receptor–ligand engagement and subsequent activation of downstream intracellular signaling cascades. This conventional, largely protein-based, model has long been considered necessary and sufficient to explain coordinate tissue and organismal function. Intriguing recent work indicates that many cells can also transfer RNA directly via cell–cell trafficking of nanometer-sized, lipid-bilayer vesicles. The distinct biogenesis pathways that give rise to the different vesicle types described to date are just beginning to be elucidated. Notwithstanding their diverse origin, all types of vesicles seem to contain a broad, cell-specific, nonrandom representation of cellular protein and RNA species. The cell–cell trafficking of coding and small noncoding RNAs in particular constitutes a new paradigm for the direct phenotypic modulation of cells in the local microenvironment and in distal organs. Here, we review the current understanding of RNA vesicle trafficking and its emerging role in cell–cell signaling. Cancer Res; 73(11); 3200–5. ©2013 AACR.
Validity of Cancer Registry Data for Measuring the Quality of Breast Cancer Care
Authors: Jennifer L Malin, Katherine L Kahn, John Adams, Lorna Kwan, Marianne Laouri, Patricia A Ganz
Journal: JNCI Journal of the National Cancer Institute (2002)

Background: Various groups have called for a national system to monitor the quality of cancer care. The validity of cancer registry data for quality of cancer care has not been well studied. We investigated the validity of such information in the California Cancer Registry. Methods: We compared registry data associated with care with data abstracted from the medical records of patients diagnosed with breast cancer. We also calculated a quality score for each subject by determining the proportion of four evidence-based quality indicators that were met and then compared overall quality scores obtained from registry and medical record data. All statistical tests were two-sided. Results: Records of 304 patients were studied. Compared with the medical record data gold standard, the accuracy of registry data was higher for hospital-based services (sensitivity = 95.0% for mastectomy, 94.9% for lumpectomy, and 95.9% for lymph node dissection) than for ambulatory services (sensitivity = 9.8% for biopsy, 72.2% for radiation therapy, 55.6% for chemotherapy, and 36.2% for hormone therapy). On average, quality scores calculated from registry data were 11 percentage points (95% confidence interval [CI] = 9 to 13 percentage points, P<.001) lower than those calculated from medical record data. Quality scores calculated from registry data were 5 percentage points (95% CI = 3 to 7 percentage points) lower for patients with stage I breast cancer, 16 percentage points (95% CI = 12 to 20 percentage points) lower for patients with stage II breast cancer, and 20 percentage points (95% CI = 8 to 32 percentage points) lower for patients with stage III breast cancer than were corresponding scores calculated from medical record data (all P<.001). The greater difference in quality scores for stage II and III patients revealed that disease severity and setting of care affected the validity of registry data. Conclusions: Cancer registry data for quality measurement may not be valid for all care settings, but registries could provide the infrastructure for collecting data on the quality of cancer care. We urge that funding be increased to augment data collection by cancer registries.
Human Carboxylesterase-2 Hydrolyzes the Prodrug of Gemcitabine (LY2334737) and Confers Prodrug Sensitivity to Cancer Cells
Authors: Susan E. Pratt, Sara Durland-Busbice, Robert L. Shepard, Kathleen Heinz-Taheny, Philip W. Iversen, Anne H. Dantzig
Journal: Clinical Cancer Research (2013)

Abstract Purpose: The oral prodrug of gemcitabine LY2334737 is cleaved systemically to gemcitabine; the mechanism responsible for hydrolysis is unknown. LY2334737 cytotoxicity was tested in the NCI-60 panel; mining of microarray expression data identified carboxylesterase (CES) as a top hydrolase candidate. Studies examined whether CES is responsible for hydrolysis and whether cellular CES expression confers prodrug sensitivity. Experimental Design: Human recombinant CES isozymes were assayed for LY2334737 hydrolysis. Stable CES-overexpressing HCT-116 transfectants and a SK-OV-3 knockdown were prepared. Cell lines were tested for drug sensitivity and CES expression by quantitative real time-PCR (qRT-PCR), Western blotting, and immunohistochemical staining. Bystander cytotoxicity studies were conducted with GFP-tagged PC-3 cells as the reporter cell line. Therapeutic response of the HCT-116 transfectants was evaluated in xenografts. Results: Of 3 human CES isozymes tested, only CES2 hydrolyzed LY2334737. Five cell lines that express CES2 responded to LY2334737 treatment. LY2334737 was less cytotoxic to a SK-OV-3 CES2 knockdown than parental cells. The drug response of CES2-transfected HCT-116 cells correlated with CES2 expression level. Bystander studies showed statistically greater PC-3–GFP growth inhibition by LY2334737 when cells were cocultured with CES2 and not mock transfectants. Oral treatment of xenograft models with 3.2 mg/kg LY2334737 once a day for 21 days showed greater tumor growth inhibition of CES2 transfectant than the mock transfectant (P ≤ 0.001). Conclusions: CES2 is responsible for the slow hydrolysis of LY2334737. Because intact prodrug circulates at high plasma levels after oral LY2334737 administration, improved response rates may be observed by tailoring LY2334737 treatment to patients with CES2 tumor expression. Clin Cancer Res; 19(5); 1159–68. ©2012 AACR.
Surface strain distribution in isolated single lumbar vertebrae.
Authors: J S Shah, J Coggins, R Rogers, M I Jayson, W G Hampson
Journal: Annals of the Rheumatic Diseases (1976)

The surface strains of isolated single lumbar vertebrae under compressive load were examined by the techniques of brittlecoat and photoelastic analysis. Directions of principal strain components have been determined. Areas of stress concentration were found around the vertebral rims, near the pedicles, and around the foramina of the basivertebral veins.
Arginase I Production in the Tumor Microenvironment by Mature Myeloid Cells Inhibits T-Cell Receptor Expression and Antigen-Specific T-Cell Responses
Authors: Paulo C. Rodriguez, David G. Quiceno, Jovanny Zabaleta, Blair Ortiz, Arnold H. Zea, Maria B. Piazuelo, Alberto Delgado, Pelayo Correa, Jason Brayer, Eduardo M. Sotomayor, Scott Antonia, Juan B. Ochoa, Augusto C. Ochoa
Journal: Cancer Research (2004)

Abstract T cells infiltrating tumors have a decreased expression of signal transduction proteins, a diminished ability to proliferate, and a decreased production of cytokines. The mechanisms causing these changes have remained unclear. We demonstrated recently that peritoneal macrophages stimulated with interleukin 4 + interleukin 13 produce arginase I, which decreases the expression of the T-cell receptor CD3ζ chain and impairs T-cell responses. Using a 3LL murine lung carcinoma model we tested whether arginase I was produced in the tumor microenvironment and could decrease CD3ζ expression and impair T-cell function. The results show that a subpopulation of mature tumor-associated myeloid cells express high levels of arginase I, whereas tumor cells and infiltrating lymphocytes do not. Arginase I expression in the tumor was seen on day 7 after tumor injection. Tumor-associated myeloid cells also expressed high levels of cationic amino acid transporter 2B, which allowed them to rapidly incorporate l-Arginine (l-Arg) and deplete extracellular l-Arg in vitro. l-Arg depletion by tumor-associated myeloid cells blocked the re-expression of CD3ζ in stimulated T cells and inhibited antigen-specific proliferation of OT-1 and OT-2 cells. The injection of the arginase inhibitor N-hydroxy-nor-l-Arg blocked growth of s.c. 3LL lung carcinoma in mice. High levels of arginase I were also found in tumor samples of patients with non-small cell carcinoma. Therefore, arginase I production by mature myeloid cells in the tumor microenvironment may be a central mechanism for tumor evasion and may represent a target for new therapies.
Electrocardiographic Abnormalities That Predict Coronary Heart Disease Events and Mortality in Postmenopausal Women
Authors: Pentti M. Rautaharju, Charles Kooperberg, Joseph C. Larson, Andrea LaCroix
Journal: Circulation (2006)

Background— Information is limited about the independent prognostic value of repolarization abnormalities in women. Methods and Results— We evaluated hazard ratios for ECG variables for combined fatal and nonfatal coronary heart disease (CHD) events and for CHD mortality using Cox regression in 38 283 Women’s Health Initiative (WHI) participants during up to 9.2 years of follow-up. All risk models were adjusted for demographic, clinical, and therapeutic variables. Evaluated as single ECG variables, wide QRS/T angle and ECG-demonstrated myocardial infarction (ECG-MI) were the strongest predictors of CHD events, with hazard ratios (95% CI) of 1.90 (1.50 to 2.42) and 1.62 (1.29 to 2.03), respectively. Six other repolarization variables were also significant, strong predictors of CHD events. Wide QRS/T angle, ECG-MI, and QT prolongation appeared as dominant predictors when evaluated simultaneously with other ECG variables in a multiadjusted risk model. QRS/T angle, ECG-MI, and high QRS nondipolar voltage were the strongest predictors of CHD mortality, with hazard ratios of 2.70, 2.41, and 2.18, respectively. The risk increase ranged from 63% to 95% for the other 4 significant predictors. Five ECG abnormalities were identified as dominant mortality risk predictors: wide QRS/T angle, ECG-MI, high QRS nondipolar voltage, reduced heart rate variability, and QT prolongation (in the cardiovascular disease–free group only). Conclusions— Ventricular repolarization abnormalities in postmenopausal women are as important predictors of CHD events and CHD mortality as ECG-MI and other QRS abnormalities. Repolarization variables and QRS nondipolar voltage warrant attention in future investigations.
Phosphodiesterase-4 Inhibitor Therapy for Lung Diseases
Authors: Bianca Beghè, Klaus F. Rabe, Leonardo M. Fabbri
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Section:ChooseTop of pageAbstract <<Mechanisms of ActionPharmacokinetics and Phar...Clinical UseDosing StrategiesCombination TherapyMeasuring Effects and Out...Adverse EffectsStrategies to Improve the...Safety SystemsGuidelinesFuture DevelopmentsReferencesCITING ARTICLES
Gene manipulation and improvement of athletic performances: new strategies in blood doping
Authors: G Lippi, G C Guidi
Journal: British Journal of Sports Medicine (2004)

Aerobic athletic performances are greatly improved by optimisation of mechanisms of oxygen transport and delivery to peripheral tissues and muscles. There are both lawful and banned methods to achieve better muscular oxygenation; of these, the administration of erythropoiesis stimulating molecules, namely human recombinant erythropoietin (rHuEpo) or NESP, has been widely used by endurance athletes since the early 1990s.1 However, the introduction of a reliable laboratory test to detect blood doping with rHuEpo or derivatives has forced athletes to rely on alternative techniques, including blood …
E-learning in ultrasonography: a web-based approach
Authors: E. Filippucci, G. Meenagh, A. Ciapetti, A. Iagnocco, A. Taggart, W. Grassi
Journal: Annals of the Rheumatic Diseases (2007)

Objective: To propose e-learning methods that address the fundamental problems related to sonographic training in rheumatology. Methods: The project was designed for rheumatologists with strong motivation to learn ultrasound. A modular approach was constructed, consisting of a basic 3-day residential course, followed by a 6-month period of web-based tutoring, and culminating in a final 2-day residential course with a formal assessment of competency. Results: The website (<http://www.e-sonography.com>) was accessed by all 60 participants. A mean of 20 (range 10–80) log-on sessions were registered for each participant, and a mean of 250 min (range 60–600 min) of web access was recorded. A total of 163 sonographic images were submitted by 18 (30%) participants. The majority of the images focused on the following anatomical areas: shoulder 49 (30%), hand 34 (21%) and knee 20 (12%). A total time investment of approximately 14 h was made by the US tutors over the 6-month period for interaction with the participants. Conclusions: The e-learning methods described in this report represent the first attempt to adopt a novel technique to circumvent several of the inherent barriers to the many facets of teaching musculoskeletal ultrasound to a wide audience.
The cBio Cancer Genomics Portal: An Open Platform for Exploring Multidimensional Cancer Genomics Data
Authors: Ethan Cerami, Jianjiong Gao, Ugur Dogrusoz, Benjamin E. Gross, Selcuk Onur Sumer, Bülent Arman Aksoy, Anders Jacobsen, Caitlin J. Byrne, Michael L. Heuer, Erik Larsson, Yevgeniy Antipin, Boris Reva, Arthur P. Goldberg, Chris Sander, Nikolaus Schultz
Journal: Cancer Discovery (2012)

Abstract The cBio Cancer Genomics Portal (http://cbioportal.org) is an open-access resource for interactive exploration of multidimensional cancer genomics data sets, currently providing access to data from more than 5,000 tumor samples from 20 cancer studies. The cBio Cancer Genomics Portal significantly lowers the barriers between complex genomic data and cancer researchers who want rapid, intuitive, and high-quality access to molecular profiles and clinical attributes from large-scale cancer genomics projects and empowers researchers to translate these rich data sets into biologic insights and clinical applications. Cancer Discov; 2(5); 401–4. ©2012 AACR.
MORPHOLOGICAL STUDIES ON ALLERGEN INDUCED BLAST TRANSFORMATION OF SENSITIZED LYMPHOCYTES
Authors: B. PETRUNOV, J. TZVETANOV
Journal: Allergy (1975)

The morphological and ultrastructural changes occurring in blast transformed lymphocytes, isolated from patients sensitive to grass pollen and penicillin, were studied. Certain differences in the appearance of the blast cells, as evidenced by light microscopic observation, were not found by electron microscopy. The blast cells showed foamy protoplasm regardless of the nature of the allergens employed. An increased number of either single or rosette-forming ribosomes was established. Numerous vesicles were visible in the cytoplasm. The endoplasmic sacs were more numerous. Golgi apparatus was well-developed; the mitochondria were increased and had a dense matrix.
THE PINEAL GLAND AND MELATONIN: Molecular and Pharmacologic Regulation
Authors: Jimo Borjigin, Xiaodong Li, Solomon H. Snyder
Journal: The Annual Review of Pharmacology and Toxicology (1999)

The pineal gland expresses a group of proteins essential for rhythmic melatonin production. This pineal-specific phenotype is the consequence of a temporally and specially controlled program of gene expression. Understanding of pineal circadian biology has been greatly facilitated in recent years by a number of molecular studies, including the cloning of N-acetyltransferase, the determination of the in vivo involvement of the cAMP-inducible early repressor in the regulation of N-acetyltransferase, and the identification of a pineal transcriptional regulatory element and its interaction with the cone-rod homeobox protein. Likewise, appreciation the physiological roles of melatonin has increased dramatically with the cloning and targeted knockout of melatonin receptors. With these molecular tools in hand, we can now address more specific questions about how and why melatonin is made in the pineal at night and about how it influences the rest of the body.
Sleep {middle dot} 5: Driving and automobile crashes in patients with obstructive sleep apnoea/hypopnoea syndrome
Authors: C F P George
Journal: Thorax (2004)

Driving is a complex task involving distinct cognitive, perceptual, motor, and decision making skills. After placing the vehicle on the road, the driver must constantly survey the ever changing roadway environment to keep the vehicle in the lane and moving at an appropriate safe speed. This surveillance involves two distinct visual tasks: estimating and responding to the oncoming curvature and controlling lane position. Driving is therefore a divided attention task involving speed and lane control as well as monitoring. To do this in a safe manner requires careful attention and alertness which can be problematic for patients with obstructive sleep apnoea/hypopnoea syndrome (OSAHS) or other sleep disorders.
Chondroitin sulfate A is a cell surface receptor for Plasmodium falciparum-infected erythrocytes.
Authors: S J Rogerson, S C Chaiyaroj, K Ng, J C Reeder, G V Brown
Journal: The Journal of Experimental Medicine (1995)

Adherence of Plasmodium falciparum-infected erythrocytes to cerebral postcapillary venular endothelium is believed to be a critical step in the development of cerebral malaria. Some of the possible receptors mediating adherence have been identified, but the process of adherence in vivo is poorly understood. We investigated the role of carbohydrate ligands in adherence, and we identified chondroitin sulfate (CS) as a specific receptor for P. falciparum-infected erythrocytes. Parasitized cells bound to Chinese hamster ovary (CHO) cells and C32 melanoma cells in a chondroitin sulfate-dependent manner, whereas glycosylation mutants lacking chondroitin sulfate A (CSA) supported little or no binding. Chondroitinase treatment of wild-type CHO cells reduced binding by up to 90%. Soluble CSA inhibited binding to CHO cells by 99.2 +/- 0.2% at 10 mg/ml and by 72.5 +/- 3.8% at 1 mg/ml, whereas a range of other glycosaminoglycans such as heparan sulfate had no effect. Parasite lines selected for increased binding to CHO cells and most patient isolates bound specifically to immobilized CSA. We conclude that P. falciparum can express or expose proteins at the surface of the infected erythrocyte that mediate specific binding to CSA. This mechanism of adherence may contribute to the pathogenesis of P. falciparum malaria, but has wider implications as an example of an infectious agent with the capacity to bind specifically to cell-associated or immobilized CS.